KERALA HEART JOURNAL KERALA HEART JOURNAL Editor: Stigi Joseph the Official Journal of Cardiological Society of India, Kerala Chapter

The Official Journal of Cardiological Society of India, Kerala Chapter

p-ISSN: 2347-5267 e-ISSN: 2454-6755

January-June 2019 Volume-8, Issue-1

KHJKERALA HEART JOURNAL KERALA HEART JOURNAL Editor: Stigi Joseph The official Journal of Cardiological Society of India, Kerala Chapter

KERALA HEART JOURNAL (p-ISSN: 2347-5267), (e-ISSN: 2454-6755) January – June 2019, Volume – 8, Issue – 1.

Edotorial Board Editor Stigi Joseph Little Flower Hospital & Research Centre, Angamaly. Executive editor International Editorial Board Jonhson Francis, Baby Memorial Hospital, Kozhikode Chief International Editorial Advisor (Founder and emeritus editor Indian Pacing & Salim Yusuf. McMaster University. Hamilton Health Electrophysiology Journal) Sciences (President, World Heart Federation) Associate editors International Editorial Advisors Bhim Shankar: VPS Lakeshore Hospital, Kochi Navin. C. Nanda. University of Alabama, Birmingham Jo Joseph : Lisie Hospital, Ernakulam (Editor-in Chief, Echocardiography) Hisham Ahammed, Amrita Institute of Chandrashekhar, Minnesota Unversity (Deputy Editor Medical Sciences, Kochi JACC Cardiovascular Imaging) Boban Thomas, Navan, Ireland, Past Editors Syamkumar Divakaramenon, Hamilton,

Rajesh G, Govt. Medical College, Kozhikode Shahul Hameed, Doha, Qatar

(Founder Editor) Mithun Jacob Varghese, New York, USA Sanjay G, SCTIMST – Thiruvananthapuram Sajeer Kalathingathodika, Govt. Medical College, Kozhikode National Editorial Board Sandeep Mishra, New Delhi Editorial Associates (Past Editor, Indian Heart Journal) Anand Kumar V, Kochi Ajay Kumar Sinha, (P ast Associate Editor, Arun Gopi, Kozhikode Indian Heart Journal) Cibi Issac, Kochi Imran Ahammed, Kolkatta | Kiron Varghese, Bangaluru | Georgie Thomas, Abudhabi Arati D Lalchandani, Kanpur | Jyotsna M Hyderabad | Mukundan C, Thrissur BP Sing, Patna | MG Pillai, Mumbai | Rajasekhar Varma, Kochi BC Sreenivas, Bangaluru | George Joseph, Velloor | Sajan Ahamad, Thiruvalla Anita Saxena, New Delhi

January – June 2019, Volume – 8 Issue – 1 The official Journal of Cardiological Society of India, Kerala Chapter

Editorial Advisory Board Research P. P. Mohanan, Thrissur Cibu Mathew, Thrissur

Preventive Cardiology Electrophysiology Geevar Zachariah, Thrissur K. U. Natarajan, Kochi Shyam. N, Kollam Narayanan Namboothiri KK, Thiruvananthapuram (Editor in Cardiac Epidemiology chief Indian Pacing & A. George Koshy, Tvm. Electrophysiology Journal) Jayadeep C Menon, Angamaly Coronary Interventions Clinical Cardiology Sunitha Viswanathan, Tvm. N. Sudhayakumar, Kottayam. P. K. Ashokan, Kozhikode Prabha Neeni Gupta, Tvm. Peripheral Interventions Echocardiography M. N. Krishnan, Kozhikode Rajan Joseph Manjooran, Thiruvalla Prathapkumar, Kollam Balu Vaidhyanathan, Kochi Valvular Interventions CT & MRI Rajiv. C, Kochi, Ajithkumar V. K, Tvm. Shafeeq Mattummal Rajeev. E, Perinthalmanna Bijulal, Thiruvananthapuram

Coronary Imaging Rheumatic Heart Disease Rony Mathew, Kochi Abdul Khader, Thrissur , Asharaf, Pariyaram K. P. Balakrishnan, Kozhikode

Hemodynamics Cardiac Infections Jagan Mohan Tharakan, Palakkad Raju George, Kochi , Rajesh Muraleedharan,Kozhikode Saji Subramanyam, Kochi

Cardiovascular Therapeutics Cardiomyopathy Rajalakshmi, Thiruvananthapuram V. L. Jayaprakash, Kottayam , Varghese George, Thiruvalla Praveen. G. K, Tvm.

Heart Failure Cardiac Inflammation Harikrishnan. S, Tvm. Ramakrishna D, Kozhikode, Jabir.A. Kochi. Deepa, Thiruvananthapuram

Cardio Diabetology Biostatistics Jayagopal, Palakkad Tiny Nair, Tvm. Rupesh George, Thrissur Haridasan, Kozhikode

Geriatric Cardiology Cardiothoracic Surgery Venugopal. K, Thiruvalla Nandakumar, Kozhikode Editorial Secretariat: Mathew Abraham, Thodupuzha Rafeeq. A. K, Angamaly Stigi Joseph Little Flower Hospital and Paediatric Cardiology Cardiac Anaesthesia Research Centre, Sivasankaran. S, Tvm. Jacob Abraham, Kochi, Angamaly, Kochi. 683572. Krishnakumar. R, Kochi, Deepu Antony Mob: +91 9446279889 Edwin Francis, Kochi Email: [email protected]

January – June 2019, Volume – 8 Issue – 1 The official Journal of Cardiological Society of India, Kerala Chapter

CSI Kerala Office Bearers

President Markose K.P Vice President Sajeev CG Secretary Karunadas CP Treasurer Manikandan TV Imm. Past President Raju George Imm. Past Secretary Syam N

EC Members Cibu Mathew Mathew Abraham Mathew Iype Mathews Paul Ramakrishna CD Shifas Babu Stigi Joseph Sunil Shivdas

January – June 2019, Volume – 8 Issue – 1 The official Journal of Cardiological Society of India, Kerala Chapter

KERALA HEART JOURNAL (p-ISSN: 2347-5267), (e-ISSN: 2454-6755) January – June 2019, Volume – 8, Issue – 1.

Table of Contents

Non-Inflammatory Risk Markers for Cardiovascular Disease...... 7 Ramakrishna C.D. MD,DM, Ish Kalra

Does Serum Uric Acid Fare Similar To Serum High-sensitivity C-reactive protein as Vascular Inflammatory Marker Of Coronary Artery Disease In Young Asian Indians?...... 13 Santanu Guha MD.DM, Imran Ahmed MD.DM

An Interesting Case of Restrictive Cardiomyopathy...... 19 Madhu sreedharn.MD.DM.

Principles and practice of modern endovascular therapy in patients with acute ischemic stroke...... 22 MuneerEesa MD Bijoy K. Menon MD

Endovascular thrombectomy for acute ischemic stroke...... 32 Sajan Narayanan MD. DM.

Image Challenge...... 35 Rajiv C. MD. DM, Hisham Ahammed MD. DM

A simplified approach to wide complex tachycardia in emergency room...... 37 Abhilash SP, MD.DM

Management of arrhythmogenic inflammatory cardiomyopathy: a case based discussion...... 44 Thachil A, Mathew R, Jose J, Abdullakutty J, Joseph J, George J, Sundaram PS

ECG Challenge...... 50 Bhim Shankar MD. DM.

Spontaneous Coronary Artery Dissection- A Disease of Young Males?...... 52 K J Raihanathul Misiriya MD, DN, Narayanapillai Jayaprasad MD, DM Anwar C Varghese MD, DM, K Jayaprakash MD, DM, Suresh Madhavan MD, DM V. Sudhakumary MD, DM, V.L Jayaprakash MD, DM, Raju George MD, DM

Anomalous Origin of Left Coronary Artery from Pulmonary Artery ...... 57 presenting with Atrial Fibrillationand Angina CP Karunadas MD, DNB, DM, DNB, FESC, Cibu Mathew MD, DNB, DM, DNB

January – June 2019, Volume – 8 Issue – 1 The official Journal of Cardiological Society of India, Kerala Chapter

An unusual cause of angina...... 62 Vijin Joseph V.F MD, Jo Joseph MD.DM. Jimmy George MD. DM, Jabir Abdullakutty MD. DM Jacob Joseph MD.DM, Rony Mathew MD. DM

Non-Atheromatous Causes of Acute Coronary Syndromes...... 66 Deepak Davidson.MD.DM.

Determination Of Ventilatory Minute Volumes For Normocapnic...... 84 Ventilation In Postoperative Cardiac Surgery Patients Chaudhari Anushree A. MD.DNB, Puri Goverdhan D. MD. PhD Kumar Bhupesh. MD. DM, Bhalla Anil K.MD

January – June 2019, Volume – 8 Issue – 1 The offi cial Journal of Cardiological Society of India, Kerala Chapter

KHJKERALA HEART JOURNAL

A Journal of Cardiological Society of India Kerala Chapter

p-ISSN: 2347-5269 e-ISSN: 2454-6755 KERALA HEART JOURNAL (p-ISSN: 2347-5267), (e-ISSN: 2454-6755) January - June 2019, Volume - 8, Issue - 1

Editor in Chief Dr. Stigi Joseph

Ramakrishna C.D* Ish Kalra** *Professor, **Senior Resident Department of Cardiology, Kannur Govt Medical College, Pariyaram. Correspondence:[email protected].

REVIEW ARTICLE Non-Infl ammatory Risk Markers for Cardiovascular Disease

ABSTRACT ndians have been reported to have high prevalence rates of coronary artery disease (CAD) even in the absence of tradi- Itional risk factors. The use of risk markers has transformed cardiovascular medicine, exemplifi ed by the routine assessment of troponin, for both diagnosis and assessment of prognosis in patients with chest pain. Clinical risk factors form the basis for risk assessment of cardiovascular disease and the addition of biochemical, cellular, and imaging parameters offer further refi nement. Identifying novel risk factors may allow greater risk stratifi cation and a steady, but gradual progression toward precision medicine. Risk markers related to atherosclerosis, thrombosis, infl ammation, cardiac injury, and fi brosis are introduced in the context of their pathophysiology. Rapidly developing new areas, such as assessment of micro-RNA, are also explored. These markers may be helpful in risk assessment in premature cardiovascular disease and in individuals where traditional risk factors are not presen

INTRODUCTION routine measurement of troponin, both for diagnosis and assessment of prognosis in patients with chest pain. CCardiovascular disease is the leading cause of death, accounting for 29% of all deaths in 2017, according to the Infl ammation has a central role in the pathophysiology of WHO. The reported prevalence of coronary heart disease atherosclerosis, which is highlighted by the high cardiovas- (CAD) in adult surveys has risen 4-fold over the last 40 years cular risk of systemic infl ammatory disorders, particularly (to a present level of around 10%), and even in rural areas, systemic autoimmune disorders and systemic vasculitis. In the prevalence has doubled over the past 30 years (to a the general infl ammatory markers like IL-6, CRP and My- present level of around 4%). CAD strikes Indian population eloperoxidase(MPO) are well known for diagnosis and pro- at a younger age and kills many in their productive mid-life viding additive predictive ability for cardiovascular disease. years. Deaths due to CAD, in the age group of 35 to 64 years, More recently, but less clearly established, emerging prdic- resulted in 9.2 million potentially productive years of life tors of coronary artery disease like non-infl ammatory mark- being lost in 2012. ers have come into the light. This article provides insight into Studies suggest that most CAD events are noted in indi- non-infl ammatory markers associated with increased risk in viduals with one or more risk factors. However, at least 25 cardiovascular disease. Combined with an understanding of percent of patients have myocardial infarction or sudden the pathophysiological role of each marker, this helps to sug- death without prior symptoms. The use of risk markers has gest whether each marker could be a simple risk biomarker transformed cardiovascular medicine, as exemplifi ed by- or may also represent a modifi able risk factor.

January – June 2019, Volume – 8 Issue – 1 7 The official Journal of Cardiological Society of India, Kerala Chapter

LIPID RELATED RISK MARKERS or instead proceeds to dissolution. Because thrombosis is central to the pathophysiology of ACS and embolic stroke Coronary artery disease is the leading cause of death in atrial fibrillation (AF), both prothrombotic factors and worldwide. Atherosclerosis of the coronary arteries is pri- markers of endogenous fibrinolysis have been extensively marily driven by cholesterol and, in particular, low-densit investigated in these conditions. Following are risk markers lipoprotein cholesterol (LDL-C). The causative role of LDL-C related to thrombosis. in coronary artery disease is clearly demonstrated by the success of LDL-C lowering drugs, such as statins, and Men- 1. Platelet reactivity: Assessment of the reactivity of plate- delian randomization studies. Recently, it has been dis- let signaling pathways can be used to identify response covered that proprotein convertase subtilisin/kexin type 9 to antiplatelet therapy in the context of coronary artery has a significant role in the regulation of LDL-C, and lev- disease.3 Results of the Verify Now and Multiplate tests els of soluble proprotein convertase subtilisin/kexin type are well standardized and are predictive of adverse car- 9 have been identified as a new marker of cardiovascular diovascular events.4-6 risk. Although traditionally thought to reduce cardiovascu- 2. Circulating progenitor cells: These cells are inversely as- lar risk, the role of highdensity lipoprotein cholesterol has sociated with cardiovascular risk factors. These are Im- now been brought into question by negative findings from mature bone marrow-derived cells, which are mostly of clinical trials of drugs that increase high-density lipopro- hematopoietic origin.7 They are involved in endothelial tein cholesterol and by negative Mendelian randomization repair and angiogenesis.7 studies. Following are lipid-related risk markers. 1. PCSK9: Influenced by the use of statins and diurnal variation. Promotes the degradation of hepatocyte LDL re- RISK MARKERS RELATED TO CARDIAC ceptors, which have an important role in lowering plas- malevels of LDL.1 INJURY, HEALING AND FIBROSIS During acute and chronic cardiac injury, reparative mecha- 2. OxPL(Oxidized Phospholipids): OxPL are covalently nisms must find a careful balance between remodeling the bound to lipoproteins that contain apoB100. Suggested heart to maintain structural integrity while also preserving to be a specific biomarker for oxidation 2 and contribute myocardial function. toward atherogenesis.2 1. Troponin T and troponin I: Contained within myocardial contractile apparatus and cardiac muscle tissue.8 Re- THROMBOSIS RELATED RISK MARKERS leased via proteolytic degradation on cell death.8 After atherosclerotic plaque rupture, platelets adhere to 2. NT-proBNP: Released in response to Myocardial stretch. exposed subendothelial components, such as collagen and It is Inactive N-terminal fragment of the precursor for von Willebrand factor, which promotes platelet activation BNP 9. and aggregation. Besides, platelet activation is potentiated 3. MR-proANP: Released in response to Myocardial stretch, by exposure to released soluble agonists, such as thrombin derived from cleavage of the midregional part of the and ADP. Activated platelets then further release ADP, which precursor of ANP.104. MR-proADM: Released in response acts on platelet P2Y12 ADP receptors and has a central role to Myocardial stretch, derived from cleavage of the mid- in amplifying the response of platelets to the initial stimu- regional part of the precursor of adrenomedullin.11 Ad- lus. The VerifyNow and Multiplate point of care tests allow renomedullin(ADM) is synthesized by the endothelium for the measurement of platelet aggregation in response to and has many cardiovascular effects that are similar to stimulation, and it has been shown that high platelet reac- nitric oxide, including potent vasodilation.12 tivity is associated with adverse cardiovascular events. Platelet micro particles are released on platelet activation, and their RISK MARKERS RELATED TO HEMODY- role in cardiovascular disease is an area of active inves- NAMIC STRESS AND RENAL FUNCTION: tigation. Circulating microparticles are released from cells undergoing activation or apoptosis and are a type of small Mechanical stretch and other mediators, such as angioten- plasma membrane vesicle that retains defined properties sin II and adrenergic agonists, induce cleavage of prepro- from their original cell lineage. Platelet activation and ag- hormones and secretion of natriuretic peptides by cardio- gregation lead to the activation of the coagulation cascade myocytes. Both atrial natriuretic peptide (ANP) and brain and the formation of a stable cross-linked fibrin clot. The natriuretic peptide (BNP) predominantly act on natriuretic balance between prothrombotic factors and endogenous peptide receptor A, which leads to the inhibition of the re- fibrinolysis determines whether the thrombus propagates nin–angiotensin– aldosterone system, diuresis, and natri-

8 January – June 2019, Volume – 8 Issue – 1 The official Journal of Cardiological Society of India, Kerala Chapter

uresis. Secretion of both ANP and BNP are increased during versely associated with left ventricular remodeling after hemodynamic overload, and cardiac remodeling and are MI.18 It has Role in megakaryopoiesis19 and also Highly therefore indicative of heart failure. Additional markers of expressed in platelets and platelet microparticles. hemodynamic stress and renal disturbance include cystatin-C. 6. miR-223: It is Reduced by platelet inhibition, and it is inversely associated with subsequent MI.20 It is highly 1. Cystatin-C: Synthesized by all nucleated cells at a con- expressed in platelets. stant rate, freely filtered by the renal glomerulus with no reabsorption into the blood.13 Less influenced by 7 miR-197: It is also reduced by platelet inhibition, diet or muscle mass than creatinine, allowing it to be a in-versely associated with subsequent MI and highly reliable marker of renal glomerular filtration rate.13 expressed inplatelets.

8. miR-126: It is reduced in diabetes mellitus. It is reduced MICRO-RNA RELATED RISK MARKERS: by platelet inhibition, and it is a regulator of endothelial and vascular integrity.21 It modulates the vascular There has been much recent interest in the role of micro- RNAs (miRNA) in the pathophysiology of cardiovascular expression of adhesion molecules22 and is highly ex- disease.mi-RNAs are short noncoding RNAs that have a pressed in platelets and platelet microparticles. Also, it significant role in pathophysiological stress responses and is predictive of subsequent MI. mediate many cellular processes by regulating gene ex- 9. miR-143/145: Released in response to shear stress. It pression. miRNAs interact with specific mRNA to regulate plays a major role in the modulation of VSMC pheno their translation,mostly by suppression of protein synthe- type.23 sis. Most miR-NAs are located intracellularly while platelets and platelet microparticlesare an abundant circulating 10. miR-622: Increased in heart failure and levels correlate- source. with BNP.24 miRNAs regulate a diverse range of processes in cardiovas- 11. miR-21: Released in response to Fibrosis and has Role cular disease, including myocardial remodeling and fibro- inmyocardial remodeling and fibrosis.25 sis, vascular inflammation, lipid processing, and electric remodeling.It has also recently been shown that miRNAs 12. miR-29: Released in response to Fibrosis and has Pos- can act as a novel biomarker for platelet reactivity and that sible role in myocardial remodeling, hypertrophy, and fibrosis.26 It also Regulates MMP expression.27 their levels can be manipulated by the administration of antiplatelet therapy. Specific synthetic antagonists of miR- 13. miR-328: Released in response to Atrial fibrillation, it NAs (antagomiRs) are currently in development, and it is Regulates possible that these could prove beneficial in cardiovascular IMAGING RELATED RISK MARKERS: disease. Micro RNA related markers are the following. In recent years, there has been a dramatic increase in the 1. miR-1: Released in response to ACS. It is Associated with number of imaging modalities that are available for use cardiomyocyte necrosis14 and inversely associated with in clinical practice. Cardiac imaging provides sophisticat- cardiac hypertrophy.15 ed measures of many different pathological processes, in- 2. miR-133: Released in response to ACS. It is Associated cluding quantification of coronary artery disease and the with cardiomyocyte necrosis14 and inversely associated presence of plaque rupture, as well as the determination of with cardiac hypertrophy.15 Also, it has Role in the mod- myocardial infarct size and the presence of microvascular ulation of VSMC phenotype.16 obstruction.

3. miR-208: Released in response to ACS. It is Associated More recent techniques, such as coronary computed to- with cardiomyocyte necrosis14 and is regulated during mographic angiography and optical coherence tomography cardiac hypertrophy.17 allow for some assessment of plaque morphology, beyond a simple assessment of luminal stenosis. Further develop- 4. miR-499: Released in response to ACS and Heart fail- ment of imaging technologies may offer the possibility for ure Muscle-specific miR that is released during acute MI detailed plaque assessment, including determination of and levels of miR-499 correlates with levels of troponin. plaque inflammation, which may suggest plaques at high 5. miR-150: It is Reduced by platelet inhibition and In- risk of rupture.

January – June 2019, Volume – 8 Issue – 1 9 The official Journal of Cardiological Society of India, Kerala Chapter

Marker Releasedin Response to Role

Myocardial infarct Myocardial infarction Demonstrated by infarcted myocardial tissue in size (CMR) late gadolinium images on CMR imaging29

Microvascular Microvascular thrombosis Demonstrated by regionsof myocardial hypoen- obstruction (CMR) and inflammation hancement during the first 2 min of gadolinium- contrast administration

CTCA Coronary artery disease Noninvasive investigation for detecting obstructive and nonobstructive CAD, which allows rapid determination of the diagnosis of suspected angina.30 CTCA correlates well with the findings of invasive angiography, with high accuracy and sensitivity of >97% in several studies,31 although this may be lower in distal lesions. Coronary artery calcium scoring provides an indicator of the overall prevalence of coronary artery disease.32

MR coronary Coronary artery disease MR coronary angiography is appealing as it does angiography not involve radiation and provides excellent soft-tissuecontrast.33 However, current applications of MR coronary angiography are limited because of temporal resolution, which is exacerbated by the small caliber and complex motion of the coronary arteries

Optical coherence Plaque rupture Intracoronary light-based technology that allows tomography for detailed characterization of coronary artery plaque. Plaque rupture can be differentiated from an intact fibrous cap on the basis of a dis- continuity in the fibrous cap34

ENDOTHELIN of CAD): In patients who use statins, severe coronary Estimation of plasma endothelin by ELISA using DRG’s hu- artery disease (CAD) was associated with low levels of man ET-1 enzyme immunometric assay kit can also be used the highdensity lipoprotein cholesterol sub particle 3 as a marker for CAD. (HDL3-C) and with high levels of lipoprotein(a) cholesterol (Lp[a]-C). The investigators sought to identify the association of HOMOCYSTEINE high-density lipoprotein cholesterol (HDL-C) subparticles Estimation of Homocysteine was done by using dia- with severe CAD. It was seen that patients with severe CAD zyme homocysteine microtitre plate assay (EIA). The were associated with a significantly lower total HDL-C and assay employs a genetically engineered Homocysteine HDL₃-C and significantly higher Lp[a]-C. Binding Protein (HBP) as the capturing agent. LIPO- PROTEIN (a):The plasma Lp(a) can be determined using CONCLUSION: Apart from established inflammatory mark- DRG Elitest assay kit. The amount of color produced is ers, levels of non-inflammatory markers are also elevated proportional to the amount of Lp(a)present in the sam- in CAD patients. Thus, they may serve as potential markers ple. NOVEL LIPID BIOMARKER HDL3-C (Predicts severity of CAD. These biomarkers may be helpful in risk assessment

10 January – June 2019, Volume – 8 Issue – 1 The official Journal of Cardiological Society of India, Kerala Chapter

in premature cardiovascular disease and in individuals 9. Kragelund C, Grønning B, Køber L, Hildebrandt P, Stef- where traditional risk factors are not present. fensen R. N-terminal pro-B-type natriuretic peptide and long-term mortality in stable coronary heart disease. N Engl J Med. 2005;352:666–675. doi: 10.1056/NEJ- REFERENCES Moa042330. 1. Leander K, Mälarstig A, Van’t Hooft FM, Hyde C, Hellénius 10. Gegenhuber A, Struck J, Poelz W, Pacher R, Morgen- ML, Troutt JS, Konrad RJ, Öhrvik J, Hamsten A, de Faire thal-er NG, Bergmann A, Haltmayer M, Mueller T. Midre- U. Circulating proprotein convertase subtilisin/kex- gion-al pro- A-type natriuretic peptide measurements in type 9 (PCSK9) predicts future risk of cardiovascu- for diagnosis of acute destabilized heart failure in short lar events independently of established risk factors. of- breath patients: comparison with B-type natriuretic Cir-culation. 2016;133:1230–1239. doi: 10.1161/CIRCULA- peptide (BNP) and amino-terminal proBNP. Clin Chem. TIONA-HA.115.018531. 2006;52:827–831. doi: 10.1373/ clinchem.2005.065441. 2. Byun YS, Lee JH, Arsenault BJ, Yang X, Bao W, DeMicco D, 11. Klip IT, Voors AA, Anker SD, Hillege HL, Struck J, Squire I, Laskey R, Witztum JL, Tsimikas S; TNT Trial Investigators. van Veldhuisen DJ, Dickstein K; OPTIMAAL Investiga-tors. Relationship of oxidized phospholipids on apolipo- Prognostic value of mid-regional proadreno-medul- protein\ B-100 to cardiovascular outcomes in patients lin in patients with heart failure after acute myo-car- treated with intensive versus moderate atorvastatin dial infarction. Heart. 2011;97:892–898. doi: 10.1136/ therapy: the TNT trial. J Am Coll Cardiol. 2015;65:1286– hrt.2010.210948. 1295. doi: 10.1016/j. jacc.2015.01.050. 12. Kitamura K, Kangawa K, Eto T. Adrenomedullin and PAMP: 3. Thomas MR, Storey RF. Clinical significance of residu-al discovery, structures, and cardiovascular functions. Mi- platelet reactivity in patients treated with platelet crosc Res Tech. 2002;57:3–13. doi: 10.1002/jemt.10052. P2Y12 inhibitors. Vascul Pharmacol. 2016;84:25–27. doi: 10.1016/j.vph.2016.05.010. 13. Åkerblom A, Wallentin L, Larsson A, Siegbahn A, Becker RC, Budaj A, Himmelmann A, Horrow J, Husted S, Storey 4. Aradi D, Storey RF, Komócsi A, Trenk D, Gulba D, Kiss RG, RF, Asenblad N, James SK; PLATO Investigators. Cystatin Husted S, Bonello L, Sibbing D, Collet JP, Huber K; Work- C- and creatinine-based estimates of renal function ing Group on Thrombosis of the European Society of and their value for risk prediction in patients with acute Cardiology. Expert position paper on the role of platelet coronary syndrome: results from the PLATelet Inhi- function testing in patients undergoing percutaneous bi-tion and Patient Outcomes (PLATO) study. Clin Chem. coronary intervention. Eur Heart J. 2014;35:209–215. doi: 2013;59:1369–1375. doi: 10.1373/ clinchem.2012.200709. 10.1093/eurheartj/eht375. Circ Res. 2016;118:607–619. doi: 10.1161/ CIRCRE- 5. Breet NJ, van Werkum JW, Bouman HJ, Kelder JC, Ruven SA-HA.115.306360. HJ, Bal ET, Deneer VH, Harmsze AM, van der Heyden JA, 14. Wang GK, Zhu JQ, Zhang JT, Li Q, Li Y, He J, Qin YW, Jing Q. Cir- Rensing BJ, Suttorp MJ, Hackeng CM, ten Berg JM. Com- culating microRNA: a novel potential biomarker for early parison of platelet function tests in predict-ing clin- diagnosis of acute myocardial infarction in humans. Eur ical outcome in patients undergoing coronary stent Heart J. 2010;31:659–666. doi: 10.1093/ eurheartj/ ehq013. implantation. JAMA. 2010;303:754–762. doi: 10.1001/ jama.2010.181. 15. Carè A, Catalucci D, Felicetti F, et al. MicroRNA-133 controls cardiac hypertrophy. Nat Med. 2007;13:613–618. doi: 6. Sibbing D, Braun S, Morath T, Mehilli J, Vogt W, Schömig 10.1038/nm1582. A, Kastrati A, von Beckerath N. Platelet reactivity after clopidogrel treatment assessed with point-of-care anal- 16. Torella D, Iaconetti C, Catalucci D, Ellison GM, Leone A, ysis and early drug-eluting stent thrombosis. J Am Coll Waring CD, Bochicchio A, Vicinanza C, Aquila I, Curcio Cardiol. 2009;53:849–856. doi: 10.1016/j.jacc.2008.11.030. A, Condorelli G, Indolfi C. MicroRNA-133 controls vascu- 7. Rigato M, Avogaro A, Fadini GP. Levels of circulating lar smooth muscle cell phenotypic switch in vitro and progenitor cells, cardiovascular outcomes and death: vas-cular remodeling in vivo. Circ Res. 2011;109:880–893. a meta-analysis of prospective observational stud- doi: 10.1161/CIRCRESAHA.111.240150. ies. Circ Res. 2016;118:1930–1939. doi: 10.1161/ CIRCRE- 17. Van Rooij E, Sutherland LB, Qi X, Richardson JA, Hill J, Ol- SA-HA.116.308366. son EN. Control of stress-dependent cardiac growth and 8. Apple FS, Collinson PO; IFCC Task Force on Clinical Appli- gene expression by a microRNA. Science. 2007;316:575– cations of Cardiac Biomarkers. Analytical characteristics 579.doi: 10.1126/science.1139089. of high-sensitivity cardiac troponin assays. Clin Chem. 18. Devaux Y, Vausort M, McCann GP, Kelly D, Collignon O, Ng 2012;58:54–61. doi: 10.1373/ clinchem.2011.165795. LL, WagnerDR, Squire IB. A panel of 4 microRNAs facili-

January – June 2019, Volume – 8 Issue – 1 11 The official Journal of Cardiological Society of India, Kerala Chapter

tates the prediction of left ventricular contractility after of miR- 29 in cardiac fibrosis. Proc Natl Acad Sci U S A. acute myocardial infarction. PLoS One. 2013;8:e70644. 2008;105:13027–13032. doi: 10.1073/ pnas.0805038105. doi: 10.1371/journal.pone.0070644. 27. Chen KC, Wang YS, Hu CY, Chang WC, Liao YC, Dai CY,- 19. Barroga CF, Pham H, Kaushansky K. Thrombopoie- Juo SH. OxLDL up-regulates microRNA-29b, leading to tin regulates c-Myb expression by modulating micro epigenetic modifications of MMP-2/MMP-9 genes: a RNA 150 expression. Exp Hematol. 2008;36:1585–1592. novel mechanism for cardiovascular diseases. FASEB J. doi:10.1016/j.exphem.2008.07.001. 2011;25:1718–1728. doi: 10.1096/fj.10-174904. 20. Zampetaki A, Willeit P, Tilling L, Drozdov I, Prokopi M,Re- 28. Lu Y, Zhang Y, Wang N, Pan Z, Gao X, Zhang F, Zhang Y, nard JM, Mayr A, Weger S, Schett G, Shah A, Boulanger Shan H, Luo X, Bai Y, Sun L, Song W, Xu C, Wang Z, Yang B. CM, Willeit J, Chowienczyk PJ, Kiechl S, Mayr M. Prospec- MicroRNA-328 contributes to adverse electrical remod- tive study on circulating MicroRNAs and risk of myocar- eling in atrial fibrillation. Circulation. 2010;122:2378– dial infarction. J Am Coll Cardiol. 2012;60:290–299. doi: 2387. doi: 10.1161/CIRCULATIONAHA.110.958967. 10.1016/j.jacc.2012.03.056. 29. Eitel I, de Waha S, Wöhrle J, Fuernau G, Lurz P, Paus- 21. Zernecke A, Bidzhekov K, Noels H, Shagdarsuren E, Gan chinger M, Desch S, Schuler G, Thiele H. Comprehensive L, Denecke B, Hristov M, Köppel T, Jahantigh MN, Lutgens prognosis assessment by CMR imaging after ST-seg- E, Wang S, Olson EN, Schober A, Weber C. Delivery of ment elevation myocardial infarction. J Am CollCardiol. microRNA-126 by apoptotic bodies induces CXCL12-de- 2014;64:1217–1226. doi: 10.1016/j.jacc.2014.06.1194. pendent vascular protection. Sci Signal. 2009;2:ra81. doi: 10.1126/scisignal.2000610. 30. SCOT-HEART Investigators. CT coronary angiography in patients with suspected angina due to coronary heart 22. Asgeirsdóttir SA, van Solingen C, Kurniati NF, Zwiers disease (SCOT-HEART): an open-label, parallel-group, PJ, Heeringa P, van Meurs M, Satchell SC, Saleem MA, multicentre trial. Lancet. 2015;385:2383–2391. Mathieson PW, Banas B, Kamps JA, Rabelink TJ, van Zonneveld AJ, Molema G. MicroRNA-126 contributes to 31. Stehli J, Fuchs TA, Bull S, Clerc OF, Possner M, Buechel renal microvascular heterogeneity of VCAM-1 protein RR, Gaemperli O, Kaufmann PA. Accuracy of coronary CT expres-sion in acute inflammation. Am J Physiol Renal angiography using a submillisievert fraction of radiation Physiol. 2012;302:F1630–F1639. doi: 10.1152/ajprenal. exposure: comparison with invasive coronary angiog-ra- 00400.2011 phy.J Am Coll Cardiol. 2014;64:772–780. doi:10.1016/j. jacc.2014.04.07. 23. Lovren F, Pan Y, Quan A, Singh KK, Shukla PC, Gupta N, Steer BM, Ingram AJ, Gupta M, Al-Omran M, Teoh H, 32. Yeboah J, Young R, McClelland RL, Delaney JC, Polonsky Mars-den PA, Verma S. MicroRNA-145 targeted therapy TS, Dawood FZ, Blaha MJ, Miedema MD, Sibley CT, Carr JJ, reduc-es atherosclerosis. Circulation. 2012;126:S81–S90. Burke GL, Goff DC Jr, Psaty BM, Greenland P, Herrington doi: 10.1161/CIRCULATIONAHA. 111.084186. DM. The utility of nontraditional risk markers in ath- 24. Vogel B, Keller A, Frese KS, Leidinger P, Sedaghat-Hamed- eroscleroticcardiovascular disease risk assess-ment. ani F, Kayvanpour E, Kloos W, Backe C, Thanaraj A, Brefort J Am Coll Cardiol. 2016;67:139–147. doi: 10.1016/j. T, Beier M, Hardt S, Meese E, Katus HA, Meder B. Multi- jacc.2015.10.058. var-iate miRNA signatures as biomarkers for nonisch- 33. Dweck MR, Puntman V, Vesey AT, Fayad ZA, Nagel E. MR Im- aemic systolic heart failure. Eur Heart J. 2013;34:2812– aging of Coronary Arteries and Plaques. JACC Cardiovasc 2822. doi: 10.1093/eurheartj/eht256. Imaging. 2016;9:306– 316. doi: 10.1016/j.jcmg.2015.12.003. 25. Thum T, Gross C, Fiedler J, et al. MicroRNA-21 contrib- 34. Niccoli G, Montone RA, Di Vito L, Gramegna M, Refaat utes to myocardial disease by stimulating MAP kinase- H,Scalone G, Leone AM, Trani C, Burzotta F, Porto I, Au-ri- signaling in fibroblasts. Nature. 2008;456:980–984. doi: gemma C, Prati F, Crea F. Plaque rupture and intact fi- 10.1038/nature07511. brouscap assessed by optical coherence tomogra-phy 26. van Rooij E, Sutherland LB, Thatcher JE, DiMaio JM, Na- portend different outcomes in patients with acute seem RH, Marshall WS, Hill JA, Olson EN. Dysregulation coronary syndrome. Eur Heart J. 2015;36:1377–1384. doi: of microRNAs after myocardial infarction reveals a role 10.1093/eurheartj/ ehv029.

12 January – June 2019, Volume – 8 Issue – 1 The offi cial Journal of Cardiological Society of India, Kerala Chapter

KHJKERALA HEART JOURNAL

A Journal of Cardiological Society of India Kerala Chapter

p-ISSN: 2347-5269 e-ISSN: 2454-6755 KERALA HEART JOURNAL (p-ISSN: 2347-5267), (e-ISSN: 2454-6755) January - June 2019, Volume - 8, Issue - 1

Editor in Chief Dr. Stigi Joseph

Santanu Guha MD.DM ** Imran Ahmed MD.DM* *Assistant Professor ** Professor and Head *** Associate professor Dept. of Cardiology, IPGMER, Kolkata. Correspondence:[email protected]

Does Serum Uric Acid Fare Similar To Serum High-sensitivity C-reactive protein as Vascular Infl ammatory Marker Of Coronary Artery Disease In Young Asian Indians?

ABSTRACT Background: India is estimated to have one of the highest coronary artery disease (CAD) burden in the world. Indians manifest CAD at a younger age. Infl ammation plays a key role in CAD progression. Infl ammatory marker high sensitivity C-reactive protein (hsCRP) predicts CAD risk either by correlation with CAD extent (disease marker) or as an indicator of infl ammatory event that leads to plaque rupture (a process marker). It has been proposed that serum uric acid concentrations can be used as a cardiovascular risk marker in the same way that High-sensitivity C-reactive protein (hs CRP) is being used.

Aim: Results: To assess the role of vascular infl ammation using markers Both mean serum uric acid and hs CRP were elevated in like serum uric acid and hs CRP, and fi nd if it is a cost effec- Young CAD patients more than in those of Old CAD patients tive and relevant method for young Indians . and Controls, and this trend was found to be signifi cant by ANOVA (P=0.015/P = 0.028). Serum uric acid and hs CRP lev- Methods: els were found to be in direct proportion to both stenosis and extent score of coronary artery disease (P <0.01) in Serum uric acid (measured by colorimetry) and serum hs young adults. CRP (measured by immune-turbidimetry technique) level was measured in young adults (18–45 years) with angiographic proven CAD (60 patients), and compared with those Conclusion: >45 years age (24 patients), and in controls with no CAD (14 patients). Later, the levels of markers were compared with Serum uric acid fared similar to hs CRP as vascular infl am- the angiographic stenosis and extent score in young CAD mation markers and have a positive correlation with the patients. disease burden in the young CAD patient. Premature CAD in

January – June 2019, Volume – 8 Issue – 1 13 The official Journal of Cardiological Society of India, Kerala Chapter

Young Indians could be partly explained by increased vas- Study design: cular inflammation. Further studies to identify & reduce risk Our Study was a cross-sectional study. Among the selected factors in an economically and socially relevant section of cases, the test group of patients with age <45 years were population of a fast developing country like India is needed. labelled as “Young CAD” group and those with age >45 years were labelled as “Old CAD” group. The patients who had Keywords: chest pain but normal coronary angiograms were taken as control subjects (labelled as “controls”). Angiographic esti- Angiographic stenosis, Angiographic extent, serum uric mation of coronary atherosclerosis: Coronary angiography acid, hs CRP, Young coronary artery disease. The burden of was performed by the femoral approach and included at- CAD in developing countries has increased in the last three least 4 views of the left coronary artery and 2 views of the decades. In India, CAD continues to rise and is now involv- right coronary artery. ing middle and lower income class groups. CAD is responsible for an estimated 25% of all deaths in India.1 Symptoms of CAD arise a full 10 years earlier in India than in Western Stenosis Score: countries.2 However, only a few studies on epidemiologi- Stenosis Score used was a modified Gensini score. 5 Ste- cal data from angiographically proven cases of premature nosis score provides information related to the bulk of the CAD (≤40 –45 years) in native Indians are available. Vascular atherosclerotic lesion and is influenced by episodic pro- inflammation plays a key role in coronary artery disease cesses such as plaque rupture. Each of eight vessel seg- (CAD) and other manifestations of atherosclerosis. ments was graded according to severity of occlusion; grade High-sensitivity C-reactive protein , an inflammatory bio- 1 for 1% to 49% occlusion in lumen diameter, 2 for 50% to marker, has independently proven as one of the most pow- 74%, 3 for 75% to 99%, and 4 for total occlusion. The score erful predictors of cardiovascular disease.3 In the search in each of the eight segments were added to give a total for other novel inflammatory markers,the available evi- score out of theoretical maximum of 32. This score therefore, places emphasis on the severity of stenosis, while in- dence has established a link between hyperuricemia and cluding some of the extent of CAD. cardiovascular disease and this may be causal. It has been proposed that serum uric acid concentrations can be used as a cardiovascular risk marker.4 As a risk predictor serum Extent score: uric acid could be additive to other inflammatory markers Extent score used was a David R. Sullivan’s new angiographic like hs-CRP. Studies of serum uric acid in angiographical- score of the extent of coronary artery disease. 6 The score in- ly proven CAD in young adults are not known. This study dicates the proportion of the coronary arterial tree involved by aims to understand the significance of serum uric acid level angiographically detectable atheroma. The proportion of each versus hs CRP levels as markers of coronar artery disease vessel involved by atheroma, identified by luminal irregularity, severity (disease marker) or as an indicator of inflamma- was multiplied by the factor for each vessel. Left main artery, 5; tion that leads to an atherothrombotic event that leads to left anterior descending, 20; main diagonal branch, 10; first sep- plaque rupture (a process marker). tal perforator, 5; left circumflex artery, 20; obtuse marginal and posterolateral vessels, 10; right coronary artery, 20; and main MATERIAL AND METHODS posterior descending branch, 10. When a vessel was occluded and the distal vessel not fully visualised by collateral flow, the Patient population: This study included 100 patients admit- proportion of vessel not visualised was given the mean extent ted with CAD and underwent coronary angiography (CAG) in score of the remaining vessels. When the major lateral wall the Department of Cardiology, ICVS, IPGMER/ S.S.K.M. Hos- branch was a large obtuse marginal or intermediate vessel, this pital, Kolkata. Sixty patients ≤ 45 yrs of age, both males and was given a factor of 20 and the left circumflex artery a factor females, admitted with CAD were enrolled in this study as of 10. The score for each vessel or branch were added to give a the test population of “young adults with CAD”. Forty pa- total score out of 100, that is the percentage of coronary intimal tients (> 45 yrs of age or those with angiographically normal surface area involved by atheroma. coronary arteries, both males and females, admitted with CAD were enrolled in this study as “controls”. The patients with history of coronary angiography in the recent past, on hs-CRP estimation: statins for more than one month, any systemic infection, The CRP test was performed by using UBI MAGIWEL collagen vascular disease, recent trauma, pregnancy and CRP-quantitative AD-401 kit, a solid phase enzyme linked patients with documented extra-cardiac atherosclerosis immunosorbent assay (ELISA) as per instructions of the were excluded from the study. manufacturer (supplied with kit).

14 January – June 2019, Volume – 8 Issue – 1 The official Journal of Cardiological Society of India, Kerala Chapter

Serum uric acid estimation: Serum uric acid – was measured colorimetrically by xan- thine oxidase method.Statistical Analysis: Data were analysed with SPSS for windows statistical package and are presented as mean ± SD. Univariate comparison between groups were made with nonparametric test; Kruskal-Wal- lis test for multigroup comparison and Mann-Whitneys test for 2-group comparison. Discrete variables were compared with chi square test. The correlation between levels of hs- CRP/uric acid and angiographic stenosis and extent was assessed by Pearson’s correlation. For all results, a P value of TABLE 1: Distribution of risk factors across study groups. < 0.05 was considered significant.

RESULTS trend which was highest in the young CAD group (5.0 mg/l), followed by the old CAD patient group (3.40 mg/l) and least Out of 60 Young CAD (41 males) patients, 42 presented as in the control group of individuals with normal coronaries acute coronary syndrome and the rest 18 as chronic stable (2.30 mg/l). Mean hsCRP was therefore, elevated in Young angina. Out of 24 Old CAD (15 males) patients, 14 present- CAD patients more than in those of Old CAD patients and ed as acute coronary syndrome and the rest 10 as chron- Controls, and this trend was found to be significant by ANO- ic stable angina. There were 16 patients (12 males) in the VA (P = 0.028).(Figure 1a) Patients with ACS had the highest control group of normal coronaries. The three groups were mean serum uric acid levels among both young CAD (5.93 comparable with respect to age, sex, and other risk factors mg/l) and old CAD (4.88 mg/l) patient groups. Mean se- for coronary artery disease such as diabetes, hypertension, rum uric acid level in chronic stable angina patients was dyslipidemia, obesity and smoking. (Table 1) 4.25 mg/l in young CAD group and 4.05 mg/l in the old CAD group. Mean serum uric acid level was significantly elevat- TABLE 1: Distribution of risk factors ed in ACS Group (P = 0.01) and non-significantly in the CSA Group (P = 0.38) of Young CAD patients than in those of Old across study groups. CAD patients. When compared among age groups in total, Patients with ACS had the highest mean hs-CRP levels mean uric acid levels showed a trend which was highest amongboth young CAD (5.60 mg/l) and old CAD (3.53 mg/l) in the young CAD group (5.4 mg/l), followed by the old CAD patient groups. Mean hsCRP in chronic stable angina pa- patient group (4.5 mg/l) and least in the control group of tients was 3.89 mg/l in young CAD group and 2.95 mg/l in individuals with normal coronaries (4.1 mg/l). Mean serum the old CAD group. Mean hsCRP was significantly elevated in uric acid was therefore, elevated in Young CAD patients both ACS Group (P = <0.01) and CSA Group (P = 0.02) of Young more than in those of Old CAD patients and Controls, and CAD patients than in those of Old CAD patients. When com- this trend was found to be significant by ANOVA (P = 0.015). pared among age groups in total, mean hsCRP showed a (Figure 1b

January – June 2019, Volume – 8 Issue – 1 15 The official Journal of Cardiological Society of India, Kerala Chapter

FIGURE 1: Comparison of Inflammato- increasingly prevalent in Asian Indians and these people ry markers across CAD groups – hsCRP tend to get MI at a younger age in addition to more complex coronary artery abnormalities.9 Recent research has (a) and uric acid (b) shown that inflammation plays a key role in coronary artery To see the correlation of disease burden, angiographic disease (CAD) and other manifestations of atherosclerosis. stenosis score and extent score were compared with the In recent years, several studies have shown that CRP is as- levels of serum hsCRP and serum uric acid levels in young sociated with cardiovascular risk.10 Reports of Serum uric adults with CAD. Mean stenosis scores were 6.35 in the ACS acid as a cardiovascular risk marker are however less, es- and 3.67 in CSA group of young CAD patients. The Pearson pecially in the group of young CAD patients. In our study, Chi-square test showed a significant point to point posi- mean hsCRP as well as serum uric acid were significantly elevated in Young CAD patients than in those of Old CAD

Figure 3: Correlation of Sullivan (CAD extent) score with hsCRP (a) and uric acid (b). tive correlation between angiographic derived CAD stenosis patients and Controls, and this trend was significant (P = score (Gensini Score)and levels of inflammatory biomarker 0.028/P=0.015 respectively, ANOVA). Also, mean hsCRP and – hsCRP(P<0.01, r= 0.6692, 95% CI for r - 0.5003 to 0.7891) and serum uric acid were elevated in both ACS Group (P = <0.01, uric acid (P<0.01, r= 0.5223, 95% CI for r - 0.3094 to 0.6853). both) and CSA (chronic stable angina) Group (P = 0.02/P = 0.38) of Young CAD patients than in those of Old CAD pa- (Figure 2a, 2b) The mean extent scores were 36.90 in ACS and tients. This important 21.67 in CSA group respectively. Similar to stenosis score, the Pearson Chisquare test showed a significant point to finding indicates the role of vascular inflammation and point positive correlation between angiographic derived endothelial dysfunction in the high incidence of CAD in CAD extent score (Sullivan Score) and serum hs CRP levels young Indians. This important data suggests the possible (P<0.01, r= 0.6067, 95% CI for r - 0.4170 to 0.7457) as well as involvement of risk factors that are often not considered serum uric acid levels (P<0.01, r= 0.3882, 95% CI for r - 0.1489 in typical risk-stratification schemes. Considering the occa- to 0.5845). (Figure 3a, 3b) sional involvement of these factors in older CAD patients, their involvement in the young CAD group should be further elucidated. Different authors have mentioned that DISCUSSION the role of inflammation is understudied and it can be as- Coronary artery disease (CAD) remains as a leading cause sessed by testing levels of systemic inflammatory markers of mortality and morbidity worldwide.7 Coronary artery dis- such as high sensitivity C-reactive protein and upcoming ease is devastating precisely because an otherwise healthy markers like uric acid.11 Correlation of Inflammation with person in the prime of life may die or become disabled Angiographic CAD Severity In the present study, out of 60 without warning. CAD in the young (under the age of 45), Young CAD patients, 26 (43.3%) had single vessel disease brings sudden and unexpected distress for the individual, (SVD), 24 (40%) had double vessel disease (DVD) , 10 (16.7%) family and his friends.8 It is now established that CAD is had triple vessel disease (TVD). Out of the 24 Old CAD pa-

16 January – June 2019, Volume – 8 Issue – 1 The official Journal of Cardiological Society of India, Kerala Chapter tients, 17 (71%) had SVD, 4 (16.7%) had DVD, 1 (4.2%) had TVD. CONCLUSION (Table 2) The high prevalence of DVD and TVD in the Young CAD (56.7%) versus the Old CAD (20.9%) group has also been Significantly higher serum uric acid and serum hs CRP lev- reported previously. Klein et al. theorized that two distinct els are found in spectrum of CAD patients through acute populations exist.12 The more common subgroup is charac- coronary syndrome to chronic stable angina than to pa- terized by single-vessel, and often single-stenosis, disease, tients with normal coronary angiography – indicating a role presumably related to acute plaque rupture, with an excel- of inflammation in the process of plaque progression. Both lent three-year outcome. The favourable prognosis was be- serum uric acid and hs CRP levels and inflammation have a lieved to be related to preserved left ventricular function positive correlation with the disease burden in the young without multivessel involvement. The less common group CAD patient. The findings highlight the relevance of serum has extensive three vessel CAD with “galloping” progres- uric acid as a novel and relatively cheaper alternative to sion unrestrained by coronary artery bypass graft surgery an already established marker serum hs CRP as a correlate (CABG) and preventive measures. Pearson Chi-square test of vascular inflammation and coronary artery disease in shows a significant positive correlation between levels of young Indians. Premature CAD in Young Asian Indians could inflammatory biomarkers and angiographic derived CAD be partly explained by increased vascular inflammation. stenosis score (Gensini Score) [P <0.01] and extent (Sulli- Further observational and interventional studies are war- van Score) [P<0.01]. Serum uric acid paralleled serum hs ranted in this regard to identify & reduce risk factors in an- CRP for correlation with coronary disease severity and economically and socially relevant section of population of extent. Therefore, both serum uric acid and serum hsCRP a rapidly developing country like India. may serve as sensitive indicators of progressive increase in stenosis severity and extent of coronary artery disease in Young CAD subjects. Relevance of serum uric acid as a BIBLIOGRAPHY correlate of vascular inflammation and coronary artery 1. WHO. Global Status Report on Noncommunicable Dis- disease severity has rarely been reported from India and eases. 2014. http://www.who.int/nmh/publications/ probably none documented from Eastern India especially ncd-status-report-2014/en/ (accessed 30 Oct 2018). among young CAD patients.13 This is important because 2. Gaziano TA, Bitton A, Anand S, Abrahams-Gessel S, Mur- type and levels of risk factors may varyfrom north Indian to phy A. Growing epidemic of coronary heart disease in South Indian CAD patients.14 low- and middle-income countries. CurrProblCardiol. 2010;35(2):72-115. Strengths of the Study 3. Verma S. C-reactive protein comes of age. Nat ClinPract- There are very few reports of correlation of vascular in- Cardiovasc Med. 2005 Jan; 2(1): 29–36. flammation with CAD from India, especially among the 4. Krishnan E. Uric Acid in Heart Disease - A New C-reactive increasingly relevant young CAD population.15This report Protein? CurrOpinRheumatol. 2011;23(2):174-17. also highlights the important role of a relatively cheap inflammatory marker – serum uric acid as statistically simi- 5. Gensini GG. Coronary arteriography. Mount Kisco, New lar to an established marker like hs CRP in correlating with York: Futura Publishing Co. 1975. 6. David R, Sullivan MB, disease severity and extent of coronary artery disease. The Thomas H et al. A new method of scoring coronary an- methodology used in the study was similar to international giograms to reflect extent of coronary atherosclerosis reports of the same nature, thus making it suitable for pur- and improve correlation with major risk factors. Am poses of comparison. Heart J. 1990; 119: 1262. 7. Roth, G.A.; Johnson, C.; Abajobir, A.; Abd-Allah, F.; Abera, Limitations of the Study S.F.; Abyu, G.; Ahmed, M.; Aksut, B.; Alam, T.; Alam, K.; et al. Global, Regional, and National Burden of Cardiovas- It is a cross-sectional study of patients referred for coronary cular Diseases for 10 Causes, 1990 to 2015. J. Am. Coll. angiography. This study design may not be used to estab- Cardiol. 2017, 70, 1–25. lish causality. It can only establish an association. Therefore, this study must be considered a preliminary yet hypothesis 8. Klein WL. Coronary artery disease in young. J Am Coll- generating rather than hypothesis-proving study. A larger Cardiol. 2003; 41: 529–31. sample study to understand the interaction between role 9. Egred M. Myocardial infarction in young adults. Postgrad of inflammatory markers like uric acid and hs CRP vis-a-vis Med J. 2005; 81: 741–5. CAD is required, to investigate whether there is a ‘threshold effect’ of the markers and also to prove any diagnostic or 10. Calabrò P, Golia E, Yeh ET. CRP and risk of atherosclerotic prognostic value of these markers, especially in the young. events. SeminImmunopathol. 2009; 31: 79–94.

January – June 2019, Volume – 8 Issue – 1 17 The official Journal of Cardiological Society of India, Kerala Chapter

11. Klein L, Nathan S. Coronary artery disease in young of coronary artery disease. J. Clin. Sci. Res. 2012; 3:126–30. adults. J. Am. CollCardiol. 2003; 41(4): 529–31. 14. Kinra S, Bowen LJ, Lyngdoh T, Prabhakaran D, Reddy KS, 12. Klein LW, Agarwal JB, Herlich MB, Leary TM, Helfant RH. Ramakrishnan L, et al. Sociodemographic patterning of Prognosis of symptomatic coronary artery disease in non-communicable disease risk factors in rural India: a young adults aged 40 years or less. Am. J. Cardiol. 1987; cross sectional study. BMJ. 2010; 341. 60:1269–72. 15. Ahmed I, Sarkar A, Pande A, Naveen Chandra GS, Patil S, 13. Guruprasad S, Rajasekhar D, Subramanyam G, Srini- Kundu C. Vascular Inflammation and Angiographic Se- vasaRaoPVLNVanajakshamma V, Latheef K. High sensitiv- verity of Coronary Artery Disease. Journal of Cardiovas- ity C-reactive protein levels across spectrum and severity cular Disease Research 2014;5(1): 15-21.

18 January – June 2019, Volume – 8 Issue – 1 The offi cial Journal of Cardiological Society of India, Kerala Chapter

KHJKERALA HEART JOURNAL

A Journal of Cardiological Society of India Kerala Chapter

p-ISSN: 2347-5269 e-ISSN: 2454-6755 KERALA HEART JOURNAL (p-ISSN: 2347-5267), (e-ISSN: 2454-6755) January - June 2019, Volume - 8, Issue - 1

Editor in Chief Dr. Stigi Joseph

Madhu sreedharn.MD.DM. HOD.Cardiology, NIMS-Neyyattinkara correspondence:[email protected]

CASE REPORT An Interesting Case of Restrictive Cardiomyopathy

56-year-old gentleman was admitted to the hospital on again in shock. He expired three months after the initial ad- A15. 12.17 in Cardiogenic shock with bradycardia and a Sy mission and limited biopsies of the heart (Fig 7,8,) and liver tolic Blood Pressure of 80 mm Hg. He was admitted to a (Fig 9, 10) were done which showed extensive amyloid depo- peripheral hospital a week ago with abdominal pain and sition confi rming the diagnosis of Cardiac Amyloidosis. vomiting and was referred due to shock, on inotropic support. He had a similar admission ~ 3 months ago in another hospital when an angiogram was normal. DISCUSSION Amyloidosis refers to a collection of diseases in which His Hb was 11.4 g/dl with ESR ~ 140 mm/hr. S. Creatinine beta plated sheets of proteins infi ltrate the tissues. Based was 2.1 mg/dl. hs Trop I was 206.4 ng/L, and N t Pro BNP on nomenclature, it is divided into two main types – Light was 16,439 pg/mL. His Serum Procalcitonin was 92ng/mL. Chain Amyloidosis (AL) and Transthyretin Amyloidosis (ATTR) He was treated as septicemic shock with IV meropenem caused by the deposition of Light Chain or Transthyretin re- with which the infl ammatory markers came down, and he spectively (1). The most common form of systemic amyloido- improved clinically. ECG showed junctionalrhythm with HR sis is AL. This can get deposited in any organ – the common ~ 60/mt (Fig 1), and an Echocardiogram showed Concentric extra-cardiac sites being kidneys, Liver, GI tract, Tongue and LVH with speckled appearance (Fig2,3,4) suggestive ofre- nerves. Cardiac manifestations include heart failure and ar- strictive cardiomyopathy. rhythmias. Clues to the diagnosis of Cardiac amyloidosis in- Specifi c investigations for the etiology were done with Se- clude LVH on echo with low voltage complexes on the ECG. rum Electrophoresis showing a mild narrow band in the mid Transthyretin amyloidosis may be wild type ATTR – due to gamma region ~ 0.75g/dl implying a monoclonal gammopa- excess production of transthyretin in the liver or the mu- thy. Serum Immune fi xation showed a M band in the gamma tant type. Mutant type results from a pathological mutation region (0.84g/dl). X-Ray showed possible lytic lesions in the in the transthyretin gene leading to amyloid deposition in skull. Bone marrow aspiration study showed 24% plasmacy- the heart and nerves. tosis consistent with a plasma cell neoplasm (Fig 5). A rectal Though the diagnosis of amyloidosis can be assumed from biopsy was negative for amyloid (Fig 6). Thus a diagnosis the clinical features along with the ECG and Echo fi ndings, a of Multiple Myeloma with Cardiac Amyloidosis was made defi nitive diagnosis of amyloidosis requires biopsy. This is though we did not have any tissue diagnosis of Amyloidosis. diffi cult to obtain. Though sub-cutaneous fat or rectal biop- The oncologist saw him and started on treatment for myelo- sies are the easiest to perform, it was negative in this case. ma. However, he continued to do poorly and was readmitted The fi nal confi rmatory tissue was obtained post mortem.

January – June 2019, Volume – 8 Issue – 1 19 The official Journal of Cardiological Society of India, Kerala Chapter

Fig: 1 ECG - Junctional Rhythm, Low voltage Fig: 2 Echo: Conc LVH

Fig 3: Speckled Pattern Fig 4 : Ventricular Hypertrophy

Fig 5: Bone Marrow-Plasmacytosis Fig 6: Normal Rectal Biopsy

20 January – June 2019, Volume – 8 Issue – 1 The official Journal of Cardiological Society of India, Kerala Chapter

Fig 7: Amyloid in Heart Muscile Fig 8: Amyloid with Congo Red Stain

Fig 9: Amyloid in Liver Fig 10: Amyloid with Congo Red Stain

In either form of amyloidosis, the dominant imaging finding due to conduction disease. AF is common and poorly tolerat- is `hypertrophy.` The hypertrophy is due to amyloid fibril ed. As the disease is irreversible with high mortality, a cardiac deposition rather than myocyte hypertrophy/hyperplasia transplant may be considered in well-selected patients (4). which is the reason why the ECG voltages are decreased rather than increased. It causes abnormal patterns of late gadolinium enhancement on Cardiac Magnetic Resonance REFERENCE (CMR) (2) and Strain echocardiography reveals basal > api- 1. Amyloid Cardiomyopathy. Merril D Benson, Noel Dasgup- ta J Am CollCardiol2016; 68(1) 25-28 cal impairment in strain (3). 2. 2. Karamitos TD, Piechnik SK et al. Noncontrast T1 map- Prognosis in amyloidosis depends predominantly on the de- ping for the diagnosis of Cardiac amyloidosis. JACC Car- gree of cardiac involvement. Though the prognosis is better diovasc Imaging 2013; 6:488-97 in ATTR amyloidosis, both forms carry a high annual mortality. Treatment follows two parallel paths: treating the conse- 3. Ternacle J Bodez D et al. Causes and consequences of quence of organ dysfunction and attempting to slow the pro- longitudinal LV dysfunction assessed by 2D strain echo- gression of the disease with chemotherapy agains the plasma cardiography in cardiac amyloidosis. JACC Cardiovasc cells. Cardiac-specific treatment involves volume manage- Imaging 2016;9:126-38 ment (diuretics/salt restriction) and that of arrhythmias. ACE-I 4. Davis MK, Kale P et al. Outcomes after heart transplant / ARB and beta blockers are poorly tolerated and may result for amyloid cardiomyopathy in the modern era. Am J in profound hypotension. Pacemakers are frequently required Transplant 2015:15:650-8

January – June 2019, Volume – 8 Issue – 1 21 The offi cial Journal of Cardiological Society of India, Kerala Chapter

KHJKERALA HEART JOURNAL

A Journal of Cardiological Society of India Kerala Chapter

p-ISSN: 2347-5269 e-ISSN: 2454-6755 KERALA HEART JOURNAL (p-ISSN: 2347-5267), (e-ISSN: 2454-6755) January - June 2019, Volume - 8, Issue - 1

Editor in Chief Dr. Stigi Joseph

Muneer Eesa MD Department of Clinical Neurosciences, Cumming School of Medicine, University of Calgary, Foothills Hospital, Calgary, Alberta, Canada Department of Radiology, Cumming School of Medicine, University of Calgary, Foothills Hospital, Calgary, Alberta, Canada

Bijoy K. Menon MD Department of Clinical Neurosciences, Cumming School of Medicine, University of Calgary, Foothills Hospital, Calgary, Alberta, Canada Department of Radiology, Cumming School of Medicine, University of Calgary, Foothills Hospital, Calgary, Alberta, Canada Department of Community Health Sciences, Cumming School of Medicine, University of Calgary, Foothills Hospital, Calgary, Alberta, Canada

Principles and practice of modern endovascular therapy in patients with acute ischemic stroke

he principles of treatment in patients with acute isch- stroke treatment from the time-based selection of patients Temic stroke are simple. A thrombus occludes an artery to tissue based selection.11-13With many imaging strategies supplying blood to the brain, tiny collaterals provide some and many devices and techniques, physicians treating pa- blood supply to the ischemic brain which infarcts over time. tients with acute ischemic stroke need clarity. This review If the thrombus is removed before the entire ischemic brain will, therefore, be practical. It will focus on how to select pa- infarcts and the risks of treatment are mitigated, patients tients for EVT and how to then administer modern EVT safely benefi t. Despite these principles of acute ischemic stroke and effi ciently. By applying these simple principles and tech- treatment being so simple, for many years since the fi rst en- niques, physicians will be able to provide their patients with dovascular treatment (EVT) in patients with acute ischemic very reasonable chances of recovery from acute ischemic stroke, the treatment raised skepticism.1 Randomized clin- stroke. ical trials failed to demonstrate the effi cacy of EVT, further increasing the scepticism surrounding this treatment.2-4It took our fi eld many years to understand that selecting the Patient selection for Endovascular right patients for EVT and administering that therapy ear- Therapy (EVT) ly were core to the success of the treatment. These tenets Imaging Modality of Choice: were integral to the success of the MR CLEAN, ESCAPE, RE- VASCAT, EXTEND IA, and SWIFT PRIME trials.5-9 The HERMES The non-contrast CT (NCCT) of the Head is the work-horse of patient-level pooled meta-analyses of these recent EVT tri- acute stroke treatment.14 It is inexpensive, fast to acquire als has fi nally established EVT as standard care in patients and can be done in all patients at all times. We strongly ad- with acute ischemic stroke.10 Trials like ESCAPE, DAWN, and vocate for the use of the NCCT Head as the fi rst line imaging DEFUSE-3 have changed the paradigm in acute ischemic tool in patients presenting with symptoms and signs of acute

22 January – June 2019, Volume – 8 Issue – 1 The official Journal of Cardiological Society of India, Kerala Chapter

Figure 1: Figure 2: A non-contrast CT Head showing extensive early A CT Angiography Head showing a left ischemic changes (blue arrows) in the sided L type internal carotid artery left middle cerebral artery territory occlusion.

stroke. The NCCT Head is used to a) distinguish between a haemorrhagic and ischemic stroke and b) to determine the extent of the infarcted brain. Proponents of Magnetic Reso- nance Imaging (MRI) suggest that MRI Diffusion Weighted Im- aging (MR-DWI) is better at recognizing subtle early ischemic changes (EIC) than NCCT Head. Although arguably true, the purpose of NCCT is not to pick up subtle EICs but only to rule out very large infarcts. We call such very large infarcts “wipe- outs.” (Figure 1) Modern EVT, when administered quickly, is so efficient (Number Needed to Treat of ~2) that the therapy is invariably effective even in patients with infarcts that are moderate to large.15 A recent meta-analysis from the HER- MES collaboration shows that patients with NCCT ASPECTS Figure 3: (an ordinal 10-point scale to assess the extent of EIC) as low Multi-phase CT Angiography Head showing as 3 or infarct volume as high as 100 ml on CT Perfusion con- good collaterals beyond a left sided M1 seg- tinue to benefit from EVT, especially when they are younger ment MCA occlusion. than 80 years of age.15, 16 MRI moreover takes more time to arrange and acquire than NCCT. Every minute lost acquiring an MR vs. an NCCT Head results in approximately 2 million The CTA Head and Neck is also useful when planning ac- neurons being lost forever!17 cess for EVT. Knowledge of aortic arch and large vessel help in interventional planning (details described below in the The CT Angiogram of the Head and Neck (CTA Head and Neck) section on interventional techniques and strategies).14, 20 (Figure 2) should be the next imaging modality of choice af- The CTA also helps to identify the extent of collaterals be- ter the NCCT Head. As in acute coronary interventions, it is yond the ELVO (Figure 3).21, 22 Patients with moderate to imperative in patients with acute ischemic stroke to under- good collaterals beyond the ELVO are likely to benefit with stand if there is a target thrombus for EVT. A target thrombus EVT. If minimal or no vessels are seen beyond the ELVO on for EVT is an emergent large vessel occlusion (ELVO). An ELVO CTA, these patients are unlikely to benefit from EVT. Con- is a thrombus in the internal carotid artery (ICA), M1 segment cerns with the use of CTA Head and Neck primarily stem Middle Cerebral Artery (MCA), a proximal M2 segment MCA from the use of iodinated contrast and the risk of contrast or an intracranial vertebral or basilar artery. ELVOs are less nephropathy. This risk is so minimal in most patients, and likely to recanalize with intravenous thrombolysis alone.18, the benefits from vascular imaging are so marked that most 19A debilitating clinical deficit due to a proximal anterior ce- stroke centers perform CTA immediately after NCCT without rebral artery or posterior cerebral artery occlusion may also, waiting for a serum creatinine; the only exception being in in expert hands, be target thrombus for EVT. patients with known severe renal insufficiency who is not

January – June 2019, Volume – 8 Issue – 1 23 The official Journal of Cardiological Society of India, Kerala Chapter

on dialysis.23In summary, therefore, we recommend that or MRI in selecting patients for EVT. Principles of Patient physicians arrange an NCCT Head followed by a CTA Head Selection (Clinical Variables): The art of medicine is still not and Neck for any patient with acute ischemic stroke. Pa- lost in the modern era of medical treatment. Variables such tients with “wipe-out” infarcts on NCCT or poor collaterals as age, frailty, presence of cognitive impairment, cancer or beyond ELVO on CTA are unlikely to benefit from EVT. other co-morbidities like heart

disease or chronic kidney disease can all affect prognosis Principles of Patient Selection in patients with acute ischemic stroke. A pragmatic physician will consider these prognostic variables when making (Imaging vs. time): decisions on offering EVT to patients. At our center, not ev- Patient selection for EVT has moved on from a time win- ery patient with an ELVO without wipe-out infarct is offered dow-based strategy to a brain tissue-based strategy. This EVT. In the very elderly or those with terminal illnesses or means any patient with acute stroke symptoms with an dementia, the likelihood of poor prognosis even with EVT ELVO and salvageable brain on imaging is a candidate for is discussed with families and a considered decision made EVT. Common sense suggests that any patient who wakes that often takes into account the patient’s previous wish- up with stroke symptoms or whose stroke symptom onset es., and therefore we desist from offering any recommen- was not witnessed and is brought to the hospital should, dations. We do however suggest that the treating physician therefore, be imaged. Although guidelines suggest the use remembers Charaka’s quote “A physician should first study of 16-24 hours from last known well to define acuteness, we all the factors including the environment that influence the would much rather recommend that physicians use com- patient’s disease and only then offer treatment, if neces- mon sense and good history to find out if the stroke may sary.” have been acute even if the patient was last known well more than 24 hours earlier.11, 15, 21, 24 As an example of tis- Interventional techniques and sue-based imaging selection, imagine an 80-year-old lady Strategies living alone at home. The milkman brings milk every second day in the morning. The lady does not open the door when Endovascular techniques for acute ischemic stroke have he knocks. The milkman finds the lady on the floor unable evolved significantly from earlier case reports of intra-ar- to speak or to move. He calls neighbours and transports terial pharmacological clot lysis to thrombectomy in the the patient to the hospital with EVT facilities. The physi- modern era using stent retrieval devices and aspiration cian recognizes that the stroke may have happened > 24 techniques or combinations thereof.1, 25-28 Summarized by hours ago OR may have happened just an hour before he the aphorism “Time is Brain,” faster techniques to restore knocked. Ancillary history from the witness (milkman) may intracranial flow after a large vessel occlusion is critical in provide other clues to stroke onset, e.g. was the breakfast improving neurological outcomes.17Moreover, platelet-rich made that day etc. However, in most situations, it is dif- clots are more resistant to thrombolysis and clot contrac- ficult to know when the stroke happened. Imaging of the tion, and low plasminogen content further contributes to brain helps in such situations. An NCCT of the brain showed likely low revascularization rates.18The following sections some early ischemic changes in the left MCA territory but illustrate the technical aspects of endovascular treatmen- no “wipe-out” infarct. A CTA Head and Neck showed a left tin acute ischemic stroke. M1 segment MCA occlusion with good collaterals. The physician takes the patient to the angio-suite for Anaesthesia: EVT. EVT is successful, and the patient recovers well. The Most patients with acute ischemic stroke may be treated above example illustrates the use of tissue-based rather without the need for a General Anaesthetic. The use of than time-based patient selection strategy. If a time-based selection strategy had been used, the patient would have local anaesthesia and conscious sedation if required will been last known well (by the witness milkman) at least 48 suffice in most situations. In agitated patients or patients hours ago. A life-saving treatment such as EVT would have who have already been intubated either on scene or in the been denied to a deserving patient! Although the DAWN and Emergency departments for airway protection, a General the DEFUSE 3 trial used CT Perfusion(CTP) imaging to select anaesthetic may be required.29, 30 patients in the extended time window, the ESCAPE trial used NCCT and CTA to select such patients beyond 6 hours from stroke symptom onset.11-13 CTP is technically challenging, Access: especially when patients move and in smaller hospitals.21 Most neuro-interventional practitioners use femoral arteri- We do not, therefore, recommend the additional use of CTP al access for endovascular stroke therapy. The aortic arch

24 January – June 2019, Volume – 8 Issue – 1 The official Journal of Cardiological Society of India, Kerala Chapter

anatomy and use of various selective catheters for Neu- ro-angiography render this the most preferred access route for acute stroke interventions. However, the use of larger sized access sheaths (typically 8-9 Fr) and concomitant use of intravenous fibrinolytic agents and need for anticoagulation during therapy can lead to increase in the proportion of femoral access site complications.31 Other access sites are less typically used including radial artery access for both posterior circulation and anterior circulation throm- bectomies and direct carotid access in case of tortuosity and difficulty in traversing the aortic arch.32, 33 Using ultrasound-guided direct puncture and micro-puncture kits can minimize access site complications but should not lead to unnecessary delays in getting the procedure started. The use of a short sheath will suffice in most circumstances, but in elderly patients or tortuous anatomy, the use of a long sheath helps to provide stability for multiple exchang- es of devices, and in case there is a need for simultaneous treatment of cervical carotid disease with angioplasty and stenting.34 Figure 4: Left ICA angiography demonstrates complete Guiding Catheter: occlusion of the left middle cerebral artery (A). A stent retrieval device is placed beyond the The use of a balloon-tipped guiding catheterto temporarily occlusion (B) resulting in temporary arrest flow while performing intracranial thrombectomy will restoration of flow (C). Control angiography decrease the risk of non-target emboli either in distal terri- demonstrates complete revascularization (D). tories or other vascular territories across a patent circle of Note the tip of the balloon guide catheter Willis (Figure 4).35 Larger balloon guide catheters such as within the distal cervical internal 8 Fr or 9 Fr guiding catheter will accommodate most intra- carotid artery. cranial thrombectomy devices including co-axially placed intermediate cathetersand stent delivery catheters.36 All access sheaths, guiding catheters, intermediate catheters as well as intracranial microcatheters should be placed on a continuous pressurized heparinized saline drip. De- pending on arch anatomy the guiding catheters may be placed using a simple forward curve such as a hockey stick or Head-hunter curve. Reverse curved catheters such as a Simmons curve or VTK curve might be required to engage challenging type 2/3 aortic arches or bovine configurations (Figure 5). A long hydrophilic coated wire will suffice in most cases for selective engagement of the vessel of interest. Stiff- er wires and wires of variable stiffness (softer at the tip and sturdier proximally) might be required in certain cases. In some circumstances, a smaller 5 Fr catheter might be needed to engage the target great vessel, and subsequently, the guiding catheter is placed using an exchange-length wire. A careful review of the pre-procedure CT angiography of the Figure 5: A reverse curved catheter being used to vessels from the aortic arch through the intracranial circula- selectively engage the left common carotid tion will help in appropriate selection of the catheters that artery in a patient with bovine configuration may be required for arch access. In cases with a severe carot- aortic arch anatomy. id disease or cervical carotid occlusion the guiding catheters are placed below the level of occlusion and are chosen with the intent of carotid stenting should it be required.

January – June 2019, Volume – 8 Issue – 1 25 The official Journal of Cardiological Society of India, Kerala Chapter

Intracranial access: toration. 9, 25The stent delivery microcatheter is advanced past the clot into a suitably sized vessel distal to the occlu- A review of the pre-procedural CTA and evaluation of the clot sion (Figure 6). Gentle technique and tactile feedback will location might determine the specific intracranial access determine the amount of force necessary to traverse the catheters that are required. For distal clots, smaller micro- clot. An atraumatic technique for advancing the microwire catheters such as a 0.021” or 0.017” microcatheter will be is essential to prevent inadvertent perforation from the mi- easier to navigate. The use of larger microcatheters or inter- crowire or the microcatheter. In some instances, the softer mediate catheters in vessels more distal than the MCA main tip of the stent delivery microcatheter may suffice to tra- trunk should be used with extreme caution as it may lead to verse the clot. When working within the MCA an understand- complications related to a vessel perforation.37 Smaller dis- ing of the size of the distal M2 branches may help in mentally tal clots usually do not primarily manifest with a large neu- identifying the branch to select, as antegrade flow cannot be rological deficit at presentation, however smaller catheters evaluated during angiography. Once within a suitable branch for access may be required in situations with clinically sig- distal to the clot, the position of the microcatheter tip and nificant deficits related to a smaller vessel (such as an ante- integrity of the vessel is confirmed with a small test injec- rior cerebral artery or a posterior cerebral artery occlusion) tion of contrast. The self-expandable stent at the end of a or from iatrogenic distal emboli from a proximal occlusion. delivery wire is designed to be advanced through the micro- Various microwires can be used for intracranial access, and catheter. In cases with tortuous anatomy there can be sig- mostmicrowires are in the range of 0.012” to 0.016” in thick- nificant tension within the microcatheter system as well as ness and explicitly designed for neurovascular work. The ovalisation of the lumen of the microcatheter. This can result choice of wire will depend on availability and operator pref- in difficulty in advancing the stent system through the micro- erence. Wire manipulation alone may suffice in disrupting catheter. Partial withdrawal of the microcatheter to decrease distal clots. In rare instances, low dose intra-arterial fibrino- the tension within the system can aid in advancing the stent. lytics may be used for distal occlusions that are resistant to Sometimes using an intermediate catheter can help in pro- mechanical clot disruption. Mechanical thrombectomy tech- viding an added support. This is usually the case when using niques have replaced primary use of pharmacological agents combined aspiration and stent retrieval as discussed below. such as tPA or Urokinase for larger proximal clots. Sizing of the stent in terms of the width and length is usually For larger proximal clots involving the intracranial ICA or the determined by clot location and length as well as estimation MCA main trunk, most practitioners use aspiration throm- of parent vessel size. Pre-procedure CT angiography with bectomy, stent-assisted thrombectomy or a combination of multi-phase imaging for collateral evaluation is sometimes both. Earlier devices for mechanical clot retrieval such as extremely useful in determining the distal end of the clot the Merci retrieval deviceand Catch device have been mostly and thus the size of the distal vessel and length of the clot. replaced by modern stent retrieval systems.25, 38There are The use of longer stent is preferred to ensure stable cap- also previous reports of clot disruption with angioplasty bal- ture and clot-stent integration at retrieval. Stents are usually loons. 39 However, these are suboptimal as they result in cot placed for a few minutes to allow for clot-stent integration. fragmentation and distal embolization. Laser thrombolysis, Sometimes partial re-sheathing of the stent will assist in sta- photoacoustic and micro-infusion sonography transducer ble clot-stent interface during retrieval. systems are near obsolete for intracranial work. The use of a combined aspiration and stent retrieval throm- If using an aspiration only technique (0.060” to 0.070” in- bectomy is being used increasingly wherein a coaxial tech- ner lumen systems), an intermediate microcatheter is still nique is used to deliver an intermediate catheter (0.060” to required to advance the aspiration catheter to the face of 0.070” inner lumen) proximal to the clot, and the stent de- the clot. This will depend on the manufacturer and some- livery catheter is placed distal to the clot.27, 28, 41The stent times are supplied as a single kit. Aspiration may be applied is then advanced through the stent delivery microcatheter using a specific aspiration pump using a specified protocol. distal to the clot. The added support from the intermediate In some instances, manual aspiration with a large capaci- catheter intended for aspiration makes it easier to advance ty syringe may result in revascularization and satisfacto- the stent through the microcatheter. Once the stent is deliv- ry flow restoration. The use of aspiration alone as the first ered and temporary flow restoration is re-established, the pass technique has been reported to result in faster reca- stent delivery microcatheter is withdrawn entirely from the nalization rates with decreased puncture to recanalization system. This helps in achieving optimal aspiration through time.40However, there is a possibility of clot fragmentation the intermediate catheter (Figure 6). The entire system is or non-target embolization especially if not used in conjunc- withdrawn as a system while maintaining aspiration through tion with a larger balloon guide catheter. the intermediate catheter. Sometimes larger bore aspiration Stent-retrieval thrombectomy is performed using a non-de- catheters may be left in situ, in case multiple passes are an- tachable stent specifically designed for intracranial flow res- ticipated in patients with tortuous anatomy.

26 January – June 2019, Volume – 8 Issue – 1 The official Journal of Cardiological Society of India, Kerala Chapter

multi-phase acquisition. This can be quite useful in estimat- ing the clot burden. In cases of suspected dissection based on mechanism and pathophysiology, extra care should be taken to traverse the occluded segment. There might be clues to this on the CT angiography as well such as visualization of a flap with thrombi or mid-segment cervical ICA occlusion. Some- times there is excessive calcification at the level of the carotid bifurcation. This might require angioplasty to advance the guiding catheter into the cervical carotid artery. In some cases, stenting might be required to enable satisfactory place- ment of the guiding catheter for optimal intracranial access. Ideally, definitive therapy of cervical carotid disease should be deferred to a second procedure. Certain patients may be candidates for carotidendarterectomy,angioplasty alone may be enough to sufficiently revascularize the carotid stenosis in Figure 6: some, and in patients with stenoses resistant to angioplasty, Combined aspiration and stent retrieval stenting maybe required. Management of antiplatelet therapy treatment for a left middle cerebral artery can be challenging depending on the extent of ischemia and occlusion. The tip of the intermediate outcome of intracranial revascularization. catheter is placed proximal to the clot (white arrow) while the stent is delivered across the thrombus with the tip placed Challenges in Acute ischemic distal to it (black arrowhead). stroke treatment Although there are numerous challenges in existing pathways and systems for acute ischemic stroke treatment, In certain populations, there is a high prevalence of the in- many are unique in the setting of the new era of endovas- tracranial atherosclerotic disease. There might be a clue to cular thrombectomy. Some of the questions regarding the this on the CT angiography if there is concomitant disease treatment of patients beyond existing time windows have elsewhere. A tapered appearance to the occlusion and com- been investigated and are being put into practice guide- parison to prior imaging if available are beneficial as well. lines based on recent late window trials.11-13 Imaging se- In such cases, re-occlusion following thrombectomy may re- lection remains crucial in that paradigm. Another critical quire intracranial angioplasty or even stenting for durable question is the use of the appropriate type of patient se- reperfusion. Various intracranial stents for specific indica- dation and anesthesia in the stroke patient.29 While tradi- tion in atherosclerotic disease are available in both balloon tionally Neuro-angiography procedures were almost always expandable and self-expanding platforms. Control angiogra- performed in a controlled environment and a fully anesthe- phy at the end of the procedure is used to document reper- tized patient, that needs to be balanced with the need for fusion and to evaluate for any angiographic complications. rapid recanalization and avoidance of unnecessary delays In case of suspected complications, intra-procedural cone in treating patients. There is also increasing debate regard- beam CT may be used to determine the degree of hemor- ing hemodynamic changes associated with a general anes- rhage/extravasation or for any mass effect or midline shift.42 thetic in the general setting without specific attention to the physiological characteristics in the stroke patient. Cervical carotid disease Some of the technical and procedural challenges for endovascular therapy have been alluded to in the sections In cases with a proximal cervical carotid atherosclerotic dis- above. Smaller stent retrievers are already in place for ease it might be necessary to simultaneously treat the cer- distal vessels beyond an ICA terminus or MCA main trunk. vical disease at the time of the thrombectomy procedure.34, However, the incremental gains from going ever more distal 43In cases with complete carotid occlusion at the carotid bi- in the intracranial vasculature need to be balanced by the furcation the system may be carefully advanced beyond the procedural risks involved (Figure 7). occluded segment with gentle wire manipulation. In some case, aspiration through the guiding catheter or an interme- The question of simultaneously revascularizing the cervical diate system might be useful in debulking the clot. This can carotid disease has been alluded to above, however there is sometimes be anticipated based on information from the extreme variability in the real world and no apparent consen- pre-procedure CTA, and sometimes the distal aspect of the sus as to the exact methodology and technique as well as the cervical carotid ICA may be visualized on later stages of a algorithms for managing antiplatelet therapy in the peri-pro-

January – June 2019, Volume – 8 Issue – 1 27 The official Journal of Cardiological Society of India, Kerala Chapter

Figure 7: Lateral projection demonstrates microcatheter placed distal to a middle cerebral artery M3 branch occlusion (A). Control angiography after attempted stent retrieval demonstrates active extravasation (black oval in B). Post procedure unenhanced CT of the head demonstrates extensive contrast within the subarachnoid space (C).

cedural period.43 Intra-cranial angioplasty and stenting fur- The future of clinical care in the modern era of endovascu- ther adds to the challenges in patient populations with a lar therapy for acute ischemic stroke patients looks prom- higher incidence of intracranial atherosclerotic disease. ising. However, there remains much work to be done to ensure timely and adequate treatment to all patients who are Numerous studies are ongoing comparing the recanali- potential candidates for treatment. zation efficacy of a direct aspiration as a first pass technique versus primary stent retriever thrombectomy as well as procedural and clinical outcomes.28, 44As mentioned References: in the sections above a combined approach with aspira- 1. Zeumer H, Hacke W, and Ringelstein EB. Local intraar- tion and simultaneous use of stent retrieval devices are terial thrombolysis in vertebrobasilar thromboembolic being increasingly used. In many situations, the decision disease. AJNR Am J Neuroradiol. 1983;4:401-4. is made on a case by case basis with significant influence from practitioner preferences. Ongoing improvements in 2. Broderick JP, Palesch YY, Demchuk AM, Yeatts SD, Khatri device development and stent design allow for the use of P, Hill MD, Jauch EC, Jovin TG, Yan B, Silver FL, von Kum- safer devices for intracranial use and improved recanaliza- mer R, Molina CA, Demaerschalk BM, Budzik R, Clark WM, tion rates while minimizing the complication rates.Some of Zaidat OO, Malisch TW, Goyal M, Schonewille WJ, Mazighi the challenges relating to vascular access have been de- M, Engelter ST, Anderson C, Spilker J, Carrozzella J, Ryck- scribed above, and non-femoral access such as trans-radial borst KJ, Janis LS, Martin RH, Foster LD, Tomsick TA and / trans-brachial or even direct carotid puncture might be Interventional Management of Stroke III. Endovascular useful in the appropriate setting.32, 33 Innovative tech- therapy after intravenous t-PA versus t-PA alone for niques using imaging-guided access might be needed in stroke. N Engl J Med. 2013;368:893-903. certain situations.45 3. Ciccone A, Valvassori L, and Investigators SE. Endovascu- Other challenges include EVT in distal occlusions or in the lar treatment for acute ischemic stroke. N Engl J Med. 2013;368:2433-4. setting of stroke patients with documented large vessel occlusion with mild stroke scale scores at presentation.19, 4. Kidwell CS, Jahan R, Gornbein J, Alger JR, Nenov V, Ajani 46Use of newer thrombolytic agents such as tenecteplase Z, Feng L, Meyer BC, Olson S, Schwamm LH, Yoo AJ, Mar- shall RS, Meyers PM, Yavagal DR, Wintermark M, Guzy J, and ongoing research in the use of ancillary use of neuro- Starkman S, Saver JL and Investigators MR. A trial of protective agents are looking at improved clinical and imaging outcomes in the era of modern endovascular throm- imaging selection and endovascular treatment for ischemic bectomy. 47-49 stroke. N Engl J Med. 2013;368:914-23.

28 January – June 2019, Volume – 8 Issue – 1 The official Journal of Cardiological Society of India, Kerala Chapter

5. Berkhemer OA, Fransen PS, Beumer D, van den Berg LA, vin TG and collaborators H. Endovascular thrombectomy Lingsma HF, Yoo AJ, Schonewille WJ, Vos JA, Nederkoorn after large-vessel ischaemic stroke: a meta-analysis of PJ, Wermer MJ, van Walderveen MA, Staals J, Hofmeijer J, individual patient data from five randomised trials. Lan- van Oostayen JA, Lycklama a Nijeholt GJ, Boiten J, Brou- cet. 2016;387:1723-31. wer PA, Emmer BJ, de Bruijn SF, van Dijk LC, Kappelle LJ, 11. Evans JW, Graham BR, Pordeli P, Al-Ajlan FS, Willinsky R, Lo RH, van Dijk EJ, de Vries J, de Kort PL, van Rooij WJ, Montanera WJ, Rempel JL, Shuaib A, Brennan P, Williams van den Berg JS, van Hasselt BA, Aerden LA, Dallinga RJ, D, Roy D, Poppe AY, Jovin TG, Devlin T, Baxter BW, Krings Visser MC, Bot JC, Vroomen PC, Eshghi O, Schreuder TH, T, Silver FL, Frei DF, Fanale C, Tampieri D, Teitelbaum J, Heijboer RJ, Keizer K, Tielbeek AV, den Hertog HM, Ger- Iancu D, Shankar J, Barber PA, Demchuk AM, Goyal M, rits DG, van den Berg-Vos RM, Karas GB, Steyerberg EW, Hill MD, Menon BK and Investigators ET. Time for a Time Flach HZ, Marquering HA, Sprengers ME, Jenniskens SF, Window Extension: Insights from Late Presenters in the Beenen LF, van den Berg R, Koudstaal PJ, van Zwam WH, ESCAPE Trial. AJNR Am J Neuroradiol. 2018;39:102-106. Roos YB, van der Lugt A, van Oostenbrugge RJ, Majoie CB, Dippel DW and Investigators MC. A randomized trial 12. Nogueira RG, Jadhav AP, Haussen DC, Bonafe A, Budzik of intraarterial treatment for acute ischemic stroke. N RF, Bhuva P, Yavagal DR, Ribo M, Cognard C, Hanel RA, Engl J Med. 2015;372:11-20. Sila CA, Hassan AE, Millan M, Levy EI, Mitchell P, Chen M, English JD, Shah QA, Silver FL, Pereira VM, Mehta BP, 6. Goyal M, Demchuk AM, Menon BK, Eesa M, Rempel JL, Baxter BW, Abraham MG, Cardona P, Veznedaroglu E, Thornton J, Roy D, Jovin TG, Willinsky RA, Sapkota BL, Hellinger FR, Feng L, Kirmani JF, Lopes DK, Jankowitz BT, Dowlatshahi D, Frei DF, Kamal NR, Montanera WJ, Poppe Frankel MR, Costalat V, Vora NA, Yoo AJ, Malik AM, Fur- AY, Ryckborst KJ, Silver FL, Shuaib A, Tampieri D, Williams lan AJ, Rubiera M, Aghaebrahim A, Olivot JM, Tekle WG, D, Bang OY, Baxter BW, Burns PA, Choe H, Heo JH, Holmst- Shields R, Graves T, Lewis RJ, Smith WS, Liebeskind DS, edt CA, Jankowitz B, Kelly M, Linares G, Mandzia JL, Shan- Saver JL, Jovin TG and Investigators DT. Thrombectomy 6 kar J, Sohn SI, Swartz RH, Barber PA, Coutts SB, Smith EE, to 24 Hours after Stroke with a Mismatch between Defi- Morrish WF, Weill A, Subramaniam S, Mitha AP, Wong JH, cit and Infarct. N Engl J Med. 2018;378:11 21. Lowerison MW, Sajobi TT, Hill MD and Investigators ET. Randomized assessment of rapid endovascular treat- 13. Albers GW, Marks MP and Lansberg MG. Thrombectomy ment of ischemic stroke. N Engl J Med. 2015;372:1019-30. for Stroke with Selection by Perfusion Imaging. N Engl J Med. 2018;378:1849-1850. 7. Jovin TG, Chamorro A, Cobo E, de Miquel MA, Molina CA, Rovira A, San Roman L, Serena J, Abilleira S, Ribo M, Mil- 14. Menon BK, Campbell BC, Levi C and Goyal M. Role of im- lan M, Urra X, Cardona P, Lopez-Cancio E, Tomasello A, aging in current acute ischemic stroke workflow for en- Castano C, Blasco J, Aja L, Dorado L, Quesada H, Rubi- dovascular therapy. Stroke. 2015;46:1453-61. era M, Hernandez-Perez M, Goyal M, Demchuk AM, von 15. Roman LS, Menon BK, Blasco J, Hernandez-Perez M, Kummer R, Gallofre M, Davalos A and Investigators RT. Davalos A, Majoie C, Campbell BCV, Guillemin F, Lingsma Thrombectomy within 8 hours after symptom onset in H, Anxionnat R, Epstein J, Saver JL, Marquering H, Wong ischemic stroke. N Engl J Med. 2015;372:2296-306. JH, Lopes D, Reimann G, Desal H, Dippel DWJ, Coutts S, 8. Campbell BC, Mitchell PJ and Investigators E-I. En- du Mesnil de Rochemont R, Yavagal D, Ferre JC, Roos Y, dovascular therapy for ischemic stroke. N Engl J Med. Liebeskind DS, Lenthall R, Molina C, Al Ajlan FS, Reddy 2015;372:2365-6. V, Dowlatshahi D, Nader-Antoine S, Oppenheim C, Mitha AP, Davis SM, Weimar C, van Oostenbrugge RJ, Cobo E, 9. Saver JL, Goyal M, Bonafe A, Diener HC, Levy EI, Pereira Kleinig TJ, Donnan GA, van der Lugt A, Demchuk AM, VM, Albers GW, Cognard C, Cohen DJ, Hacke W, Jansen O, Berkhemer OA, Boers AMM, Ford GA, Muir KW, Brown BS, Jovin TG, Mattle HP, Nogueira RG, Siddiqui AH, Yavagal Jovin T, van Zwam WH, Mitchell PJ, Hill MD, White P, Bra- DR, Baxter BW, Devlin TG, Lopes DK, Reddy VK, du Mesnil card S, Goyal M and collaborators H. Imaging features de Rochemont R, Singer OC, Jahan R and Investigators and safety and efficacy of endovascular stroke treat- SP. Stent-retriever thrombectomy after intravenous t-PA ment: a meta-analysis of individual patient-level data. vs. t-PA alone in stroke. N Engl J Med. 2015;372:2285-95. Lancet Neurol. 2018;17:895-904. 10. Goyal M, Menon BK, van Zwam WH, Dippel DW, Mitch- 16. Campbell BCV, Majoie C, Albers GW, Menon BK, Yassi N, ell PJ, Demchuk AM, Davalos A, Majoie CB, van der Lugt Sharma G, van Zwam WH, van Oostenbrugge RJ, Dem- A, de Miquel MA, Donnan GA, Roos YB, Bonafe A, Jahan chuk AM, Guillemin F, White P, Davalos A, van der Lugt R, Diener HC, van den Berg LA, Levy EI, Berkhemer OA, A, Butcher KS, Cherifi A, Marquering HA, Cloud G,Ma- Pereira VM, Rempel J, Millan M, Davis SM, Roy D, Thorn- cho Fernandez JM, Madigan J, Oppenheim C, Donnan GA, ton J, Roman LS, Ribo M, Beumer D, Stouch B, Brown S, Roos Y, Shankar J, Lingsma H, Bonafe A, Raoult H, Her- CampbellBC, van Oostenbrugge RJ, Saver JL, Hill MD, Jo- nandez-Perez M, Bharatha A, Jahan R, Jansen O, Richard

January – June 2019, Volume – 8 Issue – 1 29 The official Journal of Cardiological Society of India, Kerala Chapter

S, Levy EI, Berkhemer OA, Soudant M, Aja L, Davis SM, Stroke (ESCAPE) Randomized, Controlled Trial. Circula- Krings T, Tisserand M, San Roman L, Tomasello A, Beum- tion. 2016;133:2279-86. er D, Brown S, Liebeskind DS, Bracard S, Muir KW, Dip- 25. Nogueira RG, Lutsep HL, Gupta R, Jovin TG, Albers GW, pel DWJ, Goyal M, Saver JL, Jovin TG, Hill MD, Mitchell PJ Walker GA, Liebeskind DS, Smith WS and Trialists T. Trevo and collaborators H. Penumbral imaging and functional versus Merci retrievers for thrombectomy revasculariza- outcome in patients with anterior circulation ischaemic tion of large vessel occlusions in acute ischaemic stroke stroke treated with endovascular thrombectomy ver- (TREVO 2): a randomised trial. Lancet. 2012;380:1231-40. sus medical therapy: a meta-analysis of individual patient-level data. Lancet Neurol. 2019;18:46-55. 26. Maus V, Henkel S, Riabikin A, Riedel C, Behme D, Tsog- kas I, Hesse AC, Abdullayev N, Jansen O, Wiesmann M, 17. Saver JL. Time is brain--quantified. Stroke. 2006;37:263-6. Mpotsaris A and Psychogios MN. The SAVE Technique : 18. Menon BK, Al-Ajlan FS, Najm M, Puig J, Castellanos M, Large-Scale Experience for Treatment of Intracranial Dowlatshahi D, Calleja A, Sohn SI, Ahn SH, Poppe A, Mi- Large Vessel Occlusions. Clin Neuroradiol. 2018. kulik R, Asdaghi N, Field TS, Jin A, Asil T, Boulanger JM, 27. McTaggart RA, Tung EL, Yaghi S, Cutting SM, Hemendinger Smith EE, Coutts SB, Barber PA, Bal S, Subramanian S, M, Gale HI, Baird GL, Haas RA and Jayaraman MV. Contin- Mishra S, Trivedi A, Dey S, Eesa M, Sajobi T, Goyal M, Hill uous aspiration prior to intracranial vascular embolec- MD, Demchuk AM and Investigators INS. Association of- tomy (CAPTIVE): a technique which improves outcomes. Clinical, Imaging, and Thrombus Characteristics With J Neurointerv Surg. 2017;9:1154-1159. Recanalization of Visible Intracranial Occlusion in Pa- tients With Acute Ischemic Stroke. JAMA. 2018;320:1017- 28. Menon BK and Goyal M. Thrombus aspiration or retrieval 1026. in acute ischaemic stroke. Lancet. 2019;393:962-963. 19. Menon BK, Hill MD, Davalos A, Roos Y, Campbell BCV, 29. Wang A and Abramowicz AE. Role of anesthesia in en- Dippel DWJ, Guillemin F, Saver JL, van der Lugt A, Dem- dovascular stroke therapy. Curr Opin Anaesthesiol. chuk AM, Muir K, Brown S, Jovin T, Mitchell P, White P, 2017;30:563-569. Bracard S and Goyal M. Efficacy of endovascular throm- 30. Campbell BCV, van Zwam WH, Goyal M, Menon BK, Dippel bectomy in patients with M2 segment middle cerebral DWJ, Demchuk AM, Bracard S, White P, Davalos A, Majoie artery occlusions: meta-analysis of data from the HER- C, van der Lugt A, Ford GA, de la Ossa NP, Kelly M, Bourci- MES Collaboration. J Neurointerv Surg. 2019. er R, Donnan GA, Roos Y, Bang OY, Nogueira RG, Devlin 20. Zerna C, Assis Z, d’Esterre CD, Menon BK and Goyal M. TG, van den Berg LA, Clarencon F, Burns P, Carpenter J, Imaging, Intervention, and Workflow in Acute Ischemic Berkhemer OA, Yavagal DR, Pereira VM, Ducrocq X, Dixit Stroke: The Calgary Approach. AJNR Am J Neuroradi- A, Quesada H, Epstein J, Davis SM, Jansen O, Rubiera M, ol.2016;37:978-84. Urra X, Micard E, Lingsma HF, Naggara O, Brown S, Guille- min F, Muir KW, van Oostenbrugge RJ, Saver JL, Jovin TG, 21. Menon BK and Goyal M. Imaging Paradigms in Acute Hill MD, Mitchell PJ and collaborators H. Effect of general Ischemic Stroke: A Pragmatic Evidence-based Approach. anaesthesia on functional outcome in patients with an- Radiology. 2015;277:7-12. terior circulation ischaemic stroke having endovascular 22. Menon BK, d’Esterre CD, Qazi EM, Almekhlafi M, Hahn L, thrombectomy versus standard care: a meta-analysis of Demchuk AM and Goyal M. Multiphase CT Angiography: individual patient data. Lancet Neurol. 2018;17:47-53. A New Tool for the Imaging Triage of Patients with Acute 31. Shah VA, Martin CO, Hawkins AM, Holloway WE, Junna Ischemic Stroke. Radiology. 2015;275:510 20. S and Akhtar N. Groin complications in endovascular 23. Demchuk AM, Menon BK and Goyal M. Comparing Ves- mechanical thrombectomy for acute ischemic stroke: sel Imaging: Noncontrast Computed Tomography/Com- a 10-year single center experience. J Neurointerv Surg. puted Tomographic Angiography Should Be the New 2016;8:568-70. Minimum Standard in Acute Disabling Stroke. Stroke. 32. Chen SH, Snelling BM, Sur S, Shah SS, McCarthy DJ, Luther 2016;47:273-81. E, Yavagal DR, Peterson EC and Starke RM. Transradial 24. Menon BK, Sajobi TT, Zhang Y, Rempel JL, Shuaib A, versus transfemoral access for anterior circulationme- Thornton J, Williams D, Roy D, Poppe AY, Jovin TG, Sap- chanical thrombectomy: comparison of technical and kota B, Baxter BW, Krings T, Silver FL, Frei DF, Fanale C, clinical outcomes. J Neurointerv Surg. 2019. Tampieri D, Teitelbaum J, Lum C, Dowlatshahi D, Eesa 33. Mokin M, Snyder KV, Levy EI, Hopkins LN and Siddiqui M, Lowerison MW, Kamal NR, Demchuk AM, Hill MD and AH. Direct carotid artery puncture access for endovas- Goyal M. Analysis of Workflow and Time to Treatment cular treatment of acute ischemic stroke: technical as- on Thrombectomy Outcome in the Endovascular Treat- pects, advantages, and limitations. J Neurointerv Surg. ment for Small Core and Proximal Occlusion Ischemic 2015;7:108-13.

30 January – June 2019, Volume – 8 Issue – 1 The official Journal of Cardiological Society of India, Kerala Chapter

34. Jadhav AP, Zaidat OO, Liebeskind DS, Yavagal DR, Hauss- lesions: technical endovascular management and clini- en DC, Hellinger FR, Jr., Jahan R, Jumaa MA, Szeder cal outcomes from the ESCAPE trial. J Neurointerv Surg. V, Nogueira RG and Jovin TG. Emergent Management 2018;10:429-433. of Tandem Lesions in Acute Ischemic Stroke. Stroke. 44. Lapergue B, Blanc R, Gory B, Labreuche J, Duhamel A, 2019;50:428-433. Marnat G, Saleme S, Costalat V, Bracard S, Desal H, Ma- 35. Brinjikji W, Starke RM, Murad MH, Fiorella D, Pereira VM, zighi M, Consoli A, Piotin M and Investigators AT. Effect Goyal M and Kallmes DF. Impact of balloon guide cathe- of Endovascular Contact Aspiration vs Stent Retriever ter on technical and clinical outcomes: a systematic re- on Revascularization in Patients With Acute Ischemic view and meta-analysis. J Neurointerv Surg. 2018;10:335- Stroke and Large Vessel Occlusion: The ASTER Random- ized Clinical Trial. JAMA. 2017;318:443-452. 339. 45. Desai JA, Almekhlafi MA, Hill MD, Goyal M and Eesa M. 36. Wong JHY, Do HM, Telischak NA, Moraff AM, Dodd RL, Ultrasound guided V3 segment vertebral artery direct Marks MP, Ingle SM and Heit JJ. Initial experience with SOFIA as an intermediate catheter in mechanical throm- percutaneous puncture for basilar artery mechanical bectomy for acute ischemic stroke. J Neurointerv Surg. thrombectomy in acute stroke: a technical report. J Neu- 2017;9:1103-1106. rointerv Surg. 2014;6:e18. 37. Balami JS, White PM, McMeekin PJ, Ford GA and Buchan 46. Sarraj A, Hassan A, Savitz SI, Grotta JC, Cai C, Parsha KN,- AM. Complications of endovascular treatment for acute Farrell CM, Imam B, Sitton CW, Reddy ST, Kamal H, Goyal ischemic stroke: Prevention and management. Int J N, Elijovich L, Reishus K, Krishnan R, Sangha N, Wu A, Stroke. 2018;13:348-361. Costa R, Malik R, Mir O, Hasan R, Snodgrass LM, Requena M, Graybeal D, Abraham M, Chen M, McCullough LD and 38. Alshekhlee A, Pandya DJ, English J, Zaidat OO, Mueller N, Ribo M. Endovascular Thrombectomy for Mild Strokes: Gupta R and Nogueira RG. Merci mechanical thrombec- How Low Should We Go? Stroke. 2018;49:2398-2405. tomy retriever for acute ischemic stroke therapy: literature review. Neurology. 2012;79:S126-34. 47. Coutts SB, Berge E, Campbell BC, Muir KW and Parsons MW. Tenecteplase for the treatment of acute ischemic 39. Lum C, Stys PK, Hogan MJ, Nguyen TB, Srinivasan A and stroke: A review of completed and ongoing randomized- Goyal M. Acute anterior circulation stroke: recanaliza- controlled trials. Int J Stroke. 2018:1747493018790024. tion using clot angioplasty. Can J Neurol Sci. 2006;33:217- 22. 48. Campbell BCV, Mitchell PJ, Churilov L, Yassi N, Kleinig TJ, Dowling RJ, Yan B, Bush SJ, Dewey HM, Thijs V, Scroop R, 40. Turk AS, Spiotta A, Frei D, Mocco J, Baxter B, Fiorella D, Simpson M, Brooks M, Asadi H, Wu TY, Shah DG, Wijeratne Siddiqui A, Mokin M, Dewan M, Woo H, Turner R, Hawk T, Ang T, Miteff F, Levi CR, Rodrigues E, Zhao H, Salvaris H, Miranpuri A and Chaudry I. Initial clinical experience P, Garcia-Esperon C, Bailey P, Rice H, de Villiers L, Brown with the ADAPT technique: a direct aspiration first pass H, Redmond K, Leggett D, Fink JN, Collecutt W, Wong AA, technique for stroke thrombectomy. J Neurointerv Surg. Muller C, Coulthard A, Mitchell K, Clouston J, Mahady K, 2014;6:231-7. Field D, Ma H, Phan TG, Chong W, Chandra RV, Slater LA, 41. Delgado Almandoz JE, Kayan Y, Young ML, Fease JL, Scholz Krause M, Harrington TJ, Faulder KC, Steinfort BS, Bla- JM, Milner AM, Hehr TH, Roohani P, Mulder M and Tarrel din CF, Sharma G, Desmond PM, Parsons MW, Donnan RM. Comparison of clinical outcomes in patientswith GA, Davis SM and Investigators E-IT. Tenecteplase versus acute ischemic strokes treated with mechanical Alteplase before Thrombectomy for Ischemic Stroke. N Engl J Med. 2018;378:1573-1582. thrombectomy using either Solumbra or ADAPT techniques. J Neurointerv Surg. 2016;8:1123-1128. 49. Hill MD, Martin RH, Mikulis D, Wong JH, Silver FL, Terbrug- ge KG, Milot G, Clark WM, Macdonald RL, Kelly ME, Boul- 42. Heran NS, Song JK, Namba K, Smith W, Niimi Y and ton M, Fleetwood I, McDougall C, Gunnarsson T, Chow M, Berenstein A. The utility of DynaCT in neuroendovascu- Lum C, Dodd R, Poublanc J, Krings T, Demchuk AM, Goy- lar procedures. AJNR Am J Neuroradiol. 2006;27:330-2. al M, Anderson R, Bishop J, Garman D, Tymianski M and 43. Assis Z, Menon BK, Goyal M, Demchuk AM, Shankar J, investigators Et. Safety and efficacy of NA-1 in patients Rempel JL, Roy D, Poppe AY, Yang V, Lum C, Dowlatshahi with iatrogenic stroke after endovascular aneurysm re- D, Thornton J, Choe H, Burns PA, Frei DF, Baxter BW, Hill- pair (ENACT): a phase 2, randomised, double-blind, pla- MD and Trialists E. Acute ischemic stroke with tandem cebo-controlled trial. Lancet Neurol. 2012;11:942-50.

January – June 2019, Volume – 8 Issue – 1 31 The offi cial Journal of Cardiological Society of India, Kerala Chapter

KHJKERALA HEART JOURNAL

A Journal of Cardiological Society of India Kerala Chapter

p-ISSN: 2347-5269 e-ISSN: 2454-6755 KERALA HEART JOURNAL (p-ISSN: 2347-5267), (e-ISSN: 2454-6755) January - June 2019, Volume - 8, Issue - 1

Editor in Chief Dr. Stigi Joseph

Sajan Narayanan MD. DM. Senior InterventionalCardiologist, Little Flower hospital and research Centre, Angamaly. [email protected]

CASE REPORT Endovascular thrombectomy for acute ischemic stroke

Background: tomatic over subsequent 2 days and was discharged on oral metoprolol, telmisartan& amlodipine .Since his CHA2DS- cute ischemic stroke is an important cause of disability. 2VASc score was 1 and was cardioverted within 2 hours Embolic stroke is dreaded complication of atrial fi bril- A of onset of AF, oral anticoagulation was not considered. 3 lation.Intravenous thrombolysis had been cornerstone of days after discharge, he was readmitted with palpitations treatment of acute ischemic stroke, presenting within 4.5 at rest. ECG showed AF with fast ventricular response. He hours of onset of symptoms1. About 50% of patients who was hemodynamically stable during the second admission. receive thrombolysis are still severely disabled or dead2. Patient was started on intravenous amiodarone with aim of Delays in recanalization & hemorrhagic transformation pharmacological cardioversion. 2 hours after admission, he are recognized limitations of IV rtPA. Endovascular throm- developed sudden onset of weakness of right half of body bectomy with stent retrievers has evolved as an important with global aphasia. Emergency neurology service was acti- minimally invasive procedure which have shown to improve functional disability in anterior circulation strokes3 . Here vated. Initial neurological evaluation revealed dense right we describe a case of acute stroke treated with endovascu- sided hemiplegia suggestive of proximal left middle cere- lar approach. bral artery occlusion . NIHSS score was 24.

Case : Furthur evaluation: 57 year old gentleman, hypertensive since last 4 years on Patient underwent urgent MRI + angiogram . MRI showed telmisartan, has history of surgical closure of ostiumsecun- no bleed. MRA revealed occlusion of left middle cerebral dum atrial septal defect in 1997, presented with palpita- artery at M1 level.( fi gure2) tions at rest since 2 hours. Initial ECG showed atrial fl utter with 2:1 conduction,which degenerated into atrial fi brilla- Procedure: tion.(Figure 1a&b). He developed dyspnea after admission. Chest X ray revealed pulmonary venous hypertension and He was initiated on standard protocol intravenous tPA prominent interstitial shadows suggestive of early pulmo- from imaging suite. A combined neurocardio team decided nary edema. Bedside echo showed concentric left ventric- about possibility of endovascular thrombectomy. Patient ular hypertrophy with good LV systolic function. There was was trasfered to cath lab for endovascular thrombectomy. no residual shunt at atrial level and resting PA pressure es- Right femoral access. Left carotid angiogram showed total- timated from TR velocity was 34mmHg. He was cardioverted ly occluded left MCA at M1 level. ( fi gure3) Left carotid was with synchronized DC shock 100J .Patient remained asymp- engaged with 7JR4 guide. Occluded segment was crossed

32 January – June 2019, Volume – 8 Issue – 1 The official Journal of Cardiological Society of India, Kerala Chapter

with 0.012” X 200cm hybrid wire. Microcatheter was thread- 3) During initial presentation, oral anticoagulation wasn’t ed over the wire and parked distal to the occluded seg- considered since CHA2DS2VASc score was 1. Studies have ment. Guide wire was removed and check angiogram con- shown that presence of risk enhancing features like LV hy- firmed distal location of the microcatheter. ( figure4a&b). pertrophy, ethnicity ( south Asians are prone for embolic A 4X20mm stent retriever was backloaded onto microcath- complications), CKD, elevated biomarkersor echocardio- eter. Retriever was deployed across the occluded segment graphic indices of LAA emptying velocity should prompt by withdrawal of microcatheter.( Figure 5) Stent retriever consideration of OAC even in those patients with low scores. was then pulled back into guide after 2 minutes. (Figure 6) Repeat angiogram showed good filling of distal MCA and branches (TICI grade 3).(figure7) References : 1) Del Zoppo GJ, Saver JL, Jauch EC, et al., for the Ameri- can Heart Association Statistics Committee and Stroke Course in hospital: Statistics Subcommittee. Expansion of the time window There was immediate improvement of motor power of right for treatment of acute ischemic stroke with intravenous upper & lower limbs from grade 0 to 3. Aphasia improved tissue plasminogen activator: a science advisory from over ensuing days and had minor word finding difficulty at the American Heart Association/American Stroke Asso- time of discharge, Motor power was grade 5 on day 7. He ciation. Stroke 2009;40:2945–8. was initiated on oral apixaban from day 7 .Discharged on 2) Albers GW, Bates VE, Clark WM, et al. Intravenous tis- day 7 with NOAC, metoprolol, telmisartan& amlodipine. sue-type plasminogen activator for treatment of acute stroke: the Standard Treatment with Alteplase to Re- Comments: verse Stroke (STARS) study. JAMA 2000;283:1145–50. 1) Cardioembolic strokes associated with AF often causes 3) Powers WJ, Derdeyn CP, Biller J, et al., for the American Heart Association Stroke Council. 2015 AHA/ASA focused proximal vessel occlusion and large strokes update of the 2013 Guidelines for the Early Management 2) Performance of endovascular thrombectomy in combi- of Patients With Acute Ischemic Stroke Regarding Endo- nation with intravenous rtPA within 4.5 hours of presen- vascular Treat- ment: a guideline for healthcare profes- tation of ischemic stroke is associated with improved sionals from the American Heart Association/American neurological outcomes Stroke Association. Stroke 2015;46:3020–35.

Images with legends

Figure 1a&b : ECG showing atrial flutter with 2:1 conduction which degenerated into atrial fibrillation

Figure 2: MR angiogram showing totally occluded Middle Figure 3: left carotid an- cerebral artery immedi- giogram showing totally ately after origin at M1 occluded middle cerebral segment ( arrow) artery at M1 level

January – June 2019, Volume – 8 Issue – 1 33 The official Journal of Cardiological Society of India, Kerala Chapter

Figure 4 a&b :Microcatheter parked distal to occluded segment. Figure 3b showing injection through microcatheter confirming distal position

Figure 5: Figure 6: Stent retriever with 4X20mm retriever deployed across the lesion trapped embolized clot ( arrows depict the markers at two ends of the stent retriever )

Figure 7: Final angiogram after removal of stent retriever on right showing TICI grade 3 flow in distal left middle cerebral branches

34 January – June 2019, Volume – 8 Issue – 1 The offi cial Journal of Cardiological Society of India, Kerala Chapter

KHJKERALA HEART JOURNAL

A Journal of Cardiological Society of India Kerala Chapter

p-ISSN: 2347-5269 e-ISSN: 2454-6755 KERALA HEART JOURNAL (p-ISSN: 2347-5267), (e-ISSN: 2454-6755) January - June 2019, Volume - 8, Issue - 1

Editor in Chief Dr. Stigi Joseph

Rajiv.C. MD. DM*. Hisham Ahammed MD.DM *Professor,** **Asst. Professor, Dept. Of Cardiology, Amrita Institute of Medical sciences, Kochi. correspondence:[email protected].

Image Challenge

Echo Quiz This is the pulmonary artery pulse wave Doppler of a 30 year old lady with CHF. What are the fi nding? Each deflection in spectral Doppler denotes something which gives a clue to the hemodynamics.

January – June 2019, Volume – 8 Issue – 1 35 The official Journal of Cardiological Society of India, Kerala Chapter

Echo Quiz: Explanation Intersting fnding the in this Doppler tracing is the antegrade fow into the pulmonary is not only in systole but also in diastole, to be precise in late diastole, immediately after the P wave on ECG which is a surrogate for atrial contraction. This happens when the RV end diastolic pressure is very high ( higher than the pulmonary artery diastolic pressure at that point in time, causing the pulmonary valve to open). If it was a disease affecting the left side of the heart, pulmonary artery diastolic pressure would have been high or at least normal. Hence there should be a combination of normal or low pulmonary artery diastolic pressure and very high RV end diastolic pressure. This lady had isolated right ventricular endo myocardial fbrosis which satisfied both conditions. This could happen in any situation where there is isolated stiff RV.

36 January – June 2019, Volume – 8 Issue – 1 The offi cial Journal of Cardiological Society of India, Kerala Chapter

KHJKERALA HEART JOURNAL

A Journal of Cardiological Society of India Kerala Chapter

p-ISSN: 2347-5269 e-ISSN: 2454-6755 KERALA HEART JOURNAL (p-ISSN: 2347-5267), (e-ISSN: 2454-6755) January - June 2019, Volume - 8, Issue - 1

Editor in Chief Dr. Stigi Joseph

Abhilash SP Additional Professor in cardiology, Sree Chitra Tirunal Institute For Medical Sciences and Technology Thiruvananthapuram, Kerala, PIN 695 011 Email: [email protected].

A simplifi ed approach to wide complex tachycardia in emergency room

wide QRS complex tachycardia (WCT) is defi ned as a ondmost common cause of WCTs, accounting for 15-20% of A rhythm with a rate more than 100 per minute with a WCTcases (Table 1).Aberrant conduction refers to widening QRS duration more than 120 milliseconds. The differential of the QRS complex due to conduction delay or block along diagnosis of a regular, monomorphic wide QRS complex the bundle branches or fascicles. This conduction delay or tachycardia is a diagnostic dilemma in emergency room. block could be pre-existent bundle branch block (BBB) or The proper recognition of the mechanism of WCT is vital functional,when the BBB is rate dependent(usually tachycar- not only for acute arrhythmia management, but also for dia-dependent). Less commonly conduction delay or block the prognosis and chronic management of the patient. De- can occur intra-myocardial, due to slowed muscle-to-muscle spite the published numerous ECG algorithms and criteria, conduction, as in ventricular hypertrophy, cardiomyopathy the accurate and timely diagnosis in patients with WCT is and certain congenital heart diseases4,5,8,9 Preexcited SVT (SVT with anterograde conduction over an accessory pathway) not straight forward. Many of these ECG criteria are com- is another cause of SVT with wide QRS. It includes antidromic plicated and diffi cult to recall in an urgent setting. Aim of AV reentrant tachycardia (AVRT) with anterograde conduction this article is not to have a comprehensive review of all over a typical or atypical (eg: Mahaim fi bre) bypass tract. It the complex algorithms but to simplify the assessment in also includes AV nodal re-entrant tachycardia (AVNRT), atrial emergency room. The various morphological criteria are tachycardia or atrial fl utter with anterograde conduction over avoided purposefully in this discussion since they are not an accessory pathway functioning as a bystander. Ventricular easy to recollect and are complex for most. A relatively paced rhythm, drugs like class IA, IC, Class III anti arrhyth- simple approach involving 8 steps, focussing on electro- mic agents and electrolyte disorders (eg: hyperkalemia) can physiological basis of wide complex tachycardia is at- also present as WCT. However, pre excited SVTs, drugs, paced tempted. Readers are requested to refer to the standard rhythms, and electrolyte disorders constitute only a minority algorithms1,2,3 elsewhere if a comprehensive review is of WCTs, and are seen typically in less than 5% of cases. Be- needed. (Refer: Figure 1 - Annexure) cause the majority (95%) of WCTs are either VT or SVT with aberrant conduction, the main focus ofthis discussion is to distinguish VT from SVT with aberrant conduction. Remember Step 1 : that when we diagnose VT in a WCT case, we are going to be Remember a little bit of statistics! correct 75-80% of time and when we diagnose SVT, we will be The most common cause of WCT is ventricular tachycardia correct 15-20% of time! And also note that, a WCT in a patient (VT), which accounts for up to 80% of cases.4-7Supraventric- with history of coronary artery heart disease or heart failure ular tachycardia (SVT) with aberrant conduction is the sec- is going to be VT in more than 95% of time!

January – June 2019, Volume – 8 Issue – 1 37 The official Journal of Cardiological Society of India, Kerala Chapter

I. Ventricular Tachycardia (75-80%)

II. SVT with abnormal intraventricular conduction (20-25%)

A. SVT with aberrant conduction (15-20%) – pre-existent (fixed) or functional.

B. Pre – excited SVT. (Antidromic AVRT, Mahaim fibre tachycardia or SVT with bystander accessory pathway)

C. SVT with intra-myocardial conduction delay. (Cardiomyopathy, CHDs)

D. Drug toxicity. ( Class IA, IC, III, digoxin)

E. Electrolyte disturbances. (Hyperkalemia)

III. Ventricular paced rhythm

Table 1. Causes of regular wide complex tachycardia

Step 2 : History and clinical Step 3 : examination do give some clue Learn the basic principles behind the Older patients and those with a history of coronary heart major electrocardiographic criteria disease or heart failure are likely to have ventricular and apply them to the ECG.(Table 2) tachycardia, whereas, younger patients and those with long duration of symptoms are more likely to have SVT. A. If the morphology of the WCT QRS complex fits with typ- Although VT is more likely than SVT to cause hypotension ical BBB or fascicular block, the WCT is caused by SVT and hemodynamic instability, the hemodynamic stability with aberrancy. If there is no combination of BBB or of a patient does not distinguish VT from SVT, because a fascicular blocks that could result in the particular QRS significant proportion of patients with VT and mostpa- morphology, theWCT is caused by VT or pre-excited SVT. tients with SVT are hemodynamically stable. It is import- B. Most VTs are associated with slow initial ventricular ant to note that a patient with structurally abnormal heart activation close to the site of origin due to slow mus- (For example: Severe AS, Post Fontan etc) can present with cle-to-muscle conduction, which results in a more sig- hemodynamic collapse even with SVT. A careful history re- nificantly prolonged QRS duration or time to the intrin- garding intake of class IA, IC, III drugs and digoxin is to sicoid deflection, compared to SVT. be obtained. Physical findings that indicate the presence of AV dissociation suggest VT with a very high likelihood. C. The relative fastness of initial and terminal ventricular These findings include variable intensity of the first heart activation is different during SVT with aberrancy and VT. sound and the presence of irregular “Cannon” A waves in During SVT with aberrancy, the initial activation is al- jugular venous pulse. Irregular Cannon waves occur due ways fast, because it occurs via the normal His-Purkinje to occasional simultaneous atrial and ventricular contrac- system, and the conduction delay causing the wide QRS tion during AV dissociation. “Cannon” A waves should be occurs in the mid to terminal part of the QRS. During VT distinguished from ‘frog sign” (Regular, Cannon waves) the initial ventricular activation is usually slower due to which occurs during every heart beat due to simultane- initial muscle to muscle conduction. ous atrial and ventricular contraction that is usually seen D. During SVT with aberrancy, both the initial rapid septal in AVNRT and junctional tachycardia. Valsalva manoeuvre, activation (which can be either left-to-right or right- carotid sinus massage or adenosine administration may to-left) and the later main ventricular activation wave- facilitate the elucidation of WCT mechanism. The termi- front proceed in a direction away from lead aVR yielding nation a negative or predominantly negative QRS complex in of tachycardia with these strongly suggests SVT (AVNRT or lead aVR. Hence, an initial R or Rs wave cannot be pres- AVRT). However, VT due to triggered mechanism such as ent in lead aVR in a patient with SVT with aberrancy. And idiopathic outflow tract VT may also be terminated with the same explanation leads to the assumption that a these manoeuvres. northwest QRS axis (between +180 degrees and -90de-

38 January – June 2019, Volume – 8 Issue – 1 The official Journal of Cardiological Society of India, Kerala Chapter

QRS duration >160 ms with LBBB pattern or >140 ms with RBBB pattern suggests VT QRS during WCT is narrower than in sinus rhythm suggests VT

QRS axis Right superior (northwest) axis (from -90 degrees to +180 degrees) favours VT RBBB pattern with left axis deviation (to the left of -30 degrees) suggests VT LBBB pattern with right axis deviation (to the right of +90 degrees) suggests VT QRS axis shift >40 degrees between sinus rhythm and WCT suggests VT RBBB pattern with a normal axis suggests VT

Precordial QRS concordance Positive or negative concordance suggests VT

AV dissociation (suggestive of VT) Dissociated P waves AV ratio <1 VA block (VA ratio >1) Fusion beats Capture beats

Table 2 – Useful traditional ECG criteria for the differentiation of WCTs in emergency room.

grees) cannot be present duringSVT with aberrancy. In Step 4 : addition, this propagation pattern should give rise to an R wave at least in one or several precordial leads Look at lead aVR. during SVT. Therefore the absence of RS complex in the (The aVR Vereckei Algorithm) precordial leads strongly suggests VT. The following criteria are analysed in lead aVR10.(Figure 2) E. The direction of initial septal activation and that of The following criteria are analysed in lead aVR10.(Figure 2) the main ventricular activation wave front during sinus rhythm or SVT are different and results in both posi- A. The presence or absence of an initial R wave tive and negative QRS complexes in different precordial B. Presence or absence of an initial r or q wave of >40 ms leads. Hence, concordance of the QRS complexes in the width precordial leads strongly suggests VT.This finding is very specific for VT (>90%); but seen in only <20% VTs. C. Notching on the descending limb of a negative onset, predominantly negative QRS complex F. The presence of AV dissociation (Dissociated P waves, V more than A) or VA block (VA ratio more than 1) suggests D. vi/vtratio (See below for description). When any of the VT with a close to 100% specificity. Some rare SVTs like first three criteria of the algorithm is met, a diagnosis of junctional ectopic tachycardia, and nodo-fascicular/ VT is made and the analysis is stopped at that step. In nodo-ventricular accessory pathways can also have VA the 4thstep, a vi/vt <1 diagnosed VT, and if vi/vt is >1 a dissociation. diagnosis of SVT is made. G. Tell-tale evidence of two foci (sinus and ventricular) like The presence of an initial R wave in lead aVR is similar to capture beat and fusion beat confirms VT. the traditional northwest axis criterion, but not the same,

January – June 2019, Volume – 8 Issue – 1 39 The official Journal of Cardiological Society of India, Kerala Chapter

Figure 3 Figure 2. vi/vt ratio. If the distance travelled on the Y axis in the The aVR Vereckei algorithm(Ref:András Vereckei. initial 40ms of the QRS complex is smaller than that trav- Current Cardiology Reviews, 2014, 10, 262-276) elled in the terminal 40ms of the QRS complex, a VT is much more likely.

because the range of the resultant QRS vector that yields an initial R wave in lead aVR is between -60 degrees and +120 degrees whereas traditional north west axis refers to -90 degrees to + 180 degrees. The initial ventricular activation wave front via conduction system of heart during SVT and sinus rhythm should go away from lead aVR yielding a negative QRS (QS) complex. Thus, an initial dominant R wave (such as R or Rs complex) in lead aVR is not normally present in SVT with aberrancy and supports a diagnosis of VT. Sim- ilarly notching on the descending limb of a negative onset, predominantly negative QRS complex suggests initial activation wave front does not go through the conduction system of heart but initiates in the relatively slowly conducting ventricular myocardium. This also suggests a diagnosis of VT rather than SVT.

Vi/Vt Ratio Figure 4 Lead II R-wave Peak Time (RWPT) Criterion The vi/vt criterion is based on the estimation of initial (vi) (Ref:Pava et al. Heart Rhythm, 2010; 7: 922-6) and terminal (vt) ventricular activation velocity ratio (vi/vt) by measuring the vertical excursion (in millivolts) recorded on the ECG during the initial (vi) and terminal 40 ms (vt) of terminal part of the QRS. Thus, the vi/vt ratio is>1 during a the QRS complex. (Figure 3) The rationale behind the vi/vt SVT. During WCT due to VT, however, an initial slower mus- criterion is that during WCT due to SVT the initial activation cle- to-muscle spread of activation occurs until the impulse of the septum should be invariably rapid over the normal reaches the His-Purkinje system, after which the rest of the His-Purkinje system and the intra-ventricular conduction ventricular muscle is more rapidly activated, thus, the vi/vt delay causing the wide QRS complex occurs in the mid to ratio is<1 during a VT.

40 January – June 2019, Volume – 8 Issue – 1 The official Journal of Cardiological Society of India, Kerala Chapter

coronary artery disease, or heart failure will clinch the di- Step 5: Look at lead II. agnosis. Sarcoidosis is an important differential diagnosis (R-wave Peak Time – RWPT - which can present with multiple morphologies of scar VT. Criterion) It is useful to be familiar with ECG features of common idio- In a wide complex tachycardia, the time taken from the pathic VTs occurring in structurally normal heart and the pat- QRS onset to the peak of the first positive or negative wave tern recognition (For example: LBBB tachycardia with inferior measured in lead II, when >50 ms suggests VT, and when <50 axis – RVOT VT, RBBB tachycardia with left axis – PFVT) helps in easy identification of tachycardia in emergency room. ms suggests SVT11. (Figure 4) This criterion also makes use of the fundamental difference Detailed description of localisation of accessory pathways, in initial activation pattern between a VT and SVT very sim- SVTs and Mahaim fibre tachycardia is beyond the scope of this chapter and readers are advised to refer to standard ilar to aVR criteria. text books for the same.

Step6 : Look at Lead V1 to decide Step 7: whether LBBB or RBBB wide complex Remember about irregular wide tachycardia. Have a check list for complex tachycardia differential diagnosis for LBBB tachy- Most commonly a Fast, Broad, Irregular tachycardia (Remem- cardia as well for RBBB tachycardia ber as FBI) occurs due to atrial fibrillation and bundle branch This step helps to refine the differential diagnoses further block. However, considering the potential for degenerating to and gives clues to anatomic localisation of tachycardia or- VF, recent guidelines suggest to consider any Fast Broad Irreg- igin. (Table 3)Ventricular tachycardia of LBBB morphology ular tachycardia as atrial fibrillation conducted via accessory suggests origin from right ventricle and positive QRS in infe- pathway (AF with WPW syndrome). Prompt DC version is needed rior leads (II,III,AVF) localises VT to out flow tract (RVOT VT). and pre excitation in the basal ECG will confirm the diagnosis. QRS axis other than right inferior axis in LBBB morphology Polymophic VT can be irregular but, is not discussed here. VT should prompt suspicion of ARVD. A careful examination Occasionally monomorphic VT due to triggered activity/au- of basal ECG and echo for evidence of ARVD is mandatory. If in doubt, a cardiac MRI should be ordered. tomaticity can present as irregular WCT. In addition, VTs can be irregular in the initial few seconds of its onset and also Similarly VT of RBBB morphology localises the ventricular when affected by antiarrhythmic drugs. tachycardia to left side of heart and a positive QRS in II,III, AVF suggests LVOT origin. A relatively narrower QRS and negative QRS in inferior leads suggest posterior fascicular VT. Positive QRS in all precordial leads suggests mitral annular VT and Step 8: deep S waves in V5-V6 may suggest papillary muscle VT. Importance of sinus rhythm ECG Bundle branch re-entry VTs can have both LBBB and RBBB If the patient has a previous basal ECG with him at the morphology and are usually seen in patients with cardiomy- time of presentation, examine it meticulously. It may opathy and diseased conduction system. Scar VTs can be of give a clue to the nature of WCT. Basal ECG after con- LBBB or RBBB morphology and many a times, multiple mor- version of WCT also gives valuable information on the phologies of VT can occur in the same patient. A history of aetiology of tachycardia.

LBBB tachycardia RBBB tachycardia zz Ventricular tachycardia zz Ventricular tachycardia (Fascicular VT, ( RVOT VT, VT in ARVD, Bundle branch re-entry VT, scar VT) LVOT VT, Mitral annular VT, Papillary muscle VT, Bundle branch re-entry VT, scar VT) zz SVT with fixed or functional LBBB zz SVT with fixed or functional RBBB zz Mahaim fibre tachycardia zz Left sided pathway mediated z z Right sided pathway mediated anti-dromic tachycardia anti-dromic tachycardia z z SVT with a right sided bystander pathway zz SVT with a left sided bystander pathway

Table 3 – Differential diagnosis of wide complex tachycardia according to morphology in V1

January – June 2019, Volume – 8 Issue – 1 41 The official Journal of Cardiological Society of India, Kerala Chapter

l Look for pre-existing BBB- Similar QRS morphology sug sociation task force on practice guidelines and the gests SVT with aberrancy whereas different morphology European society of cardiology committee for prac- suggests VT tice guidelines (writing committee to develop guidelines for the management of patients with supra- l Look for delta wave- A similar morphology of WCT sug- ventricular arrhythmias) developed in collaboration gests anti-dromic AVRT/pre-excited SVT with NASPE-Heart Rhythm Society. J Am Coll Cardiol. l Look for QRS axis- A shift >400 suggests VT 2003, 15;42(8):1493-531. Look for markers of VT substrate- pathological Q waves 2. Brugada P, Brugada J, Mont L, Smeets J, and Andries of MI, epsilon waves in ARVD EW. A new approach to the differential diagnosis of a regular tachycardia with a wide QRS complex.Circu- l Look for QRS width- A WCT narrower than the sinus lation. 1991, 83(5):1649-59 rhythm suggests VT 3. Vereckei A, Duray G, Szénási G, Altemose GT, and Miller Above discussion is to simplify the approach to wide com- JM. Application of a new algorithm in the differen- plex tachycardia in an emergency room. However, it has to tial diagnosis of wide QRS complex tachycardia. Eur be remembered that no criterion is to be applied in isola- Heart J. 2007, 28(5):589-600. tion. All the described algorithms in literature are meant to distinguish between VT and SVT with aberrancy. It is very 4. Miller JM, Das MK. Differential diagnosis for wide QRS difficult to distinguish VT from pre-excited SVT because in complex tachycardia. In: Cardiac electrophysiology. both cases, ventricular activation begins outside the nor- From cell to bedside. 5th Edition. Eds.: Zipes DP, Jal- mal intraventricular conduction system. Pre-excited SVT ife J. Saunders, Elsevier 2009, 823-30. using a typical AV bypass tract behaves as a VT originating 5. Issa F, Miller JM, Zipes DP. Clinical arrhythmology and from the base of the ventricles. Among the various crite- electrophysiology. 2nd Edition. Approach to wide ria mentioned above, initial R wave in lead aVR is possi- QRS complex tachycardias. Elsevier, Saunders, 2012, bly the only helpful criterion which may help to rule out 499-511. pre-excited SVT and suggest VT. Luckily pre excited SVTs are rare. Exact identification of a WCT could be difficult 6. Pellegrini CN, Scheinman MM. Clinical management occasionally and when in doubt, treat any wide complex of ventricular tachycardia. Curr Probl Cardiol 2010; tachycardia as VT. Similarly any wide complex tachycardia 35: 453-504. in a patient with structurally abnormal heart or history 7. Alzand BSN, Crijns HJGM. Diagnostic criteria of broad of coronary artery heart disease should be treated as VT. QRS complex tachycardia: decades of evolution. Eu- In an unstable patient, it is important to cardio-vert the ropace 2011; 13:465-72 patient first and think later. At the same time, in a stable 8. Miller JM, Bhakta D, Scherschel JA, Yadav AV. Ap- patient, we should make every effort to reach the correct proach to the patient with wide complex tachycardia. diagnosis before treatment. In: Electrophysiology. The basics. A companion guide for the cardiology fellow during the EP rotation. References Wolters Kluwer, Lippincott Williams and Wilkins,Phil- adelphia, Baltimore, New York, London, Buenos Ai- 1. Blomström-Lundqvist C, Scheinman MM, Aliot EM, res, Hong Kong, Sidney, Tokyo, 2010, 186-94. Alpert JS, Calkins H, Camm AJ, Campbell WB, Haines DE, Kuck KH, Lerman BB, Miller DD, Shaeffer CW, Ste- 9. Strauss DG. Differentiation between left bundle venson WG, Tomaselli GF, Antman EM, Smith SC Jr, branch block and left ventricular hypertrophy: Im- Alpert JS, Faxon DP, Fuster V, Gibbons RJ, Gregoratos plications for cardiac resynchronization therapy. J G, Hiratzka LF, Hunt SA, Jacobs AK, Russell RO Jr, Pri- Eelectrocardiol 2012; 45: 635-9. ori SG, Blanc JJ, Budaj A, Burgos EF, Cowie M, Deckers 10. András Vereckei. Current Algorithms for the Diagno- JW, Garcia MA, Klein WW, Lekakis J, Lindahl B, Maz- sis of wide QRS Complex Tachycardias. Current Car- zotta G, Morais JC, Oto A, Smiseth O, Trappe HJ, and diology Reviews, 2014, 10, 262-276 European Society of Cardiology Committee, NASPE- Heart Rhythm Society. ACC/AHA/ESC guidelines for 11. Pava LF, Perafán P, Badiel M, Arango JJ, Mont L, Moril- the management of patients with supraventricular lo CA, and Brugada J. R-wave peak time at DII: a new arrhythmias--executive summary. a report of the criterion for differentiating between wide complex American college of cardiology/American heart as- QRS tachycardias. Heart Rhythm. 2010,7:922-6.

42 January – June 2019, Volume – 8 Issue – 1 The offi cial Journal of Cardiological Society of India, Kerala Chapter

Wide QRS complex tachycardia

(QRS duration grater than 120minutes)

Regular or Irregular

Regular Irregular

Is QRS identical to that during SR ? Atrial Fibrillation Vagal manuvres or Adenosine If YES, consider; Atrial Flutter / AT with variable conduction and SVT and RBBB , Antidromic AVRT (a) BBB or (b) antegrade conduction via AP

Previous Myocardial Infarction or structural heart disease? If yes ,VT likely

1 to 1 AV relationship

Yes / Unknown No

V rate faster than A rate A rate faster than V rate

Atrial Tachycardia VT QRS morphology in precordial leads Atrial Flutter

Typical Precordial leads RBBB pattern LBBB pattern

Concordant qR,Rs or Rr in V1 R in V1 longer than 30 ms RBBB or Frontal plane axis range from R to nadir of S in V1>60msec LBBB, No RS Pattern VT -90 degrees to +90 degrees. qR or qS in V6. Onset of R to nadir

SVT. longer than 100 ms VT VT

Figure 1 Approach to wide complex tachycardia – ACC/AHA/ESC algorithm.1

January – June 2019, Volume – 8 Issue – 1 43 The offi cial Journal of Cardiological Society of India, Kerala Chapter

KHJKERALA HEART JOURNAL

A Journal of Cardiological Society of India Kerala Chapter

p-ISSN: 2347-5269 e-ISSN: 2454-6755 KERALA HEART JOURNAL (p-ISSN: 2347-5267), (e-ISSN: 2454-6755) January - June 2019, Volume - 8, Issue - 1

Editor in Chief Dr. Stigi Joseph

Thachil A Mathew R, Jose J, Abdullakutty J Joseph J, George J Lisie Heart Institute, Lisie Hospital, Kochi, Kerala, India

Sundaram PS Department of Nuclear Medicine, Amrita Institute of Medical Sciences, Kochi, Kerala, India CASE REPORT correspondance:[email protected] Management of arrhythmogenic infl ammatory cardiomyopathy: a case based discussion

61 year old male presented elsewhere in December hypermetabolism. This showed focal uptake in the basal LV; A2016 with an episode of syncope strongly suggestive of there was no signifi cant extracardiac uptake. ( Figure 2). The arrhythmia. His evaluation at that time showed a left ven- same areas showed perfusion defects in a resting13N-NH3s- tricular ejection fraction (LVEF) of 40%, regional wall motion can. His Mantoux test was negative. There was no clinical or abnormalities (RWMA) in multiple areas of the left ventri- radiological ( chest X-ray, CT scan) evidence of extracardiac cle (LV), and normal coronaries. He was treated with beta disease. Considering that active disease was likely limited to blockers and angiotensin receptor blockers for dilated car- the lateral wall of the LV, an endomyocardial biopsy was not diomyopathy, and also drugs for late onset seizures. In July attempted. A diagnosis of arrhythmogenic infl ammatory car- 2017, he presented to the same center with an episode of diomyopathy (AIC), possibly active cardiac sarcoidosis (CS) self terminating presyncopal palpitation. Amiodarone was was made, and medical therapy was started. 2Amiodarone added to the treatment regime for possible ventricular ar- was stopped, and he was administered oral Prednisolone rhythmia, and he was implanted with a single chamber im- 60 mg/ day for one month, which was tapered and stopped plantable cardioverter defi brillator (ICD) ( Boston Scientifi c over the next fi ve months. By February 2018, his LVEF , LVEDV Inogen VR‐). He presented to our center in December 2017 and LVESV had improved to 52%, 108 cc, and 55 cc respec- for further evaluation, at which time he was asymptomatic. tively, though the RWMA persisted. He was advised a repeat 18F-FDG PET CT after 6 months of therapy, which he declined. His echocardiogram showed LVEF, LV end diastolic volume (LVEDV), and LV end systolic volumes (LVESV) of 43%,130 cc He presented on 25 July 2018 with three ICD shocks over the and 74 cc respectively, and severe hypokinesia of the entire past three days. ICD interrogation revealed 13 episodes of posterolateral LV. No episodes of arrhythmia were recorded ventricular tachycardia (VT) since 22 April 2018, seven of which in the ICD. The ECG showed fractionated QRS (fQRS) com- were terminated by anti tachycardia pacing (ATP); 7 of the ep- plexes in inferior leads and lead aVL( Figure 1). This clinical isodes had occurred over the past 3 days, indicating an in- picture – the combination of likely ventricular arrhythmia, creasing frequency of VT. ( Figure 3) He was initiated on oral reduced LVEF, RWMA not due to coronary artery disease, and Amiodarone 200 mg twice daily, and was scheduled for a re- fQRS in the region of RWMA suggestive of a midmyocardi- peat 18F-FDG PET CT to evaluate for reactivation of myocardial al scarring process – was strongly suggestive of an infl am- infl ammation. The ICD was programed to deliver therapies for matory cardiomyopathy. 1 Hence he underwent an 18F-FDG VTs 170 bpm, and record VTs from 140 bpm in a monitor zone. PET CT scan from the neck to the abdomen to evaluate for He experienced two more ICD shocks on 26 July 2018 evening, any myocardial infl ammation, and any extracardiac focus of and was admitted late night on 26 July 2018 with heart fail-

44 January – June 2019, Volume – 8 Issue – 1 The official Journal of Cardiological Society of India, Kerala Chapter

ure. At admission, he was in slow VT at 153 bpm which was late potentials, encircle the mid posterior wall scar, and not treated by the ICD. ( Figure3). This episode of VT had a ablate areas of low voltage electrograms within the scar. morphology consistent with a posterolateral LV exit.( Figure (Figure 9). Irrigated endocardial radiofrequency ablation 4). Considering that this was the same area involved by in- was performed to connect the annulus to the basal LV scar. flammation previously, it was reasonable to consider an ex- Post radiofrequency ablation, programmed extrastimula- acerbation of myocardial inflammation as the possible cause tion at baseline and on Isoprenaline reached VERP using a of this VT. Accordingly, he was initiated on enhanced immu- four extrastimulus protocol without inducing non sustained nosuppression in the form of intravenous (IV) MethylPred- or sustained VT. There have been no episodes of VT at fol- nisolone 1 gm/ day for three days.3Simultaneously, he was low up till 13 April 2018. Amiodarone was stopped 1 month administered IV Lidocaine, which terminated the VT within 30 post radiofrequency ablation, and the patient is currently minutes. Lidocaine was stopped after a few hours due to bra- on Metoprolol and Methotrexate. dycardia resulting in VVI pacing and hypotension. Amiodarone was withheld next day due to slightly elevated transaminases. The dose of oral Metoprolol was increased from the previous- DISCUSSION ly administered dose of 50 mg twice daily to 150 mg/ day. He This case, where VT due to both the inflammatory and the scar remained in sinus rhythm, except for another episode of slow phases of AIC was managed differently, serves to illustrate VT of the same morphology on 28 July 2018 morning, which multiple facets regarding the diagnosis and management of promptly reverted to sinus rhythm after a bolus of Lidocaine this entity. AIC, defined as focal myocardial uptake on 18F-FDG which was not followed up with an infusion. After three days of PET CT causing ventricular arrhythmia (VA), was the cause of VA IV MethylPrednisololne, he was re-initiated on oral Predniso- in 49% of patients in a cohort of patients ( n=103) with unex- lone 60 mg / day for one month, followed by a repeat 18F-FDG plained cardiomyopathy at a referral center.2 One of the com- PET CT guided tapering schedule. The follow up 18F-FDG PET mon causes of AIC is cardiac sarcoidosis, which was diagnosed CT performed on 11 December 2018 showed complete resolu- in 36% of cases of AIC in the index report.2Many of the diseases tion of myocardial inflammation. ( Figure 5). A steroid sparing causing AIC have to be labelled so due to lack of an appropri- regime of oral Methotrexate was gradually introduced as per ate tissue for histological diagnosis. Many of them cause gran- a previously described protocol. 4He remained VT free until ulomatous myocardial inflammation leading to typically non December 30, 2018. endocardial myocardial scars. Clinically, many of them have a On 31 December 2018, he presented with recurrent VT at 190 similar presentation, in that they often cause an inflammatory bpm requiring three ICD shocks over two days. Considering phase and a scar phase, either of which may be responsible the findings of the recent 18F-FDG PET CT, it was unlikely for VA.2, 5,6 These diseases can be diagnosed based on multi- that these VTs were due to myocardial inflammation. He ple clues including the following : 1) Unexplained areas of focal was initiated on IV Amiodarone, and remained VT free till uptake on 18F-FDG PET CT, 2) Non endocardial scars on con- 3rd January 2019. Despite beta blockers, Amiodarone and trast MRI not corresponding to a coronary artery distribution, IV Lidocaine, he experienced 14 episodes of rapid VT on 3rd 3) Association of VT with AV block and/or LV dysfunction.2 In January 2019, 10 of which required ICD shocks for failed ATP, addition, considering that cardiac sarcoidosis is probably the and another 10 episodes on 4th January 2019, 3 of which most common cause of AIC, some findings described in cardi- required ICD shocks for failed ATP. He underwent radiof- ac sarcoidosis may serve as clinical clues towards suspecting requency ablation for VT on January 9, 2019. Endocardial AIC. These findings include1) Presence of pleomorphic VT7, 2) substrate map of the right ventricle (RV) was normal. En- Recurrence of VT of a morphology different from the index docardial substrate map of the LV showed a minimal basal morphology8, and 3) Presence of fQRS complexes during sinus posterior wall scar without any late potentials.(Figure 6A). beats1. A tissue diagnosis should be sought for in all cases of A posteriorly directed percutaneous subxiphoid epicardi- AIC, and infective causes like myocardial tuberculosis should al access was obtained under general anaesthesia.( Figure be ruled out. However, in those cases where a tissue diagnosis 7)Epicardial substrate map of the LV showed a large mid cannot be established, it may be reasonable to apply the same posterior wall scar, separated from a smaller basal poste- treatment principles as outlined for cardiac sarcoidosis, where- rior wall scar by a channel of relatively preserved voltage. in VTs due to the initial inflammatory phase and recurrence of (Figure 6B) An area of late potentials was identified at the inflammation are managed by immunosuppression, and VTs border of the epicardial scar. ( Figure 8) Programmed ex- due to the scar phase are managed by radiofrequency ablation trastimulation at baseline induced short runs of self termi- in addition to medical therapy.9 Similar to cardiac sarcoidosis, nating VT. Irrigated epicardial radiofrequency ablation was AIC too, seems to have a reasonably good prognosis if therapy done to connect the basal LV scar to the annulus, transect is instituted in the early phase of disease wherein the LVEF is the channel between the two epicardial scars, ablate the relatively preserved.2,8,10

January – June 2019, Volume – 8 Issue – 1 45 The official Journal of Cardiological Society of India, Kerala Chapter

Figure 1. QRS fractionation in leads II, III, aVF and aVL( arrows)

Figure 2.Focal increase in 18F-FDG uptake in the basal lateral LV ( arrows)

Episode no. Date and time Type of episode Therapy

Figure 3. Episodes of VT revealed by in-clinic ICD interrogation on 25 July 2018( episodes V1- V-13) , and further episodes of VT revealed at admission late night on 26 July 2018 ( episodes V14-V-18). ATP = Antitachycardia pacing, 41J = VT terminated by 41 Joule shock

46 January – June 2019, Volume – 8 Issue – 1 The official Journal of Cardiological Society of India, Kerala Chapter

Figure 4. VT recorded at admission late night on 26 July 2018.

Figure 5.18F-FDG PET CT showing resolution of initially present myocardial uptake in basal lateral LV ( white arrows, left panels) after steroid therapy ( right panels). This correlated with resolution of VT.

Figures 6A ( left) and 6B ( right). Substrate map of the LV showing regional bipolar voltages plotted on a 3 dimensio- nalelectroanatomical map. Areas with local bipolar voltage < 0.3 mV are colored grey (“scar”), and those with local bipolar voltage > 1.0 mV are colored purple (“normal area”). Areas of in-between voltage ( “peri-scar area”) are colored as per the color bar depicted. Panel A, a posteroanterior view of the LV endocardium, shows a small scar near the basal posterior LV surrounded by a peri-scar area. Panel B, an anteroposterior view of the LV epicardium, shows a larger basal LV scar corresponding to endocardial scar ( white arrow), a larger mid posterior LV scar ( double white arrow), with an intervening channel of preserved voltage ( black arrow).

Figure 7.Left anterior oblique fluoro- scopic projection showing intracardiac catheters and the ICD. 1: Ablation catheter on the epicardial basal lateral LV introduced via percutaneous subxiphoid approach. 2: Endocardial ablation catheter (in the left atrium) introduced via the trans-septal approach. 3: Catheter in the coronary sinus. 4: Catheter in the RV endocardium. 5: ICD lead in the RV

January – June 2019, Volume – 8 Issue – 1 47 The official Journal of Cardiological Society of India, Kerala Chapter

Figure 8. Late potentials in the LV epicardium during sinus rhythm ( blue arrows) becoming even later during RV pacing ( red arrows). Such discrete areas of late activity, typically found in peri-scar areas, often serve as the critical zones in re-entrant VT circuits.

Figure 9. Sites of epicardial radiofrequency ablation lesions, depicted as brown dots. 1: Lesion set connecting the basal LV scar to the annulus. 2: Lesion set transecting the channel of preserved voltage between the basal and mid LV scars. 3: Lesions encircling the mid LV scar and lesions delivered at sites of preserved electrograms within the dense mid LV scar. Lesions were also delivered within the circled area; this was the site where late potentials were recorded at the scar border.

48 January – June 2019, Volume – 8 Issue – 1 The official Journal of Cardiological Society of India, Kerala Chapter

REFERENCES 6. Tezuka D, Terashima M, Kato Y, Toriihara A, Hirasawa K, 1. Roukoz H, Shah M, Masilamani L J, Thachil A, Jayaku- Sasaoka T, Yoshikawa S, Maejima Y, Ashikaga T, Suzuki J, mar P J, Benditt D G, Narasimhan C. fQRS as a marker of Hirao K, Isobe M. Clinical characteristics of definite or granulomatous disease in patients presenting with ven- suspected isolated cardiac sarcoidosis: Application of tricular tachycardia and normal left ventricular ejection cardiac magnetic resonance imaging and 18F-Fluo- fraction. Indian Heart J. 2015 May-Jun; 67(3): 222–226. ro-2-deoxyglucose positron-emission tomography/ 2. Tung R, Bauer B, Schelbert H, Lynch J III, Auerbach M, computerized tomography. J Card Fail. 2015; 21:313–22. Gupta P, SchiepersC, Chan S, Ferris J, Barrio M, Ajijola O, 7. Panda S, Kaur D, LalukotaK, SundarG,Pavri B B, Narasim- Bradfield J, Shivkumar K. Incidence of abnormal posi- hanC. Pleomorphism during Ventricular Tachycardia: A tron emission tomography in patients with unexplained cardiomyopathy and ventricular arrhythmias: the po- Distinguishing Feature between Cardiac Sarcoidosis and tential role of occult inflammation in arrhythmogenesis. Idiopathic VT. Pacing and ClinElectrophysiol 2015; 38 (6): Heart Rhythm. 2015 December ; 12(12): 2488–2498. 694-699 3. 1. Yalagudri S, Thu N Z, Devidutta S, Saggu D, Thachil A, 8. Thachil A, Christopher J, Sastry B K S, MD, Reddy K N, Chennapragada S, Narasimhan C. Tailored approach for Tourani V K, Hassan A, MD, Raju B S, Narasimhan C. management of ventricular tachycardia in cardiac sar- Monomorphic Ventricular Tachycardia and Mediasti- coidosis . Journal of Cardiovascular Electrophysiology nalAdenopathy Due to Granulomatous Infiltration in 2017; 28 (8) : 893–9021. Patients With Preserved Ventricular Function. J Am Coll Cardiol2011;58:48–55 4. ThachilA. “Cardiac Sarcoidosis” - chapter in “ Essentials of post graduate cardiology: An Official publication of 9. Yalagudri S, Thu N Z, Devidutta S, Saggu D, Thachil A, the Cardiological Society of India” : Goswamy K C (edi- Chennapragada S, Narasimhan C. Tailored approach for- tor); Evangel Publishing, New Delhi, 2019 (ISBN: 978-81- management of ventricular tachycardia in cardiac sar- 936703-4-7). coidosis. Journal of Cardiovascular Electrophysiology 2017; 28 (8) : 893–9021. 5. Thachil A, Christopher J, Kavitha N, Suryaprakash G, Sastry B K S, Narasimhan C. Complementary Role Of 10. Yazaki Y, Isobe M, Hiroe M. et al Prognostic determinants MRI And 18 FDG PET-CT In The Assessment Of Ventric- of long‐term survival in Japanese patients with cardiac ular Tachycardia Due To Infiltrative Myocardial Disease. sarcoidosis treated with prednisone. Am J Cardiol 2001; Heart Rhythm 2010; 7 (5):S131–S195 88: 1006–1010.

January – June 2019, Volume – 8 Issue – 1 49 The offi cial Journal of Cardiological Society of India, Kerala Chapter

KHJKERALA HEART JOURNAL

A Journal of Cardiological Society of India Kerala Chapter

p-ISSN: 2347-5269 e-ISSN: 2454-6755 KERALA HEART JOURNAL (p-ISSN: 2347-5267), (e-ISSN: 2454-6755) January - June 2019, Volume - 8, Issue - 1

Editor in Chief Dr. Stigi Joseph

Bhim Shankar.MD.DM. Consultant Electrophysiologist, VPS Lakeshore Hospital,Kochi.

ECG Challenge

Sixty years old lady developed palpitations. She sought medical attention. Her ECG is shown in Fig 1.

She had a structurally normal heart. Her biochemistry was normal. She was initiated on AV nodal blocking drugs. She continued to have palpitation. A 24-hour holter was done. One of the stripsis shown in Fig 2.

50 January – June 2019, Volume – 8 Issue – 1 The official Journal of Cardiological Society of India, Kerala Chapter

She had to undergo ablation, as she remained symptomatic. Her ECG post ablation is shown in Fig 3.

What is the arrhythmia,the possible mechanism, and the location? Fig 1. Shows paroxysms of tachycardia, atrial rate of 150 BPM, with isoelectric baseline, suggestive of focal automatic atrial tachycardia with variable conduction to the ventricle. Fig 2. Discrete P waves and the isoelectric baselines is better discernable at slower AV conduction times. A positive or negative – positive biphasic P wave in V1 suggests left atrial origin. The P wave is positive in Tachycardia.Apart from the V1 p wave, the p waves are not distinguishable from the sinus P wave. Fig 3; Post ablation ECG shows the V1 P waves positive – negative. The sinus P wave being positive – negative and tachycardia P wave being positive, is suggestive of RSPV AT. (Right Superior Pulmonary Vein origin of Atrial Tachycardia)

January – June 2019, Volume – 8 Issue – 1 51 The offi cial Journal of Cardiological Society of India, Kerala Chapter

KHJKERALA HEART JOURNAL

A Journal of Cardiological Society of India Kerala Chapter

p-ISSN: 2347-5269 e-ISSN: 2454-6755 KERALA HEART JOURNAL (p-ISSN: 2347-5267), (e-ISSN: 2454-6755) January - June 2019, Volume - 8, Issue - 1

Editor in Chief Dr. Stigi Joseph

K J Raihanathul Misiriya MD, DM* Narayanapillai Jayaprasad MD, DM** Anwar C Varghese MD, DM*** K Jayaprakash MD, DM* Suresh Madhavan MD, DM** V. Sudhakumary MD, DM** V.L Jayaprakash MD, DM**** Raju George MD, DM**** *Additional Professor, **Associate Professor, ABSTRACT ***Senior Resident, **** Professor. Department of Cardiology, Government Medical College, Kottayam Correspondence: [email protected]

ABSTRACT Spontaneous Coronary Artery Dissection- A Disease of Young Males?

Background: Spontaneous coronary artery dissection SCAD. Males constituted 86% (n=24) of the total cases and (SCAD) is the separation of two of the three arterial wall females constituted 14% (n=4). Young males (<40 years) had layers without any apparent cause,creating a false lumen. the highest prevalence of SCAD (2.2%). The most common The incidence, epidemiology and risk factors of SCAD has risk factor was smoking. Most of the patients presented not been well stuied in the Indian population. with acute coronary syndromes (ACS, n=22, 79%) and were managed medically (n=19, 68%). After a mean follow up 8.7 months 85% of the patients remained relatively asymptom- Aim: atic, whereas 3 (15%) patients had recurrent ACS. To assess the prevalence, clinical profi le, risk factors, management and short term prognosis of patients with spontaneous coronary artery dissection in patients undergoing Conclusions: coronary angiogram (CAG) in a tertiary care center in Kerala. The overall prevalence of SCAD in the study population was 0.36%. In this study, SCAD was signifi cantly more frequent in males, especially in the younger age group. Most cases present- Methods: ed as ACS and most were managed medically. Consecutive patients who underwent CAG and diagnosed to Key Words: spontaneous coronary dissection, coronary artery have SCAD were included in the analysis. Demographic, risk disease, acute coronary syndrome factor and clinical profi le were analyzed.

Results: Introduction During the study period, out of 7684 patients with coronary Spontaneous coronary artery dissection (SCAD) is a rare cause of acute coronary syndrome (ACS). SCAD is the sep- angiograms, 28(0.36%) patients were identifi ed to have

52 January – June 2019, Volume – 8 Issue – 1 The official Journal of Cardiological Society of India, Kerala Chapter

aration of 2 of the 3 arterial wall layers,creating a false lu- 2010 to December 2013 by reviewing coronary angio- men which may progress resulting in impairment of distal grams retrospectively. Two experienced interventional coronary blood flow and cause myocardial ischemia. When cardiologists read the coronary angiograms. SCAD was this dissection occurs in the absence of severe obstructive identified based on the presence of an intimal flap with coronary artery disease and history of PCI, it is considered a false lumen, and/or stagnation of contrast media in spontaneous.1,2 It is described that SCAD mainly affects the coronary artery wall. The clinical presentation risk women who have few cardiovascular risk factors. factors and the treatment strategy adopted were identified from the hospital records. Six monthly follow up SCAD is associated with various pathophysiological con- was carried out through outpatient visits or telephon- ditions, such as pregnancy, postpartum, collagen diseases, cocaine abuse, severe hypertension, smoking, oral ic interviews. Patients with extensive atherosclerosis, contraceptives, heavy exercise, or vasospasm.3,4,5 It was previous PCI or history of recent chest trauma were ex- first described in 1931 after necropsy of a 42-year-old cluded. Statistical analysis was done by SPSS 19.0 for woman who died suddenly,6 and the first angiographic Windows. report occurred almost 50 years later, in a 55-year-old woman with acute myocardial infarction. The diagnosis of SCAD has increased recently as the use of coronary Results angiography has expanded. Studies on SCAD are limited Baseline characteristics to isolated case reports and few case series. Therefore During the study period, a total of 7684 patients under- its treatment and prognosis are not well established. went CAG of which 28 cases of spontaneous coronary ar- Case reports and case series on coronary dissection from tery dissections were identified and confirmed. The prev- India have been few. Most cases that have been reported alence of dissection was 0.36%. The population consisted from India involved young men in contrast to the data of 4 (14%) women and 24(86%) males. The incidence of from other countries.7,8,9 This prompted us to look into SCAD was more in males (0.41%) compared to females the epidemiological pattern of this disease in India. In (0.22%, p-value 0.001). The mean age of males was numer- this study, we sought to identify the prevalence, clinical ically lower (43.5 years) but was not statistically different presentation, risk factors, treatment strategies and short from that of females (53 years, p-value 0.10). In this se- term prognosis of SCAD. ries, SCAD was predominantly a disease of males. Among them, the prevalence was more in those below 40 years. The prevalence in males below 40 years was 2.2% (8/362) Methods while no case was reported in females below 40 years We identified all patients diagnosed to have SCAD at (p-value 0.017). Among those above 40 years in males, the Government Medical College Kottayam from January prevalence was 0.29 % (16/5492) while in females above

The important baseline characteristics are shown in the following table.

Table 1. Baseline characteristics

January – June 2019, Volume – 8 Issue – 1 53 The official Journal of Cardiological Society of India, Kerala Chapter

40 years it was 0.25 (4/ 1559) (p-value 0.60). The important the patients presented with acute coronary syndromes baseline characteristics are shown in the following table. (79%). Of these 9 (32%) patients presented with STEMI and 13 (47%) patients presented with unstable angina Risk Factors and Presentation or NSTEMI. Figure 1 shows SCAD in the mid left anterior descending artery(LAD) of a 42-year-old male present- Smoking was the most common risk factor noted in 14 pa- ed with NSTEMI. A substantial percentage of patients tients (50%). Diabetes Mellitus was seen in 7 (25%), system- presented with stable angina (21%). Conservative line ic hypertension in 6(22%) and dyslipidemia in 5 (18%). Eight of management with antiplatelet drugs, statins, nitrates (29%) patients had 2 or more conventional coronary risk factors. Left anterior descending artery was the vessel af- and beta blockers was done in 19 (68%) patients. Eight fected in 14 (45%) patients, Left circumflex artery in 6 (16%) (28.5%) patients were managed with PCI, and 1 (3.5%) pa- and Right coronary artery in 12 (39%) patients.Most of tient underwent CABG.

Figure 1- Left coronary angiogram in left anterior oblique cranial view (Panel A) and right anterior oblique caudal view (Panel B) showing dissection in the mid LAD.

Risk factors and presentation are shown in table 2.Table 2. Risk Factors and Presentation

54 January – June 2019, Volume – 8 Issue – 1 The official Journal of Cardiological Society of India, Kerala Chapter

Follow up Conclusions Follow up data is available for 24 out of 28 patients. The The overall incidence of SCAD is 0.36 % and is highest in mean duration of follow up was 2.5 years. Three (15%) males less than 40 years in whom it was 2.2 %. Most cases of patients had acute coronary syndromes during this peri- SCAD seen in this study are in young men who smoke. In con- od. Two of these patients were in the medically managed trast to earlier studies, SCAD is rarer in women in this study. group, and one was in the PCI group. There was no death The mode of presentation is common as ACS, but it can also during the 2.5 years of follow up. present as chronic stable angina. It is usually treated with medical management or PCI with good immediate and short term outcomes. We need more studies to understand the Discussion pathogenesis of this disease in the Indian population. In this study, we identified 28 cases of SCAD among 7684 consecutive coronary angiograms with a prevalence of References 0.36%. The prevalence in our study is more than that of previous angiographic series reporting prevalence ranging 1. Kansara P, Graham S. Spontaneous coronary artery dissection: case series with extended follow up. J Invasive from 0.10% to 0.20%.10,11 In a prospective angiographic se- Cardiol. 2011;23(2):76-80. ries with intravascular ultrasound assistance in ambiguous cases, Hering et al. reported a much higher prevalence of 2. Romero-Rodríguez N, Fernández-Quero M, Villa Gil-Or- 1.10%.12 In our study 86% of the patients with SCAD were tega M, et al. Spontaneous Coronary Dissection and Its males, and only 14% were females. The incidence of SCAD- Long-Term Prognostic Implications in a Cohort of 19 was 0.41% in males and 0.22% in females. This is in contrast Cases - Rev Esp Cardiol.2010;63:1088-91. to previous studies where it was more common in females. 1,2,11 The mean age of males was numerically lower (43.5 3. Borczuk AC, van Hoeven KH, Factor SM. Review and hy- years) but was not statistically different from that of fe- pothesis: the eosinophil and peripartum heart disease males (53 years). (myocarditis and coronary artery dissection)—coincidence or pathogenetic significance? Cardiovas Res. This study is also notable for the fact that no case of dis- 1997;33:527-32. section was identified in females younger than 40 years despite 271 angiograms performed on them. In this study, 4. Adès LC, Waltham RD, Chiodo AA, et al. Myocardial in- the maximum incidence was noted in males younger than farction resulting from coronary artery dissection in an 40 years (2.2%). These patients had a higher incidence of adolescent with Ehlers-Danlos syndrome type IV due to smoking. In previous studies, SCAD was reported as affect- a type III collagen mutation.. Br Heart J. 1995; 74(2):112-6. ing women in three fourths of the cases,11 one third of them 5. Sherrid MV, Mieres J, Mogtader A, et al. Onset during ex- being in the postpartum period,13 with a mean age of on- ercise of spontaneous coronary artery dissection and set below 35 years.14 Pregnancy-associated and connective sudden death. Occurrence in a trained athlete: case re- tissue associated SCAD were not identified in this study. port and review of prior cases. Chest. 1995; 108(1):284-7. One of the reasons for the absence of SCAD associated with pregnancy could be due to selection bias for coronary an- 6. Pretty H. Dissecting aneurysm of coronary artery in a giography. Alternatively, it could be that pregnancy-associ- women aged 42. BMJ 1931;1:667. ated SCAD is not frequent in our population due to genetic or social factors. The most common traditional risk factor 7. Kumar PR, Rao DS, Jaishankar S. Spontaneous dissection identified was smoking (50%). Other risk factors were less of coronary artery causing anterior myocardial infarction in a young man. Indian Heart J. 1996;48(6):699-700. frequent than in people undergoing a coronary angiogram. The mechanism of SCAD in these patients remains mostly 8. Singh RS, Pannu HS, Agarwal R, et al. Spontaneous double unclear. It is likely that many are probably atherosclerot- vessel coronary artery dissection. A case report and sur- ic, as premature atherosclerosis is common in our country. gical management. Scand Cardiovasc J. 1997;31(3):181-3. Plaque inflammation and rupture may disrupt intimal-medial junction resulting in intimal flap and dissection. 9. Sharma S, Raut N, Potdar A. Spontaneous coronary artery dissection: Case series and review of literature. In- The mode of presentation was as an ACS in 79% of patients, dian Heart J. 2016;68(4):480-5. 47% with NSTEMI/UA and 32 % with STEMI. The interesting finding was that 21% of patients presented with stable angi- 10. Jorgensen MB, Aharonian V, Mansukhani P, et al. Spon- na. This is in contrast to previously held concept that SCAD taneous coronary dissection: a cluster of cases with this almost always presents as an acute coronary syndrome.10,11 rare finding. Am Heart J 1994;127:1382—7.

January – June 2019, Volume – 8 Issue – 1 55 The official Journal of Cardiological Society of India, Kerala Chapter

11. Vanzetto G, Berger-Coz E, Barone-Rochette G, et al. Prev- 13. Koller PT, Cliffe CM, Ridley DJ. Immunosuppressive alence, therapeutic management and medium-term therapy for peripartum- type spontaneous coronary prognosis of spontaneous coronary artery dissection: artery dissection: case report and review. Clin Cardiol results from a database of 11,605 patients. Eur J Cardio- 1998;21:40—6. thorac Surg 2009;35(2):250-4. 14. Celik SK, Sagcan A, Altintig A, et al. Primary spon- 12. Hering D, Piper C, Hohmann C, Schultheiss HP, Horstkotte taneous coronary artery dissections in atheroscle- Prospective study of the incidence, pathogenesis and rotic patients. Report of nine cases with review of therapy of spontaneous, by coronary angiography diag- the pertinent literature. Eur J Cardiothorac Surg nosed coronary artery dissection. Z Kardiol 1998;87:961-70. 2001;20:573—6.

56 January – June 2019, Volume – 8 Issue – 1 The offi cial Journal of Cardiological Society of India, Kerala Chapter

KHJKERALA HEART JOURNAL

A Journal of Cardiological Society of India Kerala Chapter

p-ISSN: 2347-5269 e-ISSN: 2454-6755 KERALA HEART JOURNAL (p-ISSN: 2347-5267), (e-ISSN: 2454-6755) January - June 2019, Volume - 8, Issue - 1

Editor in Chief Dr. Stigi Joseph

CP Karunadas MD, DNB, DM, DNB, FESC* Cibu Mathew MD, DNB, DM, DNB* *Additional Professor Cardiology, Government Medical College, Thrissur

Correspondence: [email protected]

CASE REPORT Anomalous Origin of Left Coronary Artery from Pulmonary Artery presenting with Atrial Fibrillationand Angina

ABSTRACT CASE HISTORY nomalous Origin of Left Coronary Artery from Pulmo- A 55-year-old female was admitted with one-week history Anary Artery (ALCAPA) is a rare congenital anomaly of of recurrent palpitation along with the crushing type of cen- coronary arteries usually presenting in early childhood. tral chest pain. This was occurring at rest, coming on and off However different types of presentation in adults have also and lasting for a few minutes. She had wheezing for many been described. Here we present the case of a 55-year-old years and hypertension for the last one year. There was no lady with ALCAPA. She was never diagnosed as having a car- history of Diabetes or Ischemic Heart Disease. There were diac disease until this age. She was a manual laborer and no addictions. She was on bronchodilators and Amlodipine. had three uncomplicated deliveries. She presented with She had had three uneventful deliveries and was a manual paroxysmal atrial fi brillation (AF). The diagnosis was AL- laborer by profession. CAPA, made only after a coronary angiogram was done. CT angiogram confi rmed the diagnosis. She opted to continue On examination she was obese. Cardiovascular system ex- medical therapy and is being followed up. A brief review of amination showed regular pulse at a normal rate, normal the literature regarding ALCAPA is also added. blood pressure and normal heart sounds. There were rhonchi all over the lung fi elds. Other systems were normal. Her ECG showed sinus rhythm with normal QRS and T wave KEYWORDS inversion in leads V1 to V6. Troponin-T test was positive. She Anomalous Origin of Left Coronary Artery from Pulmonary was diagnosed as Non-ST Elevation Myocardial Infarction Artery (ALCAPA), Atrial fi brillation (AF), CT Angiogram and was started on Isosorbide dinitrate, aspirin, clopidogrel,

January – June 2019, Volume – 8 Issue – 1 57 The official Journal of Cardiological Society of India, Kerala Chapter

The results of salient blood investigations are given in the table below.

Investigation Result

Hb 12.7

Total 7600

ESR 23

RBS 112

S. Creatinine 0.9

TSH 2.3

Serum Sodium 138

Serum Potassium 4.4

nebivolol, and atorvastatin. Amlodipine and bronchodilators Ischemic Heart Disease and Hypertension, Atrial Fibrilla- were continued. She was given Enoxaparin for five days. In tion with fast ventricular rate and mitral regurgitation was the hospital she had one episode of palpitation. ECG at that made. She was started on Digoxin, Diuretics, ACE Inhibitors, time showed Atrial Fibrillation which reverted spontaneous- Aspirin and Atorvastatin. Amlodipine was stopped. She im- ly. She was discharged on the above-mentioned medications proved clinically. As atrial fibrillation was persisting, she with advice to follow up after two weeks. was started on oral anticoagulation, Warfarin.The dose of Warfarin was titrated up, and upon reaching an INR value of The patient did not come for follow up and stopped her 2.6, she was discharged. medications. One month after the first hospitalization she was again admitted with dyspnoea, palpitation, and edema. One month later she was again admitted with angina, palpi- On examination, she had tachypnoea and bilateral pitting tation and worsening dyspnea. She was having atrial fibril- pedal edema. Her pulse was 130/mt, irregularly irregular, lation with a fast ventricular rate. Oral Amiodarone was blood pressure was 150/100 mm of Hg in the right arm, and added to the other drugs. She had recurrent episodes of jugular venous pressure was elevated 12cm from the symptomatic worsening over the next two weeks along with angina. Echo picture remained the same; global reduction sternal angle. The apex beat was not located. There was no in contractility with moderate LV dysfunction. Because of murmur. There were bilateral rhonchi. recurring angina, acoronary angiogram was done. During Her blood investigations were normal. Electrocardiogram coronary angiogram left coronary artery could not be can- showed Atrial Fibrillation with a fast ventricular response nulated. A left coronary sinus injection did not show any and non-specific ST segment and T wave changes. Chest artery originating from the left sinus.Right coronary artery X-ray showed mild cardiomegaly. Echocardiogram revealed (RCA)was seen originating from the aorta. RCA was hugely dilated and tortuous. Left coronary artery (LCA) was seen left ventricular hypertrophy, a global reduction in left ven- filling retrograde from the right coronary artery. LCA tricular contractility, moderate LV dysfunction with an ejection fraction of 30% and mild mitral regurgitation. A diag- was draining into the pulmonary artery.(Fig1.A,B,C,D)also, nosis of cardiac failure- moderate LV dysfunction - due to (Videos 1 to4).

58 January – June 2019, Volume – 8 Issue – 1 The official Journal of Cardiological Society of India, Kerala Chapter

Fig 1.A: Fig 1.B: Left coronary sinus Right coronary injection with no injection showing artery originating dilated tortuous from (L) sinus RCA (white arrow) Fig 1.A Fig 1.B

Fig 1.C Fig1.D Fig 1.C & 1.D: LCA filling through RCA collaterals (white arrows)

Subsequently a CT angiogram was done. It showed RCA from the pulmonary artery (ALCAPA) is one of the anomalies originating from the aorta. RCA was dilated and tortuous. with high mortality. The initial description of this anomaly Left coronary artery was seen originating from the pulmo- came in the 1860s by Krause2 and later in 1885 by Brooks3. nary artery.(Fig 2.A,B,C,D). Thus a diagnosis of anomalous However, these cases were later attributed to coronary AV origin of the left coronary artery from pulmonary artery fistula. The earliest complete clinical description was in 1933. was made.The patient refused any form of surgical inter- Bland, White, and Garland4 reported a three-month-old in- vention. Her medical therapy was optimized, and she is un- fant who had paroxysmal attacks of acute discomfort along der follow up presently. with profound vasomotor collapse. The ECG findings were similar to that of an adult with myocardial infarction. The autopsy confirmed the anomalous origin of the left coronary DISCUSSION artery from the pulmonary artery. So this disease is also In the general population,anomalies of coronary arteries known as Bland– White–Garland syndrome. The incidence of may occur in around 1%.Many of these anomalies are benign ALCAPA is considered to be 1 per 300,000 live births5. Em- and often found incidentally1.However, some of these anom- bryologically it is believed to be due to either an abnormal alies can be associated with life-threatening cardiac compli- division of the conotruncus into the aorta and pulmonary ar- cations like ischemia, arrhythmias, heart failure, and even tery or the persistence of the pulmonary buds together with death. Anomalous origin of the left main coronary artery involution of the aortic buds that form the coronary arter-

January – June 2019, Volume – 8 Issue – 1 59 The official Journal of Cardiological Society of India, Kerala Chapter

Fig 2.A Fig 2.B

Fig2.C Fig2.D

CT angiogram showing RCA originating from the aorta. RCA is dilated and tortuous. Left coronary artery is seen originating from the pulmonary artery.

ies.In the intrauterine period, the left coronary system has 2. Asymptomatic adults: Most cases of ALCAPA who survive normal blood flow (antegrade) from pulmonary artery due to infancy will have extensive collateralization of LCA and the high pulmonary artery pressure. Pulmonary vascular re- a dilated RCA. These cases may be picked up because of sistance and pulmonary artery pressure fall in the neonatal a soft continuous murmur or mild mitral regurgitation period so that the flow into left coronary artery decreases. or incidental cardiomegaly on chest X-ray. Collaterals develop from the right coronary artery to supply 3. Symptomatic adults: These cases present mainly with the branches of the left coronary artery. Finally, a reversal angina, heart failure or arrhythmias. of flow in the left coronary system occurs, and blood starts flowing into the pulmonary artery. Depending on the degree 4. Sudden cardiac death: ALCAPA is one of the causes of of collaterals clinical presentation varies.The clinical presen- sudden death in a previously asymptomatic person. tation may be of four types: Pathologic studies show a variable degree of fibrosis in myocardial tissue, which can trigger fatal ventricular 1. Infants: Around 85- 90% of cases present between 2 and tachyarrhythmias6. 4 months of age. There is poor growth, tachypnea, pro- fuse sweating, and angina-like episodes. This is observed ECG abnormalities are noted in a large number of patients. as a sudden onset of distressed state with pallor during Q waves are seen in anterior leads in 50% of patients and or after feeding. About 90% of these infants who are left ventricular hypertrophy in 28% of cases.Colour Doppler symptomatic die in the first two years of life if untreated. echocardiography may show the dilated RCA. Rarely the

60 January – June 2019, Volume – 8 Issue – 1 The official Journal of Cardiological Society of India, Kerala Chapter

retrograde flow into the left coronary artery is seen. Coro- 2. W. Krause- About the origin of accessory coronary artery nary angiography and cardiac CT scanning can be diagnos- from the pulmonary artery: Ztschr Rat Med;1865 vol. 24, tic. Cardiac MRI picks up the amount of scar tissue. pp. 225–227

Surgery is the only definitive treatment. ALCAPA has to be 3. S. J. Brooks-Two cases of an abnormal coronary artery of surgically treated in the first year of life. Several surgical the heart arising from the pulmonary artery with somer- techniques have been described.LCA ligation at origin was emarks upon the effect of this anomaly in producing cir- practiced in the initial days. But there was a high incidence soid dilatation of the vessels: Journal of Anatomy and of late deaths. The restoration of blood flow in the left cor- Physiology, 1886 vol. 20, pp. 26–32 onary artery from the aorta was considered in subsequent techniques.Direct reimplantation of the left coronary 4. F. E. Bland, P. D. White, and J. Garland - Congenital anom- artery on to aorta can be done.In the first year of life, great alies of the coronary arteries: report of an unusual case arteries are not fully developed, and tissues are more “flex- associated with cardiac hypertrophy: American Heart ible,” which allows coronary reimplantation.The Takeuchi Journal,1933 vol. 8, no. 6, pp. 787–801 procedure is often used in the pediatric population. This 5. J. D. Keith- Anomalous origin of the left coronary artery procedure, introduced in 1979, involved the creation of an from the pulmonary artery: British Heart Journal,1959 aortopulmonary window and intrapulmonary tunnel ex- vol. 21, no. 2, pp. 149–161 tending from the anomalous ostium to the window. This procedure is now unpopular due to late complications; es- 6. B. Shivalkar, M.Borgers, W.Daenen et al. - ALCAPA syn- pecially the high incidence (> 21%) of supravalvular steno- drome: an example of chronic myocardial hypoperfu- sis of the pulmonary artery.In the 10–15% of patients who sion? : Journal of the American College of Cardiology, reach adulthood, surgical correction is burdensome, due to 1994 vol. 23, no. 3, pp. 772–778 the heart dimensions and compensatory disorders in coronary circulation to the left ventricle. 7. Alsoufi B, Sallehuddin A, Bulbul Z, et al. - Surgical strategy to establish a dual-coronary system for the manage- Cardiac function normalizes within one year in the majority ment of anomalous left coronary artery origin from the of cases. Mild to moderate MR also gets corrected due to pulmonary artery: Ann Thorac Surg. 2008; 86(1): 170–176 reverse LV modeling. Severe MR due to irreversible myocardial necrosis or papillary muscle infarction will need 8. Mohanty SR, Varghese R, et al. - Evolution of surgical concomitant repair. ICD implantation has been done in pa- strategies for anomalous left coronary artery: Asian Car- tients who present with fatal ventricular arrhythmias. diovasc Thorac Ann. 2001; 9(4): 269–274

9. Murala JS, Sankar MN, Agarwal R, et al. - Anomalous ori- CONCLUSION gin of the left coronary artery from the pulmonary artery ALCAPA is a rare congenital anomaly. It can remain asymp- in adults: Asian Cardiovasc Thorac Ann. 2006; 14(1):38–42 tomatic and may present with atypical symptoms like atrial 10. Ono M, Goerler H, Boethig D, et al. - Surgical repair of fibrillation. A high index of suspicion should be kept even anomalous origin of the left coronary artery arising in adult patients regarding ALCAPA as the underlying cause from the left pulmonary artery: Ann Thorac Surg. 2009; of heart failure or arrhythmias. Coronary angiogram or CT 88(1): 275–276 Angiogram can provide a definite diagnosis. Management options will have to be discussed especially in adult pa- 11. Amanullah MM, Hamilton JR, Hasan A- Anomalous left tients and individualized for each patient coronary artery from the pulmonary artery: creating an autogenous arterial conduit for aortic implantation: Eur References: J Cardiothorac Surg. 2001; 20(4): 853–855 1. O.Yamanaka, R.E.Hobbs- Coronary artery anomalies in 12. Ginde S, Earing MG, Bartz PJ, et al. - Late complications 126595 patients undergoing coronary arteriography: after Takeuchi repair of the anomalous left coronary ar- Catheterization and Cardiovascular Diagnosis.1990 vol tery from the pulmonary artery: case series and review 21; No.1, pp 28-40 of literature: Pediatr Cardiol. 2012; 33(7): 1115–18.

January – June 2019, Volume – 8 Issue – 1 61 The offi cial Journal of Cardiological Society of India, Kerala Chapter

KHJKERALA HEART JOURNAL

A Journal of Cardiological Society of India Kerala Chapter

p-ISSN: 2347-5269 e-ISSN: 2454-6755 KERALA HEART JOURNAL (p-ISSN: 2347-5267), (e-ISSN: 2454-6755) January - June 2019, Volume - 8, Issue - 1

Editor in Chief Dr. Stigi Joseph

Vijin Joseph V.F MD* Jo Joseph MD. DM** Jimmy George MD. DM** Jabir Abdullakutty MD. DM** Jacob Joseph MD.DM** Rony Mathew MD. DM*** *DNB Resident, **Consultant Interventional Cardiologist *** HOD, Department of Cardilogy Lisie Heart Institute, Lisie Hospital, Kochi Correspondence: [email protected]

CASE REPORT An unusual cause of angina

Introduction: rest angina. He had effort angina class II for two weeks and was evaluated outside with TMT which was positive. ounis syndrome is the coincidental occurrence of an Admission ECG showed minor ST depression in Infero- acute coronary syndrome (ACS) with hypersensitivity re- K lateral leads, and the Troponin T was borderline positive actions involving activation of interrelated and interacting (0.05ng/ ml), the 2D echo showed No RWMA with Normal infl ammatory cells and including allergic or hypersensitivi- LV systolic function. Hence he was diagnosed as an acute ty and anaphylactic or anaphylactoid insults [1]. It is caused coronary syndrome, non ST elevated myocardial infarction by infl ammatory mediators such as histamine, neutral pro- and treated as per standard ACS protocol. He was taken up teases, arachidonic acid products,platelet activating factor, for coronary angiogram which revealed non-obstructive and a variety of cytokines and chemokines released during coronary artery disease. He also gives a history of allergic the hypersensitivity insult [2–4]. There are three types of to aspirin and dust. He was discharged with single anti- variants of which, Type II variant includes patients with platelet (Clopidogrel) and statins. culprit but quiescent pre-existing atheromatous disease in whom the acute release of infl ammatory mediators can He was readmitted ten days later with complaints of induce either coronary artery spasm with normal cardiac rest angina for three days which was relieved with sub- enzymes or plaque erosion or rupture manifesting as acute lingual nitrates. His ECG showed dynamic ST- T changes myocardial infarction. in anterior leads and troponin T was mildly elevated, which was not progressive in subsequent days, and 2D echo showed no RWMA and Normal LV systolic function. Case Report: His coronary angiogram was reviewed, and there were AA 44-year-old male with a two-year history of type 2 diabe- no significant obstructive lesions to account for his re- tes mellitus and systemic hypertension was admitted with current symptoms.

62 January – June 2019, Volume – 8 Issue – 1 The official Journal of Cardiological Society of India, Kerala Chapter

During the course in hospital his vitals were stable, and coronary angiogram the possibility of Type 2 Kounis syn- investigations showed Hb- 13gm%, ESR- 26mm/hr, Eosin- drome was considered, and he was treated with vasodila- ophil- 1, absolute eosinophil count- 142cells/mm3, Serum tors, antianginals, calcium channel blockers, mast cell sta- IgE- 1379, Radioallergosorbent test (RAST) showed allergy bilizers, and intravenous steroids. (Steroids were tapered to house dust and dust mite and rest of the investigations and subsequently stopped). were within normal limits. Throughout his stay, he was asymptomatic and discharged Given the strong allergic symptoms, recurrent episodes of with antianginals, calcium channel blockers, and mast cell angina and no significant obstructive lesions on his recent stabilizers.

ECG ON 20/11/2018

Fig 2- ECG after 10 days with Dynamic ST-T changes in anterior leads, marked with red arrow

January – June 2019, Volume – 8 Issue – 1 63 The official Journal of Cardiological Society of India, Kerala Chapter

Fig 3:- M mode across Left ventricle

The mechanisms of this syndrome are characterized by coronary artery vasospasm due to mast cell degranulation and the subsequent release of vasoactive mediators [5]. The most important vasoactive mediators responsible for coronary artery spasm and consequences of Kounis syndrome are histamine, serotonin, and leukotrienes. There are 3 variants of Kounis syndrome. The Type-I is observed in patients with no cardiovascular risk factors & healthy coronary arteries, in which the inflammatory cascade triggered by the allergic insult causes coronary vasospasm accompanied by elevated or normal levels of cardiac enzymes. Type II is observed in patients with the pre-exist- Fig 4:- Coronary ing atheromatous disease (whether known or not) in whom angiography image the release of these mediators would also produce coro- showing Left anterior nary vasospasm,which occurs with normal cardiac enzymes descending artery, Left or rupture of the atheromatous plaque, manifesting as an circumflex and Right acute myocardial infarction.Type III includes patients with coronary artery. Red coronary thrombosis (including stent thrombosis) in whom arrow showing minor aspirated thrombus specimens stained with hematoxy- plaque in LAD lin-eosin and Giemsa demonstrate the presence of eosino- phils and mast cells respectively [4, 6, 7].Our patient’s coronary angiography revealed non-obstructive lesions in the coronary vasculature and was diagnosed as atype II variant. Etiology of Kounis syndrome include drugs (antibiotics, an- Discussion: algesics, antineoplastics, contrast media, corticosteroids, Kounis syndrome has been defined- as an ACS that mani- intravenous anaesthetics, non-steroidal anti-inflammatory fests as vasospastic angina or ST-elevation myocardial in- drugs, skin disinfectants, thrombolytics, anticoagulants), farction/ non ST-elevation myocardial infarction triggered various conditions(angioedema, bronchial asthma, urticar- by the release o finflammatory mediators following an al- ia, food allergy, exercise-induced allergy, mastocytosis, se- lergic insult [2]. rum sickness), and environmental exposures (stings

64 January – June 2019, Volume – 8 Issue – 1 The official Journal of Cardiological Society of India, Kerala Chapter

of ants, bees, wasps, jellyfish, grass cutting, millet allergy, high awareness, rapid diagnosis, and appropriate treat- poison ivy, latex contact, shellfish eating, viper venom poi- ment are of utmost importance. soning). [8] There are no specific diagnostic criteria to differentiate Prinzmetal angina from Kounis syndrome, and the diagno- References: sis of Kounis syndrome is based on the patient’s signs and 1 Kounis NG, Kourelis T, Hahalis G, Manola A,Kourelis T, symptoms of a systemic allergic reaction associated with Theoharides T. Kounis syndrome (allergic angina and al- clinical, laboratory and electrocardiographic findings of lergic myocardial infarction). In: Gallo AP,Jones ML, edi- acute myocardial ischemia. tors. Angina pectoris etiology, pathogenesis, and treatment. NewYork: Nova Biomedical Books; 2008. The Management of patients with Kounis syndrome differs from those for non-allergic common ACS [9]. These pa- 2 Kounis NG, Kouni SN, Koutsojannis CM. Myocardial in- tients need treatment with steroids, antihistamines, fluid farction after aspirin, andKounis syndrome. J R Soc Med replacement, possibly epinephrine, oxygen, and antithrom- 2005;98:296. botics fore transfer to thecardiac catheterization labora- 3 Kounis NG, Zavras GM. Histamine-induced coronary ar- tory. Treatment should be both treating coronary lesions tery spasm: the conceptof allergic angina. Br J ClinPract and suppressing the allergic reaction.Vasodilator drugs, 1991;45:121–8. including nitrates and calcium channel blockers, should be considered as a first line therapy since vasospasm is the 4 Kounis NG, Zavras GM. Allergic angina and allergic myo- primary mechanism [9]. Aspirin is among the most frequent cardial infarction. Circulation 1996;94:1789. causes of drug-associated anaphylactic reactions [2]. Both 5 Cheng TO, Kounis NG. Takotsubo cardiomyopathy, men- fractionated and low molecular weight heparins are derived tal stress, and Kounissyndrome.Int J Cardiol 2012;161:65– from animals which are potentially antigenic and can cause 7. allergic reactions. Epinephrine is a life saving medication in anaphylaxis; however, it can aggravate the ischemia, and 6 Taggar JS, Watson T, Musarrat K. Kounis syndrome pre- induce coronary vasospasm and arrhythmias. Therefore, senting as ST-segment elevation myocardial infarction given a narrow therapeutic window, the recommended following a Hymenoptera (bee) sting. Int J Cardiol2009; dose is 0.2–0.5 mg of intramuscular injection [9]. 136:e29-30. Corticosteroids are agents playing a significant role in the 7 Gonzalez-de-Olano D, Alvarez-Twose I, Matito A, et al. treatment of allergic reactions, but they are well known to Mast cell activation disorders presenting with cere- impair wound healing and scar formation which may cause- bral vasospasm related symptoms: a “Kounis-like” syn- myocardial wall thinning, cardiac aneurysms, and wall rup- drome? Int J Cardiol 2011;150:210-1. ture [10]. Successful use of corticosteroids in allergic ACS 8 Gazquez V, Dalmau G, Gaig P, Gomez C, Navarro S, Mer- has been reported and is thus probably safe and appro- ce J. Kounis syndrome:report of 5 cases. J Invest Aller- priate. gol-ClinImmunol 2010;20:162–5. 9 Cevik C, Nugent K, Shome GP, Kounis NG. Treatment of Conclusion: Kounis syndrome.Int J Cardiol2010;143:223–6. The Kounis syndrome is probably not an uncommon dis- 10 Koutsojannis CM, Mallioris CN, Corticosteroids Kounis ease but,rather an under diagnosed one. Regarding the NG. Kounis syndromeand the treatment of refractory complex course ofACS associated with allergic reactions, vasospastic angina.Circ J 2004;68:806–7.

January – June 2019, Volume – 8 Issue – 1 65 The offi cial Journal of Cardiological Society of India, Kerala Chapter

KHJKERALA HEART JOURNAL

A Journal of Cardiological Society of India Kerala Chapter

p-ISSN: 2347-5269 e-ISSN: 2454-6755 KERALA HEART JOURNAL (p-ISSN: 2347-5267), (e-ISSN: 2454-6755) January - June 2019, Volume - 8, Issue - 1

Editor in Chief Dr. Stigi Joseph

Deepak Davidson.MD.DM. Senior Interventional Cardiologist, Caritas Hospital.Kottayam. Correspondence:[email protected].

Non-Atheromatous Causes of Acute Coronary Syndromes

Summary: bus. The remaining 5% with severe coronary luminal narrowing has a host of etiologies, including coronary arteritis, pproximately 5%of patients with acute coronary syn- systemic metabolic disorders, intimal fi brous proliferation, Adrome do not have atherosclerotic coronary artery coronary emboli and trauma. Of the 5% necropsy patients disease but have other causes for their luminal narrowing. with fatal AMI with normal or nearly normal epicardial coro- This article reviews non-atherosclerotic causes of ACS. nary arteries, perhaps 50 - 60 % represent coronary spasm, but the remaining 40 - 50 % may have congenital coronary artery anomalies, spontaneous recanalization, or coronary Introduction: supply-myocardial demand mismatches.2 Atherosclerosis is the commonest cause of luminal narrowing and coronary heart disease, but there are multiple non-atherosclerotic (congenital and acquired) causes of Acute Coronary Syndromes with Non severe luminal narrowing and subsequent clinical coronary stenotic Coronary Arteries. events. Myocardial infarction with nonobstructive coronary arter- Approximately 4 to 7% of all patients with ACS do not have ies( MINOCA) and Stress Cardiomyopathy will be discussed atherosclerotic coronary artery disease in coronary arte- towards the end of this article. riography, at necropsy or both. This percentage is 4 times in in patients aged <35 years.3-7Since Coronary angiography represents a “lumenogram,” the specifi city for the etiology 1. Congenital Coronary of the coronary luminal narrowing is extremely low. Review of necropsy studies 3, 5, 6 suggests that approximately 95% Artery Anomalies of patients with fatal AMI have severe luminal narrowing Coronary anomalies like variation in the origin, course, or or total occlusion of at least one of the major epicardial distribution of the epicardial coronary arteries are found in coronary artery. The remaining 5% of patients have normal 1-2% of the population.2,3,8,9 In young patients (<20 years epicardial coronary arteries. In those with severe coronary of age) with angina pectoris or acute Myocardial Infarction, luminal narrowing, 95% have the typical atherosclerotic a congenital coronary artery anomaly or a congenital coro- plaque with (85%)or without (15%) superimposed throm- nary artery aneurysm should be suspected.39

66 January – June 2019, Volume – 8 Issue – 1 The official Journal of Cardiological Society of India, Kerala Chapter a) Origin of Both Coronary Arteries described above and thus may be exposed to the risks of ischemia due to acute angulation.17 from the Same Sinus of Valsalva. When both the coronary arteries arises from the left or right sinus of Valsalva, the anomalous vessel transverses the base c) High-take off Coronary Ostia of the heart in a course anterior to the pulmonary trunk, pos- TTypically, the coronary ostia are located within the sinuses terior to the aorta, or between the aorta and pulmonary trunk. of Valsalva, which permits the maximal opportunity for coro- Ischemia, infarction, and or sudden death in this coronary nary artery diastolic filling. In high take off, the coronary ostia anomaly appears related to the shape of the coronary ostium is in the tubular portion of the aorta and may be associated of the anomalous vessel (Fig. 1). Typically, the coronary ostia with decreased coronary perfusion.16Menke et al. reported are round to oval in shape, but in this anomaly, the coronary morphologic evidence of chronic ischemia(13) in a patient artery has an acute take-off angle.This results in slit-like cor- with high-take off right coronary artery who had right and left onary ostium. With increased cardiac output as in exercise, ventricular wall scarring. High-take off position of the coro- the aorta dilates, and this slit-like ostium becomes severely nary ostium also has been postulated as a cause of sudden narrowed due to the aortic wall stretching. The “compression” coronary death.17 In a series of 54 major and minor coronary of the anomalous coronary artery by the aorta and pulmo- artery anomalies by Alexander18 , high take off of both coro-

Fig.1 Diagram illustrating ostial valve-like ridge and the proposed mechanism

nary trunk is an unlikely cause for the clinical symptoms given nary arteries were seen in two, right coronary artery alone in the marked differences in diastolic pressures. 12, 14 report- five , and left coronary artery alone in three patients. ed morphologic evidence of chronic ischemia(13) in a patient with high-take off right coronary artery who had right and left ventricular wall scarring. High-take off position of the coro- d) Ostial Narrowing. nary ostium also has been postulated as a cause of sudden Nonatherosclerotic causes of coronary ostial narrowing in- coronary death.17 In a series of 54 major and minor coronary clude syphilis, 20 Takayasu’s disease, 21 fibromuscular hy- artery anomalies by Alexander18 , high take off of both coro- perplasia associated with methysergide therapy, 22,23 aortic nary arteries were seen in two, right coronary artery alone in valve surgery with or without coronary artery canulation, 24 five , and left coronary artery alone in three patients. and ostial valve-like ridges.25 Baroldi has summarized other rare diseases that may narrow or occlude the coronary ostia: 26 (1) a non atheromatous, calcific protrusion from the sino- b) Single Coronary Artery tubular junction into the right or left ostium; (2) saccular an- Origin of the entire coronary circulation from a single aortic eurysm of the aorta; (3) aortic dissection extending into the ostium has been termed “single coronary artery.15 This is coronary ostium (right ostium more common than left); (4) usually associated with other congenital anomalies of the supravalvular aortic stenosis with severe intimal thickening; heart like pulmonary artery atresia, tetralogy of Fallot, and (5) obliteration of the ostium due to adhesion of the free edge patent truncus arteriosus 16. One or more branches of the of an aortic cusp to the aortic wall above the coronary ostium; single artery may cross the base of the heart in a fashion (6)occlusion by embolus and (7) occlusive fibroelastosis.2,26

January – June 2019, Volume – 8 Issue – 1 67 The official Journal of Cardiological Society of India, Kerala Chapter

Fig.2 Diagram showing high takeoff position of the right coronary artery and the non-atherosclertic fibrous ridge occluding the left main coronary ostium. LAD =Left anterior descending, LC=left circumflexa e) Anomalous Origin of One or two f) Coronary Artery Fistula coronaries from the Pulmonary A direct connection between a major epicardial coronary Trunk. artery and a cardiac chamber or major vessel (vena cava, coronary sinus, pulmonary artery) is another coronary artery Anomalous origin of a coronary artery from the pulmonary anomaly.7 Right coronary artery fistulae are more common trunk may be responsible for myocardial ischemia and in- than left coronary fistulae. Over 90% of the fistulae drain into farction in infants and children. In more than 90% of cas- the venous circulation.7 Myocardial ischemia has been docu- es, 7,9 the left main is the anomalous artery, and thus the mented in patients with coronary artery fistulae. 7 anteroseptal and anterolateral left ventricular myocardium may be at jeopardy. Asymptomatic older patients with this coronary anomaly usually are discovered by having an ab- g) Myocardial Bridges (“Tunneled” normal ECG, a precordial murmur, or by the occurrence of sudden death.9 Epicardial Coronary Artery) The coronary arteries which normally course over the epicardial surface of the heart may dip into the myocardium to travel for varying lengths and then reappear on the heart’s surface (Figs. 3- 6). The muscle overlying the intramyocardial segment of the epicardial coronary artery is the “myocardial bridge,” and the artery coursing within the myocardium is the “tunneled’coronary artery.

Fig.3 Diagram showing tunneled left anterior descending artery (LAD)(arrows).Left: Opened left ventricle showing intramyocardial segment (below). Right Transverse section of coronary artery (bottom) shows artery surrounded by myocardium.

68 January – June 2019, Volume – 8 Issue – 1 The official Journal of Cardiological Society of India, Kerala Chapter

Fig 5 Diagram showing extremes of tunneled coronary arteries: left main (LM)tunneled through the ventricular septum(left); total length of the left anterior descending artery (LAD) within the myocardium(middle); tunneled segment becoming intracavitary (right). AV=aortic valve, LC=Left circumflex, LV =left ventricle, PT=pulmonary trunk, PV= pulmonic valve. RVOFT=right ventricular outflow tract, Fig 4 RV=right ventricle, TV=Tricuspid valve R=right Diagram showing morphologic variations in tunneled (length, depth) segment of the coronary artery.

Tunneled coronary arteries have been recognized anatom- ically for more than two centuries,28 but recent reports indicating an association with myocardial ischemia and myocardial bridges have heightened clinical relevance. 29,30Tunneled coronary arteries have been presumed congenital in origin. Visscher and colleagues31 reported a tunneled left anterior descending artery in a 42- day old in- fant, supporting the presumption that myocardial bridging of coronary arteries exists at birth. At least three factors have been postulated to account for differences between the high frequency of tunneled major coronary arteries ob- Fig 6 Diagram showing various clinical and morphological served at necropsy 5-86% (32,7) and the lower frequency of factors in myocardial bridges (tunneled coronary artery). tunneled coronary arteries observed angiographically 0.5-1 2% (29,34,35) or associated with symptoms of myocardial ischemia (18%35): (1) length of the tunneled coronary segment, (2) degree of systolic compression, and (3) heart rate h) Coronary Aneurysms (Fig. 4). Isolated reports have suggested that longer tun- Congenital coronary artery aneurysms are found most com- neled segments of coronary arteries,29 more severe sys- monly in the right coronary artery.39Abnormal flow pat- tolic diameter narrowing of the tunneled segment 30 and terns within the aneurysm results in thrombus formation tachycardia36 are contributing factors in the production of with subsequent vessel occlusion, distal thrombo emboli- myocardial ischemia in association with myocardial bridg- zation, and myocardial infarction (MI). 40 The incidence of ing. The length of coronary tunneling in causing myocardial coronary arterial aneurysms is about 1.5% of patients stud- ischemia has been challenged by two recent reports.37, 38 ied at necropsy or by coronary arteriography.40 Aneurysms The authors of these reports describe three men with in- may be multiple and be acquired or congenital in origin. tramyocardial tunneling of the left main coronary artery of Causes for coronary arterial aneurysms include congenital >40 mm. Although the left main coronary artery was tun- origin, atherosclerosis, angioplasty, atherectomy and laser neled, none of the patients had clinical or morphologic ev- procedures, arteritis (including syphilis), mycotic emboli, idence of myocardial ischemia. mucocutaneous lymph node syndrome, dissection (sponta-

January – June 2019, Volume – 8 Issue – 1 69 The official Journal of Cardiological Society of India, Kerala Chapter

neous or secondary) and trauma. Atherosclerosis induced of coronary blood flow from intimal dissection and intra- aneurysms/ ectasia represent the majority (up to 50%) of mural hematoma formation. coronary aneurysms and results from primary thinning and Although SCAD can be a fatal event, most series suggest that destruction of media. early and long-term survival is good.75,80 However, the burden of subsequent complications is notable,75,80 with 10-year Kaplan-Meier estimated rates of major adverse cardiovascu- i) Spontaneous recanalization: lar events, including recurrence, congestive heart failure, MI, eg:Coronary Artery Emboli and death as high as 47% and SCAD recurrence rates as high Coronary arterial emboli are clinically suspected in patients as 29%.75 The natural history of SCAD is markedly different who develop angina under the following circumstances: in from atherosclerotic coronary disease.75 The precipitants of the presence of a left-sided prosthetic valve, left-sided coronary dissection are uncertain, a different pathophysio- native valve stenosis,active infective endocarditis, atrial logic mechanism from atherothrombotic ischemic MI is like- fibrillation, left ventricular aneurysm, dilated cardiomy- ly.75,78,81-83 Accordingly, short-term and longterm manage- opathy, cardiac tumor, or during cardiac catheterization ment strategies also differ substantially.84,85 or cardiac surgery.1The etiology of coronary emboli can be classified as natural causes, iatrogenic causes, and “par- adoxical” causes. Coronary embolism most often involves SCAD Presentations and diagnosis the left anterior descending coronary artery.27, 39 Coronary SCAD presents primarily as Acute Coronary Syndromes or embolisms is suspected as the cause of acute MI when the sudden cardiac death.75,80 Patients are usually women zone of necrosis is large but discrete lesions at necropsy (74%-92% in published series72-73,75,80) with a mean age of (there would have been little time to develop effective col- 42 to 52 years. Typical presenting symptoms include chest laterals). Embolic coronary artery lesions may resolve com- pain, dyspnea, diaphoresis, and/or nausea. Diagnostic find- pletely and and result in angiographically normal coronary ings include abnormal electrocardiographic findings, elevat- arteries several months after an acute MI.39 ed cardiac biomarkers, and regional wall motion abnormalities on echocardiography. Because these patients are often The size of the embolus and the size of the lumen of the ar- young, fit, and otherwise healthy, SCAD may not be consid- tery in which it becomes impacted are determinants of clin- ered in the initial differential diagnosis and may preclude ical consequences.41,42 The smaller the embolus, the high- or delay proper diagnosis if serial electrocardiograms and er the chance that it will travel distally to a small coronary troponin levels are not included in the evaluation. arterial segment and the likelihood of MI or fatal arrhythmia is less.41,42 A very small embolus that travels distally When ACS is recognized, coronary angiography should be im- and impacts in a single intramural vessel is clinically silent mediately performed. and may be observed only at necropsy.41,42The status of Angiographically, SCAD is of three types. 79 the coronary lumen before the embolus also determines the subsequent myocardial consequences Type:1: recognizable as a double lumen or ‘flap.’ There is open communication of the true lumen with the dissected plane (false lumen). Although being the classic finding, angiotype Acute Coronary Syndromes in 1 only accounts for 26%–43% of the cases in SCAD series.This patients with non-atheromatous pattern, when identified, is considered diagnostic itself. obstructive coronary Type 2: when the dissection plane (false lumen) encompass- es a contained intramural hematoma that does not allow lesions: contrast to enter in it (with or without intimal tear ) . In An- giography there is an abrupt change in the diameter of the 1. Spontaneous Coronary Artery vessel ( narrowing or tapering). This Dissection. (SCAD). narrowing is long with smooth borders, with or without distal Spontaneous coronary artery dissection (SCAD) is defined as recovery of vessel ́s diameter. It shows no response to intra- an epicardial coronary artery dissection that is not associat- coronary nitrates. This pattern is the most common accord- ed with atherosclerosis or trauma and not iatrogenic.71 ing to SCAD, accounting for 55%–78% of the cases. The reported prevalence ranges from 0.07% to 1.1%,71-74. Intravascular imaging is diagnostic in this situation.76,79. SCAD is more common in women 77,may be the cause of ACS in up to 35% of MIs in women <50 years of age. It is the most Type 3: is the ambiguous pattern and is the least common common cause of pregnancy-associated MI.71 SCAD causes angiographic presentation, although very likely is under- myocardial ischemia and infarction (MI) due to obstruction represented (misdiagnosed). It corresponds to a discrete,

70 January – June 2019, Volume – 8 Issue – 1 The official Journal of Cardiological Society of India, Kerala Chapter

not propagated intramural hematoma that gives the ap- for augmentation of coronary wall tone at the sites of severe pearance of a focal (single or multiple)lesion, sometimes luminal narrowing. Factor and colleagues66 have recently sug- mimicking atherosclerosis. Its ambiguity makes diagnostic gested that medial “contraction” bands may represent a mor- confirmation with Intravascular imaging mandatory. phologic-histologic marker for arteries that have spasm during life. Eccentric atherosclerotic plaques have a segment of disease-free wall that has preserved media and presumably has the potential for spasm64 Hangartner, and colleague65 have recently evaluated this form of stenosis in patients with clinical coronary spasm and ACS. Of 448 segments narrowed >75% in cross-sectional area by plaques, 15% had a variable arc of a disease-free wall (normal media). Quyyumi and colleagues68 (15%) and Hort and associates (20%) report similar data. Freudenberg and LichtIen 67and Saner et al68 report a higher percentage of disease-free wall (70%). This disease-free coronary segment represents a site of “vasospastic potential” and could convert a hemodynamically insignificant lesion or one of borderline significance to a hemodynamically significant lesion.

3. Coronary Artery Trauma Coronary artery trauma may produce myocardial ischemia and or acute MI. Traumatic injury may result from non-penetrating blunt chest wall injury (e.g., steering wheel injury). Penetrating trauma (e.g., laceration from stab wound or bul- let), or during coronary angiography. Nonpenetrating trauma may produce coronary injury and subsequent MI as a result of coronary dissection, contusion and thrombosis, fistula 2. Coronary Artery Spasm formation and or coronary artery aneurysm formation.27,43 Coronary artery luminal narrowing produced by spasm has been associated with acute Coronary Syndromes and sud- 4. Coronary Artery Arteritis den death. 18- 35 Despite the extensive clinical information about coronary artery spasm, relatively few necropsy data (Vasculitis) are available from these patients.27,44-59 Contraction of Coronary arteritis (vasculitis) is a rare event. The coro- the medial smooth muscle cells in the coronary artery wall nary injury in arteritis may directly lead to myocardial may be a response to various neurologic and pharmacolog- ischemia/infarction with or without associated coronary ic stimuli. Various postulates for the exact mechanism of artery thrombosis.87 According to Baroldi88 arteritis may spasm exist, but the specific pathogenesis of this disorder is be classified into three groups. a) Coronary arteritis that unknown.56 Enhanced alpha adrenergic tone33 and various results from direct extension from an adjacent organ or tis- vasoactive substances (histamine, catecholamines, prosta- sue infections (e.g., epicardial or myocardial abscess from glandins, thromboxaneA2) 58-59 are presently thought to aortic valve endocarditis, pericardial tuberculosis). In this be relevant factors. Roberts and colleagues28and Isner- situation, the coronary artery adventitial layer is initially 30have reviewed the necropsy involved. b)Coronary arteritis resulting from a hematoge- nous spread through the coronary lumen or through vasa findings in 13 previously reported cases of coronary artery vasorum. In this situation, the intimal layer is initially in- spasm. Although coronary angiograms during life did not rec- volved. c) the exact mechanism of vascular origin is not ognize any fixed lesions ,most of them had associated athero- understood. Specific coronary lesions a may be seen in sys- sclerotic plaque, (identified at necropsy).55 In one of the orig- temic diseases like polyarteritis nodosa.. inal patients described by Prinzmetal and colleagues,44 both major epicardial coronary arteries were “markedly sclerotic”, and the “posterior coronary artery” was 80% narrowed. Recent- Tuberculosis ly Isner and colleagues62 have demonstrated that coronary Tuberculous arteritis is seen chiefly in patients with pericar- artery smooth muscle depletion (“medial attenuation”) accom- dial or myocardial lesions. Specific coronary artery granu- panies advanced degrees of luminal narrowing by atheroscle- loma may involve the adventitia, the intima, or the entire rotic plaque. This medial attenuation diminishes the potential wall.80,82

January – June 2019, Volume – 8 Issue – 1 71 The official Journal of Cardiological Society of India, Kerala Chapter

Polyarteritis Nodosa artery thrombosis(95)or only coronary thrombosis. In 30 cases studied by Saphir,(94) only one patient had coronary Polyarteritis nodosa is probably the most common cause involvement, whereas in 19 cases studied by Averbuck and of coronary arteritis. It is a systemic necrotizing vasculitis that affects medium and small vessels. Of 66 cases studied Silbert 6 patients had coronary thrombosis. by Holsinger et al. 41 (62%) had involvement of the epicardial coronary arteries and 41 also had myocardial infarcts Wegener’s Granulomatosis of varying size.(83) The coronary lesions resemble the necrotizing vascular lesions elsewhere, with an acute cellular Wegener’s granulomatosis is a necrotizing vasculitis com- phase with the destruction of the media and internal elas- monly affecting renal and pulmonary systems. Parrilo and tic membrane and subsequent intimal proliferation and Fauci have reported Fibrinoid necrosis of the small and me- scar in the healed phase. The coronary artery may dilate dium-sized coronary arteries .87 Larger epicardial coronary to form small berry-like aneurysms, become occluded by artery occlusion, and MI was reported by Gatenby et al. 96 thrombus, or rupture (producing fatal pericardial tampon- ade)(84). Infectious Diseases Various infectious diseases have been associated with cor- Giant Cell Arteritis onary arteritis: syphilis79.93-97 infective endocarditis, 98 Giant cell arteritis affects chiefly the temporal and other salmonelloses, 99,100 typhus,101 and leprosy.100Syphilis is cranial arteries, but Ainsworth et al. have reported coro- stated to be one of the most common infectious diseases nary artery involvement and myocardial infarction,(85,86) affecting the coronary arteries.102 Up to one-quarter of The arterial wall lesion is a granulomatous inflammation patients with tertiary syphilis may have ostial stenosis98 with giant cells found along a degenerated internal elas- The first 3 to 4 mm of the left and right coronary arteries tic membrane.85 The intima becomes much thickened, and may be involved with obliterative arteritis.93 Rarely a cor- ultimately the vessel is converted into a fibrous cord. The onary artery contains a gumma.93 Angina and AMI may re- Luminal thrombus may also be present. Of I6 cases of tem- sult from syphilitic coronary disease.97 Malarial parasites poral arteritis reported by Harrison,” only 1 case involved and parasitized red blood cells also may plug larger coro- the epicardial coronary arteries. nary arteries.110,110a Schistosoma hematobium has been found in a major epicardial coronary artery unassociated Systemic Lupus Erythematosus with MI.106 Pericardial and myocardial involvement are common complications in systemic lupus erythematosus. Several young patients with lupus and absent coronary atherosclerosis Mucocutaneous Lymph Node have suffered acute myocardial infarction (AMI). 88-91 Nec- Syndrome (Kawasaki’s Disease) ropsy examination of the coronary arteries in these patients This acute febrile illness affects infants and young chil- showed intimal fibrous proliferation, which may represent dren. In about 20% of patients, vasculitis of the coronary healed arteritis. In a 16-year-old girl with lupus studied by vasavasorum leads to coronary arterial aneurysm formation, Bonfiglio et al.,90 AMI was associated with recent throm- thrombosis, and MI. Death may result from MI or ventricular botic occlusion of all three major arteries. Tsakraklides et arrhythmia in 1-2%. Late presentation with MI secondary to al. 92Studied a 29-year-old woman with lupus and fatal AMI dislodged aneurysmal thrombus may also occur.79.107-108 who had severe coronary atherosclerosis. This case sug- Occasional death may result from coronary artery aneurysm gested that lupus and other conditions causing arteritis rupture. might predispose to premature coronary atherosclerosis. Smaller intramyocardial coronary arteries are involved frequently in the diffuse vasculitis with fibrinoid necrosis and fibrosis.94 Takayasu’s Disease (Pulseless Disease) This disease results in granulomatous pan arteritis and fi- Burger’s Disease brosis of the aorta and its large branches, which in turn (Thromboangitis Obliterans) lead to luminal narrowing.25 Involvement of the coronary In a few patients with Burger’s disease, the epicardial cor- artery ostia and proximal main coronary artery segments onary arteries have shown focal polymorphonuclear infil- has been described in several patients.88, 110,111 Angina trates, histiocytes, and giant cells with or without coronary pectoris and AM1 may result from these coronary lesions.

72 January – June 2019, Volume – 8 Issue – 1 The official Journal of Cardiological Society of India, Kerala Chapter

Rheumatoid Diseases plasty of a lesion in the proximal left anterior descending coronary artery. They postulated that the left main inti- Rarely, arteritis and intimal thickening associated with mal reaction (identical to that seen at the left anterior de- rheumatoid disease severely narrow major epicardial cor- scending coronary artery angioplasty site) resulted from onary arteries. More commonly, diffuse arteritis involves balloon rubbing of the intimal surface and/or extension smaller coronary arteries (including conduction system of the fibrous process from the angioplasty dilation site. vessels) in 10-20% of necropsy patients with rheumatoid arthritis.112-114 Small myocardial vessels may also be narrowed severely in patients with ankylosing spondylitis. 7. External Compression Grismer et al. have described a patient with ankylosing External compression of the epicardial coronary arteries spondylitis who had occlusion of the left main ostium114 may result in severe luminal narrowing and progressive myocardial ischemia. External compression of a major 5. Metabolic Disorders Narrowing epicardial coronary artery has been reported in patients with sinus of Valsalva aneurysms and epicardial tumor Coronary Arteries metastases. 130-131Myocardial bridging (external mus- Specific metabolic substances may accumulate in the walls cle compression during ventricular systole) has been re- of large and small coronary arteries as a result of inborn viewed earlier. errors of metabolism. The deposition of this material may severely narrow the coronary artery lumen and produce AMI.102 Inherited inborn errors of metabolism that are 8. Metastatic Implants known to affect major epicardial coronary arteries include Myocardial metastatic lesions from various tumors (car- Hunter’s and Hurler’s diseases (mucopolysaccharidoses). cinomas, sarcomas, lymphomas) may mimic a healed 115-117 The involvement of the coronary arteries in these myocardial infarct at necropsy.79 The discrete location disorders may be so severe as to occlude the vessel totally or locations of these metastatic deposits generally are and to produce myocardial ischemia/Infarction. Other dis- unrelated to specific coronary arterial supply zones, and orders of metabolism such as primary oxalosis,118 Fabry’s the lesions are usually surrounded by normal myocardi- disease, 93 Sandhoff’s disease (gangliosidoses),119and ho- um. These two gross observations suggest the lesions are mocystinuria may affect smaller coronary vessels by severe metastatic tumor implants rather than healed myocardi- intimal proliferation120 al infarcts.79

6. Intimal Proliferation 9. Coronary Artery Thrombosis with- Fibrous hyperplasia of the coronary arteries may severely narrow the lumen and produce myocardial ischemia/ in- out Underlying Atherosclerotic Plaque farction. The process may be associated with mediastinal (Thrombosis In Situ) irradiation, 121 fibromuscular hyperplasias of the renal Thrombotic occlusion of the coronary system unassociated arteries102the use of methysergide, 122,123 ostial cannu- with underlying atherosclerotic plaque may be seen with lations during cardiac surgery or following aortic valve several hematologic diseases: thrombocytopenia purpura,93 repIacement.124.125Up to 50%of patients undergoing car- leukemia132 polycythemia vera,133 sickle cell anemia,93 and diac transplantation develop significant epicardial coro- primary thrombocytosis.134 Occasionally, AMI may be the ini- nary artery luminal narrowing or total occlusion by intimal tial manifestation of these hematologic disorders.The main fibrous proliferation within 3 to 5 years after transplan- factor responsible for the myocardial ischemia in this con- tation. 126 Myocardial infarction and sudden death may dition is blockage of small intramural coronary vessels by result from this chronic rejection process. Fibrosis of the platelet aggregates.135 These platelet aggregates initially intramural vessels may also occur. Intimal damage from form in the major coronary arteries and then embolize dis- immunologic rejection is believed to be the basis for the tally. 79 accelerated intimal fibrous hyperplasia involving thecoro- nary arteries. 79 A similar histologic picture of intimal fibrous proliferation Substance Abuse (Cocaine) is seen in epicardial coronary arteries late after undergo- Cocaine abuse is a major health hazard. More than 22 ing percutaneous balloon angioplasty127-128 Waller et al. million Americans have tried cocaine at least once in recently reported intimal fibrous proliferation of the left their life, and five million are current users.136 Recent main coronary artery occurring late after balloon angio- reports have documented that cocaine abuse can result

January – June 2019, Volume – 8 Issue – 1 73 The official Journal of Cardiological Society of India, Kerala Chapter

in myocardial ischemia and MI in the absence of coro- disorders (scleroderma; systemic lupus erythematosus),(8) nary atherosclerotic disease.136-143 Several instances metabolism abnormalities (mucopolysaccharidoses; gan- of coronary artery thrombosis and spasm have been re- gliosidoses), and (9) polyarteritis nodosa.79 ported in patients with cocaine abuse.144-148 Coronary thrombosis occurring in coronary arteries free of atherosclerotic plaque suggests the role of cocaine-induced Takotsubo cardiomyopathy: spasm or possible primary thrombogenicity of cocaine or Apical Ballooning Syndrome. its metabolites.143 (Stress Cardiomyopathy) Coronary spasm has been associated with cocaine usage A specific syndrome of stress-related reversible cardio- and has been postulated as a mechanism of MI in those myopathy, has recently been observed with greater fre- users with clean coronary arteries 136,147-152 Simpson quency. Increasingly referred to as the “broken heart and Edwards 153reported coronary artery narrowing in a syndrome,” this condition mimics myocardial infarction young patient without underlying atherosclerotic plaque. in patients without obstructive coronary artery disease. The coronary artery was severely narrowed by fibrointimal Initial signs and symptoms resemble those of acute coro- proliferation that was attributed to underlying coronary nary syndrome; chest pain, dyspnoea, electrocardiograph- artery spasm that caused focal vessel endothelial injury, ic (ECG) changes, and elevated levels of cardiac and platelet adherence and aggregation. Platelets liber- ate platelet-derived growth factor (PDGF), which induces intimal proliferation. In patients with underlying coronary Aetiology and pathogenesis : plaque, cocaine-induced spasm also may produce endo- The exact aetiology is not known. Normal myocardium utilizes thelial disruption at the surface of the plaque and promote 90% of its energy from fatty acid metabolism and only 10% platelet aggregation and further vasoconstriction from the from glucose metabolism. In Stress Cardiomyopathy, there release of platelet prostaglandins.154 appears to be a shift towards glucose pathway with impaired

biomarkers.160 Takotsubo is the Japanese name for the traditional octopus trapping pot that has a round bottom and narrow neck, resembling the appearance the left ventricle during systole. (see Figure ).161

10.Intramural Coronary Artery fatty acid metabolism. Several mechanisms have been proposed to explain the pathogenesis of Takotsubo cardiomyop-

Disease (Small Vessel Disease) athy characterized by apical ballooning of left ventricle. Acute myocardial infarction may result from abnormally thickened or occluded intramural coronary arteries in the presence of normal extramural (epicardial) coronary ar- Catecholamine theory: teries. Some conditions in this category include: (1) hyper- Due to severe emotional or physical stress, overstimula- trophic cardiomyopathy, (2) diabetes mellitus, (3) amyloid tion of hypothalamus pituitary adrenal axis occurs and re- heart disease, (4) neuromuscular disorders (Friedreich’s sults in excessive release of catecholamine. Elevated plas- ataxia; progressive muscular dystrophy). (5) cardiac trans- ma levels of epinephrine and norepinephrine have been plantation. (6) rheumatoid arthritis, (7) collagen-vascular demonstrated during the acute phase.162Acute onset of a

74 January – June 2019, Volume – 8 Issue – 1 The official Journal of Cardiological Society of India, Kerala Chapter

Takotsubo cardiomyopathy and its association with pheo- Investigations: chromocytoma or paraganglioma have also suggested that Takotsubo cardiomyopathy may be catecholamine induced Electrocardiogram (ECG) myocardial dysfunction.163 ECG reveals abnormal findings in over 95% patients in the form of ST elevation (43%) or ST depression (8%), T wave inversion (50%) and prolonged QTc interval (400ms). Myocardial bridging and myocardial oedema: Cardiac biomarkers Migliore et al.164 recently studied 42 consecutive patients of apical ballooning syndrome (ABS) by echocardiography During acute phase, serum natriuretic peptides (BNP and (ECHO), coronary angiography (CAG) with intravascular ultra- NTproBNP) are always increased along with troponin. BNP sound (IVUS), computer tomography angiography (CTA) and and NT- proBNP may be increased 3–5 times (much more cardiac magnetic resonance (Cardiac MR). Myocardial bridg- than troponin) and are considered more useful diagnostic ing was seen both by CAG and mostly by CTA in 32 ABS patients biomarkers for the diagnosis of Takotsubo cardiomyopa- (76%); 23 with partial and 9 with complete encasement. It was thy. In a recent study of cardiac biomarkers in Takotsubo compared with 401 control patients without ABS where CTA cardiomyopathy and STEMI patients, the concentration of demonstrated myocardial bridging in 31% patients (p < 0.001). NT-proBNP was greater in Takotsubo cardiomyopathy versus STEMI (4702 pg/ml vs 2138 pg/ml respectively) while Myocardial oedema is characteristic feature in patients troponin and CKMB mass were lesser in Takotsubo cardio- with ABS and can be demonstrated by cardiac magnetic myopathy vs STEMI (Troponin 2.1 ng/ml and CKMB Mass 9.5 resonance. Myocardial oedema, predispose to the development of T wave inversion, QT prolongation and often life ng/ml v/s Troponin 19 ng/ml and CKMB mass 73.3.ng/ml threatening arrhythmias (LTA).165,166 (172).

Microvascular dysfunction : Echocardiography (ECHO) Active Takotsubo cardiomyopathy may be due to micro- Transthoracic echocardiography with colour Doppler is vascular spasm/constriction/ microemboli. Microvascular always the first imaging procedure in the diagnosis of dysfunction could be secondary to excessive release of Takotsubo cardiomyopathy.173 The key ECHO findings epinephrine.167,168 Myocardial contrast echo cardiography consist of a large area of regional wall motion (akinesia) and myocardial single photon emission computed tomog- of LV extending beyond the territory of single coronary raphy have shown myocardial perfusion defect at microvas- artery. The dyskinetic/ akinetic myocardial area usual- cular level. ly involves apical portion of LV resulting in acute apical ballooning along with dilatation of mid ventricular area. Left ventricle ejection fraction (LVEF) is always compro- Hormonal and genetic factors : mised (20–45%). A recent update on Takotsubo syndrome confirmed female preponderance (88.7%) which suggest a role of various re- Angiography : productive hormones in the pathogenesis.169 Coronary angiography is urgently indicated to rule out obstructive ACS (STEMI/NSTEMI). There is no obstructive pathology is found; thrombus or plaque rupture is absent. Co- Classification. existing mild atherosclerosis without obstruction has been 1. Primary Takotsubo cardiomyopathy with/without stress trig- described in <10% cases. ger: More common in postmenopausal elderly women. The patients presents with cardiac symptoms of ACS. Physical and emotional stresses are responsible for Takotsubo car- Cardiac magnetic resonance (CMR) diomyopathy in over 70% patients. However more than one CMR provides 3-dimensional view of the anatomy of LV as quarter have no clear triggers. Patients have a higher rate of well as RV. Four major anatomic patterns of regional wall co-existing neurological and psychiatric disorders.170, 171 motion abnormality (RWMA) have been recognized apical 2. Secondary Takotsubo cardiomyopathy: Patient with clinical ballooning (81.7%), midventricular (14.6%), basal or invert- evidence of serious medical/surgical/obstetric and psychot- ed (2.2%) and focal (1.5%). CMR is indicated, first within ic disorders develop Takotsubo cardiomyopathy during the 7 days and then at 2–6 months to judge the recovery of course of primary illness. RWMA.174

January – June 2019, Volume – 8 Issue – 1 75 The official Journal of Cardiological Society of India, Kerala Chapter

Treatment Enhancement and Development of Evidence-based care in Heart disease Evaluated According to Recommended Ther- Treatment of Takotsubo cardiomyopathy during the acute phase apies (SWEDEHEART) registry, 14% died during a 4.5-year is mainly symptomatic treatment. Intra-aortic balloon pump follow-up.182 equipment is required for hemodynamically unstable patients in addition to cardiopulmonary circulatory support and continuous veno-venous hemofiltration. There is controversy on the use of References cardiac stimulants because of increased circulating catechol- 1. Waller BF: Topography of atherosclerotic coronary artery amines[ 175]. However, cardiac stimulants are used in 20%-40% diseases. Clin Cardiol l990,13:435442 of patients. Levosimendan may be beneficial because of its inotropic action and vasodilator effect[176]. Usage of anticoagulants 2. Waller BF, Orr CM, Slack JD. Pinkerton CA, VanTassel JW, may be considered at least until systolic function is recovered. Taliercio CP, Peters T Anatomy, histology and patholo- For patients with severe LV outflow tract obstruction with he- gy of coronary arteries: A review relevant to new inter- modynamic compromise, treatment with a β-blocker should be ventional and imaging techniques. Part IV. Clin Cardiol considered. For patients with suspected vasospasm, the use of 1992;15:675487 calcium channel blockers such as verapamil or diltiazem is sug- 3. Waller BF: Nonatherosclerotic causes of coronary artery gested[177]. narrowing. In The Heart, 8th edition (Eds. Schlant RC, Al- exander RW, O’Rourke RA. Roberts R, Sonnenblick EH). Prognosis. McGraw Hill.1994: 1239-1261 Patients usually have a good prognosis, and almost perfect 4. Waller BF: Atherosclerotic and nonatherosclerotic coronary recovery is observed in 96% of the cases[178]. In hospital artery factors in acute myocardial infarction. In Acute mortality rate vary from one to two percent[179]. Takotsubo Myocardial infarction (Ed.PepineCJ). Cardiovascular Clin- cardiomyopathy, though thought to follow a relatively be- ics Series. Philadelphia, nign course, have a greater risk [178] of death at the time F.A. Davis. 1989:29-104 of initial onset. Their long-term survival rate is the same as that in healthy subjects, 5. Alpert JS, Braunwald E: Acute myocardial infarction: Myocardial infarction with nonobstructive coro- pathological, pathophysiological and clinical manifes- nary arteries (MINOCA) : tations. In Heart Disease. A Textbook of Cardiovascular Medicine. Vol. 2, (b Braunwald E). Philade1phia: W.B.Saun- Myocardial infarction with nonobstructive coronary arteries ders.1984:1262 (MINOCA) is clinically defined by the presence of acute myocardial infarction (AMI), absence of obstructive coronary ar- 6. Eliot RE, Baroldi G: Necropsy studies in myocardial infarc- tery disease (≥50% stenosis), and no overt cause for the clini- tion with minimal or no coronary luminal reduction due cal presentation at the time of angiography.180 MINOCA refers to atherosclerosis Circulation 1974;49:1127-1 131 to approximately 5%-10% of acute myocardial infarction. 7. CheitlinMD, McAllister HA, deCastroCM: Myocardial infarction without atherosclerosis. J Am Med Assoc 1975;23I:95 Aetiology: 1-959 Potential underlying mechanism includes coronary causes 8. BaimDS, HarrisonDC: Nonatherosclerotic coronary dis- such as coronary spasm, coronary microvascular dysfunction, eases (including coronary artery spasm). In The Heart, plaque disruption, spontaneous coronary thrombosis/embo- 5thed.(Ed.Hurst, JW). New York: McGraw-Hill,l982:1158 li, and coronary dissection; myocardial disorders, including myocarditis, takotsubo cardiomyopathy, and other cardiomy- 9. Engel HJ, Toms C, Page HL: Major variations in anatomi- opathies & noncardiac causes like pulmonary embolism. cal origin of the coronary arteries: Angiographic observations in 4,250 patients without associated congenital heart disease. Cutber CardioVasc Diagn 1975;1:157-161 Prognosis: 10. Roberts WC: Major anomalies of coronary arterial origin Contemporary research studies of MINOCA have evaluated see in adulthood. AmHeart J 1986;111:941-963 the prognosis of these patients, reporting a 12-month all- 11. Levin DC, Fellows KE, Abrams HL: Hemodynamically sig- cause mortality of 4.7% 181 Patients with MINOCA frequent- nificant, primary anomalies of the coronary arteries. An- ly had manifestations of atherosclerotic disease in other giographic aspects, Circulation 1978;58:25-34 territories (eg, peripheral vascular disease).182 Moreover, mortality rates were substantial in the years following the 12. Roberts WC, Siege1 RJ, Zipes DP: Origin of the right cor- MINOCA event. In the nationwide Swedish Web-system for onary artery from the left sinus of Valsalva and its func-

76 January – June 2019, Volume – 8 Issue – 1 The official Journal of Cardiological Society of India, Kerala Chapter

tional consequences: Analysis of 10 necropsy patients. 25. Foster L, Waller BF Nonatherosclerotic fibrous ridges: A Am J Cardiol 1982;49: 863-868 previously unrecognized cause of ostial left main stenosis. J Indiana Med Assoc 1983;76:682-683 13. Waller BF Exercise related sudden death in young(age<30 years ) and old (age > 30 years) conditioned athletes. In 26. Baroldi G: Diseases of the coronary arteries. In Cardio- Exercise and the Heart,2nd ed. (Ed. Wenger NK). Cardio- vascular Pathology (Ed. Silver MD). New York: Churchill vascular Clinics Sene5 Philade1phia:F.A. Davis,1985:9 Livingstone1983:341 14. Menke DM. Jordan MD, Sut CH, Waller BW Isolated and se- 27. Waller BF Nonatherosclerotic causes of coronary artery vere left main coronary atherosclerosis and thrombosis: narrowing. In The Heart. 8th ed. (Eds. Schlant RC. Alex- A complication of acute angle takeoff of the left main cor- ander RW. O’Rourke RA, Roberts R, Sonnenblick EH), p. onary artery. Am Hean J 1986;112:1319-1320 1239- I26 I. New York: McGraw-Hill,1994 15. Virmani R, Chun PKC, Goldstein RE, Rabinowitz M, McAl- 28. Reyman HC: Disertatis de vasis cordis propiis. Bibl Anat lister HA: Acute takeoffs of the coronary arteries along 1737;2: 366-373 the aortic wall and congenital coronary ostial valve-like 29. Noble J, Bourassa MG, Petitclerc R, Dyrda I: Myocardial ridges. Association with sudden death. J Am Coll Cardiol bridging and milking effect of the left anterior descend- 1984;3:76&77 I ing coronary artery: Normal variant or obstruction? Am J 16. Shrivastava S, Mohan J, Mukhopadhyay S, Rajani M, Tan- Curdiol I976;37:993-999 don R. Coronary artery anomalies in tetralogy of Fallot. 30. Farugui AMA, Maloy WC, Felner JM, Schlant RC, Logan WE. Cardiovasc Interv Radiol. 1987;10:215–218. Symbas P: Symptomatic myocardial bridging of the coronary artery. Am J Cardiol1978;41:1305-130 16a. Ayman Elbadawi,Basarat Baig,Islam Y. Elgendy,Erfan Alotaki, Ahmed H. Mohamed, Kirolos Barssoum, David 31. Visscher DW, Mildes BM, Waller BF: Tunneled (“bridged”) Fries, Muhammad Khan, and Rami N. Khouzam.Single left anterior descending coronary artery in a newborn Coronary Artery Anomaly: A Case Report and Review of without clinical or morphological evidence of myocardial Literature.Cardiol Ther. 2018 Jun; 7(1): 119–123. ischemia. Ctrrlz Cath Cardiovasc Diag 1983:9;493-498 17. Foster L, Waller BF, Pless JE: Hypoplastic coronary arter- 32. Edwards JC. Burnsides C, Swarm RL. Lansing AJ: Arterio- ies and high takeoff position of the right coronary artery. sclerosis and extramural portions of coronary arteries in Chest 1985;88: 29-30 I the human heart. Circulation 1956:13:235-24I 18. Vlodaver 2, Amplatz K, Burchell HB, Edwards JE: Coronary 33. Polacek P: Relation of myocardial bridges and loops i n Heart Disease. Clinical, Angiographic and Pathologic Pro- the coronary arteries to coronary occlusions. Am Heart files. New York: Springer-Verlag,1971631 J 1961:61:44-52 19. Alexander RW, Griffith GC: Anomalies of the coro- 34. Levin DC. Fellows KE. Abrams HL: Hemodynamically signif- nary arteries and their clinical significance. Circuta- icant primary anomalies of the coronary arteries. Angio- fion1956;1480M05 graphic aspects. Circulation I978;58:25-34 20. Burch HC: Hoher und trichterformiger Ursprung der Herz- 35. Kramer JR, Kitazunie H. Proudin WI. Sones IM: Clinical sig- krmp arterien. Beitr Pathol Ana 1963;128:139-148 nificance of isolated coronary bridges: Benign and frequent condition involving the left anterior descending 21. Holt S: Syphilitic ostial occlusion. Br Heart J 1977;39: 469- artery. Am Heart J 1982: 1031283-288 470, 25. Young JA, Sengupta A, Khaja FU: Coronary arterial 36. lshimori T. Raizner AE. Chahine RA, Awdeh M, Luchi RJ: stenosis. angina pectoris and atypical coarctation of the Myocardial bridges in man: Clinical correlations and an- aorta due to nonspecific arteritis: Treatment with aorto giographic accentuation with nitroglycerin. Cath Cardio- coronary bypass graft. Am J Cad01 1973;32:35&361 vas Diag 19773: 59-65 22. Rozavi M: Unusual Forms of Coronary Artery Disease. 37. Roberts WC, Dicicco BS. Waller BF, Kishel JC. McManus BM. Cleveland Clinic Cardiovascular Consultations(Ed.Vedt D). Dawson SL. Hunsaker JC. Luke JL: Origin of the left main Cardiovascular Clinic 7. Philade1phia :F.A. Davis,l975:2546 from the right coronary artery or from the right aortic si- 23. Hudson P, Foster JB, Walton JN: Methysergide and coro- nus with intramyocardial tunneling to the left side of the nary artery disease. Am Heart J 1%7;74:854-855 heart via the ventricular septum: The case against clinical significance of myocardial bridge or coronary tunnel. Am 24. Yates JD. Kirsh MM, Sodeman TM, Walton JA, Brymer IF HenrtJ 1982:104:303-305 Coronary ostial stenosis: A complication of aortic valve replacement. Circulation 1974;49:53&.534 38. Schulte MA. Waller BF, Hull MT. Pless JE: Origin of the left

January – June 2019, Volume – 8 Issue – 1 77 The official Journal of Cardiological Society of India, Kerala Chapter

anterior descending artery from the right aortic sinus Rosen KM: Conduction system in a patient with Prinzmet- with intramyocardial tunneling to the left side of the al’s angina and transient atrioventricular block. Am J Car- heart via the ventricular septum: A case against clinical diol 197739: 12-125 and morphologic significance of myocardial bridging. Am 53. Maseri A. L‘ Abbate A, Baroldi G, Chierchia S. Marzilli M. HenrtJ 1985:110:499-501 Ballestra AM. Soveri S. Parodi 0. Biagini A, Distante A. Pe- 39. Wenger NK: Nonatherosclerotic causes of myocardial sola A: Coronary vasospasm as a possible cause of myo- ischemia and necrosis. In The Heart, 4thEd (Ed.Hurst- cardial infarction. A conclusion derived from the study of JW),p. 1345.New York: McCraw-Hill, 1978 “preinfarction” angina. N Engl J Med 1978;299:1271-1277 40. Clickel SZ, Maggs PR. Ellis FH: Coronary artery aneurysm. 54. Roberts WC, Curry RC. Isner JM, Waller BF. McManue BM. A m Tlioruc Surg 1978;25:372-376 Constantini-Mariani R. Ross AM: Sudden death in Prinz- metal’s angina with coronary spasm documented by an- 15. Roberts WC: Coronary embolism: A review of causes, con- giography. Analysis of 3 necropsy patients. Am J Cardiol sequences and diagnostic considerations. Curdiovasc I982; SO:203-2I0 Med I978:3: 609-709 55. Isner JM. Donaldson RF: Coronary angiographic and mor- 41. Waller BF, Dixon DS, Kern RW. Roberts WC: Embolus to the phologic correlation. In Cardiac Morphology left main coronary artery. Am J Cardiol 1982:50:658-660 (Ed. Waller, BF),p.571-592. Cardiology Clinics Series.Philadel- 42. Baim DS. Harrison DC: Nonatherosclerotic coronary heart phia: WBSaunders.1984 disease (including coronary artery spasm). In The Heart, 56. Brown BF: Coronary vasospasm. Observations linking the 5thed. (Ed. Hurst JW)p. 1158.New York McGraw-Hill. 1982 clinical spectrum of ischemic heart disease to the dy- 43. Pnnzmetal M, Kennamer R. Merliss R. Ekmeci A: Angina namic pathology of coronary atherosclerosis. Arch Intern pectoris. 1. A variant form of angina pectoris. Preliminary Med I981;14I:716-722 report. Am J Med 1959;27:375-388 57. Hillis LD. Braunwald E: Coronary artery spasm. N Engl J 44. Peretz DI: Variant angina pectoris of Prinzmetal. Can Med Med 1978:299:695-702 Assoc J 196I 5:1101-1 102 58. Ginsburg R. Birstow MR. Harrison DC, Stinson EB: Studies 45. Gianelly R, Mugler F, Harrison DC: Prinzmetal’s variant of with isolated human coronary arteries: Some general ob- angina pectoris with only slight coronary atherosclerosis. servations, potential mediators of spasm. Role of calcium California Med 1968:108:129-132 antagonists. Chest 1980;78:180-186 46. Silverman ME, Flamm MD: Variant angina pectoris. Ana- 59. Maseri A. Seven S, DeNes M. L‘Abbate A, Chierchia S, tomic Findings and prognostic implications. Anti Intern Marzilli M. Ballestra AM, Parodi 0, Biagini A. Distante Med 1971;75: 339-343 A: “Variant” angina. One aspect of a continuous spectrum of vasospastic myocardial ischemia. Am J Cardiol 47. Dhurandhar RW. Watt DL, Silver MD, Trimble AS. Adelman 1978:42:1019-1035 AG: Prinzmetal’s variant form of angina with arteriographic evidence of Coronary arterial spasm. Am J Car- 60. El-Maraghi NRH, Sealey BJ: Recurrent myocardial infarc- diol 1972;30902-905 tion in a young man with coronary arterial spasm demonstrated at autopsy. Circulation 1980:61:199-207 48. Cosby RS. Giddins JA, See JR. Mayo M: Variant angina. Case reports and critique. Am J Med 1972:53:739-742 61. Isner JM, Donaldson RF, Katsas GG: Spasm at autopsy: A prospective study (abstr). Circulation 1983;68: III-1028 49. Cheng TO. Bashour T, Kelser GA, Weiss L, Bacos J: Variant angina of Prinzmetal with normal coronary arteriograms. 62. Isner JM, Fortin AH, Fortin RV: Depletion of smooth mus- A variant of the variant. Circulation 1973;47:47&485 cle from the media of atherosclerotic coronary arteries: A potential factor in the pathogenesis of myocardial isch- 50. Donsky MS, Harris MD. Curry GC. Blomquest CG, Wilkerson emia and the variable response to anti anginal therapy JT. Mullins CB: Variant angina pectoris: A clinical and cor- (abstr). Clin Res 1983;3I:193A onary arteriographic spectrum. Am Heart J 1975:89:571- 63. Factor SM, Cho S: Smooth muscle contraction bands in 57883;9:493498 the media of coronary arteries: A postmortem mark- 51. Wiener L, Kasparian H. Duca PR. Walinsky P, Gottlieb RS. er of antemortem coronary spasm? J Am Coll Cardiol Henckel F. Brest AN: Spectrum of coronary arterial spasm. 1985:6:1329-1337 Clinical, angiographic and myocardial metabolic experi- 64. Waller BF: The eccentric coronary atherosclerotic plaque: ence in 29 cases. Am J Cardiol 1976:38:945-955 Morphologic observations and clinical relevance. Clin 52. Bharati S. Dhingra RC, Lev M, Towne WD, Rahimtoola SH. Cardiol 1988; 12:14-20

78 January – June 2019, Volume – 8 Issue – 1 The official Journal of Cardiological Society of India, Kerala Chapter

65. Hangartner JRW. Charleston AJ. Davies MJ. Thomas AC: nosis of spontaneous coronary artery dissection: results Morphologic characteristics of clinically significant from a database of 11,605 patients. Eur J Cardiothorac coronary artery stenosis in stable angina. Br Heart J Surg. 2009;35(2):250-254. 1986;56:501-508 76. Takahiro Kanda, Kei Tawarahara, Gaku Matsukura, Mas- 66. Quyyumi AA, Al-Rufaii HK. Olsen EGJ, Fax KM: Coro- ayoshi Matsunari, Rumi Takabayashi, Jun Tamura, Mariko nary anatomy in patients with various manifestations Ozeki, and Hiroshi Ukigai.The Diagnosis of Spontaneous of three-vessel coronary artery disease. Br Heart J Coronary Artery Dissection by Optical Coherence Tomog- 1985:54:362-366 raphy.Inernal Medicine.2018 Feb 15; 57(4): 523–526. 67. Freudenberg H, Lichtlen PR: Das normale Wandsegment 77. Saw J, Aymong E, Mancini GBJ, Sedlak T, Starovoytov A, Ric- bei Koronarstenosen-eine postmortale Studie. Z Kardiol ci D. Nonatherosclerotic coronary artery disease in young I981:70:863-869 women. Can J Cardiol. 2014;30(7):814-819. 68. Saner HE, Gobel FL, Salornonowitz E, Erlien DA. Edwards 78. Saw J, Aymong E, Sedlak T, et al. Spontaneous coronary JE:The disease-free wall in coronary atherosclerosis: artery dissection: association with predisposing arte- Its relation to degree of obstruction. J Am Coll Cardiol riopathies and precipitating stressors and cardiovascular 1985;6:1096-1099 outcomes. Circ Cardiovasc Interv. 2014;7(5):645-655. 69. Waller BF: Atherosclerotic and nonatherosclerotic cor- 79. Dr. Shahid Aziz.Spontaneous coronary artery dissection E onary artery factors in acute myocardial infarction. In Journal of Cardiology practice. European Society of Cardi- Acute Myocardial Infarction(Ed.PepineCJ),p.29104.Ccird- ology.Vol. 14, N° 38 - 22 Feb 2017. iowsculczrClinicsSeries. Phi1adelphia:WB Saunders,1989 80. Borczuk AC, Hoeven KH, Factor SM. Review and hypothe- 70. Tweet MS, Hayes SN, Pitta SR, et al. Clinical features, man- sis: the eosinophil and peripartum heart disease (myo- agement, and prognosis of spontaneous coronary artery carditis and coronary artery dissection): coincidence or dissection. Circulation. 2012;126(5):579-588. pathogenetic significance? Cardiovasc Res. 1996;33(3):527- 532. 81. Wisecarver J, Jones J, Goaley T, McManus B. “Sponta- 71. Sharonne N. Hayes, Esther S.H. Kim, Jacqueline Saw, David neous” coronary artery dissection: the challenge of de- Adlam, Cynthia Arslanian-Engoren, Katherine E. Economy, tection, the enigma of cause. Am J Forensic Med Pathol. Santhi K. Ganesh, Rajiv Gulati, Mark E. Lindsay, Jennifer H. 1989;10(1):60-62. Mieres, Sahar Naderi, Svati Shah, David E. Thaler, Mary- sia S. Tweet, and Malissa J. Woodand On behalf of the 82. Tweet MS, Eleid MF, Best PJM, et al. Spontaneous coronary artery dissection: revascularization versus conservative American Heart Association Council on Peripheral Vas- therapy. Circ Cardiovasc Interv. 2014;7(6):777-786. cular Disease; Council on Clinical Cardiology; Council on Cardiovascular and Stroke Nursing; Council on Genomic 83. Hayes SN. Spontaneous coronary artery dissection and Precision Medicine; and Stroke Council. pontaneous (SCAD): new insights into this not-so-rare condition. Tex Coronary Artery Dissection: Current State of the Science: Heart Inst J. 2014;41(3):295-298. A Scientific Statement From the American Heart Associa- 84. Nakashima T, Noguchi T, Haruta S, et al. Prognostic im- tion.Circulation. 2018;137:e523–e557. pact of spontaneous coronary artery dissection in young 72. Mortensen KH, Thuesen L, Kristensen IB, Christiansen EH. female patients with acute myocardial infarction: a re- Spontaneous Coronary Artery Dissection: Current State port from angina pectoris– myocardial infarction multi- of the Science: A Scientific Statement From the American center investigators in Japan. Int J Cardiol 2016;207:341–8. Heart AssociationSpontaneous coronary artery dissec- 85. Motreff P, Malcles G, Combaret N, et al. How and when tion: a Western Denmark Heart Registry study. Catheter to suspect spontaneous coronary artery dissection: Cardiovasc Interv. 2009;74(5): 710-717. novel insights from a single center series on the prev- 73. Maeder M, Ammann P, Angehrn W, Rickli H. Idiopathic alence and angiographic appearance. EuroIntervention spontaneous coronary artery dissection: incidence, diag- 2017;12:e2236–e2243. nosis, and treatment. Int J Cardiol. 2005;101(3):363-369. 86. Saw J, Humphries K, Aymong E, et al. Spontaneous coro- 74. Alfonso F, Paulo M, Gonzalo N, et al. Diagnosis of spon- nary artery dissection. J Am Coll Cardiol 2017;70:1148–58. taneous coronary artery dissection by optical coherence 87. Waller BF: Nonatherosclerotic causes of coronary artery tomography. J Am Coll Cardiol. 2012;59(12):1073-1079. narrowing. In The Heart, 8th edition (Eds. Schlant RC, Al- 75. Vanzetto G, Berger-Coz E, Barone-Rochette G, et al. Preva- exander RW, O’Rourke RA, Roberts R, Sonnenblick EH), p. lence, therapeutic management and medium-term prog- 1239- I26 I. New York: McGraw Hill, 1994

January – June 2019, Volume – 8 Issue – 1 79 The official Journal of Cardiological Society of India, Kerala Chapter

88. Baroldi G: Diseases of the coronary arteries. In Cardio- 104. Gatenby PA, Lytton DG, Bulteau VC, O’Reilly B, Baoten A: vascular Pathology.New York: p. 341-350. Churchill Living- Myocardial infarction in Wegener’s granulomatosis. Aust stone, 1983 NZ J Med I976;6:33&340 89. Manion WC: Infectious angiitis. In The Peripheral Blood 105. Holt S: Syphilitic ostial occlusion.Br Heart J I977:39:469- Vemels (Eds. Orbison JL, Smith DE ),p.221-228. Baltimore: 470 Williams& Wilkins, I963 106. Saphir O, KatzLN, GoreI: The myocardium in subacute 90. Gouley BA, Bellet S, McMillan TM: Tuberculosis of the bacterial endocarditis. Circdirtiorr 1950:I: I 155-1 I67 myocardium: Report of six cases, with observations on 107. Hennigar GR, Thabet R, Bundy WE, Sutton LE: Salmonel- the involvement of coronary arteries. Arch intern Med losis complicated by pancarditis. Report of a case with 1933;s I: 244-263 autopsy findings. J pediatrI953;43:524-53 j 91. Holsinger DR. Osmundson PJ. Edwards JE: The heart peri- arteritis nodosa. Circuation I962;25:6I M I18 108 .Chitlin M D McAllister H A deCastro CM: Myocardial infarction without atherosclerosis J Am Med assoc 1975:231:951- 92. Sinclair W. Nitsch E: Polyarteritis nodosa of the coronary 959 arteries. Report of a case with rupture of an aneurysm and intrapericardial hemorrhage. An Heart J 1949;38:898- 109. Allen AC. Spitz S: A comparative study of the pathology of 904 scrub typhus (Tsutsugamushi disease)and other rickett- sial diseases.AmJ Pathol I945;2I:603482 93. Crawford T Pathology of Ischemic Heart Disease. London: 110. Bairn DS, Harrison DC: Nonatherosclerotic coronary heart Buttersworth, 1977 disease (including coronary artery spasm). In Ttw Heart. 94. Ainsworth RW, Gresham GA, Balmforth G V Patholog- 5th edition (Ed. Hurst JW),p. 11.58-1165. New York: Mc- ichanges in temporal arteries removed from unselected Graw-Hill, 1982 cadavers. J Clin PrIrhd 1961;14:115-1 I9 110 a. Merkel WC: Plasmodium falciparum malaria: The coro- 95. Parrillo JE, Fauci AS: Necrotizing vasculitis, coronary angii- nary and myocardial lesions observed in autopsy in two tis, and the cardiologist. Am Heart J 1980;99:547-554 cases of acute fulminating P.faciparum infection. Arch 96. Meller .I.Conde CA, Deppisch LM. Donoso E, Dack S: Myo- Pathol 1946:41:29&298 cardial infarction due to coronary atherosclerosis in 111. Gazaycrli M: Unusual site of a schistosome worm in the three young adults with systemic lupus erythematosus. circumflex branch of the left coronary artery. J Egypt Met/ Am J Cardiol 197535: 309-3 14 Assoc 1939;22:34-39 97. Heibel RH. O’Toole JD. Curtiss El, Medsger TA, Reddy SP. 112. Fukushige J, Nihill MR. McNamara DG: Spectrum of car- Shaver JA: Coronary arteritis in systemic lupus erythema- diovascular lesions in mucocutaneous lymph node syn- tosus. C h m 1976;69:700-703 drome. Am J Cardiol I 980:45:98-107 98. Bonfiglio TA, Botti RE, Hagstrom JWC: Coronary arteritis. 113. Kitamura S, Kawashima Y, Fujita T, Mori T, Oyarna C, Fugino occlusion and myocardial infarction due to lupus erythe- M: Aortocoronary bypass grafting in a child with coronary matosus. Am HeartTJ 1972;83:153-155 artery obstruction due to mucocutaneous lymph node 99. Benisch BM, Pervez N: Coronary artery vasculitis and syndrome. Report of a case. circulation( 1976;53:1035- I040 myocardial infarction with systemic lupus erythemato- 114. Kato H, Koike S, Yamamoto M, Ito Y, Yano E: Coronary sus. NY State J Med I974;74:873-874 aneurysms in infants and young children with acute fe- 100. Tsakraklides VC; Blieden LC, Edwards JE: Coronary athero- brile mucocutaneous lymph node syndrome. J Pediatr sclerosis and myocardial infarction associated with lupus I975;86:892-898 erythematosus. Am Heart J 1974;87:637-641 115. Cipriano PR, Silverman JF, Perlroth MG, Griepp RB, Waxler 101. Wenger NK: Nonatherosclerotic causes of myocardi- L: Coronary arterial narrowing in Takayasu’s aortitis. Am J al ischemia and necrosis. In The Heart, 4th edition (Ed. Cardiol 1977;39:744-750 Hurst JW), p. 1345-1353.New York: McGraw-Hill, 1978 116. Young JA, Sengupta A, Khaja FU: Coronary arterial steno- 102. Snphir0: Thromboangiitis obliterans of the coronary ar- sis, angina pectoris and atypical coarctation of the aorta teries and its relation to atherosclerosis. Am Heart J due to nonspecific arteritis. Treatment with aortocoro- 1936:12521-535 IS. nary bypass graft. Am J Cardiol 1973;32:35&360 103. Averbuck SH, Silbert S: Thromboangiitis obliterans: a case 117. James TN: De Subitaneis Moitibus. XXIII Rheumatoid arthri- of death . Arch intern med 1934;54:436-46 tisand ankylosing spondylitis. Circulation 1977;55:669-677

80 January – June 2019, Volume – 8 Issue – 1 The official Journal of Cardiological Society of India, Kerala Chapter

118. Hoffman FG. Leight L: Complete atrioventricular block transluminal angioplasty of the proximal left anterior de- associated with rheumatoid disease. Am J C~irdio1l scending coronary artery. J Am Coll Cardiol 1987;9:1019- 965;16585-592 1023 119. Grismer JT, Anderson WR. Weiss L: Chronic occlusive rheu- 135. Gardia-Rinaldi R, Von Koch L, Howell JF: Aneurysm matic coronary vasculitis and myocardial dysfunction. of the sinus of Valsalva producing obstruction of Am J Cardiol 1976;20:739-745 the left main coronary artery. J Thorac Cardiovas Surg1976;72:123-I26 120. Brosius FC, Roberts WC: Coronary artery disease in the Hurler syndrome. Am J Cardiol 198I;47:649453 136. Kopelson G, Herwig KJ: The etiologies of coronary artery disease in cancer patients. Int J Radial Oncol Biol 121. Renteria VG, Ferrans VJ, Roberts WC: The heart in the Hurler physio I978;4:895-906 syndrome. Gross histologic and ultrastructural observations in five necropsy cases. Am J Cardiol 1976:38:487-50 I 137. Fomina LG: A case of myocardial infarct in acute leukemia. Sov, Med 1960:24:141-143 122. Lindsay S: The cardiovascular system in gargoylism. Br Heart J 1950;12:17-32 138. Wirth L: Myocardial infarction as the initial manifestation of Polycythemia Vera. Milit Med 1960;125:544-548 123. Stauflfer M: Oxalosis. Report of a case with review of the literature and discussion on pathogenesis. N Engl JMed 139. Spach MS, Howell DA, Hamis JS: Myocardial infarc- 1960;263:386390 tion and multiple thromboses in a child with primary thrombocytosis, Pediatrics 1963;31:268-276 124. Blieden LC, Desnick RJ, Carter JB, Krivit W. Moller JH, Sharp HL: Cardiac involvement in Sandhoff’s disease. An in- 140. James TN: Pathology of the small coronary arteries. Am J Cardiol 1963;20:679-691 born error of glycosphingolipid metabolism. Am J C d i o l 1974;34:83-88 141. Isner JM, Estes NAM 111, Thompson PD. Costnnro-Nor- din MR,Subramanian R, Miller S. Katsas G, Sweeney K, 125. Blieden LC, Moller JH: Cardiac involvement in inherited Stiuiier W: Acute cardiac events temporally related to disorders of metabolism. Prog Cardiovusc Dis 1974; I6:6 cocaine abuse. N Engl J Med I986;31.5: 1438-1443 I 5 4 3 I 142. Simpson RW, Edwards WD: Pathogenesis of cocaine-in- 126. Brosius FC 111, Waller BF, Roberts WC: Radiation heart dis- duced ischemic heart disease. Arch Pathol Lab Med ease. Analysis of 16young (aged I5to33years) necropsy 1986;110:479484 patients who received over 3500 rads to the heart. Am J Med I981; 70:519-530 143. Zimmerman FH, Gustafson GM, Kemp HG: Recurrent myocardial infarction associated with cocaine abuse in 127. Hudgson P, Foster JB, Waltori JN: Methysergide and coro- a young man with normal coronary arteries: Evidence nary artery disease. Am Heart J 1967;74:854855 for coronary artery spasm culminating in thrombosis. J 128. Brill IC, Brodeur MTH, Oyama AA: Myocardial infarction in Am Coll Cardiol 1987;9:964-968 two sisters less than 20 years old. J Am, Med Assoc. I97 I 144. Smith HW, Liberman HA, Brody SL, Battey LL. Dono- :2 17:1345- 1348 hue BC. Morris DC: Acute myocardial infarction tem- 129. Yates JD, Kirsh MM, Sodeman TM, Walton JA, Brymer JF: porally related to cocaine use. Clinical, angiographic A complication of aortic valve replacement. Circulation and pathophysiologic observations. Ann Intern Med I974;49:530-534 1987;107:13-18 130. Trimble AS,Bigelow WG,Wigle ED: Coronary ostial stenosis: 145. Patel R, Haider B, Ahrned S, Regan TJ: Cocaine-relat- A late complication of coronary perfusion in open heart ed myocardial infarction: High prevalence of occlusive surgery. J Thorac Cardiovasc Surg 1969;57:792-795 coronary thrombi without significant obstructive atherosclerosis (abstr). Circulution 1988;78 (suppl II):411- 131. Billingham M. Personal communication, I988 436 132. Waller BR: Pathology of transluminal balloon angioplas- 146. Lange RA. Cigarroa RG. Yancy CW, Williud JE, Popma ty used in the treatment of coronary heart disease. Hum JJ, Sill; i MN, McBride U, Kim AS, Hillis LD: Cocaine-in- Pathol 1987;18: 476484 duced coronary artery vasoconstriction. N Engl J Med 133. Prinzmetal M, Kennanier R. Merliss R. Ekmekci A: Angina I989;32I:1557-1562 pectoris. I. A variant form of angina pectoris. Preliminary 147. Waller BF: Cocaine and the heart. Indiana med report. Am J Med 1959;27:37~-3nn I988;8I:956-959 134. Waller BE Pinkeiton CA, Foster LN morphological evidence 148. Lam D, Goldschlager N: Myocardial injury associated of accelerated left main coronary artery st percutaneous with polysubstance abuse. Am Heart J 1988;115:675-680.

January – June 2019, Volume – 8 Issue – 1 81 The official Journal of Cardiological Society of India, Kerala Chapter

149. Rod JL, Zucker RD: Acute myocardial infarction shortly in reversible ventricular dysfunction of Takotsubo after cocaine inhalation. Am J Cardiol1987;59: 161 cardiomyopathy: imaging evidence, presumed mechanisms, and implications of therapy. Heart Rhythm. 150. Kossowsky WA, Lyon A F Cocaine and myocardial infarc- 2015;12(8):1867–1877. tion: A probable connection.Chest 1984;86:729-73 1 166. Migliore F, Zorzi A, Peruzza F, Marra MP, Tarantini SI, Cor- 151. Smith HWB III, Lieberman A, Brody S, Battey LL, Donohue rado D. Incidence and management of life-threaten- BC, Moms DC: Acute myocardial infarction temporally re- ing arrhythmias in Takotsubo syndrome. Int J Cardiol. lated to cocaine use. Ann Intern Med 1987;107:13-18 2013;166:261–263. 2017;238:159– 165. 152. Miller GW: The cocaine habit. Am Fam Physician 1985;31: 167. Luscher TF, Templin C. Is Takotsubo syndrome a micro- 173-1 76 vascular acute coronary syndrome? Towards a new defi- 153. Wetli CV. Wright RK: Death caused by recreational cocaine nition. Eur Heart J. 2016;37:2816–2820. use. J Am Med Assoc 1979;241:2519-2522 168. Khalid N, Ahmad SA, Umer A. Mechanims of Takotsubo 154. Benchimol A, Bartall H, Desser KB: Acceleration of ven- cardiomyopathy; role of microcirculatory dysfunction. tricular rhythm and cocaine abuse. Ann Intern Med International Cardiovascular Forum Journal. 2016;5:30–32. 1978;88:519-520 169. Kumar G, Holmes Jr. DRJr., Prasad A. Familial apical bal- 155. Nanji AA, Filipenko JD: Asystole and ventricular fibrilla- looning syndrome (Takotsubo cardiomyopathy). Int J Car- tion associated with cocaine intoxication. Chest 1984:85: diol. 2014;144:444–445. 132-1 33 170. LyonAR,BossoneE,SchneiderB,etal.Currentstateofknowl- 156, Schachne JS, Roberts BH, Thompson PD: Coronary artery edgeontakotsubo syndrome: a position statement from spasm and myocardial infarction associated with cocaine the taskforce on takotsubo syndrome of the heart failure use. N Engl J association of the european society of cardiology. Eur J Med 1984;310:1665-1666 Heart Fail. 2016;18(1):8–27. 157. Howard RE, Hueter DC, Davis GJ: Acute myocardial infarc- 171. LyonAR,BossoneE,SchneiderB,etal.Currentstateofknowl- tionfollowing cocaine abuse in a young woman with nor- edgeontakotsubo syndrome: a position statement from mal coronary arteries. J Am Med Assoc 1985;254:95-96 the taskforce on takotsubo syndrome of the heart failure association of the european society of cardiology. Eur J 158. Simpson RW, Edwards WD: Pathogenesis of cocaine-in- Heart Fail. 2016;18(1):8–27. duced ischemic heart disease. Autopsy finding in a 21-year-old man. Arch Pathol Lab Med 1986;110:479484 172. Oba Y, Takemoto M, Nakano M, Yamamoto H. Takotsubo cardiomyopathy with left ventricular outflow tract ob- 159. Virmani R, Robinowitz M, Smialek JE, Smyth D F Cardio- struction. Int J Cardiol. 2006;107:120–122. vascular effects of cocaine: An autopsy study of 40 patients. Am Heart J1988;115:1068-1076 173. Ctiro R, Rigo F, Ciampi Q, et al. Echocardiographic assessment of regional left ventricular wall motion ab- 160. Gianni M, Dentali F, Grandi AM, et al. Apical ballooning normalities in patient with Takotsubo cardiomyopathy: syndrome of takotsubo cardiomyopathy: a systematic comparison with anterior myocardial infarction. Eur J review. Eur Heart J. 2006;27(13):1523-1529. Echocardiography. 2011;12:542–549. 161. European Cardiology Review, 2015;10(1):6–8 174. Kohan AA, Yeyati EL, Stefano LD, et al. Usefulness of MRI 162. Wittstein IS, Thiemann DR, Lima JAC, et al. Neurohumoral in Takotsubo cardiomyopathy: a review of literature. Car- features of myocardial stunning due to sudden emotion- diovasc Diagn Ther. 2014;4(2):138– 146. al stress. N Engl J Med. 2005;352:539–548. 175. Sharkey SW, Lesser JR, Zenovich AG, Maron MS, Lindberg 163. Sattler K, El-Battrawy I, Langh S, et al. Prevalence of can- J, Longe TF, Maron BJ. Acute and reversible cardiomyopa- cer in Takotsubo cardiomyopathy: short and long-term thy provoked by stress in women from the United States. outcome. Int J Cardiol. Circu- lation 2005; 111: 472-479 [PMID: 15687136 DOI: 164. Migliore F, Maffei E, Perazzolo Marra M, et al. LAD coro- 10.1161/01. CIR.0000153801.51470.EB] nary artery myocardial bridging and apical ballooning 176. Padayachee L. Levosimendan: the inotrope of choice syndrome. JACC Cardiovasc Imaging. 2013;6 (1):32–41. in cardiogenic shock secondary to takotsubo cardio- 165. Migliore F, Zorzi A, Marra MP, Iliceto S, Corrado D. Myo- myopathy? Heart Lung Circ 2007; 16 Suppl 3: S65-S70 cardial oedema as a substrate of electrocardiograph- [PMID: 17616435 DOI: 10.1016/j.hlc.2007.03.018] ic abnormalities and life-threatening arrhythmias 177. Ibanez B, Navarro F, Cordoba M, M-Alberca P, Farre J. Tako-tsu-

82 January – June 2019, Volume – 8 Issue – 1 The official Journal of Cardiological Society of India, Kerala Chapter

bo transient left ventricular apical ballooning: is intravascu- K, Atar D, Kaski JC, Sechtem U, Tornvall P; Working Group lar ultrasound the key to resolve the enigma? Heart 2005; 91: on Cardio- vascular Pharmacotherapy. ESC working group 102-104 [PMID: 15604352 DOI: 10.1136/ hrt.2004.035709] position paper on myocardial infarction with non-ob- 178. Elesber AA, Prasad A, Lennon RJ, Wright RS, Lerman structive coronary arteries. Eur Heart J. 2017;38:143–153. A, Rihal CS. Four-year recurrence rate and prognosis doi: 10.1093/eurheartj/ehw149. of the apical ballooning syndrome. J Am Coll Cardi- 181. Pasupathy S, Air T, Dreyer RP, Tavella R, Beltrame JF. Sys- ol 2007; 50: 448-452 [PMID: 17662398 DOI: 10.1016/j. tematic review of patients presenting with suspected jacc.2007.03.050] myocardial infarction and nonobstructive coronary ar- 179. Dib C, Prasad A, Friedman PA, Ahmad E, Rihal CS, Ham- teries. Circulation. 2015;131:861– 870. doi: 10.1161/CIRCU- mill SC, Asirvatham SJ. Malignant arrhythmia in apical LATION AHA.114.011201. ballooning syndrome: risk factors and outcomes. Indian 182. Nordenskj€old AM, Baron T, Eggers KM, Jernberg T, Lindahl Pacing Electrophysiol J 2008; 8: 182-192 [PMID: 18679529] B. Predic- tors of adverse outcome in patients with myo- 180. Agewall S, Beltrame JF, Reynolds HR, Niessner A, Rosano G, cardial infarction with non-obstructive coronary artery Ca- forio AL, De Caterina R, Zimarino M, Roffi M, Kjeldsen (MINOCA) disease. Int J Cardiol. 2018;261:18–23.

January – June 2019, Volume – 8 Issue – 1 83 The offi cial Journal of Cardiological Society of India, Kerala Chapter

KHJKERALA HEART JOURNAL

A Journal of Cardiological Society of India Kerala Chapter

p-ISSN: 2347-5269 e-ISSN: 2454-6755 KERALA HEART JOURNAL (p-ISSN: 2347-5267), (e-ISSN: 2454-6755) January - June 2019, Volume - 8, Issue - 1

Editor in Chief Dr. Stigi Joseph

Chaudhari Anushree A. MD.DNB* Puri Goverdhan D. MD. PhD** Kumar Bhupesh. MD. DM*** Bhalla Anil K.MD****

*Assistant Professor, Department of Anaesthesia, Miraj Medical College and Hospital, Sangli-Miraj,Maharashtra

** Professor & ***Additional Professor, Department of Anaesthesia and Intensive care, Advance Cardiac Center, PGIMER, Chandigarh

****Professor, Paediatric Medicine, PGIMER Correspondence:[email protected]

ABSTRACT Determination Of Ventilatory Minute Volumes For Normocapnic Ventilation In Postoperative Cardiac Surgery Patients

BACKGROUND: Following cardiac surgery under cardiopul- end-inspiratory pause pressure (Pst) were measured and monary bypass (CPB) there is an increase in the extravas- physiological dead space (VDPHYS) was calculated from En- cular lung water. So a prospective study to quantify minute ghoff’s modifi cation of Bohr’s equation. ventilation (VE) for normocapnic ventilation in postoperative cardiac surgery patients was carried out. RESULTS: VE requirement was signifi cantly higher than those calculated based on data in healthy subjects while METHODS: 50 NYHA II cardiac surgery patients 20 to 60 yrs the Crs was lower (26 ± 6.7vs 50.8± 13.82 ml/cm H2O) and Pst of age with postoperative nasopharyngeal temperature (15.32 ± 2.57 vs. 7.6 ± 2.4 cmH2O) and VDPHYS/kg (3.34 ± 1.08 (NPT) 36.5̊C-37.5̊C, sedated to Ramsay score three were elec- vs. 2.35 ± 0.63 ml/kg) were higher. tively ventilated at a respiratory rate of CONCLUSION: Higher VE is required in cardiac surgery pa- 15. Tidal volume (VT) was set initially as per the available tients as compared to healthy subjects in the immediate published normogram for healthy subjects for normocap- postoperative period to maintain normocapnia which may nic ventilation. It was further titrated to end-tidal CO2 con- be due to higher VDPHYS/kg resulting from the pulmonary centration (PETCO2) of 35 to 40 mm Hg and cross-checked injury seen post-bypass. after 20 min with arterial blood gas analysis. VT was re-adjusted if PaCO2 was outside 38 to 42 mm Hg. VE, minute CO2 Key-words: minute ventilation, normocapnia, postopera- production (VCO2), respiratory system compliance (Crs) and tive cardiac surgery, physiological dead space.

84 January – June 2019, Volume – 8 Issue – 1 The official Journal of Cardiological Society of India, Kerala Chapter

Introduction: tion[18] and further titrated to PETCO2 of 35 to 40 mm Hg. At least 20 min were allowed at a given VT for the PET- In the postoperative period following cardiac surgery un- CO2 to get stabilized (not more than ± 1 change in PET- der cardiopulmonary bypass (CPB), there is an increase CO2 value in 20 min) after which arterial blood gas (ABG) in the extravascular lung water. Intermittent positive analysis was performed. The VT was re-adjusted if Pa- pressure ventilation (IPPV) forms an integral part of the CO2was outside 38 to 42 mm Hg. At the time of sampling, postoperative management of cardiac surgery patients PETCO2, VCO2, VE, respiratory systemcompliance (Crs) as it decreases the work of breathing[1] and improves and end-inspiratory pause pressure (Pst) were obtained. ventilation-perfusion matching. The minute ventilation Mainstream, dual-wavelength, non-dispersive infrared requirement in these patients depends on physiological- CO2analyzer module was used with a sensor and an air- dead space (VDPHYS) and minute carbon dioxide produc- way adapter (Standards: EN 864, ISO 9918). Each variable tion (VCO2)[2] both of which are altered in the immediate was measured at four hours post CPB. Ambient tempera- postoperative period due to effects of anesthesia [3-8] ture was maintained at 24◦C to26◦C. The VDPHYS was and cardiac surgery itself.[9,10]There is a need to main- calculated from the Enghoff’s modification of the Bohr’s tainnormocapnia while controlling ventilation given the equation: VDPHYS =VT x (PaCO2- PĒCO2)/PaCO2, where harmful effects of both hypercapnia as well ashypocap- the mixed expiratory carbon dioxide tension (PĒCO2) was nia.[11-13]Several nomograms/guidelines[14-18]defined in literature have been derived abouthealthy patients or calculated from (VCO2/VE) x PB. non-cardiac ICU patients. The volume of extraoral apparatus dead space (VDapp) In view of the absence of any controlled clinical study was calculated by finding the volume of the connector, cu- for normocapnic ventilation in post-cardiac surgery pa- vette, the size and length of the extraoral endotracheal tients postoperatively we evaluated the minute ventila- tube and the same was subtracted from VT and VDPHYS. tion requirement for the same and studied its relation to The same corrections were applied while calculating VD/ various preoperative patient demographic variables like VT. Each subject was also measured for body weight and weight (W), height (H), body surface area (BSA) and body height using standardized anthropometric measurements mass index (BMI). given by Weiner and Lourie. The W was measured with the help of an electronic weighing machine (Make: Avery India Limited, Capacity: 150kg machine least count: 20gm) while Materials and Methods: height was measured by using anthropometer (make: Hol- Fifty New York Heart Association (NYHA) ІІ patients 20 to tain Limited up to the accuracy of 1mm). These two mea- 60 years of age undergoing elective open heart surgery surements were used to compute BMI for every subject and having a post-operative nasopharyngeal tempera- before surgery. BSA was calculated using a standard for- ture of 36.5◦C to 37.5◦C were included in this study en- mula.[21] Similarly, the VCO2 was calculated from available suring at least ten patients in each age group of 20-30, BMR 31-40, 41-50 and 51-60. The study was approved by the studies.[22,23] Alveolar ventilation requirement (VA) was Ethics committee and written informed consent was ob- calculated by subtracting VDPHYS from VT and multiply- tained from all subjects. ing it with respiratory rate. Patients with NYHA ІІІ and ІV, BMI < 18.5 kg/m2 or >30kg/ m2, congenital cyanotic heart disease, pre-operative se- The statistical analysis was carried out using Statistical verely compromised respiratory function i.e. predicted Package for Social Sciences (SPSS Inc., Chicago, IL, ver- FEV1 (Forced expiratory volume in one second) <50% and sion 15.0 for Windows). Mean, and SD for W, H, BMI, BSA, predicted FVC (Forced vital capacity) <50%,[19] severe pul- VE, VCO2, and VDPHYSwas calculated at each age for both monary artery hypertension, high inotropic score,[20] hy- males and females. The magnitude of gender and inter- pothermic patients and those with fever were excluded. group differences were quantified by applying ANOVA and students unpaired ‘t’ test for each variable in each group Patients were sedated with propofol with Ramsay score 3 and subjects combined. Comparative assessment of dif- and electively ventilated using Maquet Servo i ferent volumes with each type of different values of age V.3.1 ventilator (Maquet Critical Care AB, SE-171 95 Solna, (A), sex (S), H, W, BSA, BMI assessed amongst sample sub- Sweden) with 4 sec cycle time, I: E ratio 1: 2 and jects and the similar data obtained for healthy subjects 10% inspiratory pause at a respiratory rate of 15 breaths was made at each age and quantified by applying students per minute (bpm). Tidal volume (VT) was set initially unpaired ‘t’ test, p<0.05 was considered to be statistically as per the earlier normogram for normocapnic ventila- significant.

January – June 2019, Volume – 8 Issue – 1 85 The official Journal of Cardiological Society of India, Kerala Chapter

Results: of 4.36 ± 1.54mm Hg in males and 4.34 ± 1.48mm Hg in females and the difference between the two sexes insignifi- As the magnitude of inter-age differences obtained for cant (p=0.970). The mean CPB time was 133.96 ± 76.14 min. each of the anthropometric and physiological traits was Male patients were taller (p<0.0001) and heavier (p<0.0001) found to be statistically insignificant, the data for different ten year age groups were pooled to have estimates than their female counterparts with higher BSA (p<0.0001) for the larger sample size to arrive at more meaningful (TABLE 2).

TABLE 1: Age distribution of subjects scientific inferences. There were 25 male patients and 25 VE for normocapnic ventilation in the immediate post-op- female patients. There were relatively more number of erative period was significantly higher in males than in fe- patients in the age groups of 40 to 60 (TABLE 1). males (p=0.000) though VE/kg was not significantly different Males and females were found to be comparable for the (TABLE 3). VE – VECONTROL i.e. the difference in the minute obesity indices of BMI and H/W1/3 as well as age, BMI, ventilatory requirements as found by the present study CPB time, PaCO2, and PETCO2. End-tidal CO2 tension and the earlier study in healthy subjects[18] was statisti- matched arterial CO2(r=0.365, p=0.009) with P(a-ET)CO2 cally significant (p=0.000) (TABLE 4).VE showed a significant

TABLE 2: Inter age group comparison between males and females for the patient variables of W, H, BMI, BSA

86 January – June 2019, Volume – 8 Issue – 1 The offi cial Journal of Cardiological Society of India, Kerala Chapter

linear correlation with W, H, BSA, and S, with BSA showing BSA best with BSA (r=0.661, p=0.000).VCO2/kg showed sig- the best relation (r=0.751, p=0.000). VE/kg showed signifi - nifi cant negative correlation with BMI (r= -0.298, p=0.035) cant negative correlation with BMI (r=-0.464, p=0.001)(TA- (TABLE 5).VCO2/BSA was 109.85 ± 21.60 ml/m2. BLE 5). This indicates that for similar weights, taller patients VDPHYS was signifi cantly higher in males as compared to fe- require higher VE. Study in Healthy subjects VCO2 though signifi cantly higher in males (p=0.000) was not different if males(p<0.001) (TABLE 3). VD/VT was 0.45 ± 0.10, compliance of indexed to weight (p=0.576) (TABLE 3). VCO2/kg measured in lungs was 26.02 ± 6.73 ml/cm H2O and airway pressure was 15.31 the present study though similar to healthy subjects intra- ± 2.54 cm H2O (TABLE 4).VDPHYS/kg was signifi cantly higher as

operatively under general anesthesia [18](p=0.757)(TABLE 4) compared to the previous control study done in healthy subjects was signifi cantly higher than that calculated according to (p=0.000).[18] VDPHYS showed signifi cant correlation with A, W, Benedict and Talbot[22] (p=0.000) and Kleiber’s formula[23] H, BSA, best with BSA(r=0.444, p=0.001).VDPHYS/kg showed a sig- (p=0.000). VCO2 showed signifi cant correlation with W, H, nifi cant negative correlation with BMI (r=-0.285, p=0.045)(TABLE 5)

Study in Healthy Present study post subjects CPB

VE/kg 99.72 ± 7.42 108.51 ±17.61**

VCO2/kg 3.02 ± 0.49 3.04 ± 0.66

VDPHYS/kg 2.35 ± 0.63 3.34 ± 1.08**

Pst 7.6 ± 2.4 15.32±2.57** Values are mean ± SD,* Crs 50.8 ± 13.82 26.02±6.73** p<0.001signifi cant, **

highly signifi cant

TABLE 4: Comparison of ventilator data in cardiac patients with healthy subjects18

January – June 2019, Volume – 8 Issue – 1 87 The official Journal of Cardiological Society of India, Kerala Chapter

‘r’ Pearson Correlation Co- efficient, p<0.05 significant, ** highly significant TABLE 5: Linear relation of ventilator data and weight indexed data with the patient preoperative demographic data

Discussion: ance may increase ventilation-perfusion mismatch by resulting in increased VDALV. Perez and colleagues[25] report- As we had expected, the VE requirement in cardiac patients ed still higher VDPHYS/kg of 4.8 ±0.6 ml(p=0.000) in their post cardiac surgery was significantly higher than that in study. This may be due to the inclusion of patients who al- available published data in healthy subjects intraopera- ready had some pulmonary dysfunction before they under- tively[18](p=0.000). This can be attributed to higher VD- went surgery and also because their patients were hyper- PHYS/kg found in the present study which may be due to ventilated as compared to our study to a PaCO2 of 28 to 32 the increase in anatomical (VDAW)or alveolar dead space [26-30] (VDALV). This may be due to pre-existing pulmonary mm Hg requiring larger tidal volumes which are associated dysfunction in cardiac patients or due to the effects of car- with larger dead space values. Higher VErequirement for diac surgery or CPB on lung function. Once CPB commences, normocapnic ventilation in post-cardiac surgery patients microembolism and contact activation of blood by extra- may also be due toincreased VCO2 which can be due to the corporeal circuit results in activation of the complement stress response of anesthesia, surgery, CPB and rewarming. system, anaphylatoxins, and neutrophils. This leads to cap- The resting energy expenditure is markedly elevated in the illary leak syndrome increasing extravascular lung water first 6 hours post CPB.[30] As compared to an earlier study and closure of smaller airways colloquially referred to as in healthy individuals under anesthesia VCO2in the pres- “pump lung” and increases the VDALV. The Pst measured ent study was not significantly higher (Table 4). This may was significantly higher, and Crs was lower in the postop- be because of the difference in the time of samplings in erative period in these patients (TABLE 4). Increase in stat- two studies as 20 minutes were allowed to elapse before ic airway pressure can increase airway dimensions and so we took samples whereas in the control study samples increase VDAWwhile decreasing respiratory system compli- were taken after 10 minutes. Hence the earlier study might

88 January – June 2019, Volume – 8 Issue – 1 The official Journal of Cardiological Society of India, Kerala Chapter

have overestimated the VCO2. Nunn and Mathews[31] stat- general anaesthesia. Anaesthesia. 1960;15(4):381-93. ed that CO2 output during anesthesia might not become 5. Askrog VF, Pender JW, Smith TC, Eckenhoff JE. Changes constant until 60 minutes after a step change in ventila- in respiratory dead space during halothane, cyclopro- tion. However, this will not affect PaCO2 values as it has pane, and nitrous oxide anesthesia. Anaesthesiolo- been shown previously that during the fall of PaCO2 with gy.1964;25(3):342. an increase in ventilation, half of the total change in PaCO2 is completed in 3 minutes.[32] The measurements in the 6. Bain JA, Spoerel WE. Carbondioxide output in anaesthe- present study were also performed under controlled con- sia. Can Anaesth Soc J.1976;23(2):153-62. ditions with the patients sedated to Ramsay score 3 and 7. Fletcher R, Jonson B. Dead space and the single breath adequately rewarmed to mean temperature 37̊C. This might test for carbon dioxide during anaesthesia and artifi- have led to better equilibration in PaCO2, and so VCO2 was cial ventilation: effects of tidal volume and frequency of comparable yet higher than that of the published study. It respiration. Brit J Anaesth. 1984;56(2):109-119. was also higher than the estimated norms of Benedict and Talbot[23]and Kleiber[24] (p=0.000) thus showing that no- 8. Hedenstierna G, McCarthy G. The effect of anaesthesia mograms from the nonsurgical setups cannot be applied to and intermittent positive pressure ventilation with dif- the perioperative period. ferent frequencies on the anatomical and alveolar dead Ralley and colleagues[33]reported similar VCO2/m2in space. Brit J Anaesth.1975;47(8):847. non-shivering patients scheduled for cardiac surgery at the 9. Tenling A, Hachenberg T, Tyden H, Wegenius G, Heden- end of 4 hours post CPB as compared to present study(111.36 stierna G.Atlectasis and gas exchange after cardiac sur- ml/min/m2vs109.85 ± 21.60 ml/min/m2p=0.624). Our VCO2 gery. Anesthesiology. 1998;89(2):371-78. was at variance with that of Damask and colleagues[34] who reported higher values (3.2 ± 0.53 ml/min/kg)amongst 10. Sladen RN. Temperature and ventilation after hy- patients with open heart surgery which can be because of pothermic cardiopulmonary bypass.AnesthAnalg. the inadequate and ongoing 1985;64(8):816-20. rewarming in their subjects and metabolism of recirculat- 11. Anderson MN, Mouritzen CS. Effect of acute respiratory ed blood lactate.[35]These findings were also at variance and metabolic acidosis on cardiac patient and periph- with Cruise et al35 who reported lower values (2.54 ± 0.10 eral resistance. Annals of Surgery. 1966;163(2):161-68. ml/min/kg, p<0.000) in non-shivering patients after cardiac 12. Michenfelder JD, Fowler WS, Theye RA. CO2 levels and surgery may be due to higher BMI and extended rewarming pulmonary shunting in anaesthetized man. J of Appl done before the end of CPB that may have decreased the Physiol. 1966;21(5):1471-76. postoperative BMR and VCO2. We found an inverse relationship between BMI and VCO2. 13. Sullivan SF, Patterson RW, Papper EM. Post hyperventilation hypoxia. J Appl Physiol. 1967;22:431-35. It emerges from the aforementioned discussion that cardiac patients undergoing surgery under CPB appear to re- 14. Nunn JF. Predictors for oxygen and carbon dioxide levels quire significantly higher VE for maintenance of normocap- during anaesthesia. Anaesthesia. 1962;17(2):182-94. nia during the postoperative period. This may be attributed 15. Radford EP. Ventilation standards for use in artificial to the influence of increased respiratory physiological dead ventilation. J Appl Physiol 1955;7(4):451-54. space owing to its lower respiratory system related compliance in the cardiac surgery patients post CPB. 16. Nunn JF. Ventilation nomograms during anesthesia. An- aesthesia. 1960;15(1):65. 17. S Kenny. The Adelaide Ventilation Guide. Brit J Anaesth. References: 1967;39(1):21. 1. Gold MI, Martin H. Influence of Tidal Exchange during 18. Puri GD, Singh H, Kaushik S, Jindal SK. Determination of IPPB on Pulmonary mechanics and blood gases in anes- ventilatory minute volumes for normocapnic ventilation thetized humans. Anesthesiology. 1967; 28:254. under anaesthesia in healthy adults. Nat Med J India. 2. Benumof LJ. Respiratory physiology and respiratory 1999;12(1):6-11. function during anesthesia. In: Miller DR, ed. Anesthe- sia. 3rd ed. Churchill Livingstone;1990. 19. Glidea TR, McCarthy K. Pulmonary function testing. In- :William.D.Carey, ed. Current Clinical Medicine Cleveland 3. Cooper EA. Physiological dead space in passive ventila- Clinic. 2nd ed. Philadelphia: Elsevier; 2009. p. 1084-95. tion. Anaesthesia.1967;22(1):199-218. 20. Zaccaria R, Stefano M, Claudio R, Angelo P et al. Ino- 4. Thornton JA. Physiological dead space changes during tropic support and peritoneal dialysis adequacyin neo-

January – June 2019, Volume – 8 Issue – 1 89 The official Journal of Cardiological Society of India, Kerala Chapter

nates after cardiac surgery. Interact CardioVascThorac- changes after coronary artery bypass surgery. Can J An- Surg 2008;7:116-20. aesth. 1985;32(3):272-77 21. Aub JC, Dubois EF. The basal metabolism of old men. 30. Chiara O, Giomarelli P, Biagioli B, Rosi R, Gattinoni L. Hy- Arch Int Med.1917;19:823. permetabolic response after hypothermic cardiopulmonary bypass. Crit Care Med. 1987;15(11):995-1000 22. Benedict FG, Talbot FB. Metabolism and growth from birth to puberty. Carnegie Institution ofWashington. 31. Nunn JF, Mathews RL. Gaseous exchange during halo- 1921;302. thane anaesthesia: the steady respiratory state. Brit J Anaesthesia. 1959;31:330. 23. Kleiber M. Body size and metabolic rate. Physiological Reviews. 1947;27(4):511–41. 32. Ralley FE, Wynards JE, Ramsay JG, Carli F, MacSullivan R. The effects of shivering on oxygenconsumption and 24. WA Neill, M Hattenhauer. Impairment of myocardial O2 carbon dioxide production in patients rewarming from supply due to hyperventilation. CirculationAm Heart As- hypothermic cardiopulmonary bypass. Can J Anaesth. soc. 1975;52:854-58. 1988;35(4):332-37. 25. Garcia-Perez ML, Llau JV, BadenesR, Aguilar G, Belda FJ. Effect of cardiopulmonary bypass on alveolar dead- 33. Damask MC, Weissman C, Askanazi J, Rosenbaum SH, El- space. European Journal of Anaesthesiology. 2000;17:61- wyn D, Hyman AI. Do oxygen consumption and carbon 62. dioxide production affect cardiac output after cardiopulmonary bypass?.Arch Surg. 1987;122(9):1026-31. 26. Daniel S. Energy Balance. In: Best JB, ed.Physiologi- cal basis of medical practice. Baltimore: Williams and 34. Abbott TR, Goodwin B, Clark G, Rees GJ. Mass spectrom- Wilkins,1990. p. 773. eter measurementof oxygen uptake and carbon dioxide exchange during cardiopulmonary bypass. Br J Anaesth. 27. Singh M. Stress response and anesthesia altering the 1980;52(1):29-40. peri and post-operative management. Indian J 35. Cruise C, MacKinnon J, Tough J, Houstan P. Compar- Anaesth. 2003;47:427–34. ison of meperidine and pancuronium for treatment 28. Smith NT, Eger EI, Stoelfing RK, Whqne TF, Cullen D, of shivering after cardiac surgery. Can J Anaesth Ktrdis LB. The cardiovascular and sympathomimetic re- 1992;39(6):563-8. sponses to the addition of nitrous oxide to halothane in 36. Garcia-Perez ML, Llau JV,BadenesR, Aguilar G, Bel- man. Anesthesiology 1970;32(5):410-21. da FJ. Effectof cardiopulmonary bypass onalveolar 29. Francois D, JeanGuy M, Robert B, Marcel B, Philippe S. deadspace. European Journal of Anaesthesiology. End-tidal carbon dioxide tension and temperature 2000;17:61-62.

90 January – June 2019, Volume – 8 Issue – 1

Proposed Kerala Heart House