Cardiovascular

Notes compiled for Pediatrics

Cardiovascular

(Med I, Block 3, CV) Contents

CV 036 Valvular Heart Disease A CV Dr. J Tam

CV 042 Valvular Heart Disease II T1 CV Dr. J Tam

CV 044 Development of the Heart and Lung L AN Dr. M Torchia

CV 045 Valvular Heart Disease III T5 CV Dr. J Tam CV 046 Congenital Heart Disease I A PD Dr. R Soni CV 048 Development of the Heart and Lung A AN Dr. M Torchia CV 049 Congenital Heart Disease II L PD Dr. R Soni CV 050 Congenital Heart Disease III T1 PD Dr. R Soni CV 075 Genetic Aspects of Cardiomyopathy L GN Dr. A Chudley

CV 076 Acquired Pediatric Heart Disease L PD Dr. R Soni

CARDIOVASCULAR COURSE: MED I BLOCK III Valvular Heart Disease I & II (CV036) OBJECTIVES: Assigned Reading to be completed prior to CV042 University of Manitoba –Faculty of Medicine Instructor: Dr. J. Tam

Objectives:

At the completion of these sessions, the student will be able to:

1. Describe the common etiology, pathology and pathophysiology of: a) aortic stenosis b) aortic regurgitation c) mitral stenosis d) mitral regurgitation e) tricuspid regurgitation 2. Apply the above knowledge to describe the clinical manifestations and physical findings of the above valvular abnormalities. 3. Describe the laboratory findings (chest x-ray, ECG, echocardiogram) that assist in the diagnosis of the above entities. 4. Relate the pathophysiology to therapeutic approaches (both medical and surgical). 5. Briefly discuss the indications for surgical intervention of valvular heart disease. 6. List the various surgical options – repair, mechanical replacement, bioprosthetic replacement, homograft replacement, autograft replacement. 7. Describe the acute and chronic pathologic changes with rheumatic heart disease. 8. Describe the common features of acute rheumatic fever.

Knowledge from these sessions will be integrated with the Clinical Skills Program to allow students to: 1. Differentiate between innocent and pathologic murmurs. 2. Distinguish between regurgitate murmurs, flow murmurs and obstructive murmurs. 3. Assess the severity of valvular heart disease based on physical examination findings alone.

References:

Please feel free to find your own page references within Lilly, Cecil‟s and Harrison‟s textbook and any other sources of information that you feel are appropriate to allow you to understand the subject material. Also see notes for Valvular Heart Disease I.

1. Kirklin and Barratt-Boyes, Cardiac Surgery, 1993. 2. Glenn‟s Thoracic and Cardiovascular Surgery, 1996. 3. L. Henry Edmunds, Jr. Cardiac Surgery in the Adult, 1997. 4. Pascoe, Teskey, Bhattacharya. Surgical Treatment of Valvular Heart Disease. Manitoba Medicine; 1989: 59(2).

CARDIOVASCULAR COURSE: MED I BLOCK III Valvular Heart Disease I & II – CV042 OBJECTIVES University of Manitoba –Faculty of Medicine Instructor: Dr. J. Tam (2006)

Objectives: NB: See assigned study CV036

At the completion of the sessions, the student will be able to:

1. Describe the common etiology, pathology and pathophysiology of: f) aortic stenosis g) aortic regurgitation h) mitral stenosis i) mitral regurgitation j) tricuspid regurgitation 2. Apply the above knowledge to describe the clinical manifestations and physical findings of the above valvular abnormalities. 3. Describe the laboratory findings (chest x-ray, ECG, echocardiogram) that assist in the diagnosis of the above entities. 4. Relate the pathophysiology to therapeutic approaches (both medical and surgical). 5. Briefly discuss the indications for surgical intervention of valvular heart disease. 6. List the various surgical options – repair, mechanical replacement, bioprosthetic replacement, homograft replacement, autograft replacement. 7. Describe the acute and chronic pathologic changes with rheumatic heart disease. 8. Describe the common features of acute rheumatic fever.

References:

Objectives

• 1) Describe the common etiology, pathology and pathophysiology of : – aortic stenosis (we will cover today) VALVULAR HEART DISEASE – aortic regurgitation (we will cover today) – mitral stenosis (this is in your notes!!) – mitral regurgitation (we will cover today) – tricuspid regurgitation (do this on your own) James W. Tam, MD, FRCP(C), FACC • 2) Apply the above knowledge to describe the clinical manifestations and physical findings of Associate Professor of Medicine the above valvular abnormalities. (today and [email protected] on own)

Objectives Objectives

• 3) Describe the laboratory findings (chest X-ray, • 7) Describe acute and chronic changes with ECG, echocardiogram) that assist in the diagnosis of the above entities. (today and PR sessions) rheumatic heart disease • 4) Relate the pathophysiology to therapeutic • 8) Describe the common features of acute approaches (both medical and surgical). (today) rheumatic fever (read on your own) • 5) Briefly discuss the indications for surgical intervention of valvular heart disease. (later today) • 6) List various surgical options: repair, mechanical replacement, bioprosthetic replacement, homograft replacement, autograft replacement. (read this on your own)

References History

• Lilly, Pathophysiology of Heart Disease, 3rd Edition, • 54 year old man Chapter 8, pages 185 - 209; Chapter 2 pages 29 - 43 • • Cecil’s Essentials of Medicine, 4th edition Shortness of breath and chest pain on exertion. pages 10 - 19; 45 - 52 • Began 2 years ago symptoms after running 2k • Berne and Levy, Physiology, 2nd edition, • Progressed to the symptoms now at about 400m pages 249 - 255 Supplemental Sources: • WHAT IS THE DIFFERENTIAL DIAGNOSIS? Harrison’s Principles of Medicine Braunwald’s Heart Disease • WHAT ADDITIONAL INFORMATION WOULD YOU Supino PG et al, Am J Cardiol 2007; 100: 1274-81. NEED?

1 Differential Diagnosis More History

• Heart Disease – Coronary artery disease • Central tightness without radiation – Myocardial disease – Valvular heart disease • Duration is short, min after slowing or stopping – Pericardial disease • Pulmonary Disease • Increases with further walking or running – Obstructive Airways disease • Not worse with breathing, eating or a change in – Pulmonary interstitial disease – Pulmonary arterial disease body position • Other • Shortness of breath felt as an inability to – Gastroesphageal spasm “catch his breath” – Acid Reflux – Peptic Ulcer Disease

More History Refined Differential Diagnosis

• No orthopnea, PND, fainting, wheezing, • Heart Disease cough or bitter taste in the mouth (pyrosis) – Coronary artery disease – Myocardial disease – Valvular heart disease • Still able to carry out his usual activities but is – Pericardial disease unable to participate in weekend sporting • Pulmonary Disease events such as basketball or tennis. – Obstructive Airways disease – Pulmonary interstitial disease • CAN WE REFINE THE DIFFERENTIAL Dx? – Pulmonary arterial disease

More History Take a Poll of Likely Diagnosis

• Previously healthy, without known hypertension, • A) Coronary artery disease diabetes or abnormal cholesterol • B) Obstructive valvular heart disease • Never smoked • C) Regurgitant valvular heart disease • No known history of asthma, previous lung infections or allergies to medications or • D) Primary pulmonary hypertension (primary environmental elements pulmonary arterial disease) • No history of rheumatic fever • E) Pulmonary fibrosis • Brother with a heart condition in his 50’s, which required open heart surgery; ?? details

2 Physical Examination Physical Examination

• Average build, normal appearance • Apex beat is prominent and sustained • No apparent distress • S1 normal. S2 is single. S4 • HR 72 and regular. BP 150 / 90 both arms • Loud late peaking systolic ejection murmur heart • Jugular venous pressure is normal and does not everywhere, radiating well to the base of the neck increase with abdominal compression • No increase with handgrip or with standing • Carotid pulse is delayed and diminished • No diastolic murmur is heard • Chest exam is normal • Remainder of physical exam also normal

Murmurs

http://www.blaufuss.org/tutorial/ • “The noise of bloodflow in motion” • May or may not be related to valvular disease # (eg. “flow” murmur) • May or may not represent PATHOLOGY I just found this tutorial site! • May or may not represent ABNORMAL VALVE • Characteristics of murmur and association with Author won educational award for this other cardiac findings ESSENTIAL in diagnosis • Essential to have an “approach” to murmurs

Murmurs Re-order Differential Diagnosis

Systolic murmur Ejection Regurgitant or flow Left sided Right sided Right sided Left sided ?? (? valvar PS subvalvar PS supravalvar PS) "Flow" Obstructive Tricuspid Mitral Ventricular Regurgitation Regurgitation Septal Defect Fixed Dynamic

Valvar Supravalvar Muscular Aortic or membranous Hypertrophy Stenosis subvalvar (HOCM or Aortic Stenosis IHSS)

3 Time for Another Poll Pathology of the Obstruction

• A) Valvular aortic stenosis • Anatomy of aortic valve and possible location of • B) Subvalvular aortic stenosis obstruction (Hypertrophic cardiomyopathy) • SUBVALVULAR structures • C) Supravalvular aortic stenosis • Valve leaflets (VALVULAR obstruction) • D) Mitral regurgitation • SUPRAVALVULAR structures • E) Coronary artery disease

VALVULAR Obstruction Pathophysiology of Aortic Stenosis

• Calcific aortic stenosis • Valvular thickening produces fixed obstruction • Congenital defect (bicuspid or unicuspid) • Obstruction to forward flow diminishes oxygen • Rheumatic aortic stenosis supply • Compensatory hypertrophy of LV • Increases oxygen demand - - - -> angina • SHOW EXAMPLES from CD ROM • Elevation in filling pressures transmitted back to the lungs - - - > SOB and eventually pulmonary edema

Investigations Natural History of AS

• Of consequences of AS: ECG, CXR (show) • Asymptomatic phase long but variable • Symptomatic phase • Of structure of AS: echocardiogram (show) – Median survival with angina = 5 years – Median survival with syncope = 3 years • Of severity of AS: Doppler echocardiogram (show) – Median survival with CHF = 2 years – Median survival with Afib = 6 months

4 Treatment • Antibiotic prophylaxis no longer required • Avoidance of situations producing hypotension • Indications for surgery: SYMPTOMS in proper clinical setting Take a break • Surgical options: – Percutaneous balloon valvuloplasty (POOR) – Surgical repair and decalcification – Valve replacement (mechanical, bioprosthetic, homograft, autograft)

Other Valve Lesions Mitral Stenosis

• Mitral Stenosis • Etiology: Rheumatic Heart Disease (see previous • Mitral Regurgitation lecture), rarely CONGENITAL • Pathology: thickening of leaflets, cords, fusion of • Aortic Regurgitation commissures • Tricuspid Stenosis • Pathophysiology: • Tricuspid Regurgitation – obstruction to LA emptying • Pulmonic Stenosis – increased LA pressure and LA size • Pulmonic Regurgitation – reduced filling of LV and forward output • Any combination of above – increased pulmonary pressure and RV strain

Mitral Stenosis Mitral Stenosis

• Symptoms: (can be predicted from previous slide) • Signs: (can also be predicted) – shortness of breath – JVP has prominent A wave – RV enlargement (parasternal lift) – fatigue – LOUD S1 (thick mitral leaflets close at higher pressure) – pulmonary congestion and hemoptysis – OPENING SNAP (heard in early DIASTOLE) – peripheral swelling • as severity of stenosis incr, snap CLOSER to S2 – chest pain • if valve is heavily calcified and IMMOBILE, then S1 – palpitations if atrial fibrillation and SNAP not heard – DIASTOLIC murmur – severity depends on how much stenosis

5 Mitral Stenosis Mitral Stenosis

• Laboratory Findings: • Treatment: – CXR (LA enlargement) – Antibiotic prophylaxis no longer required – ECG (LA enlargement or maybe Atrial Fib) – Reduce heart rate if fast (esp in Atrial Fib) – Echo Doppler (upcoming lecture) – Diuretics maybe – Cardiac Catheterization (direct pressure measurements) – 10 y survival 64% • Prognosis (Table 8.2 of Lilly) – Balloon valvuloplasty (stretch it open) – – Asymptomatic = 84% ten year survival Surgical considerations generally when symptomatic (NYHA functional class 2 or more) – Mild symptoms = 42%, Moderate = 15%

Mitral Regurgitation Mitral Regurgitation

• Etiology and Pathology: • Symptoms (of chronic regurgitation): – maybe NONE (especially if early on) – Valvular problem (eg. rheumatic, myxomatous or prolapse, endocarditis) – shortness of breath, fatigue, etc. – Annular (LAE, LVE, pap muscle, calcium) • Signs: (extent depends on severity of • Pathophysiology: (if chronic) regurgitation) – enlarged LV (apex dilated and displaced) – progressive LA enlargement – soft S1 – progressive LV enlargement – REGURGITANT systolic murmur – eventual pulmonary hypertension • (holosystolic, blowing quality) – eventual LV muscle dysfunction (late) – S3 or even diastolic FLOW murmur

Mitral Regurgitation Mitral Regurgitation

• Laboratory: • Treatment: – CXR (LA and LV enlargement) – Antibiotic prophylaxis no longer required – ECG (LA enlargement and LVH) – Diuretics • recall that LVH denotes “more muscle” which may – ?? Medications to reduce blood pressure and to represent increased wall thickness diffusely as with AS reduce the degree of regurgitation or due to increased LV size/volume as with MR – Surgery (repair or replace) if symptomatic or even if asymptomatic if there is any hint of ventricular – Echo Doppler (upcoming lecture) dysfunction (as this is usually irreversible even with surgery)

6 ACUTE Mitral Regurgitation Aortic Regurgitation

• NO TIME for the LA and LV to adapt • Etiology and Pathology: – Valvular problem (congenital bicuspid, rheumatic, • SUDDEN increase in LA pressure leading to endocarditis) ACUTE Pulmonary Edema – Supporting Structure problem (big aortic root such as • SUDDEN loss of forward output leading to aneurysm, ectasia, Marfan) • SHOCK Pathophysiology (if CHRONIC): – progressive LV enlargement • soft S1 – eventual LV muscle dysfunction (late) • the murmur is still systolic but is NOT loud • Pathophysiology (if ACUTE): • listen for S3 – sudden cardiovascular collapse (SHOCK)

Aortic Regurgitation Aortic Regurgitation

• Symptoms (if chronic regurgitation): • Laboratory: – often NONE – CXR (LV enlargement ± dilated aorta) – progressive shortness of breath, fatigue, angina – ECG (LVH) • Signs: (extent depends on severity of – Echo Doppler (upcoming lecture) regurgitation) – increased pulse pressure, bifid carotid pulse – enlarged LV (apex dilated, displaced, hyperdynamic) – soft S2, maybe S3 – REGURGITANT diastolic m (blowing quality) – Systolic FLOW murmur

Aortic Regurgitation Infective Endocarditis

• Infection of the lining (endocardium) of the heart especially the heart valves • Treatment: – endocardial surface injury (chronic turbulence) – Antibiotic Prophylaxis no longer required – thrombus formation at site of injury – – Medications to reduce blood pressure and to reduce bacterial entry into the circulation – bacterial deposition to injured endocardium the degree of regurgitation CONTROVERSIAL • eg. ACE inhibitors, Calcium channel blockers, • For most people, the risks of taking prophylaxis antibiotics for certain hydralazine procedures outweigh the benefits • Recognize the heart conditions that lead to injury (cyanotic heart disease, – Surgical intervention (similar indications to mitral prosthetic material including artificial valves, prior endocarditis, heart transplants with valve disease) regurgitation) • Recognize the situations leading to bacterial entry (dental, GI, GU) • Recognize the bugs (you will learn treatment later)

7 Valvular Heart Disease

• Questions ??

• Hand over to Dr. Manji

8 7/21/2009

Outline • To Operate or Not to Operate – Calculation of Risk Surgery for Valvular Heart – Outcomes post operatively Disease • Prosthetic valve choices – mechanical, bioprosthetic, homografts, autografts Rizwan A. Manji – Advantages and disadvantages of the types – When to chose which type • Anatomy of aortic and mitral valves

Outline (cont’d) BEFORE WE START….. • Operative indications and techniques aortic valve disease – Aortic stenosis – aortic valve replacement, percutaneous aortic valve replacement – Aortic insufficiency – aortic valve replacement, aortic valve repair • Operative indications and techniques for mitral valve disease – Mitral regurgitation – mitral valve repair, mitral valve replacement – Mitral stenosis – mitral balloon valvuloplasty, mitral valve replacement

Acute vs. Chronic Aortic Valve and Mitral Valve

• Aortic valve – important and generally easy • Mitral valve – important and much more complicated – “Mitral valve apparatus”

“Acute” almost always requires surgery or palliation.

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Mitral valve anatomy Investigations in most patients

• Echo:

• Angiogram:

The mitral valve consists of the mitral annulus, anterior and posterior leaflets, chordae tendineae, and the papillary muscles. Mitral regurgitation may be due to a disease that primarily affects the valve leaflets, such as mitral-valve prolapse or rheumatic mitral-valve disease, or may result from alterations in the function or structure of the left ventricle, such as those induced by ischemic disease or dilated cardiomyopathy. Reproduced with permission from: Otto, CM. Clinical practice. Evaluation and management of chronic mitral regurgitation. N Engl J Med 2001; 345:740. Copyright © 2001 Massachusetts Medical Society.

NOW WE CAN GET STARTED?

• Does this patient need an operation? Calculation of Risk and Outcomes Post Surgery

Calculation of Risk Calculation of Risk (cont’d) (most look at in-hospital events or events • Need to consider pre-operative “frailty” , level of functioning and • Severity systems used independence, cognition as most will have some degree of “hit” post within 30 days of operation): cardiac surgery (eg. cognitive). – APACHE III8 • Need to also consider morbidity that may cause patient – eg. stroke, and renal failure. (Cardiac Surgery in Adult – 3rd edition) – Pennsylvania – New York – Society for Thoracic Surgeons –EuroSCORE – Veterans Administration – Parsonnet – Canadian • For many diseases and patient population, cardiac surgery is not curative, it is palliative (exceptions – aortic stenosis, left main, 3VD with decreased – Northern New England ventricular function, others). – Cleveland Clinic • Sometimes conservative medical management may be the best for the patient and the health care system.

Cardiac Surgery in Adult – 3rd edition

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Calculation of Risk (cont’d) Calculation of Risk (cont’d)

Relative risk of outcome

Variable Serious morbidity (95% CI) Mortality (95% CI) Decreased cost (95% CI) Decreased LOS (95% CI)

Congestive heart failure 4.81 (2.16–5.98) 9.20 (6.02–14.0) 0.56 (0.51–0.63) 0.79 (0.73–0.85) NYS predicted mortality risk 1.28 (1.16–1.41) 0.93 (0.89–0.97) 0.78 (0.76–0.80) Type of operation 6.04 (3.48–10.5) 0.43 (0.40–0.47) 0.53 (0.48–0.59) Creatinine > 2.5 mg/100 mL 0.40 (0.33–0.49) 0.47 (0.38–0.58) Priority 18.6 (7.42–46.6) 0.53 (0.50–0.56) Age/RBC volume (per 0.01 unit increase) 6.93 (3.21–11.5) 0.61 (0.55–0.67) 0.32 (0.30–0.36) Reoperative procedure 0.68 (0.62–0.76) Preoperative IABP 0.65 (0.56–0.75) Hypertension 5.62 (2.11–15.2) 0.86 (0.81–0.92) 0.83 (0.78–0.89) More than one prior Ml 0.83 (0.75–0.91) Dialysis-dependent renal failure 0.61 (0.47–0.78) Peripheral vascular disease 0.85 (0.71–0.94) Prior CNS disease 3.41 (2.99–4.91) 0.81 (0.72–0.92) COPD 0.87 (0.79–0.94)

Cardiac Surgery in Adult – 3rd edition Cardiac Surgery in Adult – 3rd edition

Outcomes – Chronic Aortic Outcomes - Aortic Stenosis Post OR Insufficiency Post OR

Long-term postoperative survival in aortic regurgitation

Patients with aortic regurgitation who are in functional class I or II before surgery have a survival after surgery that is similar to that expected in an age and gender matched normal population. In contrast, the outcome among patients who are in functional class III or IV before surgery is worse than for those with functional class I and II (p<0.0001) and worse than expected for a matched control group. Data from Klodas, E, Enriquez-Sarano, M, Tajik, AJ, et al, J Am Coll Cardiol 1997; 30:746.

Survival after mitral valve surgery is better for patients in NYHA class I/II Outcomes – Chronic Aortic independent of procedure Insufficiency Post OR (cont’d)

Survival in severe chronic aortic regurgitation varies with left ventricular volume

Among 246 patients with severe aortic regurgitation managed conservatively, the 10-year survival of those with a baseline left ventricular end systolic volume (LVESV) 25 mm/m2 was significantly lower than that of patients with an LVESV <25 mm/m2 (34 versus 81 percent). Survival in the patients without left ventricular dilatation was not different from expected. Data from Dujardin, KS, Enriquez-Sarano, M, Schaff, HV, et al, Long-term patient survival after mitral valve surgery for chronic mitral regurgitation is better in those with NYHA class I/II compared to those in class III/IV at the time of Circulation 1999; 99:1851. surgery. This benefit is independent of the type of procedure performed (replacement versus repair), although the outcomes are better in those undergoing repair. Data from Tribouilloy, CM, Enriquez-Sarano, M, Schaff, HV, et al, Circulation 1999; 99:400.

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What type of valve to use? Options for Valve Replacement

How to choose a valve?

• Mechanical – durability but 1%/yr risk of bleeding and 1%/yr risk of thromboembolism related to coumadin • Bioprosthetic – shorter durability (age, renal failure) but less issues with bleeding and thromboembolsim – risks of repeat OR • Homograft – endocarditis, young age, ROSS procedure

Complications of Mechanical Valve

Anatomical Considerations for the Cardiac Surgeon

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Relationships of Valves, Coronaries and Important Structures around Aortic Conduction Tissue Valve

rd Cardiac Surgery in Adult – 3 edition Edmunds et al. Cardiac Surgery in the Adult 2003

Location of Important Structures General Operative Points for Mitral Valve • Median sternotomy

• Cardiopulmonary bypass (post heparinization ~ 35000 units & start to cool)

Cardiac Surgery in Adult – 3rd edition

General Operative Points (cont’d)

• Cross clamp aorta and inject cardioplegia

Aortic Valve Surgery

• Proceed with specifics of operation

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AORTIC INSUFFICIENCY AORTIC STENOSIS NOTE: Wall thickness

Natural history of chronic aortic regurgitation mostly based upon data from nine series with a total of 593 patients followed for a mean of 6.6 years Data from Bonow, RO, Lakatos, E, Maron, BJ, et al. Serial long-term assessment of the natural history of asymptomatic patients with chronic aortic regurgitation and normal left ventricular systolic function. Circulation 1991; 84:1625.

Asymptomatic patients with normal left ventricular (LV) systolic function

Progression to symptoms and/or LV < 6 percent/year dysfunction Progression to symptoms, LV dysfunction, or death According to LV end-systolic dimension* >50 mm 19 percent/year 40 to 50 mm 6 percent/year <40 mm 0 percent/year

Progression to asymptomatic LV dysfunction Less than 3.5 percent/year

Sudden death Less than 0.2 percent/year Asymptomatic patients with LV systolic dysfunction Progression to cardiac symptoms More than 25 percent/year

Symptomatic patients Mortality rate More than 10 percent/year

ACC/AHA guideline summary: Criteria for selection of an aortic valve in patients undergoing aortic valve replacement (AVR) Class I - There is evidence and/or general agreement for the choice of a mechanical or bioprosthetic valve in patients undergoing AVR in the following settings Steps in AVR A mechanical valve in patients who already have a mechanical valve in the mitral or tricuspid position.

A bioprosthetic valve in patients who will not take or are incapable of taking warfarin or have a major contraindication to warfarin therapy.

Class IIa - The weight of evidence or opinion is in favor of the choice of a mechanical or bioprosthetic valve in patients undergoing AVR in the following settings

A bioprosthesis in patients 65 years of age who do not have risk factors for thromboembolism.

Patient preference can be considered in patients less than 65 years of age:

1. A mechanical valve is reasonable in patients who do not have a contraindication to warfarin therapy.

2. A bioprosthetic valve may be chosen after a detailed discussion of the risks of warfarin therapy compared to the likelihood of repeat valve replacement in the future.

A homograft when aortic valve re-replacement is performed for active prosthetic valve endocarditis.

Class IIb - The weight of evidence or opinion is less well established for the choice of a mechanical or bioprosthetic valve in patients undergoing AVR in the following setting

A bioprosthesis in women of child-bearing age to avoid the problems associated anticoagulation during pregnancy. Data from Bonow, RO, Carabello, BA, Chatterjee, K, et al. ACC/AHA 2006 guidelines for the management of patients with valvular heart disease. A report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Writing committee to revise the 1998 guidelines for the management of patients with valvular heart disease). J Am Coll Cardiol 2006; 48:e1. Cardiac Surgery in Adult – 3rd edition

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Various Aortic Valve Repairs LONGNECK FREESTYLE Cardiac Surgery in Adult – 3rd edition

Repair for stress fenestration

Repair of cusp prolapse

Repair for incompetent bicuspid valve Repair for dilated sinotubular junction

LONGNECK FREESTYLE LONGNECK FREESTYLE

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LONGNECK FREESTYLE LONGNECK FREESTYLE

Pre op Post op

Bentall Procedure

Mitral Valve Surgery

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Mitral Regurgitation (cont’d)

• Chronic MR: – Etiology: • Primary (problem with valve apparatus)- myxomatous mitral valve (most common in developed world, floppy valves), rheumatic (developing world), infective endocarditis, trauma, anorectic drugs, congenital • Secondary (functional) – ischemic heart disease, left ventricular systolic dysfunction, hypertrophic cardiomyopathy (papilary muscles don’t work or MITRAL REGURITATION MITRAL STENOSIS ventrical is dilated)

Note: Ventricular Geometry

ACC/AHA Guidelines: Management strategy for asymptomatic patients with chronic severe mitral regurgitation (MR) Mitral Regurgitation (cont’d)

LVEF: left ventricular ejection fraction; LVESD: left vendricular end-systolic dimension; AF: atrial fibrillation. •Mitral valve repair may be performed in asymptomatic patients with normal left ventricular function if performed by an experienced surgical team and the likelihood of •successful MV repair is greater than 90 percent. Adapted from Bonow, RO, Carabello, BA, Chatterjee, K, et al. ACC/AHA 2006 Guidelines for the management of patients •with valvular heart disease. A report of the American College of Cardiology / American Heart Association Task Force on Practice Guidelines (Writing committee to revise the •1998 guidelines for the management of patients with valvular heart disease). J Am Coll Cardiol 2006; 48:e1.

ACC/AHA guidelines: Management strategy for symptomatic patients with chronic severe mitral regurgitation (MR)

LVEF: left ventricular ejection fraction; LVESD: left ventricular end-systolic dimension. Adapted from Bonow, RO, Carabello, BA, Chatterjee, K, et al. ACC/AHA 2006 Guidelines for the management of patients with valvular heart disease. A report of the American College of Cardiology / American Heart Association Task Force on Practice Guidelines (Writing committee to revise the 1998 guidelines for the management of patients with valvular heart disease). J Am Coll Cardiol 2006; 48:e1.

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Surgical Approach Surgical Approach Lateral Atriotomy Lateral Atriotomy Superior extension Transseptal extension

Most common approach

Effective in virtually all cases

Interatrial (or Sondergaard’s) groove +/- Division of SVC

Intraoperative Assessment Mitral Valve Repair of Mitral Valve Quadrangular Resection

Direct inspection –Cold saline injection Posterior leaflet –Nerve hook –(usually middle scallop) inspection Transesophageal echo (TEE) Pledgeted annular suture

Mitral Valve Repair Sliding Leaflet Repair Mitral Valve Repair Triangular Resection

Less stress on Reduces height of posterior leaflet suture line and Used in combination with less distortion of quadrangular resection annulus (than Prophylactic / therapeutic for SAM quadrangular in some centers resection)

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Mitral Valve Repair Mitral Valve Repair Plication Artificial Chordae

Simple and durable Most effective for small prolapsing ePTFE suture from PM to the free edge segments of of prolapsing posterior leaflet segment

Gaining popularity

Mitral Valve Repair Mitral Valve Repair Anterior Leaflet Prolapse Chordal Transfer

Transpose well- supported segment of posterior leaflet to prolapsing anterior leaflet

Edge-to-edge (Alfieri) Repair, 1991

Annuloplasty Types of Annuloplasties

Purposes

• Reinforces leaflet repair Pericardium Medtronic Cosgrove-Edwards • Increases coaptation of leaflets

• Restores annular circumference

• Prevents further annular dilatation C-E Classic

Carbomedics Annuloflex Carpentier-Edwards (C-E) Physio

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Annuloplasty Complete vs. Partial Ring Only posterior annulus dilates

Advantages of partial ring –Reduce risk of injury to AoV, conduction system, & anterior leaflet MV –Reduce crossclamp & CPB time

Prolapsing middle scallop of posterior leaflet

Annuloplasty sutures

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• Post-operative management of valve surgery patients – Bleeding issues – Hemodynamics issues – Rhythm issues – Anticoagulation issues – Endocarditis, paravalvular leak, hemolysis – Patient-prosthesis mismatch

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Acknowledgments

1. Dr. Alan Menkis slides – Cardiac Sciences Program – St. Boniface Hospital 2. Dr. Luis Quinonez – Mayo Clinic slides 3. Cardiac Surgery in the Adult – 3rd Edition - Editor: Lawrence H. Cohn 4. Pathophysiology and clinical features of valvular aortic stenosis in adults Catherine M Otto, MD - www.uptodate.com 5. Pathophysiology, clinical features, and management of acute mitral regurgitation Catherine M Otto, MD – www. uptodate.com 6. Pathophysiology and stages of chronic mitral regurgitation William H Gaasch, MD – www. uptodate.com 7. Etiology, clinical features, and evaluation of chronic mitral regurgitation Catherine M Otto, MD -- www. uptodate.com 8. Course and management of chronic aortic regurgitation in adults William H Gaasch, MD 9. Surgical management of mitral stenosis Matthew J Sorrentino, MD, FACC 10. Various Google Image sites – Mayo Clinic, Yale Medical Center, Ohio University

14 CARDIOVASCULAR COURSE: MED I BLOCK III Development of the Heart [CV044] University of Manitoba –Faculty of Medicine Instructor: Dr. M. Torchia

Objectives

At the end of the study session on the development of the heart, the student should be able to:

1. Describe the developmental events occurring between the third and sixth week, which change the simple heart tube into the shape that characterizes the adult heart. 2. Explain how the major septa of the heart are formed and discuss the clinically significant atrial and ventricular septal defects. 3. Discuss the fetal circulation and the changes in the vascular system at birth. 4. Discuss the embryological basis of important congenital defects of the heart and great vessels.

Reference:

1. Moore and Persaud, The Developing Human: clinically oriented embryology 7e. pp. 330-380

Notes:

1. Primitive Heart Tube (Fig. 14-7) a. Cardiogenic region (mesoderm) is located at the most rostral part of unfolded embryo b. A pair of endocardial heart tubes develop in cardiogenic region by process of angiogenesis and neovascularization (note that the myocardium and epicardium form from surrounding mesoderm) c. As the embryo folds, endocardial heart tubes approach each other and fuse to form primitive heart tube i. Generates endothelium, myocardium, visceral pericardium and cardiac jelly d. Over time, this heart tube elongates and also forms a series of dilations termed: i. Sinus venosus – becomes coronary sinus ii. Primitive atrium – becomes atria iii. Primitive ventricle – become trabeculated parts of ventricles iv. Bulbus cordis – becomes smooth parts of both ventricles v. Truncus arteriosus – becomes aorta/pulmonary trunk e. Elongation of heart tube within confined space of developing thoracic cavity results in bending and twisting of heart tube.

CARDIOVASCULAR COURSE: MED I BLOCK III Development of the Heart [CV044] University of Manitoba –Faculty of Medicine Instructor: Dr. M. Torchia

2. Septation of Heart a. AV Septum (Fig 14-11) i. Dorsal and Ventral Endocardial (AV) cushions bulge into lumen of heart tube and fuse at the level of separation between atria and ventricles 1. DEFINITLY EXAM QUESTION 2. Neural crest cells from developing neural tube contribute to endocardial cushions, thought to control the process 3. Dorsal and ventral aspects, grow toward each other 4. Fuse 5. FIRST PARTITIONING OF THE HEART 6. Act as anchors for partitions, and believed to be the start of AV valve formation

b. Atrial Septum (Fig 14-13) i. A crescentic membrane grows from superior to inferior aspect of atria (septum primum). The ever decreasing foramen primum (window resulting from formation of septum primum) is obliterated when septum primum contacts AV cushions. ii. As the foramen primum is finally obliterated, the cells in the central portion of the septum primum undergo apoptosis resulting in the formation of the foramen secundum iii. A second partial septum – the septum secundum, develops (to the right of the septum primum) iv. In combination, the septae and foramen act as a “flap valve” (ovale foramen) allowing blood to shunt R-to-L side of heart in fetus v. At birth, the pressure changes cause this „valve‟ to close

c. Interventricular Septum (Fig 14-18) i. Composed of two distinct parts 1. Muscular component (majority of IV septum) grows from floor of ventricle towards endocardial cushions 2. Membranous component forms from AV cushions and R and L Bulbar ridges and fuses to the muscular IV septum

d. Aorticopulmonary (AP) Septum (Fig 14-21) – divides truncus arteriosus into aorta and pulmonary trunk i. Truncal and bulbar ridges grow in a spiral fashion along length of truncus arteriosus. Results from neural crest cell migration into the truncus.

CARDIOVASCULAR COURSE: MED I BLOCK III Development of the Heart [CV044] University of Manitoba –Faculty of Medicine Instructor: Dr. M. Torchia

3. Fetal circulation (Fig 14-46) a. Shunts i. Ductus arteriosus – blood shunts from pulmonary trunk to aorta (bypassing the lungs) ii. Ductus venosus – blood shunts from umbilical vein to inferior vena cava (bypassing the liver) iii. Oval foramen – blood shunts from R to L atrium (bypassing the pulmonary

4. Clinical Correlations a. Cyanotic and non-cyanotic defects b. Septal defects (p.354-356) – non cyanotic i. VSD – usually in membranous aspect

c. Persistent truncus arteriosus (p.357) - cyanotic i. Membrane splitting aorta and pulmonary doesn‟ t form d. Coarctation of aorta (p.366) – non cyanotic i. Constriction can be removed e. Tetralogy of Fallot (p.360) i. Misaligned truncal ridges 1. Pulmonary stenosis 2. Overriding aorta – overrides the ventricular septum 3. Ventricular septal defect 4. Right ventricular hypertrophy

CARDIOVASCULAR COURSE: MED I BLOCK III Valvular Heart Disease III [CV045] OBJECTIVES University of Manitoba –Faculty of Medicine Instructor: Dr. J. Tam

Objectives:

Please refer to CV36 and CV42 Objectives.

CARDIOVASCULAR COURSE: MED I BLOCK III Valvular Heart Disease III [CV045] OBJECTIVES University of Manitoba –Faculty of Medicine Instructor: Dr. J. Tam

Question #1: A forty year old female presents to hospital with marked dyspnea. She denies any past cardiac disease. She had been well until one hour prior to presentation when she noted a thumping in her chest and a sudden onset of dyspnea. She denies any previous shortness-of-breath on exertion, chest pain, ankle edema nor orthopnea. She had noticed previous bouts of chest fluttering which lasted a few minutes. These attacks were not associated with chest pain. She complains of mild chronic fatigue. She also complains of vague bouts of left inframammary chest discomfort. These discomforts do not seem to be specific on exertion.

On exam, blood pressure was 110/90. Pulse was irregular at 139 beats per minute (see attached). She was in obvious respiratory distress breathing at 25 breaths per minute. The pertinent points of her physical exam include prominent crackles throughout both lung fields, a 6 cm jugular venous distention (above the sternal angle), a normal carotid upstroke and a palpable S1 which was quite loud on auscultation. No murmurs, no extra heart sounds were otherwise audible. Chest x-ray revealed pulmonary edema and a straight left heart border.

1. What is the likely underlying valvular disease? 2. What has precipitated this bout of pulmonary edema? What is the rhythm? 3. Would you expect her stroke volume to be low, normal or high? 4. After appropriate therapy her heart rate became regular at 70 beats per minute. The following physical findings were noted: - a prominent A-wave in the jugular venous pulsations - a palpable and loud S1 - a loud single S2 - a Grade III/6 diastolic rumble with pre-systolic accentuation - a prominent opening snap a) Explain each of the above findings. b) How does the severity of the mitral stenosis relate to the murmur and the timing of the opening snap?

Question 2: A fifty year old male presents to the Emergency Room complaining of headache, backache, fever, chills and dyspnea. He had these complaints for about one week following a tooth extraction. He saw a general practitioner at the onset of the illness who diagnosed "bronchitis" and prescribed oral Ampicillin. Over the last few days his dyspnea has become quite severe at rest. He now requires four pillows in bed. He denies past symptoms of dyspnea, chest pain nor palpitations. He has been troubled with psoriasis for many years. He was told five years ago that he has a "heart murmur" and that no therapy was necessary for this.

On examination, he was in obvious respiratory distress breathing at 30 breaths per minute. His blood pressure was 160/60. His pulse was 120 and regular. He had palpable radial, ulnar and digital pulses. Capillary pulsations could be detected in his fingertips. Apex beat was hyperdynamic and felt in the fifth intercostal space just lateral to the mid-clavicular line. Carotid artery pulsations were quite prominent. A soft S1, a soft A2 with low P2 was audible. An S3 was present. Grade II/VI high pitch murmur was heard following A2. The murmur appeared to extend throughout diastole. The diastole murmur was heard best along the sternal border. The physical examination was unremarkable apart from a few petechiae evident under both eyelids. CARDIOVASCULAR COURSE: MED I BLOCK III Valvular Heart Disease III [CV045] OBJECTIVES University of Manitoba –Faculty of Medicine Instructor: Dr. J. Tam

Explain the abnormal physical findings. a) What is the underlying valvular heart disease? Is it acute, chronic or both? b) What investigations are most important in the initial management of this patient? c) What medications would be of use in stabilizing the patient?

Question 3: A seventy-three year old male collapsed at home and was brought to the Emergency Room by ambulance. On arrival he was in severe respiratory distress and was promptly intubated for respiratory failure. The past history obtained from the wife indicates the patient had been unwell for the past six months complaining of exertional fatigue, dyspnea and chest discomfort. There were two episodes of pre-syncope in the last month. These episodes were both while the patient was climbing stairs. The patient refused to seek medical advice prior to today.

On examination the blood pressure was 130/80 and the pulse was 120 beats per minute and regular. The chest had diffuse inspiratory crackles. The carotid upstroke did not seem slow. The apex beat was in the fifth intercostal space and was sustained. S1 was normal, S2 was soft and single. A Grade IV/6 mid-pitch systolic ejection murmur was heard at the aortic area and radiated to both carotids. A higher pitch mid-systolic Grade II/6 murmur was present at the apex. The EKG revealed left ventricular hypertrophy. The chest x-ray revealed pulmonary edema, a mild cardiomegaly and a prominent ascending aorta. Some calcification appeared to be present in the heart shadow on the lateral chest x-ray. An echocardiogram revealed severe calcific aortic stenosis with severe left ventricular hypertrophy and mildly globally reduced systolic function. a) What are the mechanisms of dyspnea, chest discomfort and syncope that were present in this patient prior to presentation? b) Why is S2 soft? c) Would you expect the carotid upstroke to be slow? Why is it not slow in this case? d) What drugs should be used to stabilize the patient? e) What other investigations are required prior to definitive therapy? f) What therapeutic options are there beyond medical therapy?

Question 4: A fifty-four year old male was admitted for elective cholecystectomy. He was found to have cardiomegaly on chest x-ray. He denies past medical problems or illness. He complains of easy fatigability though he attributes this to being "out of shape". He denies chest pain on exertion, orthopnea, ankle edema nor palpitations.

On examination, his blood pressure was 120/80 and his heart rate was 70 and regular. He was in no respiratory distress. His carotid upstroke was normal. The apex beat was hyperdynamic and was felt in the fifth intercostal space lateral to the mid-clavicular line. A systolic thrill was present in the vicinity of the apex beat. No jugular venous distension was evident. The S1 was soft, S2 was difficult to hear and a Grade IV/6 pansystolic murmur was audible throughout the precordium. This appeared to radiate to the axilla though was also faintly heard at the clavicles and lower neck. A Grade II/6 low pitch diastolic murmur was audible at the apex. An S3 was present. a) Explain the physical findings b) Do you think the systolic murmur is aortic stenosis or mitral regurgitation? Why? c) Do you think that mitral stenosis is also present? d) What are possible underlying etiologies of this valvular disease? How could you best determine etiology? e) Contrast the risks and benefits of surgical correction of the valvular abnormality.

7/24/2009

1 7/24/2009

2 CARDIOVASCULAR COURSE: MED I BLOCK III Congenital Heart Disease I [CV046] OBJECTIVES: Assigned Reading University of Manitoba –Faculty of Medicine Instructor: Dr. Reeni Soni

Objectives:

1. Discuss the transition from fetal physiology to postnatal physiology 2. Discuss classification of types of congenital heart disease 3. Discuss acyanotic heart lesions (left to right shunts vs. obstruction) 4. Discuss features of CHF in children 5. Discuss Eisenmenger Syndrome (etiology, prognosis) 6. Discuss cyanotic heart lesions 7. Discuss diagnostic modalities utilized in pediatrics 8. Discuss common forms of surgical intervention of CHD 9. Discuss complications associated with CHD

Reference:

Cecil. Essentials of Medicine, Ch. 5 pp. 40-44.

The following presentation will be covered in CV049

Introduction to Objectives Congenital Heart Disease • Fetal Physiology Review • Adaptation to Postnatal Circulation • Basic Pathophysiology Dr. Reeni Soni • Investigations Section of Pediatric Cardiology Department of Pediatrics and Child Health FE241 (Community Services Bldg.) • Congenital Heart Defects • Management

Fetal Physiology Fetal Physiology continued

• Fetal lungs not expanded or utilized for • Right heart blood is diverted away from the oxygenation of fetal blood (pulmonary circuit lungs at two levels: has “high resistance” • foramen ovale • maternal placenta responsible for oxygenation • ductus arteriosus (low resistance) • right sided blood mixes with left atrial blood • deoxygenated blood from body mixes with and descending aortic blood oxygenated blood from placenta in right • development of cardiac structures is atrium completed by week 5 of gestation

Fetal Physiology Fetal Hemodynamics

PULMONARY VASCULAR RESISTANCE

SYSTEMIC VASCULAR RESISTANCE

1 Transition of Circulation at Birth Transition continued

• First breaths result in expansion of lungs and • Ductal closure initially due to smooth muscle beginning of drop in pulmonary vascular contraction followed by permanent fibrosis resistance (usually complete by Day 3) • disconnection of low resistance placenta • increased left atrial pressure results in results in sudden increase in pulmonary vascular resistance functional closure of foramen ovale “trap door” followed by permanent sealing • increased arterial oxygen level promotes beginning of spontaneous closure of ductus • right ventricular blood now directed to arteriosus pulmonary vascular bed

Transition continued Postnatal Hemodynamics

• Factors which alter normal transition: SYSTEMIC – prematurity (delayed ductal closure) VASCULAR – neonatal stresses (hypoxia, acidosis, sepsis) result RESISTANCE in delayed fall in pulmonary vascular resistance • majority of fall in PVR occurs in first 48 hours but full drop occurs by 2 months of age

PULMONARY VASCULAR RESISTANCE

Normal Heart Congenital Heart Disease • Involve alterations in fetal cardiac embryology • affects 1% of all live births • defects range from insignificant to life threatening • may present as murmur, congestive heart failure or cyanosis or combination of above • timing of presentation depends on type of lesion

2 Common Terms in CHD Acyanotic Heart Defects

Stenosis: narrowing of valve, artery • Most common group Coarctation: narrowing of blood vessel • Subdivided into: Atresia: complete blockage • lesions associated with a left to right shunt Regurgitation: valve leakage • lesions associated with obstruction • presentation depends on type of lesion and severity

Lesions with Left to Right Shunt ASD

4 most common types:

• Atrial Septal Defect • Ventricular Septal Defect • Patent Ductus Arteriosus • AV Canal Defect

VSD PDA

3 AV Canal Defect Clinical Features

• All of these lesions do not present immediately as they require fall in neonatal pulmonary vascular resistance in order to manifest left to right shunt • large shunts will usually result in cardiac failure by 2-4 months of age • may be no clinical signs initially because of equal right and left ventricular pressures

Clinical Features Eisenmenger Syndrome

• All of these lesions do not present • Refers to the development of irreversible immediately as they require fall in neonatal pulmonary hypertension in someone who has pulmonary vascular resistance in order to long standing significant left to right shunt manifest left to right shunt (VSD, AV Canal etc) • large shunts will usually result in cardiac • due to permanent hypertrophy of pulmonary failure by 2-4 months of age arterioles in response to chronically excessive • may be no clinical signs initially because of blood flow equal right and left ventricular pressures • leads to progressive cyanosis and death

Manifestations of L-R Shunt Cardiac Failure in Childhood Lesions • Cardinal Signs: • tachycardia • No symptoms if shunt is small • tachypnea • signs and symptoms of cardiac failure if shunt • hepatomegaly is large • failure to thrive • frequent respiratory infections • poor growth • peripheral edema, lung crackles not commonly seen, JVP difficult to assess

4 Acyanotic Lesions with Obstruction Aortic Stenosis

• Usually obstruction of left side of circulation

• most common types: • aortic stenosis • coarctation of the aorta

Coarctation of the Aorta

Interrupted Aortic Arch Cyanotic Heart Lesions

• Usually present in newborn period when ductus arteriosus closes • suspected when infant presents with cyanosis which fails to correct with supplemental oxygen Hyperoxic Test: administration of 100% oxygen with failure to raise pO2 above 150 mmHg

5 Pulmonary Stenosis Transposition of the Great Arteries

• Commonest cause of cyanotic CHD in the newborn period • typically presents with cyanosis without a murmur • CXR typically shows “egg on a string” cardiac silhouette

Transposition of the Great Arteries

Pulmonary Atresia Tetralogy of Fallot

4 Hallmark Features: large VSD pulmonary stenosis overriding aorta right ventricular hypertrophy

commonest cause of cyanotic CHD past neonatal period

6 Tetralogy of Fallot Truncus Arteriosus

Total Anomalous Pulmonary Venous Tricuspid Atresia Return (TAPVD)

Hypoplastic Left Heart Syndrome Cyanotic Heart Disease

Stabilization: • most crucial aspect is to maintain patency of patent ductus arteriosus in ductal dependent lesions…life saving • this is accomplished by administration of Prostaglandin E1 which acts on ductal smooth muscle…should be started as soon as cyanotic CHD is suspected while awaiting definitive diagnosis

7 Diagnostic Tools Fetal Echocardiography

• Echocardiography is mainstay of • Current echocardiographic capabilities enable diagnosis…provides detailed hemodynamic detailed imaging of fetal cardiac structures and anatomical information in this age group • ideal time for assessment is 18-24 weeks • Cardiac catheterization: • early diagnosis allows for early parental • hemodynamic measurements, oximetry counselling, surgical planning, termination • angiography • performed by pediatric cardiology • CXR, EKG

Cardiac Catheterization Hemodynamic Measurements

• Catheter passed from femoral artery and vein • RA pressure usually less than LA pressure into cardiac chambers…pressures measured in • RV/PA systolic pressure usually < 30% of each chamber and oxygen saturation LV/aortic systolic pressure measured at each point • usually no pressure gradient between RV and • measurement of intracardiac shunts MPA or LV and aorta (I.e.movement of blood between systemic and pulmonary circulations)

Oximetry Important Calculations

• Refers to measurement of oxygen saturations • Systemic Blood Flow: amount of blood in various chambers pumped out to body per minute • right sided saturations usually all the same • Pulmonary Blood Flow: amount of blood (60-70%) pumped to lungs per minute • left sided saturations usually all the same (95- • Systemic to Pulmonary blood flow ratio: ratio 100%) of flow of one circuit to the other (increased in • left to right shunts…acyanotic left to right lesions, decreased in right to left • right to left shunts…cyanotic lesions)

8 Pulmonary to Systemic Flow Ratio Fick Principle (Qp:Qs Ratio) • Enables calculations of pulmonary and Aortic Sat - SVC Sat systemic blood flows LA sat - PA sat

Oxygen Consumption O2 Content Difference X Oxygen Capacity should be 1:1 in absence of intracardiac shunt

Management Interventional Catheterization

• Medical management (e.g. diuretics for cardiac failure, prostaglandin infusion) • interventional cardiac catheterization • cardiac surgery • definitive repair vs. palliative surgery • cardiac transplantation

Interventional Catheterization

9 Cardiac Surgery for CHD

• Complete Repair when possible • eg. VSD, AV Canal, Transposition • Palliative Surgery when complete repair not feasible (single ventricle circulation) • all surgery performed out of Manitoba…infants require medical stabilization prior to transport

Definitive Repair Palliative Surgery

• PA Banding • Systemic to PA Shunts • Fontan Circulation

Palliative Surgery - Systemic to PA Bidirectional Glenn Anastamosis shunt

10 Fontan Procedure Fontan Procedure

• Allows deoxygenated blood from SVC and IVC to bypass heart and go straight to lungs • oxygenated blood returns to heart and is pumped by single ventricle to rest of body • relies on passive blood flow to lungs (no pump within that portion of the circuit) • used in any lesion where there are not two viable ventricles

Complications of CHD Summary

• Endocarditis common because of turbulent • Congenital heart disease includes a wide flow…SBE prophylaxis for dental work, surgical spectrum of anatomical problems interventions • presentation can be predicted based on • chronic cyanosis can cause polycythemia, anatomy and hemodynamics thrombosis (CVA) • each case is unique…essential to reason out • increased recurrence risk in first degree the above variables each time relatives • therapeutic options available for almost all lesions in the present era

11 CARDIOVASCULAR COURSE: MED I BLOCK III Development of the Heart & Lungs [CV048] OBJECTIVES University of Manitoba –Faculty of Medicine Instructor: Dr. M Torchia

Objectives:

At the end of the study session on the development of the heart, the student should be able to:

Reference: 1. Moore and Persaud, The Developing Human: clinically oriented embryology 7e. pp. 330-380.

TAKE THESE NOTES TO THE LAB THEY ARE NOT PROVIDED IN THE LAB

CARDIOVASCULAR COURSE: MED I BLOCK III Development of the Heart & Lungs [CV048] OBJECTIVES University of Manitoba –Faculty of Medicine Instructor: Dr. M Torchia

Case 1 – Patent Ductus Arteriosus (PDA) Radiological Findings: On the Frontal radiograph, there is cardiomegaly and increased pulmonary vascularity associated with prominence of the pulmonary trunk. The Aortic arch and descending aorta are both prominent. On the lateral view, the left mainstem bronchus is displaced posteriorly by the dilated left atrium.

Discussion:  Third most common congential heart lesion (15% of total)  In the fetus the PDA shunts blood from main pulmonary artery to ascending aorta  Postnatal, increased arterial oxygenation leads to closure  Functional closure early, anatomic closure within one week  Patent ductus may be lifesaving in neonates with obstructed LV outflow or severely diminished pulmonary blood flow  In the neonate the systemic pressure>pulmonary artery pressure, leading to a L to R shunt across the PDA from aorta to pulmonary artery  Increased flow in pulmonary artery leads to increased pulmonary shunt vascularity and dilation of the LA, LV, and aorta proximal to ductus  PDA Clinical picture: 1. Classic form without severe pulmonary tension seen in older kids and associated with a continuous murmur (machinery murmur) 2. That seen in infant with large shunt and cardiac failure 3. PDA with severe pulmonary changes 4. PDA complicating respiratory distress in premature infants 5. PDA coexisting with other cardiac malformation

Other Possible radiological findings:  In a small PDA – may be normal chest X-ray  Large PDA – shunt vascularity and L sided cardiac enlargement  Thoracic aortography can define PDA  Ductus may at times be same caliber as aorta and pulmonary artery

CARDIOVASCULAR COURSE: MED I BLOCK III Development of the Heart & Lungs [CV048] OBJECTIVES University of Manitoba –Faculty of Medicine Instructor: Dr. M Torchia

Case 2 – Atrial Septal Defect Radiological Findings: Chest X-ray: The chest X-ray reveals minimal cardiomegaly (cardiothoracic ratio of 54%) with prominence of the R heart border. The lateral view shows encroachment on the retrosternal superior mediastinum by the enlarged RV. Pulmonary vascularity is increased and of the “shunt type”. The superior vena cava which normally forms the R lateral margin of the superior mediastinum is not seen. The aorta is normal.

Right ventriculography: Film 3 – trabeculated RV with unimpeded flow across the pulmonary valve into a dilated main pulmonary artery and branches Film 4 – the pulmonary veins drain into a normal sized LA Film 5 – loss of normal sharp R margin of the LA with contrast extending to the margin of the RA. Progressive opacification of the dilated RA and simultaneous opacification of the AO and PA Film 6 – retrograde injection into the R upper lobe vein shows pulmonary drainage into the LA. The superior atrial septum is intact with L- to-R shunting through a secundum type atrial septal defect in to the RA

Discussion:  Accounts for ~8% of congential heart defects  Most common congential defect presenting in adults  One of the most benign form of congential heart disease  Most common ASD – ostium secundum (60%) 1-4 cm hole in region of fossa ovalis  Hemodynamics – L-to-R shunting of blood through ASD into R heart and the pulmonary vascular bed with concomitant dilation to accommodate toe blood volume overload  L atrium does not enlarge since the increased pulmonary return is immediately shunted across the ASD

Other Possible radiological findings:  Normal chest radiograph with small shunts  Moderate size ASD – heart enlarged and increased pulmonary vascularity

CARDIOVASCULAR COURSE: MED I BLOCK III Development of the Heart & Lungs [CV048] OBJECTIVES University of Manitoba –Faculty of Medicine Instructor: Dr. M Torchia

Case 3 – Aortic Valve Stenosis Radiological Findings: Chest X-ray: The chest radiograph reveals normal heart size: the left ventricle is rounded with the apex pointed downward. The prominent ascending aorta projects to the right of the spine, forming the R superior mediastinal boarder. The aortic arch and descending aorta are normal. On the lateral view, the LV projects posterior to the inferior vena cava, and the retrosternal space is filled in posteriorly by the enlarged descending aorta.

Discussion:  Comprises ~6% of congenital cardiovascular lesions  Obstruction of LV outflow occurs at level of aortic valve in 60-75% of cases  Associated with a bicuspid valve in >50% of cases  Supravalvular stenosis is rare  Hemodynamic sequelae – related to degree of obstruction and pressure gradient across the stenotic valve and cardiac output o LV hypertrophy develops in response to increased V end-systolic pressure o Dilation does not occur until stenosis is complicated by ventricular decompensation  Most patients are asymptomatic although may have chest pain and syncope (in severe stenosis)  About 10-15% of infants with aortic stenosis develop CHF in the first 12 months of life; subsequently, CHF rarely occurs during childhood

Other Possible radiological findings:  Normal CXR in mild cases  V hypertrophy combined with dilation results in LV enlargement that is associated with downward projection of cardiac apex (often to a point below level of left hemidiaphragm)  Most consistent finding – post-stenotic dilation of the ascending aorta which is a result of the jet of blood through the stenotic valve striking the lateral aortic walls  Normal AO arch and descending AO are important in differentiating isolated AO valve stenosis from coarctation of AO (aortic valve stenosis and bicuspid aortic valve are also seen in coarctation).

CARDIOVASCULAR COURSE: MED I BLOCK III Congenital Heart Disease II [CV049] OBJECTIVES University of Manitoba –Faculty of Medicine Instructor: Dr. Reeni. Soni

Objectives:

See objectives and notes from Congenital Heart Disease I CV 46

CARDIOVASCULAR COURSE: MED I BLOCK III Congenital Heart Disease III [CV050] CLINICAL PROBLEMS University of Manitoba –Faculty of Medicine Instructor: Dr. R. Soni

Objectives:

See Objectives for Congenital Heart Disease I. & II (CV 46 and CV49).

Problem #1 A “pink” 10-week old female infant presents for assessment of a murmur and failure to thrive. Unremarkable prenatal history and delivery. Normal neonatal cardiac exam at the time of discharge from hospital on Day 2 of life.

1. What other questions should you ask the parent? 2. What features are important to assess on physical examination? 3. What is the relevance of the presence of the diastolic murmur? 4. What are the features of cardiac failure in an infant? 5. What congenital heart defects can present in this manner? 6. Did the pediatrician make a mistake during his neonatal examination? 7. What is the most important diagnostic tool in this situation? 8. What are the medical/nutritional treatment modalities available? 9. What are indications for surgical intervention?

Problem #2 You are asked to assess a newborn infant at six hours of age because of dusky colour in Thompson. The baby is fullterm with an uncomplicated prenatal course. The baby‟s vital signs are as follows: heart rate is 150 beats per minute, respiratory rate is 40-45 beats per minute, BP 70/40 right arm, oxygen saturation 70% in the right hand.

1. What other information do you want? 2. What broad categories of conditions can cause cyanosis in a newborn? 3. Describe your initial approach to the management of this infant? 4. What other test/s available in Thompson may be helpful? 5. What management will you institute while waiting for the baby to be transferred to Winnipeg for a cardiology assessment? 6. What is the most common cause of cyanosis from CHD in a newborn? 7. What else can be done to stabilize the infant prior to surgery?

Problem #3 A five year old child known to have a large ventricular septal defect since two months of age, and who has been lost to follow-up, comes to your office. At present here are mild symptoms of exercise intolerance, the child is mildly cyanosed and has the following cardiac catheterization date.

1. Explain the significance of the various saturations recorded. What is the systemic to pulmonary blood flow ratio? Is this unusual in the setting of a large VSD? 2. What is the cause of the shunting in both directions across the VSD? 3. What is the status of this child‟s pulmonary vascular resistance? 4. What do you tell the family about this child‟s prognosis? 5. What long-term complications may this child experience? 13

CARDIOVASCULAR COURSE: MED I BLOCK III Congenital Heart Disease III [CV050] CLINICAL PROBLEMS University of Manitoba –Faculty of Medicine Instructor: Dr. R. Soni

Problem #4 Two five year old boys are admitted with fever for seven days. The first one has conjunctivitis, rash, palmar erythema and lymphadenopathy. The second one has pain and swelling of his ankles and knees, loud murmur and a rash.

1. Describe the difference in your differential diagnosis for both patients. 2. What criteria are required to make a diagnosis of Kawasaki disease? 3. What is the treatment during the acute phase of this condition? How quickly should treatment be started and why? What other investigation is important? 4. What are the Jones criteria? 5. What other investigations are warranted for the second patient? 6. What treatment does patient B require in the short-term and long-term?

CARDIOVASCULAR COURSE: MED I BLOCK III Genetic Aspects of Cardiomyopathy [CV075] LECTURE NOTES University of Manitoba –Faculty of Medicine Instructor: Dr. A. Chudley

LEARNING OBJECTIVES   Review classification.  Review prevalence.  Discuss genetic causes and issues of variable expression, penetrance, and heterogeneity (genetic & molecular ).  Issues of Utility of Molecular testing  Ethics, Costs, Practicality

CARDIOMYOPATHY CLASSIFICATION Cardiomyopathies (from the Greek: kardia, heart; mys, muscle; pathos, suffering) are defined by the World Health Organization as diseases of the myocardium associated with ventricular dysfunction.

Dilated Cardiomyopathy (DCM): Characterized by dilatation and impaired contractility of the left (or right) ventricle. Presentation is usually with heart failure. Arrhythmia, thromboembolism, and sudden death are common.

Hypertrophic Cardiomyopathy (HCM): Characterized by left (or right) ventricular hypertrophy, which is usually asymmetric and involves the interventricular septum. Typically, left ventricular volume is reduced. Systolic gradients are sometimes present. Typical presentations include dyspnea, arrhythmia, and sudden death.

Restrictive Cardiomyopathy (RCM): Characterized by restrictive filling of the left (or right) ventricle with normal or near normal ventricular contractility and wall thickness. Presentations are usually with heart failure.

The cardiomyopathies are not the only causes of heart failure syndrome. In western countries, coronary artery disease with resultant ischemic cardiomyopathy remains the primary cause of the heart failure syndrome.

Other components to aid in the classification of CM: Age, appearance, etiology (toxic esp. alcohol, ischemic, metabolic, infectious), genetic

PREVALENCE of CM

HCM: 1 in 500

DCM 1 in 2500

Approximately 30% are confirmed inherited — many more probably are genetic!

CARDIOVASCULAR COURSE: MED I BLOCK III Genetic Aspects of Cardiomyopathy [CV075] LECTURE NOTES University of Manitoba –Faculty of Medicine Instructor: Dr. A. Chudley

FAMILIAL DILATED CARDIOMYOPATHY (DCM)

Several cytoskeletal protein genes are associated with mutations that lead to DCM (e.g. dystrophin, desmin, tafazzin, lamin A/C, and cardiac actin genes). Most are part of syndromes: Skeletal myopathy or specific conduction system defects.

DCM as non-syndromic disorders have been linked to 5 different chromosome regions and 2 disease causing mutations in the cardiac actin gene. All are dominantly inherited. Recently, sarcomeric protein defects have been confirmed to cause DCM: Cardiac myosin heavy chain gene mutations and troponin T- mutations which make up about 10% of the familial cases.

FAMILIAL HYPERTROPHIC CARDIOMYOPATHY (HCM)

1. Previously known as IHSS (idiopathic hypertrophic subaortic stenosis) 2. >13 mm LV wall thickness without dilation of the ventricular cavity on cardiac echo 3. Histology shows myofibrillar and myocyte disarray 4. Inherited as an autosomal dominant trait 5. Most with the gene are asymptomatic until there is obstruction or syncope or sudden death in young people 6. Sudden death in a subset-most due to arrhythmias and massive LVH (left ventricular hypertrophy). Mortality is 1% per year

There are 10 sarcomeric contractile proteins; all have been associated with mutations that cause HCM: (Troponin T; β- cardiac myosin heavy chain; cardiac myosin-binding protein C account for most- (Figure 1 genotype-phenotype correlation between the mutations). Over 150 disease causing mutations have been described, and cardiac myosin binding protein C accounts for 15% (Figure 2).

Treatment:

Β-blockers and calcium channel blocking agents, (promise of ACE inhibitors is emerging), dual chamber pacing with defibrillator, septal myomotomy-myomectomy, alcohol septal ablation.

Detection

DNA testing for disease causing mutations in these 10 genes is only available to families in Manitoba of Mennonite background (where one mutation in the myosin-binding protein C gene identifies most affected due to a founder effect in this population) Testing in families with more than 4 affected individuals in at least 2 generations is possible but less practical. This recommendation may change in time as more reliable, inexpensive DNA microchip technology becomes commercially available. Harvard Laboratories offers a kit that will test a panel of the more common mutations in 7 of these genes. Costs are very high.

Benefits of DNA testing:

1. Identify those at highest risk 2. Risk stratification for treatment/ genotype-phenotype correlation (See Figure 1) 3. Excludes those not at risk, cost benefit by stopping surveillance 16

CARDIOVASCULAR COURSE: MED I BLOCK III Genetic Aspects of Cardiomyopathy [CV075] LECTURE NOTES University of Manitoba –Faculty of Medicine Instructor: Dr. A. Chudley

Dilemmas of DNA Testing:

1. Limitations of tests 2. Should we test children? 3. Risk psychological harm 4. Discrimination/ stigmatization (insurance, employer) 5. Needs to be voluntary

Genetic counseling

Counseling is recommended before DNA testing is offered to families. The future is bright for more targeted therapy as we learn more about the function of these altered proteins and develop more rational protein specific therapy or through transcriptional or translational inhibition.

Figure 1. Age-Related Penetrance of Familial Hypertrophic Cardiomyopathy Caused by Mutations in the Genes for Cardiac Myosin-Binding Protein C, Cardiac Troponin T, and Cardiac -Myosin Heavy Chain. Solid bars denote the percentage of persons with both cardiac myosin-binding protein C mutations and cardiac hypertrophy. Significant differences in the penetrance of familial hypertrophic cardiomyopathy caused by cardiac myosin-binding protein C mutations and hypertrophic cardiomyopathy caused by mutations in cardiac troponin T or cardiac -myosin heavy chain are indicated as follows: asterisks denote P<0.05, the dagger P<0.005, and double daggers P<0.001. From Niimura et al, N Engl J Med. 1998 Apr 30;338(18):1248-57.

CARDIOVASCULAR COURSE: MED I BLOCK III Genetic Aspects of Cardiomyopathy [CV075] LECTURE NOTES University of Manitoba –Faculty of Medicine Instructor: Dr. A. Chudley

Figure 2. The Human Cardiac Myosin-Binding Protein C Polypeptide and Gene and 12 Mutations Causing Familial Hypertrophic Cardiomyopathy. FN denotes fibronectin-like motif, Int intron, DS donor splice site, AS acceptor splice site A, Del deletion, and Ins insertion. Positive numbers indicate residues following exons; negative numbers indicate residues preceding exons. The Manitoba Mennonite mutation is InsG791 in exon 25. From Niimura et al, N Engl J Med. 1998 Apr 30;338(18):1248-57.

CARDIOVASCULAR COURSE: MED I BLOCK III Acquired Pediatric Heart Disease [CV076] OBJECTIVES University of Manitoba –Faculty of Medicine Instructor: Dr. R. Soni

Objectives:

Discuss the more common forms of acquired pediatric heart disease with respect to:

1. Diagnostic features 2. Management 3. Prognosis

The specific conditions to be discussed will be:

1. Kawasaki Disease 2. Acute Rheumatic Fever 3. Endocarditis 4. Myocarditis

Acquired pediatric heart disease

Acquired Pediatric Heart Disease

Acute rheumatic fever (ARF) Kawasaki disease (KD) • Reeni Soni, MD FRCPC Infective endocarditis (IE) • Associate Professor and Head • Section of Pediatric Cardiology Myocarditis • Director, Variety Children’s Heart Center

Acute rheumatic fever Incidence and epidemiology

ARF is an inflammatory disease Typical age of presentation 5 and 15 years sequel to pharyngeal infection with group A beta- hemolytic streptococci – usually follows untreated “strep Overcrowding throat” Genetic predisposition (especially 1st most likely immune mediated occurs after time lag Nations) characteristic tendency to recur without prophylaxis

Incidence and epidemiology Pathophysiology Throat infection with rheumatogenic strain ❖Primary attack rate 3 % (after Strep throat) One or more putative ❖Secondary attack rate as high as 5-65 % streptococcal antigen (hence need for prophylaxis) initiates molecular ❖Recurrences decline over years (determines mimicry M-like protein - duration of chemoprophylaxis) only 4-8% of myocardial damage recurrences occur >10 years after last attack Group A polysaccharide - heart valves Cell membrane antigens - chorea

1 Pathophysiology

Verrucous vegetations on the leaflets chordae subchordal apparatus Healing with fibrosis and thickening

Acute rheumatic fever : Jones ARF : Jones criteria criteria

Major manifestations Minor manifestations

Dr. T Duckett Jones - 1944 Carditis Clinical Revised in 1965 and 1984 and most recently Polyarthritis - migratory Fever Arthralgia 1987 by the WHO Rheumatic Fever Study Chorea Previous rheumatic fever or Group Erythema marginatum rheumatic heart disease Lab Currently used guidelines are referred to as Subcutaneous nodules the “Modified Jones criteria” Elevated acute phase reactions – ESR, CRP Prolonged PR interval

ARF : Jones criteria ARF carditis

2 major criteria or 1 major and 2 minor criteria PLUS: pancarditis supporting evidence of preceding Strep Valvulitis (usually mitral and aortic) infection Myocarditis Pericarditis history of scarlet fever positive throat culture increased ASO titer or other antibodies • occurs within first 2 to 3 weeks of ARF episode

2 Carditis Carditis  Endocardial disease –valvulitis - heart murmurs Mitral regurgitation Aortic regurgitation Carey Coombs murmur - mid diastolic - relative mitral stenosis [mitral valvulitis and volume  Pericarditis related to MR]

 Myocarditis – S/S of congestive heart failure  Chest pain relieved by bending forwards Tachycardia out of proportion to fever, gallop (S3,S4)  Pericardial rub Hepatomegaly Tachypnea, crepitations Muffled heart sounds Cardiomegaly – x-ray 14 EKG prolonged PR interval – nonspecific

ARF – migratory polyarthritis ARF – migratory polyarthritis

“migratory polyarthritis” – may move Dramatic response to aspirin from joint to joint within hours one should reconsider the diagnosis of ARF if inadequate Occurs early in the disease response Exquisitely painful compared to the degree of swelling Arthralgia – joint pain without objective Usually involves the large joints (knees, signs of inflammation elbows, ankles) Responds dramatically to ASA

ARF – chorea - long latent period ARF - chorea

Sydenham’s chorea or St Vitus’s dance Movement disorder and muscle weakness Abrupt, purposeless, small amplitude involving the distal Incidence as high as 30 percent muscle groups Female preponderance F:M - 2:1 Handwriting becomes clumsy Jack in the box, lizard tongue Only clinical feature which can definitely Milkmaids grip make a diagnosis of ARF (after excluding Pronator drift - dinner fork deformity other causes of Chorea – Wilson’s) Emotional lability

3 ARF – subcutaneous nodules ARF – erythema marginatum Occur after the first few weeks of illness

Almost always associated with carditis

Pea sized

Painless nodules over the bony prominences without involvement of the skin or the underlying tissues

Characteristic distribution over the extensor aspect

ARF: laboratory tests ARF - Differential diagnosis

Musculoskeletal ASO titer - > 250 units in an adult and > 330 infectious arthritis, Lyme disease, rheumatoid arthritis, units in a child reactive arthritis, allergic reactions, viral infections, Additional evidence of streptococcal hematological disorders infection includes anti-DNase B Movement disorders ESR, CRP ticks or habit spasms, Huntington’s chorea, encephalitis, attention deficit hyperactivity disorder

Treatment of ARF Treatment of ARF

Primary prophylaxis - identification and Secondary prophylaxis treatment of streptococcal throat infection IM benzathine penicillin 1.2 million units q 1 mo IM benzathine penicillin - 0.6 -1.2 million units Pen V K 500 -1000 mg PO BID Pen V K - oral 10 days Erythromycin 250 mg PO BID Erythromycin 25 mg/kg/day - 10 days Duration is controversial Lifetime vs until age of 18 years Reduces attack rate from 3 to 0.3 % 5 years if no evidence of carditis Socioeconomic and sanitary improvement

4 ARF - Treatment ARF -Treatment

REMEMBER there is no specific cure for ARF

General supportive treatment Suppressive therapy using anti-inflammatory agents Aspirin - 90-120 mg/kg/day, monitor serum levels Control of fever, Bed rest - controversial Corticosteroids - 2 mg/kg/day (if significant carditis) Eradication of streptococcus - even if throat Management of congestive heart failure culture negative Diuretics, Afterload reduction, Digoxin, Steroids, ICU penicillin, erythromycin, sulfa, cephalosporins, measures - ventilation, inotropic support macrolides

Treatment of ARF Treatment of chorea

As corticosteroids are weaned, aspirin is added to Self - limiting - 3 months (6-12 mo) prevent rebound Rest Injury prevention Resting heart rate, erythrocyte sedimentation rate, Chlorpromazine, diazepam, haloperidol and CRP used to monitor “rheumatic activity”

Introduction Kawasaki disease Kawasaki disease is an acute, self-limited vasculitis of unknown etiology - predominantly in infants and young children • The most common acquired pediatric heart disease in North First described in Japan in 1967 by Tomisaku America Kawasaki

5 Introduction Epidemiology

Occurs both endemic and community wide epidemic forms in - all races (but especially More common during winter and early spring Japanese and Filipino populations) months Male: female 1.5-1.7: 1 Coronary artery aneurysms or ectasia More than 76 % < 5 years old develop in 15-25 percent of untreated children

Etiology and pathogenesis Typical Kawasaki Disease Clinical diagnosis (no definitive lab test) > 5 days of fever and > 4 of 5 principal clinical features Changes in the extremity Remains unknown Acute: erythema of palms, soles; edema of hands, feet Strong suggestion of transmissible infectious Subacute: periungual peeling of fingers, toes in second and third week etiology Polymorphous exanthem Bilateral bulbar conjunctival injection without Ubiquitous infectious agent - clinical disease exudate in genetically predisposed Changes in the lips and oral cavity: erythema, lip cracking, strawberry tongue, diffuse injection of oral and pharyngeal mucosae Cervical lymphadenopathy (> 1.5 cm), usually unilateral

Diagnosis Clinical Features

Diagnosis suspected - fever of unknown origin Cardiovascular associated with any of the principal clinical features Diagnosis can be made on the fourth day or earlier Congestive heart failure, myocarditis, if > 4 principal criteria are present pericarditis, valvular regurgitation Coronary artery abnormalities Patients with fever > 5 days and < 4 principal Aneurysms of medium-size non-coronary features can be diagnosed if coronary artery arteries disease is noted by echocardiography

6 Clinical pearls - laboratory investigations Kawasaki vs Viral? Differential diagnosis

Viral infections (measles, adenovirus, enterovirus, Epstein - Moderately to markedly elevated CRP and Barr virus) Scarlet fever ESR is uncommon in viral infections Staphylococcal scalded skin syndrome, Toxic shock syndrome, Mercury hypersensitivity reaction Platelet counts > 450,000/mm3 Bacterial cervical lymphadenitis Low WBC count , lymphocyte predominance, Drug hypersensitivity reaction, Steven - Johnson syndrome Juvenile rheumatoid arthritis low platelet count in the absence of DIC Rocky Mountain spotted fever suggests viral etiology Leptospirosis

Incomplete (atypical) Kawasaki disease Incomplete (atypical) Kawasaki disease

More common in young infants Echocardiography in infants less than 6 Consider in all children with unexplained fever > 5 days associated with two or three months with fever > 7 days duration and of the principal clinical features laboratory evidence of systemic Laboratory findings similar to classic cases Coronary, myocardial findings may be helpful inflammation surrogates Young infants and adolescents are

particularly at risk for missed diagnoses

Echocardiography Echocardiography Initial - at time of diagnosis Echocardiography is the ideal imaging initiation of treatment should not be delayed modality FU - 2 weeks and 6-8 weeks after onset of noninvasive disease high sensitivity and specificity Final - 1 year after initial diagnosis More frequent - in children at high risk - persistent fever, positive coronary findings or myocardial involvement

7 High risk for coronary aneurysms Other tests for coronary abnormalities

Age < 12 months Male sex Cardiac catheterization and angiography WBC count > 12,000 MRI and MRA Platelet count < 350,000 Nuclear stress testing for reversible ischemia, CRP > 3+ stress echocardiography Hematocrit < 35% Albumin < 3.5 g/dl

Aspirin IVIG Does not lower frequency of coronary abnormalities During the acute febrile phase of illness 80 to 100 mg/kg per day in 4 doses additive anti-inflammatory effect with IVIG Once afebrile low-dose aspirin (3–5 mg/kg per day) Standard of care maintain until no evidence of coronary changes at 3 Needs to be given within first 10 days of months fever onset for children who develop coronary abnormalities, Reduces risk of coronary aneurysms from continued indefinitely 20% to 1% Theoretical risk of Reyes syndrome Annual influenza vaccine Generalized anti-inflammatory effect +/- discontinue ASA 6 weeks for varicella immunizations Substitute other antiplatelet agent during influenza or varicella

IVIG IVIG

IVIG, 2 g/kg in a single infusion (evidence level A) instituted within the first 10 days of illness and, if With IVIG - 5% develop transient coronary possible, within 7 days of illness. Treatment before day 5 appears no more likely to prevent cardiac sequelae artery dilation and 1% develop giant may be associated with an increased need for retreatment IVIG also should be administered to children presenting aneurysms after the 10th day of illness if persistent fever Measles and varicella immunizations should aneurysms and ongoing systemic inflammation manifested by elevated ESR or CRP Gamma globulin is a biological product be deferred for 11 months

8 Natural History of Coronary Lesions Coronary Interventions

Bypass grafting - CABBAGE

Angiographic resolution in 1 to 2 years observed in Percutaneous coronary intervention 50% to 67% of vessels with coronary aneurysms Risk of rupture or distal coronary stenosis Angioplasty Contact sports are contraindicated Stents - ? all drug eluting Stenotic lesions progressive

Myocarditis Incidence

Unknown Inflammatory infiltrate of the myocardium with necrosis and/or degeneration of Clinical presentation infrequent adjacent myocytes not typical of ischemic Asymptomatic - likely higher incidence damage associated with coronary artery ? Leads to dilated cardiomyopathy disease

Etiology Epidemiology

Viral Enteroviruses, CB3 Bacterial Sporadic Diphtheria Epidemic Rickettsial, Protozoal, Parasitic, Fungal Toxins and drugs Enteroviruses Hypersensitivity/Autoimmune Rubella Others

9 Pathophysiology

Clinical presentation - spectrum

Differential diagnosis Treatment - supportive

Inotropic support Sepsis Digoxin Metabolic disorders Dobutamine/dopamine/epinephrine Structural heart disease Milrinone Diuretics Supraventricular tachycardia Afterload reduction Anomalous left coronary artery from the ACE inhibitors pulmonary artery Milrinone/nitroprusside Pericarditis Positive pressure ventilation Beta blocker - counterintuitive

10 Treatment - supportive Controversial Therapy

Mechanical support Steroids Bridge to transplant Bridge to recovery Intravenous immunoglobulin ECMO/ECLS/VAD (Berlin Heart) Immunosuppressive agents

Investigations Infective endocarditis

EKG Echocardiogram colonization or invasion of the heart Cardiac Enzymes CKMB/Troponin valves or the mural endocardium by a Cardiac Catheterization microbe. Endomyocardial biopsy (routine +/- PCR +/- The aorta, aneurysmal sacs, other blood immunohistochemistry) vessels, and prosthetic devices can also Viral titers and cultures become infected. MRI

Acute and sub-acute IE

Acute endocarditis - destructive, tumultuous infection with a highly virulent organism

Sub-acute endocarditis - low virulence, insidiously protracted course of weeks to months

11 Treatment

• Longterm IV antibiotics (6-8 weeks)

• May require cardiac surgical intervention for severe valve destruction