VOLUME XXIII No. 1 JANUARY-FEBRUARY 2019 PAGES 1-40 Rs. 1700/- ISSN 0971-9172 RNI No. 66903/97 www.cimsasia.com

MANAGING DIRECTOR & PUBLISHER Dr. Monica Bhatia TODAY EDITOR IN CHIEF OP Yadava SECTION EDITORS SR Mittal (ECG, CPC), David Colquhoun (Reader’s Choice) EDITORIAL NATIONAL EDITORIAL ADVISORY BOARD Circadian Rhythm of the Body - Is it the Holy Arun K Purohit, Arun Malhotra, Ashok Seth, Grail ? 3 Ashwin B Mehta, CN Manjunath, DS Gambhir, OP YADAVA GS Sainani, Harshad R Gandhi, I Sathyamurthy, Jagdish Hiremath, JPS Sawhney, KK Talwar, K Srinath Reddy, KP Misra, ML Bhatia, Mohan Bhargava, MR Girinath, Mukul Misra, Nakul Sinha, PC Manoria, Peeyush Jain, Praveen Jain, Ramesh Arora, Ravi R Kasliwal, S Jalal, S Padmavati, Satyavan Sharma, SS Ramesh, Sunil Kumar Modi, Yatin Mehta, Yogesh Varma, R Aggarwala. INTERNATIONAL EDITORIAL ADVISORY BOARD REVIEW ARTICLE Andrew M Tonkin, Bhagwan Koirala, Carlos A Mestres, Chuen N Lee, David M Colquhoun, Davendra Mehta, Contrast Induced Nephropathy: How to Enas A Enas, Gerald M Pohost, Glen Van Arsdell, Indranill Basu Ray, James B Peter, James F Benenati, Predict and Prevent? 5 Kanu Chatterjee, Noe A Babilonia, Pascal R Vouhe, RAGHAV BANSAL, VIVEKA KUMAR Paul A Levine, Paul Simon, P K Shah, Prakash Deedwania, Salim Yusuf, Samin K Sharma, Sanjeev Saxena, Sanjiv Kaul, Yutaka Imoto. DESK EDITOR Gandhali DESIGNER Arun Kharkwal REVIEW ARTICLE OFFICES CIMS Medica India Pvt Ltd How do I Manage My Patients with (Previously known as UBM Medica India Pvt Ltd.) Failure with Preserved Ejection Fraction? 10 Registered Office MOHAMMED SADIQ AZAM, DAYASAGAR RAO V Margosa Building, No. 2, 3rd Floor, 13th Cross, Margosa Road, Malleshwaram, Bengaluru-560 003 Karnataka, India Tel: +91-80-4346 4500 Fax: +91-80-4346 4530

Corporate Office Boomerang (Kanakia Spaces), Wing-B1, 403, 4th Floor, Chandiwali Farm Road, Chadiwali Powai, Mumbai - 400 072 REVIEW ARTICLE Tel.: +91-22-6612 2600 Fax : +91-22-6612 2626 Practical Approach to Constrictive Pericarditis 15 Regional Office 709, 7th Floor, MONIK MEHTA Devika Tower, Nehru Place, New Delhi-110 019, India. Tel: +91-11-4285 4300 Fax: +91-11-4285 4310

1 Cardiology Today VOL.XXIII NO. 1 JANUARY-FEBRUARY 2019 FOR MARKETING QUERIES REVIEW ARTICLE Aparna Mayekar: +91-9930937020 +91-22-6612 2612 Transesophageal in [email protected] Children with Congenital Heart Defects 18 SNEHAL KULKARNI FOR EDITORIAL QUERIES Dr Gandhali : +91-22-6612 2657 [email protected]

©2019 CIMS Medica India Pvt Ltd (Previously known as UBM Medica India Pvt Ltd) Copyright in the material contained in this journal (save for advtg. and save as otherwise indicated) is held by CIMS Medica India Pvt Ltd Margosa Building, No. 2, 3rd Floor, 13th Cross, REVIEW ARTICLE Margosa Road, Malleshwaram, Bengaluru-560 003, Karnataka, India. All rights reserved. No part of this When to Refer for CABG in Today’s Era publication may be reproduced, stored in a retrieval of Affordable Stents and PTCA and Wide system or transmitted in any form or by any means, Application of Technologies 24 electronic, photocopying or otherwise, without prior permission of the publisher and copyright owner. C N MANJUNATH, PRABHAVATHI, C RAGHAVENDRA

The products and services advertised are those of individual advertisers and are not necessarilty endorsed by or connected with the publisher or with Cardiology Today or CIMS Medica India Pvt Ltd. Cardiology Today does not guarantee, directly or indirectly, the quality or efficacy of any product or services described in the advertisements in this issue, which are purely commercial in nature.

The editorial opinions expressed in this publication ECG OF THE MONTH are those of individual authors and not necessarily those of the publisher. Whilst every effort has been Cause of Increase in P Wave Amplitude made to ensure the accuracy of the information in this During Exercise Induced Tachycardia 30 publication, the publisher accepts no responsibility for errors or omissions. SR MITTAL

For reprints (minimum order: 500) contact the production Department. Further copies of Cardiology Today are available from CIMS Medica India Pvt Ltd, 709, Devika Tower, Nehru Place, New Delhi-110 019, India.

Cardiology Today is Published and Printed by CIMS Medica India Pvt Ltd, Margosa Building, No. 2, 3rd Floor, 13th Cross, Margosa Road, Malleshwaram, PICTORIAL CME Bengaluru - 560 003, India Tel: +91-80-4346 4500 (Board); Isolated Tricuspid Valve Prolapse 31 Fax: +91-80-4346 4530 SR MITTAL

Printed at Modest Print Pack (P) Ltd., C-52, DDA Sheds Okhla Industrial Area, Phase-I, New Delhi-110 020. Congenital Fused Cervical Vertebrae 38 MONIKA MAHESHWAR

2 Cardiology Today VOL.XXIII NO. 1 JANUARY-FEBRUARY 2019 EDITORIAL

Circadian Rhythm of the Body - Is it the Holy Grail ?

Existence of a circadian rhythm for the activities of the brain is a given and a common knowledge, but that there is a similar peripheral clock in gastro-intestinal tract and other organs and tissues is not that well appreciated. It is intuitive that when one defi es nature, some penalties would have to be paid, but it is only now that scientifi c sanctity has been accorded to this rather obvious fact of life. Long duration manipulation and disruption of the circadian rhythm has been associated with metabolic disorders like obesity, diabetes, hypertension etc. But it is not clear, whether this is modulated through the central pacemaker in the brain, or to certain products of metabolism, which too have a circadian rhythm.

In a recent study conducted at the Washington State University, two groups - one having a night-shift sleep routine and the other a day-shift pattern were studied1. Melatonin and Cortisol were used as markers of the brain master clock and another 132 metabolites were used to study the peripheral clock of other organs and tissues. It was found that both Melatonin and Cortisol showed only negligible diff erences between the day and night shift patterns, suggesting that the master clock of the brain is resistant to the shift patterns. However, of the 132 other metabolites, nearly half (65) had a signifi cant daily rhythm and only 3 metabolites (Taurine, Serotonin and Sarcosine) mirrored Melatonin and Cortisol, the markers of the brain's master clock. Metabolites that were aff ected by the night-shift sleep pattern were found to be related to the liver, pancreas and the gastrointestinal tract, prompting Van Dongen, the lead author, to comment, 'no one knew that the biological clocks in people's digestive organs are so profoundly and quickly changed by shift-work schedules, even though the brain's master clock barely adapts to such schedules. As a result, some biological signals in shift workers' bodies are saying its day, while other signals are saying its night, which causes disruption of metabolism.'1

These fi ndings assume special importance for countries in Asia, especially India, which have become back offi ce data analysis and storage repositories for North America. As such, we have genetic predisposition for metabolic syndrome, and if to this 'nature', we add another confounder in terms of the 'nurture', and that too in a young work force, then it is going to have disastrous consequences for the country, besides the individuals DR. OP YADAVA and their families. Lack of exercise and frequent unhealthy snacking, that is attendant CEO and Chief Cardiac Surgeon to the night shift workers' profi le, complemented by the unhealthy genes, make matters National Heart Institute, worse. New Delhi

3 Cardiology Today VOL.XXIII NO. 1 JANUARY-FEBRUARY 2019 The Business Process Outsourcing (BPO) model therefore needs to be regulated and norms drawn to protect the health of individuals involved, as they may not be aware of the occult health issues attendant to night shifts. They should be suitably counselled and informed and healthy behaviours inculcated by cajoling and regulations, besides voluntary self discipline in culinary matters.

Could this circadian rhythm be applicable to the gut microbiome too? This is indeed another interesting thought and worthy of scientifi c pursuance, as it has not been evaluated till date. In these two facets - the circadian rhythm of the human body and the gut microbiota, and their interaction, may lie the answers to a lot of imponderables on causation of disease.

REFERENCE 1. Skene DJ, Skornyakov E, Chowdhury NR, Gajula RP, Middleton B, Satterfield BC, Porter KI, Van Dongen HPA, Gaddameedhi, S. Separation of circadian- and behavior-driven metabolite rhythms in humans provides a window on peripheral oscillators and metabolism. S. Proc Natl Acad Sci U S A. 2018 Jul 10. Epub ahead of print. PMID: 29991600.

4 Cardiology Today VOL.XXIII NO. 1 JANUARY-FEBRUARY 2019 REVIEW ARTICLE

Contrast Induced Nephropathy: How to Predict and Prevent?

Keywords RAGHAV BANSAL, VIVEKA KUMAR  contrast media  acute kidney injury  renal replacement therapy  european society of cardiology rec- ommendation Abstract Contrast-induced nephropathy (CIN) is a serious complication of angiographic procedures resulting from the administration of contrast media (CM). CIN is usually transient, with serum creatinine levels peaking at 2–3 days after administration of contrast medium and returning to baseline within 7–10 days after administration. Multiple studies have been conducted using a variety of therapeutic interventions in an attempt to prevent CIN. Of these, careful selection of patients, using newer radiocontrast agents, maintenance of hydration status, and avoiding nephrotoxic agents pre- and post- procedure are the most effective interventions to protect against CIN. This review focuses on the basic concepts of CIN and summarizes our recent understanding of its pathophysiology. In addition, this article provides practical recommendations with respect to CIN prevention and management.

INTRODUCTION exposure for intravenous pyelography in Contrast-induced nephropathy (CIN) multiple myeloma patients with already represents the iatrogenic renal injury compromised kidneys.1 With the ever- secondary to exposure to iodinated expanding number of diagnostic and contrast media used during interventional interventional procedures involving cardiology procedures and contrast contrast media, the risk of CIN continues enhanced computed tomography scans. to haunt every interventional cardiologist CIN remains a feared complication after and radiologist. Even after signifi cant a percutaneous coronary intervention advances of our understanding, CIN (PCI) as it is associated with poor remains common, being the cause of cardiovascular outcomes even after hospital acquired acute kidney injury achieving a good procedural success. (AKI) in one third of all the cases.2 CIN was fi rst described in the 1950s Although it aff ects only 1 to 2% of the as fatal renal toxicity after contrast general patient population, it affl icts

Dr. Raghav Bansal is Associate Consultant, Cardiology, Max Super Speciality Hospital, Saket, New Delhi & Dr. Viveka Kumar is Senior Director, , Max Heart and Vascular Institute, Saket, New Delhi

5 Cardiology Today VOL. XXIII NO. 1 JANUARY-FEBRUARY 2019 REVIEW ARTICLE

Direct cytotoxicity of iodine compounds >0.5 mg/dL absolute Direct Toxicity or 25% as compared 48-72 hours after to baseline contrast exposure, Reactive oxygen species, Decreased anti-oxidant creatinine value peaks at 3-5 days enzyme activity Imbalance of vasoactive mediators (Nitric oxide, prostaglandin, adenosine and endothelin) Absence of Contrast media Increased viscosity leading to impaired blood flow alternate causes Ischaemic injury of AKI in microvessels

Increased oxygen consumption Figure 1. The three important considerations of definition of CIN. Figure 2. Pathogenesis of CIN. up to 50% of patients in high risk Pathophysiology of CIN is related to number of cases CIN is still considered 3 groups. Considering the adverse events medullary ischaemia and direct toxicity ominous. Observational studies have and increased healthcare costs which after contrast exposure.4 All iodinated demonstrated a fi ve-fold increase in CIN portends, the importance of risk contrast media contain concentrated in-hospital mortality in patients who prediction followed by prevention of CIN iodinated benzene compounds which are develop CIN as compared to those who cannot be overemphasized. cytotoxic to a variable extent depending do not.10 In a sample size of 1826 patients, upon the ionic strength, viscosity and McCullough et al demonstrated an in- DEFINITION AND osmolality.5 The initially used high hospital mortality rate of 7.1% in patients PATHOPHYSIOLOGICAL osmolar contrast media were highly developing CIN as compared to patients CONSIDERATIONS nephrotoxic and had been subsequently who do not.10 The 1-year mortality rate The generally accepted defi nition of CIN phased out. Though the low osmolar was also signifi cantly higher in a study by has threefold considerations (Figure 1). or the latest generation iso-osmolar Gruberg et al.11 Thus, long term mortality There is an AKI component which is contrast media are less nephrotoxic, they rates on 1 year and 5 years follow-up may defi ned as 0.5 mg/dL or >25% increase in entail a greater risk of ischaemia to the also be up to four-fold higher in patients serum creatinine values from the baseline renal medulla. Viscosity is inversely who develop CIN.11 The risk of persistent value. The AKI should occur within proportional to osmolality. Thus the renal dysfunction is also signifi cant 72 hours of contrast exposure. And lastly, newer generation compounds are more with almost one-fi fth of patients having to label as CIN there should not be any viscous and interfere with normal renal persistent dysfunction after CIN in an apparent alternative explanation for the blood fl ow. In addition, the contrast observational study by Maioloi et al.12 3 AKI. Thus, there is a defi nite time course media is vasoactive. Within minutes of Renal replacement therapy may be of CIN. It begins within 24 to 48 hours of contrast exposure a state of prolonged required in a number of cases ranging contrast exposure and usually peaks at 3-4 vasoconstriction sets in with imbalance from 0.7 to 7%.13-14 The healthcare costs days. There is an array of proposed novel of many vascular mediator compounds thus incurred are signifi cant.15 biomarkers including Cystatin C, Urinary including nitrous oxide, adenosine, However, a direct causal association Kim-1, Interleukin 18 and NGAL that endothelin, prostaglandin and reactive of CIN with mortality is diffi cult to prove may be helpful for earlier identifi cation oxygen species.6 The outer medullary as there are many confounders. CIN more of CIN. Unfortunately, to date, these portion of the kidneys is the most commonly develops in patients with high biomarkers have yet to progress beyond ischaemia sensitive and generally the risk features such as diabetes, pre-existing the realms of clinical research. CIN may worst hit area.7 In cases of pre-existing CKD, left ventricular dysfunction and be oliguric or non-oliguric. Non-oliguric CKD, the oxygen requirement of the severe cardiac disease. Thus, CIN may CIN resolves in most of the patients within overburdened nephrons is higher than be a marker of severe disease leading a time period of 7 days. In contrast, the normal and thus suff er a greater ischaemic to increased cardiovascular mortality. In oliguric CIN is more ominous with the injury.8 a recent meta-analysis by James et al, greater requirement of renal replacement development of CIN was associated with therapy and often taking a longer time WHY CIN IS IMPORTANT: an increased mortality.16 But when the (typically 1 to 3 weeks) to recover. Risk CORRELATION WITH ADVERSE baseline risk factors were compared, the of progression of underlying chronic EVENTS group developing CIN was already at a kidney disease (CKD) and acute injury CIN is mostly transient with more than higher risk of mortality due to strong risk becoming a chronic problem with partial 80% of the cases resolving within 3 factors. Although adjustment is done in recovery is present in each case, even weeks.9 In view of a number of short most of the studies, interpreting causality when the renal dysfunction is mild and term and long term adverse events in from observational data may be fl awed transient in most of the cases. a small proportion but a signifi cant in present of confounders. There remains

6 Cardiology Today VOL. XXIII NO. 1 JANUARY-FEBRUARY 2019 medications is also considered as a Table 1. Risk Factors for CIN risk marker. These commonly include Non Modifiable Modifiable metformin, NSAIDs and nephrotoxic 1. Elderly 1. Volume depletion antibiotics. However, the risk with ACE 2. Diabetic Nephropathy 2. Hypotension inhibitors and angiotensin receptor 3. CKD with eGFR <60 ml/min/1.73m2 3. Volume and type of contrast blockers (ARBs) is less well defi ned and 4. Proteinuria 4. Anaemia/ blood loss it is considered safe to continue these 5. CHF/Cardiogenic shock 5. Diuretics medications if already a part of standard 6. Acute Myocardial infarction 6. NSAIDs therapy received by the patient.18 7. Intra-aortic balloon pump 7. Other nephrotoxins Procedural factors for contrast media volume used and history of previous a void of large randomized controlled The next major risk factor for CIN is contrast media exposure within 72 hours trials regarding this to prove causality, dehydration. Being primarily a clinical are also considered as important risk which remain almost impossible with diagnosis it has been impossible to factors.22 Total contrast volume of > 350 ethical and cost considerations involved. quantitate and directly study its eff ects. ml or > 4 ml/kg is considered a risk factor It can be said that prognosis of patients But a surrogate in the form of hypotension, for CIN.20 Laskey et al demonstrated that developing is signifi cantly worse as defi ned by systolic pressure of less than a volume of contrast to eGFR (estimated compared to patients who do not. 80 mmHg for more than 60 minutes, Glomerular Filtration Rate) greater than is a recognized risk marker for CIN. 3.7:1 is strongly correlated with risk of PREDICTION OF CIN Hypotension, secondary to cardiogenic CIN.23 The presence of hemodynamic Risk assessment remains an important shock and even excessive vasodilation instability in the peri-procedural period tool in clinical medicine to improve the (as seen in septic shock and anaphylaxis), also plays a signifi cant role. Thus in a yield of interventions. Same holds true is also a signifi cant risk marker for CIN. PCI done on inotropic or balloon support, for the case of CIN. If it can be identifi ed Hypotension adversely aff ects renal one should be wary of development of that which patient is going to develop CIN perfusion and predisposes to greater renal CIN and should try to limit the volume of then special precautions in these cases injury with contrast media. Congestive contrast media as far as possible. may be warranted to improve outcomes. heart failure, acute myocardial infarction A number of scoring systems Employing preventive interventions and left ventricular dysfunction with are available for the prediction of universally, may not be cost eff ective and ejection fraction less than 45% are also development of CIN. The most may complicate things unnecessarily as associated with renal hypo-perfusion, commonly employed is the one proposed most of the patients undergoing contrast and thus increased risk of CIN.19 There by Mehran et al (Table 2).20 But the major exposure are not going to develop CIN. is ample of data now available which drawback of this system is that it gives There are many risk factors which have suggest diabetes as a major risk factor risk prediction only after the procedure is an implication for the development for CIN, especially when associated over as it also involve procedural factors. of CIN (Table 1). Most of these risk with CKD.19 Other common risk factors It is often desirable for risk prediction factors can be assessed with history, include elderly age group (>75 years to be accurate before the procedure. For examination and routine biochemical of age)20 and anemia (haematocrit of this purpose, another scoring system by investigations. The most important of <0.39 in males and <0.36 in females).21 Miaoli et al has often been employed.22 the risk factors is the pre-existing CKD. Co-administration of other nephrotoxic In 1999, the risk of signifi cant CIN was 20 defi ned by a creatinine level above 1.3 Table 2. Mehran risk score for the prediction of CIN. mg/d in males and 1.0 in females by the Risk Factors Score European society of urogenital radiology Hypotension (SBP <80 mm Hg or >1 h of inotropic support) 5 consensus working panel.17 These fi gures Intra-arterial balloon pump therapy 5 were found to correlate with a eGFR level Chronic heart failure, (NYHA III/IV or recent pulmonary oedema) 5 of 60 ml/min/1.73 m.2 CKD stage 3-5 Age >75 years 4 corresponding with an eGFR level of 60 Diabetes mellitus 3 ml/min/1.73 m2 or below is now generally Anaemia (male: HCT<0.39, female: HCT<0.36) 3 recognized as the CIN risk threshold.18 Estimated glomerular filtration rate <20 mL/min 6 Thus, serum creatinine remains the most Estimated glomerular filtration rate 20–40 mL/min 4 eff ective and a simple tool to screen for Estimated glomerular filtration rate 40–60 mL/min 2 risk of CIN. The creatinine value is an Contrast media volume 1 per cc insensitive marker of renal dysfunction, Score <5 6-10 11-16 >16 however, and thus fails to predict many CIN risk Low 7.5% Moderate 14% High 26.1% Very High 57.3% cases of CIN. Dialysis risk 0.04% 0.12% 1.09% 12.6%

7 Cardiology Today VOL. XXIII NO. 1 JANUARY-FEBRUARY 2019 REVIEW ARTICLE

of various contrast media is given in Table 3. Nephrotoxic medications requiring withdrawal 24 hours before contrast Table 4. media exposure. Till date, adequate hydration remains Drug Class Examples the most important prophylactic measure NSAIDs Naproxen, Ibuprofen, Diclofenac, Celecoxib for prevention of CIN. Suffi cient Antibiotics Aminoglycosides (Amikacin, Gentamicin, Tobramycin) intravascular volume ensures adequate Antifungals Amphoterecin B dilution of contrast media along with Antivirals Acyclovir, Tenfovir, Foscarnet generous blood fl ow to the kidneys. Immunomodulatory Cyclosporin A In patients who are at low risk, even Antineoplastic Cisplatin, Ifosfamide, Mitomycin oral hydration may suffi ce. However, intravenous hydration with crystalloids Table 4. Classification of contrast dyes. is preferred in patients who are at higher High Osmolar Contrast Medium Osmolality ~ 1500 mOsm risk of development of CIN. The nature Diatrizoate (Gastrograffin, Hypaque) of crystalloid to be preferred still remains Iothalamate (Conray) a matter of debate. The general fl uid of Low Osmolar Contrast Medium Osmolality ~ 320-800 mOsm choice remains isotonic saline (0.9% Iohexol (Omnipaque) NaCl solution), with soda-bicarbonate Ioxaglate (Hexabrix) being still used at many centres. The Ioversol (Optiray) initial trials had shown some benefi t Iomeprol (Imeron) with the use of bicarbonates over saline, Iopromide (Ultravist) however, a contemporary randomized Iopamidol (Isovue, Iopamiro, Niopam) Higher rate of AKI controlled trial (PRESERVE trial) failed Lower rate of AKI to show superiority of bicarbonate Iso-Osmolar Contrast Medium Osmolality ~ 290 mOsm 24 Iodixanol (Visipaque) solution over normal saline. The current guidelines recommend hydration with Newer risk markers are continuously 24 hours before the procedure and for normal saline at the rate of 1 to 1.5 ml/ being evaluated for even more accurate 48 hours following the contrast media kg/hour for 12 hours pre-procedure and 27 prediction of CIN. However, none of exposure (Table 3). Metformin should 24 hours post procedure. Small trials these have percolated down into the also be discontinued for the fear of lactic have suggested benefi t of left ventricular clinical practice yet. acidosis and not for nephrotoxicity per se. end diastolic pressure guided intravenous Limiting the contrast exposure to as low hydration and also hydration with PREVENTION OF CIN as reasonably possible forms an important intravenous furosemide to maintain good 25-26 In all the patients who are referred for principle for the prevention of CIN. Using urine output. These methods may help contrast media based procedures, it is biplane catheterization laboratories for in the prevention of CIN at the same time essential to perform a comprehensive patients at high-risk may be preferred precipitating less heart failure events. All review of indication and to evaluate to limit contrast exposure. The current patients who are at risk should be assessed whether the procedure can be avoided in guidelines recommend the use of iso- at 48-72 hours after the procedure to view of alternate options. Every patient osmolar or low osmolar contrast media screen for the development of CIN. It should undergo an assessment for the risk over high osmolar ones. The comparison is essential to rule out athero-embolic of development of CIN, especially if the eGFR is <60 ml/min. If two procedures Recommendation Class Grade involving are to be done, they should Risk assessment for CI-AKI before CAG IIa C be spaced out by at least 72 hours. The Hydration with isotonic saline I A second procedure should be further Low or Iso-osmolar contrast media (Contrast volume/GFR <3.4) I A delayed up to the complete resolution of Short term high dose statin IIa A nephropathy if there is development of CIN after the fi rst procedure. All said, Iso-osmolar preferred over Low-osmolar contrast media IIa A it is also important to remember that Volume of contrast should be minimized IIa B the patients who are at high risk of CIN Furosemide with matched hydration in patients at high-risk IIb A are also at higher risk of cardiovascular N-Acetylcysteine III A complications and poor outcomes, and Sodium Bicarbonate 0.84$ infusion III A thus an indicated procedure should not be Prophylactic hemodiafiltration 6 hrs before complex PCI in CKD patients IIb B unnecessarily delayed. Prophylactic renal replacement therapy in CKD III B All the patients should be advised to stop all nephrotoxic medications at least Figure 3. European Society of Cardiology CIN prevention guidelines, 2014.27

8 Cardiology Today VOL. XXIII NO. 1 JANUARY-FEBRUARY 2019 renal insult before making a diagnosis of risk by careful evaluation to employ 14. Gruberg L, Mintz GS, Mehran R, et al. The prognostic of CIN. In athero-embolic renal disease, targeted intervention in those who are at implications of further renal function deterioration within 48 h of interventional coronary procedures in patients the rise in serum creatinine occurs a later high-risk. Pre-existing CKD, diabetes, with pre-existent chronic renal insufficiency. J Am Coll (typically 1 to 3 weeks), and does not left ventricular dysfunction, hypotension, Cardiol 2000; 36:1542–8. resolve as commonly as in CIN. Other elderly age group, anaemia and use of 15. Weisbord SD, Chen H, Stone RA, et al. Associations of peripheral signs of athero-embolism, other nephrotoxic drugs are the most increases in serum creatinine with mortality and length of hospital stay after coronary angiography. J Am Soc peripheral eosinophilia, low complement important risk markers. The importance Nephrol 2006;17:2871–7. levels, and proteinuria with WBCs on of avoiding interventions, that are not 16. James MT, Samuel SM, Manning MA, et al. Contrast- urinalysis help in clinching the diagnosis essential, cannot be over-emphasized. Till induced acute kidney injury and risk of adverse clinical outcomes after coronary angiography: a systematic of athero-embolic renal involvement. date, intravenous hydration with normal review and meta-analysis. Circ Cardiovasc Interv Many pharmacological interventions saline, avoiding nephrotoxic drugs and 2013;6:37–43. have been tried for the prevention of CIN, limiting contrast media exposure to 17. Lameire N, Adam A, Becker CR, et al., Panel CINCW. but none has proved to be eff ective in the as minimum as possible remains the Baseline renal function screening. Am J Cardiol 2006; 98: 21K–6K. long run. The most commonly used of most eff ective preventive measures for 18. Stacul F, van der Molen AJ, Reimer P, et al., Contrast Media these agents is N-Acetyl Cysteine (NAC). CIN. Pharmacological interventions Safety Committee of European Society of Urogenital R. However, it has gone out of favour after it are not recommended at present for the Contrast induced nephropathy: updated ESUR contrast prevention of CIN. media safety committee guidelines. Eur Radiol 2011;21: failed to show benefi t in the randomized 2527–41. controlled PRESERVE trial.25 Other 19. Rihal CS, Textor SC, Grill DE, et al. Incidence and agents that have been considered REFERENCES prognostic importance of acute renal failure after as preventive in this regard include 1. Bartels ED, Brun GC, Gammeltoft A, et al. Acute anuria percutaneous coronary intervention. Circulation 2002; following intravenous pyelography in a patient with 105: 2259–64. adenosine receptor antagonists, ascorbic myelomatosis. Acta Med Scand 1954;150:297–302. 20. Mehran R, Aymong ED, Nikolsky E, et al. A simple risk acid, atrial natriuretic peptides, diuretics, 2. Hou SH, Bushinsky DA, Wish JB, et al. Hospital-acquired score for prediction of contrast-induced nephropathy dopamine and prostaglandins. But none renal insufficiency: a prospective study. Am J Med 1983; after percutaneous coronary intervention: development 74:243–8. and initial validation. J Am Coll Cardiol 2004;44:1393–9. of them have proved to be an eff ective 3. Mehran R, Nikolsky E. Contrast-induced nephropathy: 21. Nikolsky E, Mehran R, Lasic Z, et al. Low hematocrit and thus their use is not recommended. definition, epidemiology, and patients at risk. Kidney Int predicts contrast-induced nephropathy after Suppl 2006:S11–15. percutaneous coronary interventions. Kidney Int There is some data that suggest statins 4. Sendeski MM. Pathophysiology of renal tissue damage 2005;67:706–13. may be helpful for prevention of CIN, but by iodinated contrast media. Clin Exp Pharmacol Physiol 22. Maioli M, Toso A, Gallopin M, et al. Preprocedural score still, they need to be tested in larger trials 2011;38:292–9. 5. Heinrich MC, Kuhlmann MK, Grgic A, et al. Cytotoxic for risk of contrast-induced nephropathy in elective before being universally recommended. effects of ionic high-osmolar, nonionic monomeric, and coronary angiography and intervention. J Cardiovasc Lastly, it remains important to remember non-ionic iso-osmolar dimeric iodinated contrast media Med (Hagerstown) 2010;11:444–9. 23. Laskey WK, Jenkins C, Selzer F, et al. Volume-to- that there is no role of prophylactic renal on renal tubular cells in vitro. Radiology 2005;235:843– 9. creatinine clearance ratio: a pharmacokinetically based replacement therapy for the prevention 6. Tumlin J, Stacul F, Adam A, et al., Panel CINCW. risk factor for prediction of early creatinine increase after of CIN. And renal replacement therapy Pathophysiology of contrast-induced nephropathy. Am J percutaneous coronary intervention. J Am Coll Cardiol should be considered only for standard Cardiol 2006;98:14K–20K. 2007;50:584–90. 7. Brezis M, Rosen S. of the renal medulla—its 24. Weisbord SD, Gallagher M, Jneid H, et al. Outcomes after indication after the development of CIN. implications for disease. N Engl J Med 1995;332:647– angiography with sodium bicarbonate and acetylcysteine. The European society of cardiology 55. N Engl J Med 2018;378:603-14. recommendation for the prevention of 8. Pruijm M, Hofmann L, Vogt B, et al. Renal tissue 25. Brar SS, Aharonian V, Mansukhani P, et al. Haemodynamic oxygenation in essential hypertension and chronic kidney guided fluid administration for the prevention of contrast- CIN has been presented in Figure 3. disease. Int J Hypertens 2013;2013:696598. induced acute kidney injury: The PSOEIDON randomised 9. McCullough PA, Sandberg KR. Epidemiology of contrast- controlled trial. Lancet 2014;383:1814–23. SUMMARY induced nephropathy. Rev Cardiovasc Med 2003;4(Suppl 26. Briguori C, Visconti G, Focaccio A, et al. Renal 5):S3–9. insufficiency after contrast media administration trial ii CIN remains fairly common and has 10. Finn WF. The clinical and renal consequences of (REMEDIAL ii): RenalGuard system in high-risk patients contrast-induced nephropathy. Nephrol Dial Transplant increasing prevalence with increasing for contrast-induced acute kidney injury. Circulation 2006;21:i2–10. 2011;124:1260–9. numbers and complexity of contrast media 11. Levy EM, Viscoli CM, Horwitz RI. The effect of acute based procedures. Although resolving renal failure on mortality. A cohort analysis. JAMA 27. Windecker S, Kolh P, Alfonso F, et al., Authors/ spontaneously in 80% of the cases, it 1996;275:1489–94. Task Force members. 2014 ESC/EACTS guidelines 12. Maioli M, Toso A, Leoncini M, et al. Persistent renal on myocardial revascularization: the task force on remains an important cause of signifi cant damage after contrast-induced acute kidney injury: myocardial revascularization of the European Society morbidity leading to increased health care Incidence, evolution, risk factors, and prognosis. of Cardiology (ESC) and the European Association for costs. Association of CIN with adverse Circulation 2012; 125: 3099–107. Cardio-Thoracic (EACTS) developed with the 13. McCullough PA, Wolyn R, Rocher LL, et al. Acute renal special contribution of the European Association of cardiovascular outcomes is defi nite, failure after coronary intervention: incidence, risk factors, Percutaneous Cardiovascular Interventions (EAPCI). Eur thus making CIN ominous. Assessment & relationship to mortality. Am J Med 1997;103:368–75. Heart J 2014;35:2541–619.

9 Cardiology Today VOL. XXIII NO. 1 JANUARY-FEBRUARY 2019 REVIEW ARTICLE

How do I Manage My Patients with Heart Failure with Preserved Ejection Fraction?

Keywords MOHAMMED SADIQ AZAM, DAYASAGAR RAO V  preserved ejection fraction  natriuretic peptide  pharmacologic therapy Abstract  nonpharmacologic therapy Heart failure with preserved ejection fraction (HF-PEF) is the clinical  hypertension syndrome of heart failure associated with normal or near-normal  tailored management approach systolic function. Because inhibition of the adrenergic and renin-  systolic heart failure angiotensin-aldosterone systems has been so effective in the treatment of systolic heart failure, these therapies have been the subject of recent clinical trials of HF-PEF. In this review, we examine the current evidence about treatment of HF-PEF, with particular emphasis on reviewing the literature for large-scale randomized clinical studies. The lack of signifi cant benefi t with neurohormonal antagonism in HF- PEF suggests that this condition might not involve neurohormonal activation as a critical pathophysiologic mechanism. Perhaps heart failure, as we traditionally think of it, is the wrong paradigm to pursue as we try to understand this condition of volume overload known as HF-PEF.

INTRODUCTION They share many features including “Medicine is a science of uncertainty abnormal left ventricular (LV) fi lling and an art of probability” dynamics, elevated LV diastolic - Sir William Osler pressure, LV systolic and diastolic dysfunction, neurohormonal activation, Patients with heart failure can be impaired exercise tolerance, frequent broadly classifi ed as those with heart hospitalization, and reduced survival.1-4 failure with reduced (≤50%) ejection When compared to patients with fraction (HFrEF) and heart failure with HFrEF, those with HFpEF tend to be preserved (>50%) ejection fraction older and mostly females with atleast (HFpEF). Irrespective of the ejection 85% of them having associated systemic fraction (EF) all these patients have the hypertension.5 Despite having a preserved clinical syndrome of heart failure (HF). EF, patients with HFpEF have a mortality

Dr. Mohammed Sadiq Azam, Dr. Dayasagar Rao V, Department of Cardiology, Krishna Institute of Medical Sciences, Secunderabad

10 Cardiology Today VOL. XXIII NO. 1 JANUARY-FEBRUARY 2019 rate that approaches 60% and a 6 month THERAPY treatment of comorbid diseases, of which hospitalization rate of around 50% and Many therapies have been proposed for the most important is hypertension. debilitating symptoms.6 Hence, early the management of this unique subset of Control of blood pressure at rest as well recognition and appropriate management patients, but sadly, there is a huge lacuna as modifying the blood pressure response are essential to reduce the mortality and in evidence based therapies, that have to exercise, controlling blood sugar, morbidity associated with HFpEF. shown to reduce mortality and morbidity treatment of ischemia, maintaining renal in patients with HFpEF. function and maintaining a healthy body DIAGNOSIS The practical management of patients weight form the crux of this component. Diagnosis of HFpEF as with any case of with HFpEF has three main components. The third component is optimisation heart failure is primarily based on clinical The fi rst is reduction and prevention of cardiac functional status-avoiding a signs and symptoms which should be of pulmonary and peripheral venous demand-supply mismatch, preventing present in association with an EF greater congestion, which can be achieved using inappropriate heart rate response to than 50% with a normal LV end-diastolic a combination of fl uid and salt restriction, exercise as well as metabolic stress, volume along with a presence of expected diuretics, nitrates, and, prudent use of maintenance or restoration of sinus antecedent or comorbid conditions and neurohormonal modulation therapies. rhythm and control of ventricular rate an exclusion of all non-cardiac causes of The second component is an aggressive during episodes of atrial . the signs and symptoms. The presence of these fi ndings is suffi cient to make the Table 1: Summary of major clinical trials of drugs for HFpEF10 diagnosis of HFpEF as per major society Trial Drug Salient features guidelines of the AHA, ACC, HFSA and DIG Trial Digoxin In the HFpEF group (EF >45%) in sinus rhythm, digoxin ESC. If these criteria are insuffi cient or did not alter the primary endpoint of HF-related lead to an ambiguous diagnosis a fourth hospitalization or CV mortality but did reduce the set of data using noninvasive and invasive number of such hospitalizations. methods to gather evidence of cardiac CHARM Candesartan Fewer patients in the candesartan group than in the dysfunction should be used to arrive at placebo group reached the primary endpoint of CV the diagnosis of HFpEF.7 death or HF-related hospitalization. No impact on mortality. ROLE OF BIOMARKERS IN THE PEP-CHF Perindopril Enrollment and event rates were lower than expected. DIAGNOSIS OF HFPEF Study did not show significant reduction in primary The most useful and best-characterized endpoint. Some trend towards benefit was seen in biomarkers in patients with HFpEF are the a post-hoc analysis at 1 year driven by a decrease in natriuretic peptides - BNP and N-terminal hospitalizations for HF. (NT)-proBNP. Circulating levels of these I-PRESERVE Irbesartan Irbesartan did not effect any of the prespecified are elevated in patients with HFpEF when outcomes. compared to persons without HF but are SENIORS Nebivolol Included elderly patients without an EF requirement. lower than in patients with HFrEF. The A modest but significant reduction in primary endpoint increase in BNP is directly related to LV of all cause mortality or CV hospitalizations was observed diastolic fi lling pressure and end-diastolic in the nebivolol arm driven primarily by the effect on wall stress. For any given LV diastolic hospitalizations. fi lling pressure in patients with HFpEF, Included very few patients with EF >50%. BNP levels are lower in obese patients TOPCAT Spironolactone Hospitalization for HF was significantly lower in the (for every 1 kg/m2 increase in BMI spironolactone group than the placebo group. above 25, natriuretic peptide levels fall RELAX Sildenafil Sildenafil did not improve exercise capacity or clinical by 4%)8 and higher in women, elderly, in status. those with associated COPD, pulmonary NEAT-HFpEF Isosorbide Patients who received isosorbide mononitrate were less hypertension and pulmonary embolism mononitrate active and did not have better quality of life or and in patients with renal dysfunction. submaximal exercise capacity than patients who received An elevated BNP also has a prognostic placebo. value as it predicts the risk of future PARAMOUNT-HF ARNI Phase II trial. events, even in asymptomatic persons. At 36 weeks, sacubitril/valsartan (ARNI) significantly Soluble ST2 and Galectin 3 have been reduced LA volume by approximately 5% and also approved by USFDA and TIMP-1 is improved NYHA functional class compared with under development as a biomarker to aid valsartan (ARB). in diagnosis, prognosis and management PARAGON-HF ARNI Trial underway to test if the findings of PARAMOUNT HF of HFpEF.9 will translate into improved clinical outcomes.

11 Cardiology Today VOL. XXIII NO. 1 JANUARY-FEBRUARY 2019 REVIEW ARTICLE

PHARMACOLOGICAL THERAPY measurement of standing blood pressure remote monitoring-based tailored therapy. Pharmacological therapies like ACE to adjust antihypertensive drug therapy in These include implantable hemodynamic inhibitors, ARBs, beta blockers, the elderly population. Adequate treatment monitors (IHMs), subcutaneous and mineralocorticoid antagonists, nitrates/ of hypertension not only includes control cutaneous sensors, noninvasive monitors hydralazine, that have an indisputable of the blood pressure but also prevention (assess volume status, heart rate, rhythm, benefi t in HFrEF have failed to show a of LV hypertrophy or measures to induce sympathetic tone and activity), and clear benefi t in patients with HFpEF. regression of the hypertrophy which will serum/plasma-measured biomarkers. Eight large RCTs have enrolled patients lead to reduced mortality and morbidity, with HFpEF of which six had HF improved exercise tolerance and diastolic REMOTE MONITORING SYSTEMS hospitalisation or CV death as the primary function.13 - TAILORED MANAGEMENT endpoint, two had exercise or activity Diabetes and obstructive sleep APPROACH level endpoints. Six of these RCTs had a apnea are often commonly associated The COMPASS-HF (Chronicle Off ers neutral outcome, and one study in a post- with HFpEF and their treatment has Management to Patients with Advanced hoc analysis demonstrated a reduction in demonstrated an improvement in diastolic Signs and Symptoms of Heart Failure) HF hospitalization or CV death in patients function and benefi t in clinical status and trial studied patients in whom an IHM with HFpEF and were treated with better outcomes compared to untreated was implanted that measured an estimated spironolactone, and one demonstrated cases. diastolic pressure that therapy could be facilitated using Many patients with HFpEF are (which in the absence of pulmonary an implantable hemodynamic sensor. found to have associated obesity. In the vascular disease equals to PCWP). This The salient features of the RCTs are ADHERE registry, for example, >25% study demonstrated that many patients summarized in Table 1. of patients weighed >200 pounds.14 who were considered clinically to be Obesity leads to impaired exercise well-compensated by their physicians NONPHARMACOLOGIC THERAPY tolerance and also contributes to the demonstrated measures of elevated fi lling Attention to well-being and overall development of diabetes, hypertension pressures which rose on decompensation health of an individual is of paramount and obstructive sleep apnea. BMI is and that these changes in fi lling pressures importance in the management of patients an important predictor of outcomes in predicted outcomes - including rates of with HFpEF which includes an attention patients with HFpEF. Hence, weight HF hospitalization and CV mortality.15-18 to diet and a healthy lifestyle, regular loss through pharmacological and The investigators hypothesized that physical activity, weight monitoring, nonpharmacological therapies such as off ering a tailored treatment that was patient education and close medical diet and bariatric surgery may form modifi ed on the basis of data obtained follow-up taking the advantage of home important interventional strategies for from an IHM device would decrease monitoring systems. Sodium restriction patients with HFpEF. baseline pressure, prevent an increase in to <2g/day and maintaining a fl uid intake, The eff ect of obesity on natriuretic pressure, and lower HF events in HFpEF. balanced to renal function, is important. peptide levels as mentioned above has to This hypothesis was tested in the be kept in mind since a high BMI may CardioMEMS Heart Sensor Allows TREATMENT OF COMORBIDITIES lead to a falsely low level of BNP despite Monitoring of Pressure to Improve Approximately >85% of the patients the patient having HF. Ergo, over-reliance Outcomes in NYHA class III Heart with HFpEF have associated systemic on BNP alone in such cases might lead to Failure Patients (CHAMPION) trial. hypertension (either current or previous). an underdiagnosis of HF. Those patients in the active treatment Untreated hypertension is a strong Chronic kidney disease is frequently arm demonstrated a 152% decrease in risk factor for the development of HF. associated with HFpEF and a decline pulmonary artery diastolic and systolic Treatment of systolic hypertension in in GFR generally signals a drop in pressures and a 52% decrease in HF- the elderly is associated with a >50% the prognosis for the patient. Anemia related events and a decrease in CV reduction in HF frequency. Recent studies in patients with HFpEF is generally mortality rate. In addition to implantable (SPRINT, HOPE 3) have demonstrated multifactorial with causes ranging from devices, noninvasive systems measuring the benefi t of an aggressive BP targets associated CKD to iron defi ciency. indices of impedance and heart rate (systolic BP <120) even in the elderly Anaemia, irrespective of its etiology, variability, rhythm, and activity are under population.11,12 However, it has to be kept is generally associated with a worse development.19-22 in mind that due to the arterial stiff ening prognosis in patients with HFpEF and that develops with age, achieving the hence forms an important therapeutic DEVICE THERAPY FOR HEART targets may not always be easy. Another target in these patients. FAILURE signifi cant cause of falls and frequent An elevated left (LA) pressure is morbidity in the elderly population is the SENSOR-BASED STRATEGIES central to the pathogenesis of HFpEF. development of orthostatic hypotension. These are novel therapies that provide Hence there has been a lot of research Some authors have hence advised the facilitated management of HFpEF using into methods to reduce LA pressure and

12 Cardiology Today VOL. XXIII NO. 1 JANUARY-FEBRUARY 2019 an important technological update in this 1 year after device placement and aspirin from opposing the right atrial side of the area is the development and testing of indefi nitely. The REDUCE LAP-HF implant.27 devices that reduce the LA pressure and study showed that 52% of patients had improve the diastolic function. Devices a reduction in PCWP at rest and 58% of ATRIAL FLOW REGULATOR aim to mediate a selective reduction had a lower PCWP during exertion with The atrial fl ow regulator (AFR) of the LA pressure, such that there is a 39% fulfi lling both these criteria. Mean (Occlutech, Istanbul, Turkey) (Figure symptomatic improvement, without exercise PCWP was lower at 6 months 1c) is a self-expandable double-disc the complications of pharmacological than at baseline, both at 20-W workload wire mesh device constructed from therapy such as diuresis and hypotension. and at peak exercise. Sustained device 0.004–0.0075-in. nitinol braided into patency at 6 months was confi rmed two fl at discs connected by a waist of THE RATIONALE OF INTERATRIAL with shunt ratio of 1.3:1. Using this data 1–2 mm and central fenestration, which SEPTOSTOMY IASD received CE mark approval in May enables bidirectional fl ow. The fi rst LA is an elastic chamber receiving blood 2016.26 clinical utilization of the device followed from pulmonary passively which The V wave device (V-Wave Ltd., a compassionate use approval from modulates LV fi lling by acting as an Or Akiva, Israel) (Figure 1b), in the fi rst the US Food and Drug Administration. active booster during atrial systole. The generation, consisted of an hourglass The patient was a 54-year-old woman LA buff ers pressure and fl ow coupling shaped, self-expanding nitinol frame that with severe and irreversible pulmonary between the LV and the pulmonary contains a tri-leafl et porcine artery hypertension. Implantation was circulation due to the cyclic nature of tissue valve sutured inside, which allowed associated with immediate right-to-left cardiac hemodynamics.23 At identical unidirectional fl ow from the LA to the shunting and a corresponding decrease mean LA pressure in patients with heart RA, if the pressure gradient exceeded in arterial saturation (from 95 to 89%). failure, HFrEF patients had larger LA 2 mmHg achieving a Qp:Qs of 1.1-2.1. The She reported functional improvement volumes while HFpEF patients had valve prevents reverse shunting of blood at 6 weeks.28 This experience was later higher LA peak pressures and higher LA and prevents paradoxical embolism. The extended to 12 patients (mean age 28.3 stiff ness. LA function has been related to V wave device (Figure 1b) was evaluated ± 8.5 years) with severe irreversible mortality in HFpEF patients but not in in 10 HFrEF patients in a single center in pulmonary arterial hypertension HFrEF patients.24 Canada using the special access process [U29]. All the patients were receiving There are multiple established to prove the concept. The patients were optimal doses of two oral pulmonary techniques for creating large interatrial evaluated at 3 months after the index vasodilators of which one belonged to communication like percutaneous procedure and in this small population, endothelin receptor antagonists and the perforation, balloon dilation, and stent there was a reduction in NYHA class, other belonged to phosphodiesterase-5 implantation. However, complications improved their 6-min walk distance, and inhibitors. All procedures were successful of these procedures include excessive reported improved quality of life (QoL) without any major complications and desaturation, spontaneous fenestration and physical function. At 1-year follow- antiplatelets were given to maintain closure, stent occlusion or migration, up, resting shunt fraction had declined patency of the device. All patients had diffi culties in adjusting shunt size to from a mean of 1.2:1 to 1.1:1, with 14% relief of syncope and 6-min walk distance achieve the desired hemodynamic of patients having no interatrial fl ow. improved signifi cantly. The cardiac index eff ect, and the inability to remove or This occurred in conjunction with pannus and systemic oxygen transport also close the shunt.25 Now, there are three thickening of the bioprosthetic leafl ets showed a signifi cant improvement.29 percutaneously deployed innovative and lumen loss, which prompted the Complete endothelialization of nitinol devices which avoid these complications creation of a second-generation device, atrial septal occluders was demonstrated and are currently undergoing clinical with an expanded ePTFE coating and within a few months after implantation, trials. without a unidirectional valve, including a permitting withdrawal of antiplatelets hood to prevent potential thromboemboli after 6–12 months. INTER ATRIAL SHUNT DEVICES The Inter Atrial Shunt Device (Corvia Medical Inc., Tewksbury, MA, USA) (Figure 1a) is a nitinol device percutaneously inserted in the interatrial septum to produce a permanent 8-mm atrial septal communication. The device is deployed after trans-septal puncture of the mid-fossa ovalis. The device achieves bidirectional fl ow with a Qp:Qs ratio of 1.3:1. Antiplatelets are recommended for Figure 1: Devices being studied for HFpEF: a) Corvia Inter Atrial Shunt Device, b) V wave, c) Atrial flow regulator

13 Cardiology Today VOL. XXIII NO. 1 JANUARY-FEBRUARY 2019 REVIEW ARTICLE

CoROLLA have given promising results which has drugs on diastolic function in patients with hypertension and diastolic dysfunction: a randomised trial. Lancet. CoRolla (CorAssist Inc., Haifa, Israel) lead to regulatory approval. The atrial 2007;369:2079. is an intraventricular device invented fl ow regulator is notable amongst these 14. Fonarow GC, Stough WG, Abraham WT, et al. by Dr. Yair Field which is designed to to have received USFDA approval Characteristics, treatments, and outcomes of patients with preserved systolic function hospitalized for heart be implanted by minimally invasive, for clinical use. However, costs and failure. J Am Coll Cardiol. 2007;50:768. transapical approach, off the pump. It is availability around to globe continue to 15. Zile MR, Bennett TD, El Hajj S, et al. Intracardiac pressures be limiting factors and also long term measured using an implantable hemodynamic monitor: an elastic self-expanding internal spring relationship to mortality in patients with chronic heart like device which is based on mechanical data with these devices is lacking. To failure. Circ Heart Fail. 2017;10(1). principles of energy transfer from systole sum it up we are standing at an exciting 16. Stevenson LW, Zile M, Bennett TD, et al. Chronic ambulatory intracardiac pressures and future heart to diastole. The device applies direct frontier in the management of HFpEF failure events. Circ Heart Fail. 2010;3:580. internal expansion forces distributed and the results of ongoing trials as well as 17. Zile MR, Adamson PB, Cho YK, et al. Hemodynamic long term data with the use of devices for factors associated with acute decompensated heart on the left wall and septum to failure. Part 1. Insights into pathophysiology. J Card Fail. directly improve diastolic function. The HFpEF might set the stage for a defi nitive 2011;17:282. device improves fi lling performance and therapy soon. 18. Adamson PB, Zile MR, Cho YK, et al. Hemodynamic factors associated with acute decompensated heart diastolic dynamics without needing an failure. Part 2. Use in automated detection. J Card Fail. external power source. Preclinical studies REFERENCES 2011;17:366. 1. Little WC, Zile MR. HFpEF. Cardiovascular abnormalities 19. Zile MR, Sharma V, Johnson JW, et al. Prediction of all- have shown safety over the 24-month not just co-morbidities. Circ Heart Fail. 2012;5:669. cause mortality based on the direct measurement of duration and fi rst in human implantation 2. Lam CSP, Roger VL, Rodeheffer RJ, et al. Cardiac structure intrathoracic impedance. Circ Heart Fail. 2016;9:e002543. was carried out in RAMBAM medical and ventricular-vascular function in persons with heart 20. Bourge RC, Abraham WT, Adamson PB, et al. Randomized 30 failure and preserved ejection fraction: from Olmstead controlled trial of an implantable continuous center, Haifa, Israel, in July 2017. County, Minnesota. Circulation. 2007;115:1982. hemodynamic monitor in patients with advanced heart 3. Kitzman DW, Little WC. Left ventricle diastolic dysfunction failure: the COMPASS-HF study. J Am Coll Cardiol. and prognosis. Circulation. 2012;125:743. 2008;51:1073. CONCLUSION 4. Iwano H, Little WC. Heart failure: What does ejection 21. Abraham WT, Adamson PB, Bourge RC, et al. Wireless Heart failure with preserved ejection fraction have to do with it? J Cardiol. 2013;62:1. pulmonary artery haemodynamic monitoring in chronic fraction is currently one of the greatest 5. McMurray JJ, Carson PE, Komajda M, et al. Heart failure heart failure: a randomised controlled trial. Lancet. with preserved ejection fraction:clinical characteristics of 2011;377:658. enigmas facing cardiologists all over the 4,133 patients enrolled in the I-Preserve trial. Eur J Heart 22. Ritzema J, Troughton R, Melton I, et al. Hemodynamically globe. It is in this regard that the quote Fail. 2008;10:149. Guided Home Self-Therapy in Severe Heart Failure Patients by Sir William Osler, with which we 6. Little WC, Zile MR, Klein A, et al. Effect of losartan and (HOMEOSTASIS) Study Group. Physician-directed patient hydrochlorothiazide on exercise tolerance in exertional self-management of left atrial pressure in advanced began this article, is so apt because never hypertension and left ventricular diastolic dysfunction. chronic heart failure. Circulation. 2010;121:1086 before has the treatment of a disease in Am J Cardiol. 2006;98:383. 23. Braunwald E, Frahm CJ. Studies on starling’s law of the 7. Ponikowski P, Voors AA, Anker SD, and Authors/Task heart: IV. Observations on the hemodynamic functions of cardiology been so full of uncertainties Force Members. 2016 ESC Guidelines for the diagnosis the left atrium in man. Circulation. 1961;24:633–42. but still so full of possibilities. While and treatment of acute and chronic heart failure: The 24. Melenovsky V, Hwang SJ, Redfield MM, Zakeri R, Lin many drug therapies have been tried, Task Force for the diagnosis and treatment of acute G, Borlaug BA. Left atrial remodeling and function and chronic heart failure of the European Society of in advanced heart failure with preserved or reduced not a great many of them have shown Cardiology (ESC) developed with the special contribution ejection fraction. Circ Heart Fail. 2015;8: 295–303. any benefi t. In those that have shown of the Heart Failure Association (HFA) of the ESC. Eur 25. Sivaprakasam M, Kiesewetter C, Veldtman GR, Salmon Heart J. 2016;37(27):2129–2200. AP, Vettukattil J. New technique for fenestration of the a benefi t, the benefi t is limited to a 8. Frankenstein L, Remppis A, Nelles M, et al. Relation interatrial septum. J Interv Cardiol. 2006;19:334–6. reduction in hospitalization with a drug of N-terminal pro-brain natriuretic peptide levels and 26. Hasenfuss G, Hayward C, Burkhoff D, Silvestry FE, yet to demonstrate a mortality benefi t. their prognostic power in chronic stable heart failure to McKenzie S, Gustafsson F, et al. investigators RL-Hs. A obesity status. Eur Heart J. 2008;29:2634–2640. transcatheter intracardiac shunt device for heart failure Aldactone in the TOPCAT trial has shown 9. Chow SL, Maisel AS, Anand I, et al. the role of biomarkers with preserved ejection fraction (REDUCE LAP-HF): a a defi nite reduction in hospitalization for for the prevention, assessment, and management of multicentre, open-label, single-arm, phase 1 trial. Lancet. heart failure. a consensus statement for healthcare 2016;387:1298–304. HF in patients with HFpEF, while digoxin professions from the American Heart Association. 27. Stone GW R-CJ, Amat-Santos IJ, Ben Gal T, et al. and candesartan have also demonstrated Circulation. 2017;135:e1054–e1091. Interatrial shunting for heart failure: the V-wave shunt. a similar benefi t to a lesser extent in 10. Zile MR, Litwin SE. Heart Failure with a Preserved Ejection Presented at transcatheter therapeutics (TCT); October Fraction. In: Zipes, Libby, Bonow, Mann Tomaselli (Eds.). 31. 2017; Denver, Colorado. their respective trials. While ARNI has Braunwald’s Heart Disease - A Textbook of Cardiovascular 28. Patel MB, Samuel BP, Girgis RE, et al. Implantable atrial shown benefi t in PARAMOUNT-HF with Medicine. 11th edition. Elsevier. 2018:523-542. flow regulator for severe, irreversible pulmonary arterial 11. Wright JT Jr, Williamson JD, Whelton PK, et al. SPRINT hypertension. EuroIntervention. 2015;11:706–9 respect to improvement in LA volume Research Group. A randomized trial of intensive 29. Ramasamy R, Pavithran S, Sivakumar K, Vettukattil JJ. and NYHA functional class, the ongoing versus standard blood-pressure control. N Engl J Med. Atrial septostomy with a predefined diameter using a PARAGON-HF trial will answer the 2015;373:2103– 2116. novel occlutech atrial flow regulator improves symptoms 12. Lonn EM, Bosch J, López-Jaramillo P, et al; HOPE-3 and cardiac index in patients with severe pulmonary important question of whether this will Investigators. Blood-pressure lowering in intermediate- arterial hypertension. Cardiovasc Interv. translate into an improvement in clinical risk persons without cardiovascular disease. N Engl J 2017;90:1145–53. Med. 2016;374: 2009–2020. 30. Gupta A, Bailey SR. Update on Devices for Diastolic outcomes or not. Many novel device 13. Solomon SD, Janardhanan R, Verma A, et al. Effect of Dysfunction: Options for a No Option Condition? Current therapies have been tried and initial trials angiotensin receptor blockade and antihypertensive Cardiology Reports. 2018;20:85.

14 Cardiology Today VOL. XXIII NO. 1 JANUARY-FEBRUARY 2019 REVIEW ARTICLE

Practical Approach to Constrictive Pericarditis

MONIK MEHTA

Abstract Constrictive pericarditis (CP) represents a form of severe diastolic Keywords heart failure (HF), secondary to a noncompliant pericardium. The  pericardial sac true prevalence of CP is unknown but it is observed in 0.2-0.4% of  edema patients who have undergone or have had pericardial  portopulmonary trauma or infl ammation due to a variety of etiologies. Despite its poor  venous pressure prognosis if untreated, CP is a potentially curable disease and surgical  pericardiectomy can now be performed at low perioperative mortality  in tertiary centers with surgical expertise in pericardial diseases. Cardiologists should have a high index of suspicion for CP in patients presenting with predominant right-sided (HF), particularly when a history of cardiac surgery, pericarditis or pericardial effusion is present. Transthoracic two-dimensional and Doppler echocardiography is usually the fi rst diagnostic tool in the evaluation of HF and can reliably identify CP in most patients by characteristic real-time motion of the heart and hemodynamic features. has been the gold-standard for the diagnosis of CP, but may not be necessary if non- invasive test(s) demonstrate diagnostic features of CP; it should then be reserved for selected cases or for assessment of concomitant coronary disease. Although most patients with CP require pericardiectomy, anti- infl ammatory therapy may be curative in patients presenting with subacute symptoms, especially when evidence of marked ongoing infl ammation is seen.

INTRODUCTION diseases or radiation therapy.1,5 The risk Constrictive pericarditis (CP) is of developing constrictive pericarditis is characterized by impaired ventricular however rare post-acute viral pericarditis, fi lling, secondary to a scarred pericardium. as compared to specifi c aetiologies such The scarred pericardium, involving as tuberculosis.12 both parietal and visceral layers may be thickened or calcifi ed, with resultant loss CLINICAL FEATURES of normal elasticity of the pericardial sac. After a detailed history taking is done The common causes include patient is clinically evaluated. The idiopathic etiology, post cardiac surgery predominant symptoms are dyspnea and systemic diseases aff ecting the with peripheral oedema and on clinical pericardium such as tuberculosis, collagen evaluation, there is evidence of systemic vascular diseases, malignancy, renal venous congestion with hepatomegaly

Dr. Monik Mehta is Consultant Cardiologist, Artemis Hospital, Department of Cardiology, Sector 51, Gurgaon, Haryana, India.

15 Cardiology Today VOL. XXIII NO. 1 JANUARY-FEBRUARY 2019 REVIEW ARTICLE

and ascites. scan or MRI. Radiological presence of early velocity (E)/ Ea with the LV fi lling Clinically the patient will present as calcifi cation should be looked for in left pressures which is usually positive and a case of predominant right heart failure2 lateral projections suggestive of CP. An linear in primary myocardial diseases but and CP will be an important diff erential enlarged cardiac silhouette in X-Ray PA gets reversed (annulus paradoxus) in CP.7 diagnosis in this setting. Other conditions, view would be suggestive of pericardial Cardiac cath study fi ndings which will need to be excluded, would be eff usion or eff usive-constrictive demonstrate increase in right atrial restrictive cardiomyopathy, pathologies pericarditis and the diff erence would pressures, equalization of diastolic causing failure of the right side of become apparent when there would be fi lling pressures i.e. <5 mm diff erence heart e.g. tricuspid stenosis, pulmonary persistently elevated right atrial pressures between mean right atrial (RA) pressure, stenosis, ebstein's anomaly, cor pulmonale post in the latter. A right ventricular (RV) diastolic pressure, and other diseases such as liver cirrhosis, pericardial thickness exceeding 4 mm pulmonary- artery (PA) diastolic pressure, (SVC) obstruction on echocardiography, CT scan or MRI is and pulmonary capillary wedge pressure and portopulmonary stenosis etc. highly suggestive of CP, with the former (PCWP) and pericardial pressures, dip The clinical fi ndings in vast majority being the least sensitive. However, CP and plateau confi guration of right and left refl ect elevated systemic venous can also occur in the setting of a non- ventricular diastolic waveforms while the congestion such as increased jugular thickened pericardium. simultaneous LV and RV systolic pressure venous pressure (JVP) and hepatomegaly. Doppler of the hemodynamics is tracings in CP will show discordant Venous pressure often paradoxically extremely helpful in diagnosing CP changes with respiration i.e. LV systolic increases with inspiration (Kussmaul in which the pathologically increased will decrease with inspiration while RV sign) due to an inability of the right heart pericardial restraint results in an enhanced systolic will increase. to accept increased venous return with ventricular interaction or interdependence To summarize patient will present inspiration and a prominent y descent and prevents transmission of as a case of right heart failure. History (Freidrich sign) may be discernable. intrathoracic pressures into the cardiac taking should aid in identifying systemic With high atrial pressures, the rapid right chambers. The respiratory variation in disorders or infections. Clinical ventricular fi lling causes the ventricle ventricular fi lling velocity in restrictive evaluation followed by logical usage of to “knock” onto the rigid thickened cardiomyopathy is usually minimal (less various investigative modalities should pericardial shell in very early diastole – than 10 percent), while patients with help in arriving at the diagnosis of the “pericardial knock”. CP may have respiratory variations as constrictive pericarditis. Cardiac cath The important bedside clues, which high as 30 to 40 percent in ventricular may not be required in every case, if the one should remember, are a prominent fi lling velocity (similar to that seen in other tests produce a decisive conclusion. “y” descent on JVP, a pericardial knock cardiac tamponade). Similar fi ndings (to be diff erentiated from opening snap may be present in COPD patients but in MANAGEMENT which is higher pitched, occurring later them additionally, a marked increase in Medical management has a limited role in diastole and best heard in expiration), inspiratory superior vena cava systolic with diuretics and salt restriction to absence of a palpable apex beat and a fl ow velocity would also be seen. relieve volume overload, digoxin for silent heart with no regurgitant murmurs. Measurement of hepatic venous fl ows atrial fi brillation with fast ventricular is also helpful as a reversal of forward rates, anti-infl ammatory agents if there INVESTIGATIONS fl ow during expiration is seen in CP, are features of pericardial infl ammation The next step should be to confi rm while it happens during inspiration in and treatment of specifi c aetiologies e.g. the diagnosis and investigations are restrictive cardiomyopathy. TB. Once the diagnosis of CP is made accordingly ordered i.e. ECG, Pericardial Tissue Doppler imaging records defi nitive therapy i.e. complete surgical imaging studies, serum NTpro-BNP, and the velocity of the myocardium and pericardiectomy should be done in lastly cardiac cath study. has signifi cant diagnostic value. The addition to management of comorbidities ECG may show low voltage early diastolic Doppler tissue velocity if any.8 complexes. Depolarization abnormalities at the mitral annulus (Ea) is decreased Pericardiectomy usually leads to (such as bundle branch block), ventricular (<8 cm/sec, normally >10cm/sec) in rapid hemodynamic and symptomatic hypertrophy, pathologic Q waves, or restrictive cardiomyopathy, due to improvement in 80-90% of patients who impaired atrioventricular conduction decreased myocardial relaxation in achieve symptomatic improvement to would, however, favor restrictive myocardial diseases, but is preserved NYHA Class I or II postoperatively. cardiomyopathy. Thus there are no or even increased in CP. Therefore, if The surgical procedure itself can characteristic ECG fi ndings in CP.3 the Ea is more than 8 cm/s in a patient often be a technically complex procedure Elevation of Serum NT proBNP of heart failure one should consider CP. with high mortality9 requiring extensive values would again point against CP. Additionally this preserved, or even surgical experience and aim should Pericardial imaging may be done by accentuated Ea value, gets refl ected in the be to achieve as extensive pericardial X-ray chest, Echocardiography, CT relationship between Transmitral infl ow decortication as possible.

16 Cardiology Today VOL. XXIII NO. 1 JANUARY-FEBRUARY 2019 If the surgery is performed early in REFERENCES “Constrictive pericarditis in a contemporary Danish the course of the disease as evidenced 1. Andreu Porta-Sánchez, Jaume Sagristà-Sauleda, Ignacio cohort: aetiology and outcome”. Scand Cardiovasc J. Ferreira-González, Asunción Torrents-Fernández, 2015; 49(2):101–8. by less pericardial calcifi cation and Ivo Roca-Luque, David García-Dorado. Constrictive 12. Lin Y, Zhou M, Xiao J, Wang B, Wang Z. Treating no myocardial dysfunction, then the Pericarditis: Etiologic Spectrum, Patterns of Clinical constrictive pericarditis in a Chinese single-center study: A five-year experience. Ann Thorac Surg. 2012; 94:1235– 10-12 Presentation, Prognostic Factors, and Long- term Follow- outcomes are excellent. In others up .Spanish Journal of Cardiology (Revista Española de 40. especially if patients, particularly Cardiología, English Edition).December 1, 2015. Volume 8. Adler Y, Charron P, Imazio M, et al. 2015 ESC Guidelines those with left ventricular systolic 68, Issue 12. Pages 1092-1100. for the diagnosis and management of pericardial 2. William R. Miranda and Jae K. Oh : Progress in diseases: The Task Force for the Diagnosis and dysfunction, advanced New York Heart Cardiovascular Diseases,2017-01-01, Volume 59,Issue Management of Pericardial Diseases of the European Association (NYHA) functional class, 4, Pages 369-37 Society of Cardiology (ESC)Endorsed by: The European 3. Martin M. Lewinter and Massimo Imazio.Braunwald's Association for Cardio-Thoracic Surgery (EACTS). Eur concomitant myocardial disease and also Heart Disease: A Textbook of Cardiovascular Medicine. Heart J 2015; 36:2921. comorbidities, symptoms may persist 83, Pericardial Diseases; 1662-1680. 9. Vistarini N, Chen C, Mazine A, et al. Pericardiectomy 4. Welch TD. Constrictive pericarditis: diagnosis, for Constrictive Pericarditis: 20 Years of Experience at after surgery. management and clinical outcomes. Heart 2018; the Montreal Heart Institute. Ann Thorac Surg 2015; Patients with endstage CP manifested 104:725. 100:107. by cachexia reduced resting cardiac 5. Bertog SC, Thambidorai SK, Parakh K, et al: Constrictive 7. Ha JW1, Oh JK, Ling LH, Nishimura RA, Seward JB, Tajik pericarditis: etiology and cause-specific survival after AJ .Transmitral Flow Velocity to Mitral Annular Velocity output, hypoalbuminemia or liver pericardiectomy. J Am Coll Cardiol 2004; 43: pp. 1445- Ratio Is Inversely Proportional to Pulmonary Capillary dysfunction form a group with markedly 1452. Wedge Pressure in Patients With Constrictive Pericarditis. 10. Ariyoshi T, Hashizume K, Taniguchi S, Miura T, Tanigawa Circulation. 2001;104:976–978. increased operative risk and hence K, Matsukuma S, et al. Surgical experience with chronic 6. Risk of Constrictive Pericarditis After Acute Pericarditis: pericardectomy may not be benefi cial in constrictive pericarditis. Gen Thorac Cardiovasc Surg. Massimo Imazio, Antonio Brucato, Silvia Maestroni, such cases.8 2012;60:796–802. Davide Cumetti, Riccardo Belli, Rita Trinchero, and 11. NL Landex, N Ihlemann, PS Olsen, F Gustafsson. Yehuda Adler .Circulation. 2011;124:1270–1275.

17 Cardiology Today VOL. XXIII NO. 1 JANUARY-FEBRUARY 2019 REVIEW ARTICLE

Transesophageal Echocardiography in Children with Congenital Heart Defects

SNEHAL KULKARNI Keywords  transesophageal echocardiography Abstract  transcatheter interventions Intraoperative transesophageal echocardiography (TEE) is a valuable  congenital heart defects diagnostic and monitoring tool during surgical repair of congenital heart defects (CHD). It also has a vital role in the cardiac catheterization laboratory during transcatheter interventions in children. With the development of miniaturized probes and novel techniques, applications for TEE in children for management of congenital heart defects will continue to expand.

INTRODUCTION repair of complex congenital heart Transesophageal echocardiography defects. With the availability of smaller (TEE) is regularly used in the adult sized transesophageal echocardiography cardiac population because of its probes, the use of this technique is ability to provide important diagnostic expanding.1,2,3 As the transcatheter information in older patients with interventions are increasing for treatment congenital and acquired heart diseases of complex congenital heart defects, the in various outpatient, intraoperative, and need for imaging during the procedures even intensive care unit settings. Its use in also started increasing. In addition the the pediatric population is always limited, number of adult congenital heart defects because of non-availability of small- with diffi cult transthoracic windows is sized probes for pediatric population. increasing, where the transesophageal In addition, with the development of echocardiography is regularly being used. newer higher end echocardiography The fi rst TEE probe for use in machines and imaging techniques with children (1989) consisted of a single excellent echocardiography windows plane, phased-array, 28-element, 5-MHz in children, its regular use in outpatient unit mounted on an endoscope measuring clinics has become signifi cantly less. In 6.8 mm in diameter. Then the biplane addition children need anesthesia during probe came in use and now the newer the procedure, so it becomes an invasive TEE probes are multiplane probes. The procedure in these situations. smaller probes don’t have the facility for At the same time there is always a 3 dimensional imaging. The adult probes, need for intraoperative monitoring and which can be used in bigger children assessment of residual defects after above 15kg weight, have the facility for

Dr Snehal Kulkarni is Chief-Division of Pediatric Cardiology, Kokilaben Ambani Hospital & Research Center, Mumbai

18 Cardiology Today VOL. XXIII NO. 1 JANUARY-FEBRUARY 2019 surgery. In addition, there is always limited time to perform complete study, Doppler alignment with TEE may not be optimal. It usually confi rms the preoperative fi ndings and assesses the immediate preoperative hemodynamics and ventricular function. The same information can be communicated to the surgical team just prior to the operation. Preoperative TEE may also facilitate the placement of central venous , selection of anesthetic agents, and use of preoperative inotropic support by demonstrating ventricular systolic function and size. Multiple studies have defi ned the need for going on bypass immediately after the recognition of residual defects.4,5 It has major impact on morbidity, mortality after surgical repair of the defects. It also reduces the postoperative stay in the intensive care units, reducing the cost for the procedures as well. TEE can assess heart function Figure 1. Description of micro TEE probe after cardiac surgery very well and helps in adjusting inotropes in the intensive 3 D imaging as well. Relative Contraindications care units. Performance of TEE in the Availability of transesophageal probes  Esophageal varices or diverticulum patient with CHD immediately after [Figure 1]  Gastric or esophageal bleeding surgery, but before chest closure, has been  Micro TEE – 2.75 Kg onwards  Severe coagulopathy a contributor to the overall excellence in  Pediatric TEE – 3.5 Kg onwards  Vascular ring/arch anomaly the outcomes of congenital heart surgery.  Adult TEE – 2D, 3D – 15 Kg and  C-spine injury or deformity Based upon the TEE and clinical fi ndings, above  Oropharyngeal injury or deformity the surgeon, in conjunction with the TEE Micro TEE and pediatric TEE probes  History of esophageal surgery echocardiographer and anesthesiologist, don’t have facility for 3 D imaging. determines whether the surgical repair is INTRAOPERATIVE acceptable. TEE provides the opportunity SPECIFIC APPLICATIONS FOR TEE IN TRANSESOPHAGEAL to detect signifi cant and potentially CHILDREN ECHOCARDIOGRAPHY treatable disease before disconnection Most of the TEE studies in children are Though there are specifi c recom- of bypass cannula, sternal closure, and performed under general anesthesia mendations for use of transesophageal return to the intensive care unit.6 In with intubation or under heavy sedation. echocardiography in all children addition, it assesses cardiac function, Pediatric TEE probe should be inserted undergoing open heart for presence of intracardiac air, and may after ensuring empty stomach. A repair of congenital heart defects, there aid in the diagnosis of cardiac rhythm nasogastric tube need to be inserted to are institutional protocols for its regular abnormalities. aspirate the stomach content prior to use in operating rooms. It depends upon inserting the TEE probe. the availability of specifi c machines with TEE IN SPECIFIC CONGENITAL small TEE probes and the expertise for LESIONS IN OPERATING ROOM CONTRAINDICATIONS doing the examination. Intraoperative Atrial Septal defects (ASD) TEE should not stand alone as the sole FOR TRANSESOPHAGEAL Though its use in regular surgical diagnostic study, since there are inherent ECHOCARDIOGRAPHY IN CHILDREN closures is not warranted, it has specifi c Absolute contraindications limitations in imaging certain important role in patients with sinus venosus defects  Esophageal obstruction or stricture structures by TTE (i.e, transverse aortic especially when the echocardiography  Unrepaired tracheoesophageal fi stula arch, aortic isthmus, distal left pulmonary windows are suboptimal in adult patients.  Severe respiratory decompensation artery, and collateral pulmonary vessels). It confi rms the presence of the defect and  Inadequate airway control The detailed diagnosis should always its size. After surgical repair, it assesses  Perforated hollow viscus be made prior to taking the patient for complete closure and smooth fl ows from

19 Cardiology Today VOL. XXIII NO. 1 JANUARY-FEBRUARY 2019 REVIEW ARTICLE

superior vena cava to right atrium and after the surgery. Intracardiac repair for Tetralogy of right upper pulmonary vein to left atrium. Fallot ( TOF), Double outlet right Atrioventricular septal defect ventricle (DORV) Ventricular septal defects This defect can be seen very well With advanced imaging techniques, Its mandatory to have TEE prior to on TEE. Though the transthoracic preoperative assessment for these lesions surgeries for multiple VSDs. The echocardiography windows are excellent is usually complete by transthoracic number, location of the defects can be in this group, it may be important to echocardiography, computed tomography demonstrated very well. In addition revise these details prior to surgery. or angiography if required. TEE plays a prolapse of aortic valve with degree All these patients defi nitely need major role in postoperative assessment as of aortic regurgitation and need for postoperative assessment on the table. residual lesions are common which have aortic valve repair can be assessed well Residual VSD, degree of atrioventricular major impact on immediate postoperative (Figure 2). As the incidence of residual valve (AV valves) regurgitation, recovery as well as long term outcomes. ventricular defects can be high, its very and ventricular TEE should evaluate residual VSDs, important to image the ventricular septum function should be assessed in all the outfl ow tracts, residual obstruction, patients before shifting the patient out of pulmonary regurgitation and ventricular operating room. There is a high chance function. Though the distal branch for reoperation if there are residual pulmonary arteries are diffi cult to defi ne, signifi cant defects (Figure 3). the proximal right ventricular outfl ow tract can be seen well (Figure 5). Surgery for AV valves Intraoperative TEE plays a very Surgery for outfl ow tracts important role in surgical repair of AV Usually preoperative assessment is valves. Repair of Ebstein’s anomaly will performed prior to surgery. TEE just prior defi nitely need postoperative assessment to surgery will help the surgical team to Figure 2. Preoperative TEE showing large for revision / replacement of tricuspid freshen up their assessment especially subaortic VSD with prolapse of right valve (Figure 4). Surgery for congenital coronary cusp in complex surgical procedures like abnormalities of left sided AV valves is ROSS operations. Postoperative TEE always a challenge in pediatric practice. helps in assessment of right ventricular Preoperative TEE helps in proper outfl ow tract and degree of pulmonary assessment of AV valve, especially for regurgitation. It has a major role in demonstration of supramitral membrane, assessment of left ventricular outfl ow subvalvar assessment. Postoperative tract and degree of aortic regurgitation TEE will help in assessment of residual and need for replacement of valves. lesion which have major impact on (Figure 6). postoperative recovery.

Figure 3. Postoperative TEE after repair of atrioventricular septal defect showing moderate left AV valve regurgitation

Figure 4. Postoperative TEE after repair of Figure 5. Postoperative TEE after repair of Tetralogy of Fallot showing wide open right Ebstein’s anomaly of tricuspid valve ventricular outflow tract with no evidence of pulmonary regurgitation

20 Cardiology Today VOL. XXIII NO. 1 JANUARY-FEBRUARY 2019 Closure of intracardiac defects in the cardiac catheterization laboratory Transcatheter closure of atrial septal defects is solely performed under the guidance of transesophageal echocardiography. It gives very important information to the operator, like size of the defects, number of defects, size of the surrounding rims, quality of the rims and its proximity to the AV valves (Figure 7,8). Proper sized device can be chosen, just on the assessment of preprocedural TEE. Placement of the device is done only under the guidance of TEE. After the deployment, the defect and the device are completely assessed (Figure 9). TEE Figure 6. Postoperative TEE after surgical closure of perimembranous VSD showing mild gives important information regarding aortic regurgitation proper placement of device, residual Atrial switch operations procedures in catheterization laboratory, shunt, impingement of the device on the With the practice of early diagnosis TEE is a very important tool during AV valves causing AV valve regurgitation. of transposition of great vessels in the procedure. Regular procedures Transesophageal echocardiography has neonatal life, atrial switch operations are like closure of atrial septal defects, become integral part of the procedure for 9 performed less frequently. During the ventricular septal defects are performed transcatheter closure of ASD. Certain perimembranous and muscular preoperative assessment. It is important under the guidance of transesophageal VSDs can be closed successfully in the to assess the size of left ventricle and AV echocardiography.7,8 Three dimensional cardiac catheterization laboratory. TEE valve regurgitation, if any. Postoperative TEE probes are available. These probes TEE has an important role in assessment can be used safely in bigger children of systemic and pulmonary venous during the procedures, where the baffl es, baffl e obstruction or leak. structures can be shown in 3 dimensions and the structures like ASDs, VSDs TEE IN THE CARDIAC and paravalvar leaks can be closed with CATHETERIZATION LABORATORY proper assessment. With the advent of newer complex

Figure 8. Preprocedural TEE prior to transcatheter closure of ASD – Bicaval view showing adequate SVC and IVC rims

Figure 7. Preprocedural TEE prior to transcatheter closure of showing Figure 9. Postprocedural TEE showing ASD deficient retroaortic rim closure-device in position

21 Cardiology Today VOL. XXIII NO. 1 JANUARY-FEBRUARY 2019 REVIEW ARTICLE

becomes an invasive procedure in them. surgical team and the interventional At the same time there is a growing cardiologist during the procedure for population of adult congenital heart need of reintervention or change of plan. defects. The echocardiographic windows The experience can be obtained only are suboptimal in patients because of by performing many procedures with prior multiple surgeries. TEE has bigger diff erent anatomical spectrum. potential for its use in adult patients with repaired or palliated congenital heart IMPACT OF TRANSESOPHAGEAL defects.10 ECHOCARDIOGRAPHY ON Like in adult population, TEE is OUTCOMES sometimes performed in children for Preoperative information changes the assessment of patent or surgical plan in approximately 2% of Figure 10. TEE in a patient with peri- presence of thrombus in children with patients. It is usually in complex surgical membranous VSD prior to transcatheter stroke. It is also used in children with procedures like routability of VSDs in closure prolonged fever of unknown origin to see patients with double outlet right ventricle for vegetations. or need for repair of AV valves. In 3-5% of patients, postoperative fi ndings SIDE EFFECTS AND COMPLICATIONS prompt for immediate revision. These are Overall incidence of complications mainly for residual outfl ow obstructions, reported in many series is 1-3%.11 It most residual ventricular septal defects which likely occurs in the smaller patients need closure or repair of AV valves after  Most frequent are oropharyngeal or surgical repairs of AV septal defects . In esophageal trauma addition there are minor postoperative Hoarseness fi ndings on TEE, which may not need Dysphagia immediate revision, but may need close Laceration or perforation of the follow-up on long term. oropharynx, esophagus or stomach  Ventilatory Compromise RECOMMENDATIONS FOR Figure 11. The same VSD is shown in Airway Obstruction INFECTIVE ENDOCARDITIS colours Bronchospasm, Laryngospasm PROPHYLAXIS plays an important role in the assessment Position the probe in hypopharynx Though transient bacteremia may of size, number of defects, the margins when there is no active imaging to occur after the endoscopies, infective surrounding VSD for suitability (Figure reduce the airway related problems endocarditis attributable to endoscopy 10,11). After deployment of device,  Thermal pressure trauma is very rarely reported. Endocarditis it is very important to see the proper  Arrhythmias antibiotic prophylaxis is not recommended placement of device , assessment of aortic  Compression of other adjacent for TEE procedures. and tricuspid valve regurgitation if any. structures like atria, descending As more and more complex procedures causing hypotension. SUMMARY are being performed in the catheterization TEE in pediatric patient requires special laboratory, TEE plays an important role skills and complete knowledge of during the procedures like trans-septal KNOWLEDGE, SKILLS AND TRAINING puncture in children, closure of paravalvar REQUIRED FOR PERFORMING TEE IN congenital heart defects. It has substantial leaks and placement of stents across right CHILDREN positive impact on management of ventricular outfl ow tracts. The physician performing TEE in children with congenital heart defects. pediatric patients requires training, skill There is growing need for advanced USE OF TEE IN THE OUTPATIENT and complete knowledge of congenital imaging in assessment of complex heart CLINICS heart defects. As every patient has defects. In this situation the scope of TEE As the echocardiographic windows are a diff erent spectrum of the disease, is going to expand in future. excellent in children, there is no need the physician need to know complete for regular use of TEE in children. In anatomical details of the cardiac defect REFERENCES and how to assess the surgical results 1. Stümper OF, Elzenga NJ, Hess J, Sutherland GR. addition as there is a need for anesthesia Transesophageal echocardiography in children with during the procedure in children, it after the procedure. They needs to give congenital heart disease: An initial experience. J Am Coll clear and complete information to the Cardiol 1990;16:433-41.

22 Cardiology Today VOL. XXIII NO. 1 JANUARY-FEBRUARY 2019 2. Weintraub R, Shiota T, Elkadi T, Golebiovski P, Zhang J, 5. Ungerleider RM, Kisslo JA, Greeley WJ, Li JS, Kanter RJ, 8. Rigby ML. Transesophageal echocardiography during Rothman A, et al. Transesophageal echocardiography Kern FH, et al. Intraoperative echocardiography during interventional cardiac catheterization in congenital heart in infants and children with congenital heart disease. congenital heart operations: Experience from 1000 cases. disease. Heart 2001;86:1123-9. Circulation 1992;86:711-22. Ann Thorac Surg 1995;60:S539-42. 9. Elzenga NJ. The role of echocardiography in transcatheter 3. Ritter SB. Transesophageal real-time echocardiography in 6. Rosenfeld HM, Gentles TL, Wernovsky G, et al. Utility of closure of atrial septal defects. Cardiol Young infants and children with congenital heart disease. J Am transesophageal echocardiography in the assessment of 2000;10:474-83. Coll Cardiol 1991;18:569-80. resid- ual cardiac defects. Pediatr Cardiol 1998;19:346- 4. Stevenson JG, Sorensen GK, Gartman DM, Hall DG, 51. 10. Masani ND. Transesophageal echocardiography in adult Rittenhouse EA. Transesophageal echocardiography 7. Tumbarello R, Sanna A, Cardu G, Bande A, Napoleone A, con-genital heart disease. Heart 2001;86:1130-40. during repair of congenital cardiac defects: Identification Bini Rm. Usefulness of transesophageal echocardiography 11. Stevenson JG. Incidence of complications in pediatric or residual problems necessitating reoperation. J Am Soc in the pediatric catheterization laboratory. Am J Cardiol trans- esophageal echocardiography: experience in 1650 Echocardiogr 1993;6:356-65 1993;71:1321-5. cases. J Am Soc Echocardiogr 1999;12:527-32.

23 Cardiology Today VOL. XXIII NO. 1 JANUARY-FEBRUARY 2019 REVIEW ARTICLE

When to Refer for CABG in Today’s Era of Affordable Stents and PTCA and Wide Application of Technologies

Keywords  percutaneous transluminal coronary C N MANJUNATH, PRABHAVATHI, C RAGHAVENDRA angioplasty (PTCA)  drug-eluting stents  percutaneous coronary interventions  left main Abstract  stable ischemic heart disease Percutaneous transluminal coronary angioplasty (PTCA) reduces symptoms of angina, but its application has been limited in patients with multivessel coronary artery disease (CAD) because of signifi cant risk of periprocedural ischemic complications and moderate long- term effi cacy. In contemporary clinical practice, coronary artery bypass grafting (CABG) is recommended for treatment of complex patients, including those with multivessel coronary artery disease (MVCAD), while percutaneous coronary intervention (PCI) is preferred in patients with single-vessel disease or acute myocardial infarction (MI). Technological advancement in PCI, such as the introduction drug- eluting stents (DES) in the past decade, however, revived the debate of whether PCI is appropriate for patients with complex multivessel disease, leading to several randomized clinical trials (RCTs) investigating the clinical and cost-effectiveness of CABG compared with PCI with DES. Recent trials also showed that compared with bare-metal stents (BMS), DES were associated with signifi cantly lower restenosis rates, higher initial procedural costs, small but signifi cant risk of very late stent thrombosis, and similar mortality rates.

BACKGROUND demonstrate a signifi cant survival benefi t Since its introduction in the 1960s, when compared with PCI in certain subset coronary artery bypass grafting (CABG) of patients.8–11 The introduction of drug- has become the standard-of-care for eluting stents (DESs) into interventional patients with multivessel coronary artery cardiology has further catalyzed the trend disease.1–5 However, due to the rapid to perform coronary revascularization evolvement of percutaneous coronary more frequently by a percutaneous interventions (PCI), the number of approach and less frequently by surgery. CABGs performed has continuously Currently, 70% to 75% of all coronary decreased over the past two decades,6,7 revascularization is performed by a even though several multicentre trials percutaneous approach.12 Dr C N Manjunath is Professor of Cardiology, Director, Sri Jayadeva Institute of Cardiovascular Sciences & Research, Bannerghatta Road, 9th Block Jayanagar, Bangalore

24 Cardiology Today VOL. XXIII NO. 1 JANUARY-FEBRUARY 2019 The pre-planned land mark analysis from Table 1. 30 days to 3 years showed a signifi cant Advantages of CABG Advantages of PCI diff erence for the primary endpoint in Angina relief Initially cost effective favour of CABG (7.9 vs. 11.5%, P = Complete revascularization Fast recovery / Angina relief 0.02). Mortality benefit in selected patient groups Reduced acute complications The NOBLE (Nordic-Baltic-British (eg: stroke) Left Main Revascularization Study) Reduced reintervention Non surgical trial compared CABG with PCI using Complex anatomy new-generation DES [biolimus-eluting Disadvantages Disadvantages stents (BES)] among 1201 patients with Potential high costs, morbidity signifi cant LM disease (mean SYNTAX Invasive score of 23).19 At a median follow-up Higher rate of stroke of 3.1 years, the primary endpoint of Results are not uniform across countries Repeat revascularization death, non-procedural MI, stroke, and repeat revascularization occurred more An ideal revascularization modality COMPARISON OF CABG AND PCI frequently in the PCI than the CABG cannot be generalized to all patient Following is a table comparing group (29 vs. 19%; HR 1.48, 95% CI groups. The decision to choose PCI advantages and disadvantages of PCI vs 1.11–1.96,P = 0.007). as a revascularization strategy should CABG (Table 1). Current evidence indicates that PCI be based not only on whether it can be is an appropriate alternative to CABG done safely and successfully, based on ISOLATED PROXIMAL LEFT in LM disease and low-to-intermediate the coronary anatomy, but it should be ANTERIOR DESCENDING (LAD) CAD anatomical complexity.21 Among patients done based on evidence and favorable Comparing CABG and PCI among with LM disease and low anatomical immediate and long-term outcomes when patients with isolated proximal complexity, there is evidence that the compared to the alternative medical or LAD disease, the available evidence outcomes with respect to major clinical surgical treatment. suggests similar outcomes in terms endpoints are similar for PCI and CABG, Indications for CABG in current era of death, Myocardial infarction (MI), resulting in class I recommendation in in diff erent subsets of patients are dealt and stroke, but a higher risk of repeat ESC guidelines for revascularization separately. 13a,13b,13c revascularization with PCI. (ESC-2018).1 Among patients with LM disease and STABLE ISCHEMIC HEART DISEASE LEFT MAIN (LM) CORONARY ARTERY high anatomical complexity, the number (SIHD) DISEASE of patients studied in RCTs is low due The indications for revascularization Available evidence from Randomized to exclusion criteria. The risk estimates in patients with SIHD who receive control trials (RCTs) and meta-analyses and contraindications are imprecise, but guideline-recommended medical comparing CABG with PCI using DES suggest a trend towards better survival treatment are persistence of symptoms among patients with LM disease suggests with CABG. despite medical treatment and/or for equivalent results for the safety composite improvement of prognosis.13 of death, MI, and stroke up to 5 years of MULTIVESSEL CAD 17 follow-up. A signifi cant interaction with The observation of survival advantage WHY IS CABG BETTER THAN PCI? time is notable, providing early benefi t for of CABG over PCI has been consistent PCI treats an isolated lesion in the PCI in terms of MI and peri interventional among patients with severe three-vessel proximal vessel. CABG bypasses the stroke, which is subsequently off set by a CAD (intermediate to high SYNTAX proximal 2/3rd of the vessel, where the higher risk of spontaneous MI during score), and has been attributed at least current lesion and future threatening long-term follow-up. The need for repeat in part to the placement of bypass grafts lesions occur. This advantage of CABG revascularization is higher with PCI than to the mid coronary vessels providing will persist, even if stent restenosis is with CABG. prophylaxis against the development of zero. The EXCEL trial compared CABG new proximal disease. with PCI using new-generation DES CABG is preferred revascularization PCI VS CABG [everolimus eluting stent (EES)] among modality over PCI especially in patients Predicted surgical mortality, the 1905 patients with signifi cant LM with Multivessel CAD with diabetes or anatomical complexity of CAD, 18 disease. At 3 years of follow-up, the patients with left ventricular ejection and the anticipated completeness of primary endpoint of death, stroke, or MI fraction (LVEF) <35% as shown in revascularization are important criteria occurred with similar frequency in the trials.26 Even with newer generation stents for decision making with respect to the CABG and PCI group (14.7 vs 15.4%; like EES, trials like BEST showed benefi t type of revascularization (PCI or CABG). HR 1.00, 95% CI 0.79–1.26, P = 0.98). of CABG in reducing primary endpoint

25 Cardiology Today VOL. XXIII NO. 1 JANUARY-FEBRUARY 2019 REVIEW ARTICLE

and Aggressive Drug Evaluation) trial Table 2: Subset of people who benefi t most from CABG demonstrated an incremental benefi t Patients with survival benefit after CABG versus PCI in reducing the risk of death and MI by Three-vessel disease with high syntax scores reducing residual stress induced ischemia Multivessel disease including proximal LAD from >10% of the myocardium to <5%.14 Diabetics and Multi vessel disease In SYNTAX trial, anatomical MVD with decreased ejection fraction complete revascularization was defi ned as PCI or bypass of all epicardial vessels [death, target vessel revascularization CABG or PCI with stents, all-cause death with a diameter exceeding >1.5 mm (TVR), MI]. was signifi cantly diff erent after CABG and a luminal reduction of >50% in The available evidence suggests that (9.2%) and PCI (11.2%) (P = 0.0038), at least one angiographic view.15 Not in multivessel CAD without diabetes which was evident in patients with all CABG patients undergo complete and low anatomical complexity, PCI diabetes (10.7 vs. 15.7%, respectively; revascularization as commonly believed. and CABG achieve similar long-term P = 0.0001) but not in patients without In SYNTAX trial, only 63.2% had outcomes with respect to survival and diabetes (8.4 vs. 8.7%, respectively; complete revascularization (56.7% 2 the composite of death, MI, and stroke, P = 0.81) (P interaction= 0.0077). Current by PCI). Anatomical incomplete justifying a class I recommendation for evidence continues to favour CABG as revascularization was associated with 1 PCI (ESC 2018). the revascularization modality of choice inferior long-term outcomes after both 20,21 In patients with multivessel CAD in patients with MVD and diabetes. CABG and PCI.15 A residual SYNTAX and intermediate-to-high anatomical When patients present with a comorbidity score >8 after PCI was associated with complexity, the two large trials using that increases surgical risk, the choice of signifi cant increase in the 5-year risk of 30 31 DES, SYNTAX and BEST, found revascularization method is best decided death and of the composite of death, MI, a signifi cantly higher mortality and a by multidisciplinary individualized risk and stroke. Any residual SYNTAX score higher incidence of death, MI, and stroke assessment (Table 2). >0 was associated with the risk of repeat with PCI even in the absence of diabetes. intervention.16 The benefi t of complete Consistent results were also obtained IMPORTANCE OF COMPLETENESS revascularization was independent of the for patients with multivessel CAD in OF REVASCULARIZATION treatment modality. the recent individual patient-level meta- The aim of myocardial revascularization Off pump procedure may lead to in- 21 analysis. is to minimize residual ischaemia. In complete revascularization which was A collaborative, individual patient data support of this concept, the nuclear shown in older trials (ROOBY).28 But pooled analysis of 11,518 patients with substudy of the COURAGE (Clinical newer trials (CORONARY) have shown multivessel or LM disease randomized to Outcomes Utilizing Revascularization no signifi cant diff erence between com- pleteness of revascularization between Table 3: Characteristics of patients which decide PCI vs CABG 29 FAVOURS PCI FAVOURS CABG off pump and on pump. Clinical characteristics Clinical characteristics Presence of severe co-morbidity Diabetes CHOICE OF REVASCULARIZATION (not adequately reflected by scores) When patient is eligible for both modalities of revascularization, over all Advanced age/frailty/reduced life Reduced LV function (EF<35%) decision of PCI vs CABG depends on expectancy multiple factors like clinical, anatomical Restricted mobility and conditions that Contraindication to DAPT and technical aspects (Table 3). affect the rehabilitation process Summary of recommendations for Recurrent diffuse in-stent restenosis the type of revascularization (CABG or PCI) in patients with SIHD with suitable Anatomical & technical aspects Anatomical & technical aspects coronary anatomy for both procedures MVD with SYNTAX score 0–22 MVD with SYNTAX score >22 and low predicted surgical mortality are Anatomy likely resulting in incomplete Anatomy likely resulting in incomplete summarized in Table 3 ( ESC – 2018).1 revascularization with CABG due to poor revascularization with PCI quality or missing conduits CTO NON ST ELEVATION ACUTE Severe chest deformaties or scoliosis Severely calcified coronary artery lesions CORONARY SYNDROME (NSTE-ACS): limiting lesion expansion Approximately 5–10% of NSTE-ACS Sequelae of chest radiation Need for concomitant interventions patients require CABG,22 and they Porcelain aorta a) Ascending aortic pathology with represent a challenging subgroup given indication for surgery their high-risk characteristics compared b) Concomitant valve surgery with patients undergoing elective

26 Cardiology Today VOL. XXIII NO. 1 JANUARY-FEBRUARY 2019 patients undergoing PCI, there has been Table 4: Recommendation for the tye of revascularization in patients with stable a marked decrease in the incidence of coronary artery disease with suitable coronary anatomy for both procedures and patients requiring emergency CABG. low predicted surgical mortalityd This is because of improvement in PCI techniques and ability to manage complications of PCI. Most common indication being iatrogenic coronary artery dissection not amenable for PCI.

B) REVASCULARIZATION IN-PATIENTS REQUIRING CONCOMITANT VALVE INTERVENTIONS CABG is recommended in patients with a primary indication for aortic/mitral valve surgery and coronary artery diameter stenosis >70%. (class I ESC2018) and 50–70% (class IIa ESC2018).

C) ISCHEMIA POST CABG In this subset of patients redo CABG has two to four fold increased mortality compared with fi rst-time CABG, and

SYNTAX score calculation information is available at http://www.syntaxscore.com repeat CABG is generally performed CABG = coronary artery bypass grafting, CAD = coronary artery disease; LAD = left anterior descending coronary artery; PCI = percutaneous coronary infrequently. In view of the higher risk intervention; SYNTAX = Synergy between Percutaneous Coronary Intervention with TAXUS and Cardiac Surgery. aClass of recommendation. bLevel of evidence. cPCI should be considered if the Heart Team is concerned about the surgical risk or if the patient refuses of procedural mortality with redo CABG CABG after adequate counselling by the Heart Team. dFor example, absence of previous cardias surgery, severe morbidities, frailty, or immobility precluding CABD and the similar long-term outcome, PCI is the preferred revascularization strategy in CABG.23 In the absence of randomized studies compared the outcome of CABG patients with amenable anatomy.27 data, optimal timing for non-emergent with that of PCI in 1246 patients with CABG in NSTE-ACS patients should stabilized NSTE-ACS and multivessel or NEWER SURGICAL TECHNIQUES: be determined individually. The risk LM disease.25 The 5-year incidence of the During the last decade, newer of ischemic events possibly related to primary outcome (composite of death, suboptimal antiplatelet therapy while MI, or stroke) was signifi cantly lower techniques have been introduced for awaiting surgery is <0.1%, while that with CABG than with PCI (13.4 vs.18%, CABG to improve the surgical outcomes. of perioperative bleeding complications P = 0.036). The fi ndings of this meta- 1) Multiple arterial grafts: Various associated with platelet inhibitors is analysis were consistent with the main arterial conduits are being used like >10%.24 In patients with ongoing ischemia fi ndings of the studies included, thus bilateral internal mammary artery, or hemodynamic instability with an supporting the concept that the principles gastro epiploic artery, radial artery. indication for CABG, emergency surgery of SIHD should apply to stabilized But real-world usage of multiple should be performed and not postponed patients with NSTE-ACS as well. arterial grafts is still less. as a consequence of antiplatelet treatment 2) Minimally invasive direct CABG exposure. ST ELEVATION MI (STEMI) PATIENTS: (MIDCAB) In the setting of STEMI, PCI as primary 3) Hybrid MIDCAB approach PCI VS CABG IN STABILIZED PCI or as pharmocoinvasive is the 4) Robotic assisted CABG PATIENTS WITH NSTE-ACS: preferred reperfusion strategy. CABG 5) Instrumentation: Introduction of There is no randomized comparison of should be considered in patients with cardiac stabilization devices for PCI vs. CABG in the specifi c setting ongoing ischaemia and large areas of off pump CABG like octopus and of NSTE-ACS. The currently available jeopardized myocardium if PCI of the evidence indirectly suggests that the star fi sh, Intra operative graft fl ow infarct related artery (IRA) cannot be assessment techniques. criteria applied to patients with SIHD performed (class IIa, ESC 2018). to guide the choice of revascularization 6) Methods to extend saphenous vein modality should be applied to stabilized graft patency OTHER SUBSETS OF PATIENTS patients with NSTE-ACS.25 Recent a) Endoscopic vein harvesting REFERRED FOR CABG: individual-patients data analysis from b) Research on SVG External A. EMERGENCY CABG FOR PCI: the BEST, PRECOMBAT, and SYNTAX Stenting: Despite the increase in high-risk

27 Cardiology Today VOL. XXIII NO. 1 JANUARY-FEBRUARY 2019 REVIEW ARTICLE

Kappetein AP. Coronary artery bypass grafting: Part 2--optimizing outcomes and future prospects. Eur Heart J. 2013;34:2873-86. 8. Farkouh ME,et al. Strategies for multivessel revascularization in patients with diabetes. N Engl J Med. 2012;367:2375-84. 9. Mohr FW, Morice MC, Kappetein AP, Feldman TE, Stahle E, Colombo A, Mack MJ, Holmes DR, Jr., Morel MA, Van Dyck N, Houle VM, Dawkins KD and Serruys PW. Coronary artery bypass graft surgery versus percutaneous coronary intervention in patients with three-vessel disease and left main coronary disease: 5-year follow- up of the randomised, clinical SYNTAX trial. Lancet. 2013;381:629-38. 10. Velazquez EJ, Lee KL, Jones RH, Al-Khalidi HR, Hill JA, Panza JA, Michler RE, Bonow RO, Doenst T, Petrie MC, Oh JK, She L, Moore VL, Desvigne-Nickens P, Sopko G, Rouleau JL and Investigators S. Coronary-Artery Bypass Surgery in Patients with Ischemic Cardiomyopathy. N Engl J Med. 2016;374:1511-20. Unsupported SVG to OM Supported SVG to RCA 11. Weintraub WS, Grau-Sepulveda MV, Weiss JM, O'Brien SM, Peterson ED, Kolm P, Zhang Z, Klein LW, Shaw RE, McKay C, Ritzenthaler LL, Popma JJ, Messenger Low patency rates of saphenous decision of revascularization modality JC, Shahian DM, Grover FL, Mayer JE, Shewan CM, vein grafts remain a major predicament for patients who are eligible for both Garratt KN, Moussa ID, Dangas GD and Edwards FH. in surgical revascularization. The CABG and PCI should be individualized, Comparative effectiveness of revascularization strategies. N Engl J Med. 2012;366:1467-76. expandable SVG external support system considering associated comorbidities 12. Mack MJ, Prince SL, Herbert M, et al. Current 18-month was found to be effi cacious in reducing of patient, and should be discussed by clinical outcomes of percutaneouscoronary intervention SVGs non-uniform dilatation and Heart team containing Interventional in coronary artery bypass grafting: the CARE (Coronary ArteryREvascularzation) Study. Ann Thorac Surg. 2008. neointimal formation in an animal model cardiologist, Cardiac surgeon, and 13. Montalescot G, Sechtem U, Achenbach S, Andreotti F, early after CABG. This novel technology Cardiac anesthetist. Patient choice plays Arden C, BudajA,Bugiardini R, Crea F, Cuisset T, Di Mario may have the potential to improve SVG an important role in taking fi nal decision. C, Ferreira JR, Gersh BJ, GittAK,Hulot JS, Marx N, Opie LH, Pfisterer M, Prescott E, RuschitzkaF,SabateM,Senior patency rates after surgical myocardial Improvement in PCI techniques R, Taggart DP, van der Wall EE, Vrints CJ. 2013 ESC revascularization. and wide spread use of newer imaging guidelines on themanagement of stable coronary artery. modalities for assisting PCI may improve Eur Heart J 2013;34:2949–3003. 13a. Thiele H, Neumann-Schniedewind P, Jacobs S, Boudriot GAPS IN EVIDENCE IN MODERN ERA outcomes of PCI and can further reduce E, Walther T, Mohr FW, Schuler G, Falk V. Randomized 1) FFR-guided surgical revasculari- the indications for CABG especially in comparison of minimally invasive direct coronary artery zation has been associated with complex CAD. bypass surgery versus sirolimus-eluting stenting in isolated proximal left anterior descending coronary artery improved graft patency, but more stenosis. J Am CollCardiol 2009;53:2324–2331. studies are needed to investigate REFERENCE 13b. Hannan EL, Zhong Y, Walford G, Holmes DR Jr, Venditti whether it improves clinical 1. Franz-Josef Neumann et al., 2018 ESC/EACTS Guidelines FJ, Berger PB, Jacobs AK, Stamato NJ, Curtis JP, Sharma onmyocardialRevascularization. European Heart Journal S, King SB III. Coronary artery bypass graft surgery versus outcomes. (2018) 00, 1–96. drug-eluting stents for patients with isolated proximal 2) Real world usage of newer surgical 1a. Windecker S et al ,2014 ESC/EACTS Guidelines on left anterior descending disease. J Am CollCardiol techniques is still not widespread. myocardial revascularization. Eur Heart J. 2014;35:2541- 2014;64:2717–2126. 619. 13c. Blazek S, Rossbach C, Borger MA, Fuernau G, Desch S, 3) Role of CABG in era of percutaneous 2. Fihn SD et al, 2012 ACCF/AHA/ACP/AATS/PCNA/SCAI/ Eitel I, Stiermaier T Lurz P, Holzhey D, Schuler G, Mohr FW, valve repair/replacement (TAVR, STS Guideline for the diagnosis and management of Thiele H. Comparison of sirolimuseluting stenting with Mitraclip etc..,). Studies are needed patients with stable ischemic heart disease: J Am Coll minimally invasive bypass surgery for stenosis of the left Cardiol. 2012;60:e44-e164. anterior descending coronary artery: 7-year follow-up of to compare outcomes of CABG + 3. Fihn SD et al,.2012ACCF/AHA/ACP/AATS/PCNA/SCAI/ a randomized trial.JACCCardiovascInterv 2015;8:30–38. valve repair/replacement vs PCI + STS guideline for the diagnosis and management of 14. Shaw L J et al, COURAGE Investigators. Optimal concomitant valve procedures. patients with stable ischemic heart disease: Circulation. medical therapy with or without percutaneous coronary 2012;126:e354-471. intervention to reduce ischemic burden: Results from 4. Kolh P and Windecker S. ESC/EACTS myocardial the ClinicalOutcomes Utilizing Revascularization and SUMMARY revascularization guidelines 2014. Eur Heart J. Aggressive Drug Evaluation(COURAGE) trial nuclear Although the past two decades has seen 2014;35:3235-6. substudy. Circulation 2008;117(10):1283–1291 5. Kolh P et al ,2014 ESC/EACTS Guidelines on myocardial 15. Farooq V et al. The negative impact of incomplete a diminishing role for CABG in the revascularization: Eur J Cardiothorac Surg. 2014;46:517- angiographicrevascularization on clinical outcomes management of CAD, CABG continues 92. and its association with totalocclusions: The SYNTAX to play an important role in patients with 6. Aldea GS, Bakaeen FG, Pal J, Fremes S, Head SJ, Sabik (Synergy Between Percutaneous CoronaryIntervention J, Rosengart T, Kappetein AP, Thourani VH, Firestone with Taxus and Cardiac Surgery) trial. J Am Coll diabetes and multivessel CAD and LM S, Mitchell JD and Society of Thoracic S. The Society of Cardiol2013;61:282–294. with high syntax scores. Further decrease Thoracic Surgeons Clinical Practice Guidelines on Arterial 16. Farooq V, Serruys PW, Bourantas CV, Zhang Y, Muramatsu in morbidity rate associated with CABG Conduits for Coronary Artery Bypass Grafting. Ann Thorac T, Feldman T,Holmes DR, Mack M, Morice MC, Stahle Surg. 2016;101:801-9. E, Colombo A, de Vries T, Morel MA, Dawkins KD, and increasing use of arterial grafts can 7. Head SJ, Borgermann J, Osnabrugge RL, Kieser Kappetein AP, Mohr FW. Quantification of incomplete help in increasing graft patency. Final TM, Falk V, Taggart DP, Puskas JD, Gummert JF and revascularizationand its association with five-year

28 Cardiology Today VOL. XXIII NO. 1 JANUARY-FEBRUARY 2019 mortality in the synergy between percutaneouscoronary stenting for coronary artery disease: A pooled analysis of systolicdysfunction: Everolimus-eluting stents versus intervention with taxus and cardiac surgery (SYNTAX) individualpatient data. Lancet 2018;391:939–948. coronary artery bypass graft surgery. Circulation trial validation of the residual SYNTAX score. Circulation 22. Ranasinghe I, Alprandi-Costa B, Chow V, Elliott JM, Waites 2016;133:2132–2140. 2013;128:141151. J, CounsellJT,Lopez-Sendon J, Avezum A, Goodman SG, 27.Brener SJ, Lytle BW, Casserly IP, Ellis SG, Topol EJ, Lauer 17. Giacoppo D, Colleran R, Cassese S, Frangieh AH, Granger CB, Brieger D. Risk stratificationin the setting of MS. Predictors ofrevascularization method and long-term Wiebe J, Joner M, Schunkert, H, Kastrati A, Byrne RA. non-ST elevation acute coronary syndromes 1999-2007. outcome of percutaneous coronaryintervention or repeat Percutaneous coronary intervention vs coronary artery Am J Cardiol 2011;108:617–624. coronary bypass surgery in patients with multivessel bypass grafting in patients with left main coronary artery 23. Fukui T, Tabata M, Morita S, Takanashi S. Early coronarydisease and previous coronary bypass surgery. stenosis: A systematic review and meta-analysis. JAMA and long-term outcomes of coronaryartery bypass Eur Heart J2006;27:413–418. Cardiol 2017;2:1079–1088. grafting in patients with acute coronary syndrome 28. A. L. Shroyer, F. L. Grover, B. Hattler et al., “On-pump 18. Stone GW,et al; EXCEL Trial Investigators. Everolimus- versusstable angina pectoris. J ThoracCardiovascSurg versusoff-pump coronary-artery bypass surgery,” The eluting stents or bypass surgery for left main coronary 2013;145:1577–1583. New EnglandJournal of Medicine, vol. 361, no. 19, pp. artery disease. N Engl J Med 2016;375:2223–2235. 24. Malm CJ, Hansson EC, Akesson J, Andersson M, Hesse 1827–1837, 2009. 19. MakikallioT,et al; NOBLE Study Investigators. C, Shams Hakimi C,Jeppsson A. Preoperative platelet 29.Lamy A, et al CORONARYInvestigators. Off-pump or on- Percutaneous coronary angioplasty versus coronary function predicts perioperative bleeding complicationsin pump coronary-artery bypass grafting at 30 days.NEngl J artery bypass grafting in treatment of unprotected left ticagrelor-treated cardiac surgery patients: A prospective Med 2012;366:1489–1497. main stenosis (NOBLE): a prospective, randomised, open- observationalstudy. Br J Anaesth 2016;117:309–315 30.Mohr FW, et al, Coronary artery bypass graft surgery label, non-inferiority trial. Lancet 2016;388:2743–2752. 25. Chang M, Lee CW, Ahn JM, Cavalcante R, Sotomi Y, versus percutaneous coronary intervention in patients 20. Ramanathan K, Abel JG, Park JE, Fung A, Mathew V, Taylor Onuma Y, Han M, ParkDW, Kang SJ, Lee SW, Kim YH, with three-vessel disease and left main coronary disease: CM, Mancini GBJ, Gao M, Ding L, Verma S, Humphries Park SW, Serruys PW, Park SJ. Comparison ofoutcome 5-year follow-up of the randomised, clinical SYNTAX KH, Farkouh ME. Surgical versus percutaneous coronary of coronary artery bypass grafting versus drug-eluting trial. Lancet2013;381:629–638. revascularization in patients with diabetes and acute stent implantationfor non-ST-elevation acute coronary 31.Seung-Jung Park, M.D..et al.,Trial of Everolimus-Eluting coronary syndromes. J Am CollCardiol 2017;70:2995– syndrome. Am J Cardiol2017;120:380–386. Stents or Bypass Surgery for Coronary Disease for the 3006. 26. Bangalore S, Guo Y, Samadashvili Z, Blecker S, Hannan BEST Trial investigators ,N Engl J Med 2015; 372:1204- 21. Head SJ, et al.Mortality after coronary artery bypass EL. Revascularization inpatients with multivessel 1212. grafting versus percutaneous coronaryintervention with coronary artery disease and severe left ventricular

29 Cardiology Today VOL. XXIII NO. 1 JANUARY-FEBRUARY 2019 ECG OF THE MONTH

Cause of Increase in P Wave Amplitude During Exercise Induced Tachycardia

Keywords SR MITTAL   exercise stress testing  U wave Abstract Amplitude of P wave during exercise induced tachycardia is due to fusion of U and P waves.

It is a common observation that P wave blood sugar and lipid profi le. Th ere was amplitude increases during exercise no family history of premature coronary induced stress testing. Mechanism of artery disease. He had no symptoms this change is not clear. We observed an or abnormal clinical fi ndings during interesting fi nding during treadmill stress exercise and 6 minute recovery. Blood testing. pressure and pulse rate response were Treadmill stress test was performed normal. Th ere were no ST-T changes on an asymptomatic middle aged man during exercise and recovery. as a part of routine health check up. While looking at the electro- He was a non-smoker and had normal cardiographic recordings, we observed that during second minute of recovery, there was sinus . In cycles with short R-R interval, P (marked x) wave started soon aft er T wave. U wave was not visible and P wave had increased amplitude. In the next cycle with relatively longer R-R interval (marked y), T and U waves were separated by a clear U wave and P wave amplitude decreased. Our observation suggests that during tachycardia, P wave moves towards T wave due to shortening of diastole. P wave encroaches on the U wave. Fusion of U wave and P wave increases amplitude of P wave. At a relatively slower rate, P wave moves away from T wave, U wave Figure 1. Electrocardiographic recording during second minute of recovery separates from P wave and amplitude of following a treadmill stress test. Cycle ‘X’ P wave decreases. Th ese fi ndings suggest shows absence of U wave and increased that increase in the amplitude of P wave amplitude of P wave (P1) cycle ‘y’ shows during exercise induced tachycardia is clear u wave with decrease in amplitude of following P wave (P2). due to fusion of U and P waves.

Dr. SR Mittal is Head, Department of Cardiology at Mittal Hospital and Research Centre, Ajmer, Rajasthan

30 Cardiology Today VOL. XXIII NO. 1 JANUARY-FEBRUARY 2019 PICTORIAL CME

Isolated Tricuspid Valve Prolapse

Keywords SR MITTAL  echocardiography  non ejection click  right ventricle  systolic murmur Abstract  tricuspid valve prolapse  tricuspid regurgitation Tricuspid valve prolapse is mostly associated with mitral valve prolapse. Isolated tricuspid valve prolapse is rare with occasional case reports. It occurs mostly due to congenital abnormalities of the tricuspid valve apparatus or myxomatous degeneration. Most of the patients are asymptomatic and are diagnosed during routine echocardiography. There may be no abnormal fi ndings on clinical examination of cardiovascular system. Some patients may have non-ejection click and / or mid to late systolic murmur in the left lower parasternal region. Inspiratory delay in click and / or inspiratory increase in intensity of murmur strongly suggest the diagnosis of tricuspid valve prolapse but are usually not apparent on clinical examination. Electrocardiogram and skiagram of chest do not give any diagnostic information. Echocardiography shows buckling of one or more tricuspid leafl ets into right atrium during systole. Evaluation of posterior leafl et may be diffi cult on 2-dimensional echocardiography. Three-dimensional echocardiography allows simultaneous evaluation of all three leafl ets. Tricuspid regurgitation is usually mild to moderate. Severe tricuspid regurgitation and right ventricular dysfunction are rare. Clinically, it is diffi cult to differentiate the tricuspid valve click from other causes of non-ejection click. Detailed echocardiographic evaluation helps in differentiating various causes of isolated low-pressure tricuspid regurgitation. Patients with isolated tricuspid valve prolapse without severe tricuspid regurgitation have normal life span, except for the risk of infective endocarditis. Patients with severe tricuspid regurgitation should have surgical intervention. Repair of the tricuspid valve is preferred over .

INTRODUCTION sis is usually made during 2-dimensional Tricuspid valve prolapse is mostly asso- echocardiography which shows buckling ciated with mitral valve prolapse, or is a of tricuspid leafl ets into right atrium in part of polyvalvular prolapse.1,2 Isolated systole. We are reporting a case of isolated tricuspid valve prolapse is rare.3 Diagno- tricuspid valve prolapse in the setting of

Dr. SR Mittal is Head, Department of Cardiology at Mittal Hospital and Research Centre, Ajmer, Rajasthan

31 Cardiology Today VOL. XXIII NO. 1 JANUARY-FEBRUARY 2019 PICTORIAL CME

Figure 2. Short axis view in end diastole (ED) and end systole (ES) Figure 1. Apical four chamber view showing prolapse of tricuspid showing flattening of interventricular septum (IVS). RV- right ventri- valve (TVP), dilated right atrium (RA) and right ventricle (RV). Left cle. LV- left ventricle. atrium (LA), mitral valve (MV) and left ventricle (LV) are normal.

idiopathic pulmonary artery hyperten- were palpable in left second intercostal interventricular septum with D shaped sion. Literature on isolated tricuspid valve space. A Grade 3/6 mid systolic murmur left ventricular cavity (Figure 2) suggestive prolapse is reviewed. was audible along left lower sternal bor- of signifi cant increase in right ventricular der. It showed no signifi cant variation pressure. Left atrium, mitral valve and left CASE REPORT with posture or respiration. Th ere was no ventricle were normal (Figure 1). A 25 years female presented with palpita- click. Examination of other systems was Color Doppler evaluation revealed tions and progressively increasing breath- normal. moderate tricuspid regurgitation TR lessness. Pulse was regular at a rate of Electrocardiogram showed mild (Figure 3). Doppler evaluation of tricuspid around 78/minute. Jugular venous pres- right axis deviation. Skiagram of chest regurgitation fl ow revealed peak gradient sure was normal with prominent ‘a’ wave. was unremarkable. Two dimensional of 67mm Hg (Figure 4). Tricuspid forward Liver was not palpable and there was no echocardiography revealed dilated right fl ow revealed impaired relaxation of right dependent oedema. Palpation of precar- atrium and right ventricle with prolapse ventricle (Figure 5). Mitral valve fl ow was dium revealed left parasternal systolic of tricuspid leafl ets (Figure 1). Th ere was normal (Figure 6). Doppler evaluation lift . Systolic pulsations and second sound systolic as well as diastolic fl attening of of hepatic vein fl ow revealed prominent

Figure 3. Apical four chamber with color Doppler showing moderate Figure 4. Pulsed Doppler evaluation of tricuspid regurgitation jet tricuspid regurgitation (TR). showing right ventricular systolic pressure of 67.7mm Hg.

32 Cardiology Today VOL. XXIII NO. 1 JANUARY-FEBRUARY 2019 atrial reversal wave (Figure 7) suggestive mostly due to congenital abnormalities of of these are coincidental or age related co- of impaired relaxation of right ventricle. the tricuspid valve apparatus4,5 or myxo- morbidities. Pulmonary artery hyperten- Findings are suggestive of idiopathic matous degeneration.6,7 Rarely it may be sion and / or dilatation of right ventricle pulmonary artery hypertension with secondary to infective endocarditis8 or can exaggerate tricuspid regurgitation but isolated prolapse of tricuspid valve and trauma to tricuspid valve.9 In other cases, are unlikely to produce tricuspid valve moderate tricuspid regurgitation. there may be no apparent cause on clini- prolapse of their own. In one case closure cal examination and echocardiography. of associated atrial septal defect resulted REVIEW OF LITERATURE ON Cause may be clear only on surgery7 or in aggravation of tricuspid valve prolapse ISOLATED TRICUSPID VALVE at autopy.5 Most of the case reports have and tricuspid regurgitation.16 Reduction PROLAPSE not mentioned any comorbidity.10-15 Some in right ventricular dimension following A. Etiology case reports have mentioned some sys- closure of ASD, probably unmasked the Isolated tricuspid valve prolapse occurs temic, pulmonary or cardiac diseases in actual severity of prolapse. patients with isolated tricuspid valve pro- lapse (Table 1). Th ere is, however, no evi- B. Symptoms dence that these conditions have any etio- Isolated tricuspid valve prolapse per se logical role in the development of isolated is asymptomatic10,13,15,17 even when as- tricuspid valve prolapse. We feel that most sociated with tricuspid regurgitation.18

Table 1: Comorbidities reported in some cases of isolated tricuspid valve prolapse Comorbidity Number of Reference patients Systemic disorders (a)- Polyarticular arthritis One Liddell NE et al (19) (b)- Rheumatoid arthritis One Bettegowda S et al (17) Figure 5. Pulsed Doppler evaluation of 2. Systemic hypertension triscuspid flow showing A wave larger - with concentric left ventricular hypertrophy One Weinreich DJ et al (5) than E wave. - with diabetes mellitus and Ischemic left ventricular systolic dysfunction. One Weinreich DJ et al (5)

3. Coronary artery disease. Three Chandraratna PAN et al (6)

4. Idiopathic hypertrophic subaortic stenosis One Chandraratna PAN et al (6)

5. Dilated cardiomyopathy One Tei C et al (22)

6. Mitral stenosis One Tei C et al (22) 7. Mitral regurgitation secondary to chordal rupture One Werner JA et al (9)

Figure 6. Pulsed Doppler evaluation show- ing normal mitral flow. 8. Congenital heart disease - PFO with atrial septal aneurysm. One Kocabay G et al (3) - Atrial septal defect One Horgan JH et al (38) Three Chandraratna PAN et al (6) - Post ASD repair One Tei C et al (22) - Ebstein anomaly of Tricuspid valve with One Chandraratna PAN et al (6) ASD. One Jacques AM et al (7) - Congenitally bicuspid aortic valve.

9. Chronic disease Two Shimada E et al (39) - Corpulmonale One Werneich et al (5) - Progressive respiratory insufficiency One Sassel & Froelich CR (24) - Sarcoidosis and systemic hypertension One Karayannis E et al (40) Figure 7. Pulsed Doppler evaluation of hepatic vein flow showing prominent - Idiopathic pulmonary artery hypertension atrial reversal wave (A). S- systolic wave, - Pulmonary artery hypertension (cause not One Eren H et al (4) D-Diastolic wave. mentioned.

33 Cardiology Today VOL. XXIII NO. 1 JANUARY-FEBRUARY 2019 PICTORIAL CME

(i)

(ii) Figure 9. Diagram showing effect of respiration on click of tricuspid valve prolapse (TVP) and mitral valve prolapse (MVP). S1- First heart sound, C- non ejection click, M-mid to late systolic murmur, A2 aortic component of second heart sound, P2 – pulmonary component of second heart sound.

of right atrium and right ventricle.3,7,19 speed recording of and Jugular venous pressure is normal.18,19 respirometer tracing may be required for (iii) Jugular venous pulse wave form in usually diagnosis.18 In absence of such diagnostic normal18 even in presence of tricuspid fi ndings, it may be diffi cult to diff erentiate incompetence.19 Severe tricuspid a tricuspid valve prolapse click from incompetence may produce prominent ‘V’ click of mitral valve prolapse which is wave with rapid ‘Y’ descent. Liver is non relatively more common. Signifi cant pulsatile except in severe TR. Distension tricuspid regurgitation is uncommon.21 (iv) of jugular , pulsatile enlargement of Mild regurgitation may be detected Figure 8. Diagram showing auscultatory liver and dependent oedema suggest right only on color Doppler imaging and may findings in isolated tricuspid valve prolapse ventricular failure. not produce an audible murmur.22 A (i) isolated non ejection click (c) (ii) multiple Th ere may be no abnormal fi nding systolic murmur best audible along lower non ejection clicks(c) (iii) Non ejection click (c) and mid to late systolic murmur (m) on clinical examination of precordium. left sternal border suggests tricuspid (iv) isolated mid to late systolic murmur Usually it is found coincidentally on incompetence. Murmur may not show (m). S1- First heart sound, S2- second heart echocardiography performed for some appreciable variation with respiration sound. other indication. Palpation of precordium or other maneuvers.18 Murmur clearly Symptoms are usually due to associated is normal. Apical impulse is normal. increasing in intensity on inspiration illness.5 Patients with gross tricuspid re- Prominent or displaced apical impulse strongly supports the diagnosis of 3,7,14,19,23 gurgitation may complain of palpitation.14 should suggest additional left ventricular tricuspid regurgitation. Progressive fatigue, dyspnoea on exertion disease. Th ere is no parasternal heave and lower extremity oedema suggest right as right ventricular systolic pressure is D. Electrocardiogram 5,17 ventricular failure.19 Orthopnoea and normal. Presence of a systolic thrill should Th ere are no diagnostic fi ndings. paroxysmal nocturnal dyspnoea should suggest another etiology. Auscultation Rhythm is sinus. Isolated tricuspid valve suggest additional pulmonary and/or left may reveal non ejection click and / or prolapse, per se, does not produce any ventricular disease. mid to late systolic murmur (Figure 8). arrhythmia, intraventricular conduction In some patients a non ejection click may defects or repolarization abnormalities. C. Signs be the only fi nding.10,17 Tricuspid valve Any abnormalities are due to associated Th ere are no diagnostic fi ndings on sys- prolapse click should be more prominent diseases. temic examination. Like mitral valve pro- at lower left sternal border and should lapse, some patients may have skeletal move towards second sound during E. Skiagram of chest 20 abnormalities or features of connective inspiration.5,17,18 Inspiration increases It does not give any diagnostic informa- tissue disease like Marfan syndrome. diastolic volume of right ventricle tion.5,17 Abnormalities are due to associ- Th ese fi ndings have no signifi cance for resulting in delayed prolapse of tricuspid ated disease. diagnosis of isolated tricuspid valve pro- valve. Click of mitral valve prolapse lapse. occurs earlier or exhibits no changes F. Echocardiography Pulse is normal. No arrhythmias have with inspiration19 (Figure 9). Inspiratory M-mode echocardiography can only been reported even in patients with gross delay in the click may be diffi cult to detect signifi cant prolapse of anterior tricuspid regurgitation with enlargement appreciate clinically. Simultaneous high tricuspid leafl et.6,9,24 However, prolapse

34 Cardiology Today VOL. XXIII NO. 1 JANUARY-FEBRUARY 2019 attached to the right ventricular free wall leafl et27 (Figure 12). It also allows correct and septal leafl et attached to the inter- measurement of entire oval shaped ventricular septum (Figure 11-a). Poste- tricuspid annulus, something which is rior leafl et is not seen in this view. Apical not possible by 2D echocardiography.26 four chamber view also shows septal and Transesophageal echocardiography has anterior leafl ets (Figure 11-b). Posterior been used for evaluation of isolated leafl et is again not seen. Long axis plane tricuspid valve prolapse.3,19 It is useful if of the right ventricular infl ow shows an- thoracic window is not adequate. 5 Figure 10. Diagram (A) showing normal terior and posterior leafl et (Figure 11c). Color Doppler evaluation usually closure of tricuspid valve (B) showing However imaging of this view may be dif- shows mild to moderate tricuspid systolic buckling of tricuspid leaflets in fi cult at times.3 Apical four chamber view regurgitation. Severe regurgitation is isolated tricuspid valve prolapse. LA- left atrium, LV- left ventricle,, RA- right atrium, with posterior tilt (showing coronary si- uncommon. Right ventricular functions 25 RV- right ventricle, MV- Mitral valve, nus) shows septal and posterior leafl et are mostly normal. TV- tricuspid valve, TVP- tricuspid valve (Figure 11d). Inspite of using these mul- prolapse. tiple views, all three leafl ets may be vis- G. Angiography 26 can be localized to other leafl ets.15,22 In ualized only in 75% patients. Besides It is not required. It does not give any ad- detection of buckling of the leafl ets, 2-di- such situation, diagnosis is likely to be ditional information. Risks of right heart mensional echocardiography also allows catheterization and the problem of cath- missed with M-mode echocardiography. assessment of other fi ndings e.g. leafl et eter induced leafl et distortion and regur- 2-dimensional echocardiography shows redundancy, thickening, eccentric coop- gitation are additional problems.5 buckling of the leafl ets into right atrium tation and annular dilatation. in systole (Figure 10). Th is modality can Th ree dimensional echocardiography H. Diff erential diagnosis 5 evaluate all the three leafl ets. Right ven- allows simultaneous assessment of Isolated non-ejection clicks tricular infl ow view shows anterior leafl et morphology and prolapse of all three (a) Isolated mitral valve prolapse Clicks of mitral valve prolapse are better audible over cardiac apex but may be widely audible. Mitral valve prolapse clicks occur earlier with inspiration. On the other hand clicks of isolated tricuspid valve prolapse are better audible in left lower parasternal region17 and are delayed during inspiration18 (Figure 9). (b) Other causes Non ejection click have also been reported in some other conditions. Such clicks are rare. Clinical diagnosis of etiology is diffi cult. Simultaneous recording of echophonocardiography is needed before a non ejection click can be attributed to these conditions. It is also necessary to exclude any concomitant atriventricular valve prolapse. Exact pathogenesis of such clicks is not clear. (i) Atrial septal aneurysm28 During ventricular systole, left atrial pressure exceeds right atrial pressure. Sudden movement of atrial septal aneurysm to right (Figure 13) could produce a non ejection click. (ii) Adhesive pericarditis29 In adhesive pericarditis, there are Figure 11. Diagram showing various leaflets of tricuspid valve in different 2-D echocardio- fi brous adhesions between epicar- graphic view (a) right ventricular inflow view (b) apical four chamber view (c) long axis dium and visceral pericardium. Dur- view of right ventricular inflow (d) posteriorly tilted apical four chamber view, A- anterior, ing systole, myocardium contracts S- septal, P – posterior, CS- coronary sinus. and moves away from the thickened

35 Cardiology Today VOL. XXIII NO. 1 JANUARY-FEBRUARY 2019 PICTORIAL CME

Figure 18. Diagram showing cardiac apex Figure 12. Diagrammatic representation striking against left sided pneumothorax of position of various tricuspid leaflets on (P) during systole, L- left lung, D- Diastole, three dimensional echocardiography. A- S-Systole. anterior, S- septal, P- posterior. produce a non ejection click. 29 Figure 15. Diagram showing sudden move- (iv) LV aneurysm ment of atrial myxoma(M) back in atrium True left ventricular aneurysm is during systole (S), D-diastole. thin walled. During systole it bulges out due to increase in intraventricu- lar pressure (Figure 16). Th is sudden outward movement can produce a non ejection click. (v) Aneurysm of ventricular septum as- sociated with a VSD29 During systole, left ventricular pres- sure rises rapidly above right ventric- ular pressure. Th is suddenly pushes Figure 13. Diagram showing sudden the aneurysm covering the ventricu- movement of atrial septal aneurysm (A) lar septal defect towards right ventri- towards right atrium during systole. D- cle (Figure 17) and can produce a non Diastole, S-systole. ejection click. (vi) Left sided pneumothorax29 During systole, heart rotates along its long axis and apex moves anteriorly Figure 16. Diagram showing sudden dis- and touches anterior chest wall. If left tension of ventricular aneurysm (A) during pneumothorax is in contact with the systole, D- diastole, S- systole. apex of heart, during rotation the car- diac apex strikes against the pneumo- thorax (Figure 18) and can produce a non ejection click. Figure 14. Diagram showing sudden tens- ing of adhesion (A) between visceral peri- REFERENCES cardium (P) and epicardium (E) during sys- 1. Rippe JM. Angoff Y, Stoss LJ, Wynne J, Alpert JS. Multi- tole, D- Diastole, S-systole, M- myocardium. ple floppy valves; an echocardiographic syndrome. Am J pericardium. Th is results in sudden Med. 1979;66:817-24. 2. Desai HM, Amonkar GP. Idiopathic mitral valve prolapse stretching of these fi brous adhesions with tricuspid, aortic and pulmonary valve involvement: (Figure 14). Th is can produce a non an autopsy case report. Indian J Pathol Microbiol 2015; ejection click. 58 : 217-9. 29 3. Kocabay G, Sirma D, Mert, M, Tigen K. Isolated tricuspid (iii) Atrial myxoma valve prolapse: identification using two and three dimen- Pedunculated myxoma prolapses sional echocardiography and transesophageal echocardi- across atrioventricular valve during ography. Cardiovascular Journal of Africa, 2011; 22:272- Figure 17. Diagram showing sudden 3. diastole. During ventricular systole it 4. Eren H, Kalcik M, Kahveci G, Ozkan M. Tricuspid valve pushing of aneurysms (A) covering the is pushed back into the atrium (Fig- prolapse secondary to excessive long chordae evaluated ventricular septal defect towards right ure 15). Th is sudden movement can by transthoracic echocardiography. Arch Turk Soc Cardiol during systole. 2014;42:789.

36 Cardiology Today VOL. XXIII NO. 1 JANUARY-FEBRUARY 2019 5. Weinreich DJ, Bruke JF, Bharti S, Lev M. Isolated prolapse petence due to isolated tricuspid valve prolapse. Int J lapsed tricuspid valve leaflets. Am J Cardiol 1983;52: of the tricuspid valve. J Am Coll Cardiol 1985;6:475-8. Cardiol 1990;29:85-6 796-801. 6. Chandraratna PAN, Lopez JM, Fernandez JJ, Cohen LS. 15. Patane S, Marte F, Di Bella G, Di Tommaso E, Pagano GT, 23. Seder CW, Suri RM, Rehfeldt K, Pislaru S, Burkhart HM. Echocardiographic detection of tricuspid valve prolapse. Chiribiri A. Isolated tricuspid prolapse in young child. Int Robot assisted repair of tricuspid leaflet prolapse using Circulation 1975;51:823-6. J Cardiol 2009; 136:e37-8. standard valvuloplastic techniques. J Dis 7. Jacques AM van Son, Miles CM, Starr A. Tricuspid valve 16. Chandraratna PAN, Littman BB, Wilson D. The association 2012; 21:749-52. prolapse associated with myxomatous degeneration. between atrial septal defect and prolapse of the tricuspid 24. Sasse L, Froelich CR. Echocardiographic tricuspid pro- Ann Thorac Surg 1995;15:1237-9. valve. Chest 178;73:839-42. lapse and non ejection systolic click. Chest 1978;73: 8. Bashour T, Lindsay J Jr. Mid systolic click originating from 17. Bettegowda S, Iyengar VS. Pillappa SK, Koinde P. Isolated 869-70. tricuspid valve structures : a sequela of heroin induced tricuspid valve prolapse with rheumatoid arthritis- an 25. Bruce CJ, Connolly HM. Right sided valve disease. In Otto endocarditis. Chest 1975;67:620-1. unusual association. Asian Pac Health Sci 2014; 1 : 500- CM (ed). The practice of clinical echocardiography. Else- 9. Werner JA, Schiller NB, Prasquier R. Occurrence and sig- 1. vier, Philadelphia; 2012:646-62. nificance of echocardiographically demonstrated tricus- 18. Farrar MW, Engel PJ, Eppert D, Plummer S. Late systolic 26. Brown AK, Anderson V. Two dimensional echocardiogra- pid valve prolapse. Am heart J 1978;96:180-6. click from isolated tricuspid valve prolapse simulating phy and the tricuspid valve. Leaflet definition and pro- 10. Arosio G, Ettori F, Niccoli L. Isolated tricuspid valve pro- paradoxical splitting of the second heart sound. J Am lapse. Br Heart J 1983;49:495-500. lapse and meso-Lelesystolic click, Echocardiographic di- Coll Cardiol 1985;5:793-6. 27. Leeson P, Augustine D, Mitchell ARJ, Becher H. Transtho- agnosis. G Ital Cardiol 1980;10:915-20. 19. Liddell NE, Stoddard MF, Talley JD, Guinn VL, Kupersmith racic anantoms and pathology: valves. In Leeson P, Au- 11. Jackson D, Gibbs HR, Zee- Cheng CS. Isolated tricuspid J. Transesophageal echocardiographic diagnosis of iso- gustine D, Mitchell ARJ, Becher H ed. Echocardiography. valve diagnosed by echocardiography. Am J Med 1986; lated tricuspid valve prolapse with severe tricuspid regur- Oxford, United kingdom 2012;105-189. 80 :281-4. gitation. Am Heart J 1992;123:230-2. 28. Otto CM, Bonow RO. Valvular heart disease. In Mann DL, 12. Moro E, Nicolosi GL, D’ Angelo G, Zanuttini D. Isolated 20. Mardelli TJ, Morganroth J, Chen CC, Naito M, Vergel J. Zipes DP, Bonow RO (ed) Braunwald’s Heart Disease. El- tricuspid valve prolapse: identification using 2- dimen- Tricuspid valve prolapse diagnosed by cross sectional sevier, Philadelphia; 2015:1446-1514. sional and Doppler echocardiography. G Ital Cardiol echocardiography. Chest 1981;79:201-5. 29. Walsh RA, O’ Rourke RA, Shaver JA. The history, physical 1987;17:206-10. 21. Di Luzio V, Ciampani N, Capestro F, Purcaro A. Tricuspid examination and cardiac suscultation. In Fuster V, Walsh 13. Kriwisky M, Froom P, Ribak J, Cyjon A, Lewis B, Gross valve prolapse. Clincial significance and diagnostic prob- RA, Harrington RA (eds). Hurst’s The Heart. Mac Grow M. Isolated tricuspid valve prolapse. Cardiology 1988;75: lems. G Ital Cardiol 1979;9:374-82. Hill, New York; 2011: 239-306. 145-8. 22. Tei C, Shah PM, Cherian G, Trim PA, Wang M, Ormiston 14. Mittal SR, Swaroop A, Gokhroo R. Gross tricuspid incom- JA. Echocardiographic evaluation of normal and pro-

37 Cardiology Today VOL. XXIII NO. 1 JANUARY-FEBRUARY 2019 PICTORIAL CME

Congenital Fused Cervical Vertebrae

MONIKA MAHESHWARI

Th e anomalies of cervical region like fused cervical vertebrae (FCV) is of interest to anatomists, orthopedists, neurosurgeons, orthodontists and even cardiologist. It’s overall incidence of 0.4 to 0.7% and have clinical and embryological importance. In FCV two vertebrae appear both structurally and functionally as one. Th is fusion may be congenital or acquired. Acquired FCV is generally associated with diseases like tuberculosis, juvenile rheumatoid arthritis and trauma. Congenital fused cervical vertebrae is caused because of the combination of environment and genetic factors which occur during the 3rd week of pregnancy. Clinical symptoms may vary from asymptomatic to limitation of Figure 1: Cervical skiagram (lateral view) showing fused C2 and C3 vertebrae. the neck movement, muscular weakness, atrophy and neurological sensory loss or associated with Klippel-Feil syndrome (fusion of at least two vertebrae of the neck, low posterior hairline, a short webbed neck, and limited neck range of motion). Recently, we encountered one such case, which is picturized herein (Figure-1) .

Dr. Monika Maheshwari is Professor, Jawahar Lal Nehru Medical College, Ajmer, Rajasthan

38 Cardiology Today VOL. XXIII NO. 1 JANUARY-FEBRUARY 2019 CARDIOLOGY TODAY INSTRUCTIONS TO AUTHORS MANUSCRIPT tions. Identify precisely all drugs and chemicals used, includ- tify statistical measures of variations, such as standard devia- Manuscripts must be neatly typed in double space typing ing generic name(s), dose(s), and route(s) of administration. tion and standard error of the mean. Be sure that each table throughout on one side of the sheet of good quality bond pa- Authors submitting review manuscripts should include a sec- is cited in the text. If you use data from another published per of the size 28 x 22cm with 3cm margins on both sides. tion describing the methods used for locating, selecting, ex- or unpublished source, obtain permission and acknowledge Words should not be hyphenated at the end of a line. tracting, and synthesizing data. These methods should also that source fully. Authors are requested to send the article on e-mail be summarised in the abstract. Illustrations (Figures): Figures should be either professionally ([email protected]) or CD with one orginal copy of Statistics: Describe statistical methods with enough detail to drawn and photographed, or submitted as photographic-qual- the type script should be submitted alongwith to the Publisher, enable a knowledgeable reader with access to the original LW\GLJLWDOSULQWV,QDGGLWLRQ¿JXUHVFDQDOVREHLQWKHIRUPDWRI CIMS Medica India Pvt Ltd, 709, Devika Tower, Nehru Place, data to verify the reported results. When possible, quan- HOHFWURQLF¿OHV IRUH[DPSOH-3(*RU*,) /HWWHUVQXPEHUV New Delhi-1100 19. WLI\ ¿QGLQJV DQG SUHVHQW WKHP ZLWK DSSURSULDWH LQGLFDWRUV DQGV\PEROVRQ¿JXUHVVKRXOGWKHUHIRUHEHFOHDUDQGFRQVLVW- Material received for publication will be acknowledged and RI PHDVXUHPHQW HUURU RU XQFHUWDLQW\ VXFK DV FRQ¿GHQFH ent throughout, and large enough to remain legible when the the decision regarding publication will be communicated to intervals). Avoid relying solely on statistical hypothesis test- ¿JXUHLVUHGXFHGIRUSXEOLFDWLRQ)LJXUHVVKRXOGEHPDGHDV the “Author for correspondence”. ing, such as P values, which fail to convey important informa- self-explanatory as possible, since many will be used directly The manuscript of case reports/studies and original articles tion about effect size. References for the design of the study in slide presentations. Titles and detailed explanations belong should be arranged in the following sequence : Title page, and statistical methods should be to standard works when in the legends—not on the illustrations themselves. Abstract, Key Words, Introduction, Material and Methods, SRVVLEOH ZLWKSDJHVVWDWHG 'H¿QHVWDWLVWLFDOWHUPVDEEUH- Photomicrographs should have internal scale markers. Sym- Results, Discussion, Acknowledgments, References, Tables viations, and most symbols. Specify the computer software bols, arrows, or letters used in photomicrographs should con- DQGOHJHQGVWR¿JXUHV used. trast with the background. Article title: Title should be concise, easier to read and should Results: Present your results in logical sequence in the text, 3KRWRJUDSKV RI SRWHQWLDOO\ LGHQWL¿DEOH SHRSOH PXVW EH DF- include all information in the title that will make electronic re- tables, and illustrations, giving the main or most important companied by written permission to use the photograph. WULHYDORIWKHDUWLFOHERWKVHQVLWLYHDQGVSHFL¿F ¿QGLQJV¿UVW'RQRWUHSHDWDOOWKHGDWDLQWKHWDEOHVRULO- Figures should be numbered consecutively according to the $XWKRUV¶QDPHVDQGLQVWLWXWLRQDODI¿OLDWLRQV7KHQDPHRIWKH lustrations in the text; emphasise or summarise only the most RUGHULQZKLFKWKH\KDYHEHHQFLWHGLQWKHWH[W,ID¿JXUHKDV department(s) and institution(s) to which the work should be important observations. Extra or supplementary materials been published previously, acknowledge the original source attributed. and technical detail can be placed in an appendix where they and submit written permission from the copyright holder to Disclaimers, if any, Source(s) of support in the form of grants, ZLOOEHDFFHVVLEOHEXWZLOOQRWLQWHUUXSWWKHÀRZRIWKHWH[W UHSURGXFHWKH¿JXUH3HUPLVVLRQLVUHTXLUHGLUUHVSHFWLYHRI HTXLSPHQWGUXJVRUDOORIWKHVH'HFODUDWLRQRI&RQÀLFWRI or they can be published solely in the electronic version of authorship or publisher except for documents in the public Interest WKHMRXUQDO domain. Contact information for corresponding authors: The name, When data are summarised in the Results section, give nu- )RU LOOXVWUDWLRQV LQ FRORU DVFHUWDLQ ZKHWKHU WKH MRXUQDO UH- mailing address, telephone and fax numbers, and e-mail ad- meric results not only as derivatives (for example, percent- quires color negatives, positive transparencies, or color dress of the author responsible for correspondence about the ages) but also as the absolute numbers from which the de- prints. Accompanying drawings marked to indicate the region manuscript (“corresponding author-may or may not be the rivatives were calculated, and specify the statistical methods WREHUHSURGXFHGPLJKWEHXVHIXOWRWKHHGLWRU6RPHMRXUQDOV “guarantor” for the integrity of the study). The name and ad- XVHG WRDQDO\VH WKHP 5HVWULFWWDEOHV DQG¿JXUHV WRWKRVH publish illustrations in color only if the author pays the ad- dress of the author to whom requests for reprints should be needed to explain the argument of the paper and to assess ditional cost. addressed or a statement that reprints are not available from supporting data. Use graphs as an alternative to tables with $XWKRUV VKRXOG FRQVXOW WKH MRXUQDO DERXW UHTXLUHPHQWV IRU the authors. many entries; do not duplicate data in graphs and tables. ¿JXUHVVXEPLWWHGLQHOHFWURQLFIRUPDWV Abstract: Structured abstracts are preferred for all original Avoid nontechnical uses of technical terms in statistics, such Legends for Illustrations (Figures): Type or print out legends research, systematic reviews articles and case studies. The as “random” (which implies a randomising device), “normal,” for illustrations using double spacing, starting on a separate abstract should provide the background for the study or the ³VLJQL¿FDQW´³FRUUHODWLRQV´DQG³VDPSOH´ page, with Arabic numerals corresponding to the illustrations. article. In case of original research article abstract should :KHUHVFLHQWL¿FDOO\DSSURSULDWHDQDO\VHVRIWKHGDWDE\VXFK When symbols, arrows, numbers, or letters are used to iden- VWDWHWKHVWXG\¶VSXUSRVHEDVLFSURFHGXUHVPDLQ¿QGLQJV variables as age and sex should be included. tify parts of the illustrations, identify and explain each one principal conclusions, and funding sources. Discussion: Emphasise the new and important aspects of the clearly in the legend. Explain the internal scale and identify Introduction: Provide a context or background for the study study and the conclusions that follow from them in the context the method of staining in photomicrographs. WKDWLVWKHQDWXUHRIWKHSUREOHPDQGLWVVLJQL¿FDQFH 6WDWH of the totality of the best available evidence. Do not repeat UNITS OF MEASUREMENT WKHVSHFL¿FSXUSRVHRUUHVHDUFKREMHFWLYHRIRUK\SRWKHVLV in detail data or other information given in the Introduction Measurements of length, height, weight, and volume should WHVWHGE\WKHVWXG\RUREVHUYDWLRQWKHUHVHDUFKREMHFWLYHLV or the Results section. For experimental studies, it is useful be reported in metric units (meter, kilogram, or liter) or their often more sharply focused when stated as a question. Both WREHJLQWKHGLVFXVVLRQE\EULHÀ\VXPPDULVLQJWKHPDLQ¿QG- decimal multiples. WKHPDLQDQGVHFRQGDU\REMHFWLYHVVKRXOGEHFOHDUDQGDQ\ ings, then explore possible mechanisms or explanations for Temperatures should be in degrees Celsius/ Fahrenheit. SUHVSHFL¿HGVXEJURXSDQDO\VHVVKRXOGEHGHVFULEHG3URYLGH WKHVH¿QGLQJVFRPSDUHDQGFRQWUDVWWKHUHVXOWVZLWKRWKHU Blood pressures should be in millimeters of mercury, unless only directly pertinent references, and do not include data or relevant studies, state the limitations of the study, and ex- RWKHUXQLWVDUHVSHFL¿FDOO\UHTXLUHGE\WKHMRXUQDO conclusions from the work being reported. SORUHWKHLPSOLFDWLRQVRIWKH¿QGLQJVIRUIXWXUHUHVHDUFKDQG Journals vary in the units they use for reporting hematologic, Methods: The Methods section should include only informa- for clinical practice. clinical chemistry, and other measurements. Authors must tion that was available at the time the plan or protocol for the Link the conclusions with the goals of the study but avoid FRQVXOWWKH,QIRUPDWLRQIRU$XWKRUVRIWKHSDUWLFXODUMRXUQDO study was being written; all information obtained during the XQTXDOL¿HGVWDWHPHQWVDQGFRQFOXVLRQVQRWDGHTXDWHO\VXS- and should report laboratory information in both local and study belongs in the Results section. ported by the data. In particular, avoid making statements on International System of Units (SI). Editors may request that Selection and Description of Participants: Describe your HFRQRPLFEHQH¿WVDQGFRVWVXQOHVVWKHPDQXVFULSWLQFOXGHV authors add alternative or non-SI units, since SI units are not selection of the observational or experimental participants the appropriate economic data and analyses. Avoid claiming universally used. Drug concentrations may be reported in ei- (patients or laboratory animals, including controls) clearly, priority or alluding to work that has not been completed. State ther SI or mass units, but the alternative should be provided including eligibility and exclusion criteria and a description of new hypotheses when warranted, but label them clearly as in parentheses where appropriate. the source population. Because the relevance of such vari- such. ABBREVIATIONS AND SYMBOLS DEOHVDVDJHDQGVH[WRWKHREMHFWRIUHVHDUFKLVQRWDOZD\V Examples: Use only standard abbreviations; use of nonstandard ab- clear, authors should explain their use when they are included 1. Malik V, Roy D. Management of locally advanced breast breviations can be confusing to readers. Avoid abbreviations in a study report—for example, authors should explain why cancer. Cardiology Today 1997;2(5):45-51.(for Journal) in the title of the manuscript. The spelled-out abbreviation only participants of certain ages were included or why women 2. Sambasivan M. References to central nervous system in followed by the abbreviation in parenthesis should be used were excluded. The guiding principle should be clarity about the ancient texts: In: S. Venkatraman (ed). Progress in RQ¿UVWPHQWLRQXQOHVVWKHDEEUHYLDWLRQLVDVWDQGDUGXQLWRI how and why a study was done in a particular way. When Clinical Neurosciences, 11th Ed, Mediworld Publications measurement. authors use such variables as race or ethnicity, they should 1996:116-118. (for Chapter in a Book) GH¿QHKRZWKH\PHDVXUHGWKHVHYDULDEOHVDQGMXVWLI\WKHLU For full details, please refer to International Committee of Address submissions to: relevance. 0HGLFDO MRXUQDOV (GLWLRQ 8QLIRUP UHTXLUHPHQW IRU PDQX- The Publisher Technical Information: Identify the methods, apparatus (give VFULSWVXEPLWWHGWRELRPHGLFDOMRXUQDOV1(QJO-0HG CARDIOLOGY TODAY the manufacturer’s name and address in parentheses), and 324:424-8. BMJ 1991;302:338-341. SURFHGXUHVLQVXI¿FLHQWGHWDLOWRDOORZRWKHUVWRUHSURGXFHWKH Tables: Tables should capture information concisely and dis- CIMS Medica India Pvt Ltd, results. Give references to established methods, including SOD\LWHI¿FLHQWO\1XPEHUWDEOHVFRQVHFXWLYHO\LQWKHRUGHURI 709, 7th Floor, Devika Tower, Nehru Place, statistical methods (see below); provide references and brief WKHLU¿UVWFLWDWLRQLQWKHWH[WDQGVXSSO\DEULHIWLWOHIRUHDFK New Delhi-110 019. descriptions for methods that have been published but are not Give each column a short or an abbreviated heading. Authors Tel: 011-4285 4300, Fax: 011-4285 4310 ZHOONQRZQGHVFULEHQHZRUVXEVWDQWLDOO\PRGL¿HGPHWKRGV should place explanatory matter in footnotes, not in the head- give the reasons for using them, and evaluate their limita- ing. Explain all nonstandard abbreviations in footnotes. Iden- E-mail: [email protected] 39 Cardiology Today VOL. XXIII NO. 1 JANUARY-FEBRUARY 2019 40 Cardiology Today VOL. XXIII NO. 1 JANUARY-FEBRUARY 2019