Reversible Cardiomyopathies

Dr Sajeer K T Senior Resident, Dept. of Cardiology, MCH Calicut 1

Dilated cardiomyopathy (DCM) : - characterized by dilation and impaired contraction of one or both ventricles DCM - caused by a variety of specific diseases ≥ 50% of patients with DCM: - an etiologic basis will not be identified -

Idiopathic DCM

One series- 1278 patients with congestive heart failure  Idiopathic — 51 percent  Idiopathic myocarditis — 9 percent   Occult coronary disease — 8 percent Other identifiable causes — 32 percent Felker, et al. The spectrum of dilated cardiomyopathy. The Johns Hopkins experience with 1,278 patients. Medicine (Baltimore) 1999; 78:270 2

Clinical Presentation

- Most patients present between age : 20-60 years - Can occur in children and elderly - Symptoms of CHF - Incidental detection of asymptomatic cardiomegaly - Symptoms related to coexisting arrhythmia, conduction disturbance - Thromboembolic complications - Sudden death 3

Reversible causes of dilated cardiomyopathy

- Peripartum cardiomyopathy - Tachycardia-mediated cardiomyopathy - Takotsubo cardiomyopathy - Alcoholic cardiomyopathy - Cocaine - Medications - Ischemia - Endocrine dysfunction - SLE, Sarcoidosis - Nutritional deficiencies - Electrolyte abnormalities - Obstructive sleep apnea 4

Peripartum cardiomyopathy (PPCM)

- Cardiomyopathy manifesting between the last month of pregnancy and 6 months postpartum - Toxic postpartal heart failure, Meadows synd., Zaria synd.

- Incidence in published series of 1:1300 to 1:4000 live births

Criteria for PPCM :

(1) Development of CHF secondary to deceased LV systolic function in the last month of pregnancy or within 5 months after delivery (2) Absence of pre-exciting cardiac dysfunction (3) Absence of determinable cause of cardiomyopathy (4) LV systolic dysfunction: - EF < 45% - Fractional shortening of less than 30% - LV end diastolic dimension of greater than 2.7 cm/m 2 5

- Risk factors for PPCM:  Advanced age (>30 years)  Multiparity  Twin gestation  Use of tocolytic therapy - Etiology - currently unknown     Preeclampsia Obesity Chronic hypertension Black race - Current hypotheses are: (1) infectious (2) immunologic (3) nutritional (4) drug-induced (5) familial 6

Infectious: Felker et al : demonstrated a 62% prevalence of myocarditis in patients PPCM who underwent endomyocardial biopsy Immunologic: - significant elevations of TNF-Alpha, IL-6 and Fas/APO-1 in patients with PPCM - antibodies formed against actin can cross react with myocardium - antibodies to cardiac muscle proteins have been identified in patients with PPCM Nutritional: - Low selenium levels - a possible risk factor for PPCM Drug-induced: - prolonged terbutaline therapy Familial: 7

Echocardiography remains the tool for evaluation and follow-up for women with postpartum cardiomyopathy - Myocardial LV dysfunction - decrease in LV EF or FS - LV thrombus is common with a LVEF less than 35% Normal systolic function excludes postpartum cardiomyopathy - should lead to an evaluation for high output failure - anaemia - thyrotoxicosis 8

Treatment

Initial treatment of PPCM is similar to treatment for other forms of heart failure - diuretics, vasodilators (hydralazine and nitrates), digoxin - (ACEI contraindicated in pregnancy) Immunosuppression: - Pentoxifylline: inhibit proinflammatory cytokines (TNF-alpha, CRP, and Fas/Apo-133 - Intravenous immune globulin Immunosuppressive therapy : - considered if an endomyocardial biopsy indicates the presence of myocarditis - if there is no improvement after 2 weeks of standard HF therapy 9

Outcome and prognosis

- Reported mortality rate for PPCM ranges from 15% to 50% - Cardiac transplantation is an option if the patient fails to improve - no consensus on whether subsequent pregnancies should be avoided by women who survive PPCM 10

Takotsubo Cardiomyopathy A New Form of Acute, Reversible Heart Failure

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- a condition featuring symptoms and signs of AMI without demonstrable coronary artery stenosis or spasm in which the heart takes on the appearance of a Japanese octopus fishing pot called a “takotsubo” - Left ventricular dysfunction can be remarkably depressed, recovers within a few weeks - occurs predominantly in postmenopausal women soon after exposure to sudden unexpected emotional or physical stress.

Sato et al (1990) first described - reversible cardiomyopathy - tako-tsubo-like left ventricular dysfunction - Apical ballooning or stress cardiomyopathy 12

- noncardiac surgery is one of the most frequent trigger for cardiovascular events ( highest risk in those undergoing vascular surgery due to coexisting severe coronary artery disease) - incidence of ABS : 1% to 2% of patients with an acute MI 13

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Diagnostic Criteria Mayo Clinic proposed diagnostic criteria in 2004

(1) - transient hypokinesis, akinesis, or dyskinesis in the LV mid segments with or without apical involvement - regional wall motion abnormalities that extend beyond a single epicardial vascular distribution - a stressful trigger (2) - the absence of obstructive coronary disease or angiographic evidence of acute plaque rupture (3) - new ECG abnormalities (ST-segment elevation and/or T-wave inversion) or modest elevation in cardiac troponin (4) - absence of pheochromocytoma and myocarditis 15

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- syndrome much more common in women - typically preceded by exposure to emotional or physical stressors - most frequent clinical symptoms on admission are chest pain and dyspnea resembling AMI - most common ECG findings on admission : ST elevation in precordial leads - high levels of serum catecholamines and of plasma BNP - Cardiac enzyme levels (eg, CKMB , Tn T) - slightly increased.

- Cardiac magnetic resonance imaging: -lack of delayed contrast enhancement 18

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Coronary angiogram and cardiac imaging 21

Apical sparing variant Takotsubo 22

RV may develop similar regional wall motion abnormality in 30% of patients - develop congestive heart failure Inverted Tako-tsubo : - a rare variant presents with hypokinesis of the base of the heart with preserved apical function 23

- Cine sequences of CMR imaging during systole (A) and diastole (B) in the acute phase. - Normal function could be documented after 3 weeks (C, systole; D, diastole) - Contrast-enhanced CMR image did not show myocardial hyper enhancement even in the delayed phase (E).

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Pathophysiology:

Myocardial biopsy: - interstitial infiltrates( mononuclear lymphocytes, leukocytes, and macrophages) - myocardial fibrosis - contraction bands with or without overt myocyte necrosis Coagulation necrosis : seen in myocardial infarction - Catecholamine Cardio toxicity: - high local concentrations of nor-epinephrine might evoke basal hyperkinesis - increasing mechanical wall stress at the apex - increasing end-diastolic pressure and BNP levels 25

A Pathogenetic Concept About Takotsubo Cardiomyopathy Possible underlying mechanism of classic takotsubo cardiomyopathy 26

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Management Considerations in Patients Presenting with ABS 28

Prognosis

- Prognosis is generally favourable - Fatal complication - LV free wall rupture - heart failure, with or without pulmonary oedema - Recurrence rate of takotsubo cardiomyopathy : 10% - Complete recovery - by 4 to 8 weeks - Inhospital mortality from ABS is very low (1- 2%) 29

Tachycardia-mediated cardiomyopathy

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Tachycardia-mediated cardiomyopathy

- impairment in LV function secondary to chronic tachycardia, which is partially or completely reversible after normalization of heart rate and/or rhythm irregularity --- Gallagher JJ Fenelon et al : Tachycardiomyopathy: a) Pure type b) impure Type Pure type: chronic tachycardia causes LV dysfunction in a normal heart and completely recovers after termination of the tachycardia Impure Type: occurs in patients with structural heart diseases, and cardiac dysfunction may only recover incompletely after termination of the tachycardia 31

Possible mechanisms for myocardial dysfunction

- Myocardial energy depletion - Impaired energy utilization - Myocardial ischemia Abnormal calcium handling: - the severity of calcium cycling abnormalities correlates with the degree of ventricular dysfunction (extensive abnormalities in calcium channel activity and sarcoplasmic reticulum calcium transport ) - calcium availability to myocytes decreased > reduction in contractility 32

- Tachycardiomyopathy can occur at any age - reported in infants, children ,adolescents and adults - incidence of tachycardia-induced cardiomyopathy - unknown - risk factors: - type, rate and duration of tachyarrhythmia - patient’s age - underlying heart disease - drugs - coexisting medical conditions - diagnosis of tachycardiomyopathy considered - patient with LV systolic dysfunction and chronic or frequently recurring cardiac arrhythmia 33

Tachycardiomyopathy is induced by various supraventricular and ventricular arrhythmias - Ectopic atrial tachycardia (EAT) - in children - Permanent form of junctional reciprocating tachycardia (PJRT) - often incessant and refractory to antiarrhythmic drugs - commonly results in tachycardiomyopathy Fenelon et al proposed the following criteria: 1) Dilatation of the heart or heart failure 2) Chronic or very frequent cardiac arrhythmias, including incessant SVTs, AF or AFL and incessant VT If chronic tachycardia continued more than 10-15% of the day, with an atrial rate of more than 150% of that predicted for age, - tachycardiomyopathy occurs.

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Treatment

- Basic concept for the treatment of tachycardiomyopathy - controling the heart rate - SVT : digitalis or verapamil : common drugs of choice - Class I anti-arrhythmic drugs: negative inotropic effect - clinical use should be careful - In pediatric cases, EAT or PJRT : incessant - Amiodarone - class III - dofetilide, sotalol, - ibutilide or azimilide - Catheter ablation : performed as the first-line therapy 35

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Alcoholic cardiomyopathy

- ethanol may induce asymptomatic LV systolic dysfunction - 30% of asymptomatic chronic alcoholics have evidence of LV systolic dysfunction - ethanol abuse is the leading cause of nonischemic DCM in industrialized countries 37

Mechanisms of Ethanol-Induced Myocardial Injury

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- likelihood of developing an ethanol-induced DCM correlates with the amount of ethanol that is consumed in a lifetime - Men – consumption more than 80 g of ethanol/day for at least 5 yrs (1 L of wine, 8 std-sized beers, or 0.5 pint of hard liquor) -Women - more susceptible to ethanol's cardiotoxic effects than men - complete abstinence or reduction in ethanol consumption (less than 60 g of ethanol/day): substantial improvement in LV systolic function and symptoms of HF 39

Cocaine and heart

Cocaine

- commonest illicit drug used and the most frequent cause of drug related deaths

Cocaine related complications

: 1. Cardiac: myocardial ischaemia, coronary artery spasm, acute MI, myocarditis, cardiomyopathy, arrhythmia, hypertension 2. Vascular: aortic dissection and rupture, vasculitis 3. Gastrointestinal: mesenteric ischaemia or perforation 4. Pulmonary: pulmonary oedema, pulmonary infarction 40

Dilated cardiomyopathy in cocaine users: - attributable to the direct toxic effects - heart failure results from: - myofibrils destruction - interstitial fibrosis - myocardial dilatation - cocaine induced hyper adrenergic state may contribute to the cardiomyopathy (similar to pheochromocytoma) - myocardial dysfunction is reversible with abstinence of cocaine 41

Medications

- anthracycline-induced cardiomyopathy - most extensively studied - cardiomyopathy and clinical heart failure are the main dose limiting side effects of anthracyclines - cardiomyopathy can occur within the 1st year and up to a decade after completion of therapy risk factors: 1 . cumulative dose of anthracyclines administered (not to exceed 450 mg/m 2 in adults) 2. extremes of age 3. concomitant chemotherapy and radiation 4. history of cardiovascular disease 42

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Endocrine dysfunction

- thyroid dysfunction - excess sympathetic activity in pheochromocytoma - rarely Cushing's syndrome - growth hormone excess or deficiency - cardiac dysfunction which can usually be reversed by correction of the endocrine disorder - hyperthyroidism or hypothyroidism: - exact mechanisms of dilated cardiomyopathy not known - thyroid hormone is known to alter preload, after load, heart rate, and contractility - excess T3 causes myocyte hypertrophy 44

Pheochromocytoma : - excess sympathomimetic amines cause focal direct myocyte injury - inflammation, down regulation of beta receptors - reduction of viable myofibrils Catecholamines – - increase both intracellular calcium and free radicals - contribute to myocyte injury 45

Ischemia - cardiomyopathy

- coronary atherosclerosis is MC cause of DCM in US - 50 to 75 percent of patients with HF - usually

irreversibl

e due to myocardial infarction and subsequent ventricular remodeling - patients with ischemic DCM with hibernating myocardium - benefit of revascularisation - Revascularization of hibernating myocardium beneficial in patients with ischemic DCM who have less severe heart disease 46

Selenium deficiency and cardiomyopathy

Selenium deficiency: - identified as a factor causing HF syndromes in areas of very low selenium intakes( China ) - endemic selenium-responsive cardiomyopathy Keshan disease Selenium deficiency : - decreases the activity of glutathione peroxide - resulting in increased free radicals > toxic to cardiac myocytes Similar cases : - HIV-infected patients - subjects on parenteral nutrition - Crohn’s disease Possible causes of Keshan disease are: - viral infection - nutritional factors (insufficient Zn or molybdenum, excessive barium or lead) 47

Thiamine:

- plays an important role in normal oxidative phosphorylation and myocardial energy production - deficiency initially presents as a high output state secondary to vasodilation - followed by eventual depression of myocardial function – - development of a low output state 48

Obstructive sleep apnea - cardiomyopathy

- obstructive sleep apnea: contribute to the impairment of left ventricular dysfunction - history of snoring, daytime somnolence, and obesity should alert the clinician to the diagnosis - therapy : nasal continuous positive airway pressure during sleep lead to a significant improvement in LV dysfunction 49

Electrolyte abnormalities:

Chronic hypophosphatemia and hypocalcaemia: - reversible cardiomyopathy

Infections :

- Bacterial, spirochetal, rickettsial, fungal, protozoal, helminthic infections - implicated as causes of necrotic or inflammatory lesions - may lead to dilated cardiomyopathy 50

THANK YOU

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MCQs 52

1. All are causes of reversible cardiomyopathy except?

A) Sarcoidosis B) carnititine deficiency C) hypercalcemia D) hypothyroidism 53

2. All are true about PPCM except?

a) More common in primi b) Twin gestation c) Preeclampsia d) Age>30 years 54

3. True about treatment of PPCM?

a) ACEI can be used after delivery b) Petoxyphiline used in all cases c) Cardiac transplantation not indicated d) biopsy done in all cases 55

4. Apical ballooning syndrome true except?

a) More common in young females b) Female gender predilection c) Recovery over few weeks d) No specific treatment

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5. Criteria of LV systolic dysfunction by echo in PPCM: a) EF < 45% b) Fractional shortening of less than 30% c) LV end diastolic dimension of greater than 2.7 cm/m

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d) ALL

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6. False about Takotsubo syndrome a) Apical sparing can occur b) preceded by exposure to emotional or physical stressors c) most frequent clinical presentation on admission is acute pulmonary edema • d) most common ECG findings on admission : ST elevation in precordial leads 58

7. True about Takotsubo syndrome pathogenesis a) Catecholamine toxicity b) epicardial corornary artery spasm c) Plaque rupture d) all

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8. All are true regarding tachycardiomyopathy except?

a) Only seen in infants and children b) EAT and PJRT – are incessant c) Abnormal calcium handling- mechanism d) RF ablation is the preferred treatment 60

9. False about keshans disease a) Endemic in china b) Only seen in selenium deficiency c) LV function improves with selenium supplement d) Also in HIV infection 61

10. Reversibility is maximum seen in which drug related cardiomyopathy?

a) Dunorubicin b) Epirubicin c) Tratzumab d) Imatinib 62

• • • • • 1. All are causes of reversible cardiomyopathy except?

A) sarcoidosis B) carnititine deficiency C) hypercalcemia D) hypothyroidism 63

2. All are true about PPCM except?

a) More common in primi b) Twin gestation c) Preeclampsia d) Age>30 years 64

3. True about treatment of PPCM?

a) ACEI can be used after delivery b) Petoxyphiline used in all cases c) Cardiac transplantation not indicated d) biopsy done in all cases 65

4. Apical ballooning syndrome true except?

a) More common in young females

b) Female gender predilection c) Recovery over few weeks d) No specific treatment

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5. Criteria of LV systolic dysfunction by echo in PPCM: a) EF < 45% b) Fractional shortening of less than 30% c) LV end diastolic dimension of greater than 2.7 cm/m

2 d) ALL 67

6. False about Takotsubo syndrome a) Apical sparing can occur b) preceded by exposure to emotional or physical stressors c) most frequent clinical presentation on admission is acute pulmonary edema • d) most common ECG findings on admission : ST elevation in precordial leads 68

7. True about Takotsubo syndrome pathogenesis

a) Catecholamine toxicity-

b) epicardial corornary artery spasm c) Plaque rupture d) all

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8. All are true regarding tachycardiomyopathy except?

a) Only seen in infants and children b) EAT and PJRT – are incessant c) Abnormal calcium handling- mechanism d) RF ablation is the preferred treatment 70

9. False about keshans disease a) Endemic in china b) Only seen in selenium deficiency c) LV function improves with selenium supplement d) Also in HIV infection 71

10. Reversibility is maximum seen in which drug related cardiomyopathy?

a) Dunorubicin b) Epirubicin c) Tratzumab d) Imatinib 72

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