Cardiomyopathies

1. Cardiomyopathies Israel Freeman, MD Associate Professor of Clinical Medicine

2. Cardiomyopathies • The cardiomyopathies are a diverse group of disease that are not related to the usual causes of hear disease. • Cardiomyopathies are classified according to hemodynamicc characteristics and etiology.

3. Unknown cause(primary) Dilated Hypertrophic Restrictive unclassified Specific heart muscle disease (secondary) Infective Metabolic Systemic disease Heredofamilial Sensitivity Toxic CardiomyopathiesWHO Classification Br Heart J 1980; 44:672-673

4. CardiomyopathiesFunctional Classification • Dilatated (congestive, DCM, IDC) • ventricular enlargement and syst dysfunction • Hypertrophic (IHSS, HCM, HOCM) • inappropriate myocardial hypertrophyin the absence of HTN or aortic stenosis • Restrictive (infiltrative) • abnormal filling and diastolic function

5. Morphologic and Hemodynamic Characteristics of the Cardiomyopathies Dilated Hypertrophic Restrictive Obliterative(Restrictive-Obliterative) Morphologic Biventricular dilatation Marked hypertrophy of leftventricle and occasionallyof right ventricle; usuallybut not always,disproportionatehypertrophy of septum Reduced ventricularcompliance; usuallycaused by infiltrationof myocardium (e.g., byamyloid, hemosiderin,or glycogen deposits) Thickened endocardiumor mural thrombi, or both,act as space-occupyinglesions Hemodynamic Cardiac output   Normal Normal to  Normal or  Stroke volume   Normal or ↑ Normal or  Normal or  Ventricular fillingpressure ↑↑ Normal or ↑ ↑↑ Usually ↑ Chamber size ↑↑ Normal or  Normal or ↑ Typically  Ejection fraction   ↑↑ Normal to  Normal to  Diastolic compliance Normal or        Other findings May have associatedfunctional mitral ortricuspid regurgitation Obstruction may developbetween interventricularseptum and septal leafletof mitral valveMitral regurgitation maybe present Characteristic ventricularpressure tracings thatresemble those recordedin constrictive pericarditis,with early diastolic dip-and-plateau configuration May be seen as a featureof the hypereosinophilicsyndromesSome investigators considerit a form of restrictivecardiomyopathy

6. Etiologic Classification of Cardiomyopathies Cardiomyopathies of Unknown Etiology Idiopathic dilated cardiomyopathyPeripartum cardiomyopathy*Hypertrophic cardiomyopathyEndomyocardial fibrosisSubendocardial fibroelastosisEosinophilic endomyocardial disease (also called Löfflerendocarditis or fibroplastic endocarditis)Right ventricular dysplasiaIdiopathic restrictive cardiomyopathy

7. Secondary Cardiomyopathies • When a cardiomyopathy has a definite etiology (e.g. sarcoidosis or scleroderma) – signs of that process are usually evident. • On rare occasions, cardiac involvement may precede other systemic manifestations.

8. Idiopathic Known etiology Pregnancy Alcohol Toxic effects of drugs Tachycardia induced Sleep apnea? Dilated (Congestive) Cardiomyopathies

9. Etiologic Classification of Cardiomyopathies Cardiomyopathies of Known Etiology InfectiousViral and rickettsial myocarditis (e.g., human immunodeficiencyvirus, coxsackievirus B,* cytomegalovirus*)Septic (bacterial endocarditis*)SyphilisParasitic disease (e.g., Chagas disease, trichinosis, toxoplasmosis)*Bacterial toxins (e.g., diphtheria toxin) or hypersensitivity(rheumatic fever)

10. Etiologic Classification of Cardiomyopathies Cardiomyopathies of Known Etiology ToxicAlcohol*Cobalt*Carbon tetrachlorideCarbon monoxide*Thioridazine drugsAnticancer agents (e.g. daunorubicin doxorubicin, cyclophosphamide)AntimonialsCocaine*Antiretroviral agents (e.g., zidovudine,* dideoxyinosine*)Interferon alfa

11. Etiologic Classification of Cardiomyopathies Cardiomyopathies of Known Etiology Systemic Diseases Neuromuscular syndromes:muscular dystrophies (e.g., progressive muscular dystrophy, myotonic dystrophy), Friedreich ataxiaCollagen vascular diseaseSarcoidosis*Endocrine diseases* (e.g., thyrotoxicosis, myxedema,pheochromocytoma, acromegaly) * Is potentially reversible

12. Etiologic Classification of Cardiomyopathies Cardiomyopathies of Known Etiology Infiltrative†AmyloidosisHemochromatosisGlycogen storage diseaseFabry diseaseHurler syndromePrimary or metastatic tumors (e.g., lymphoma, melanoma)†Usually causes a restrictive hemodynamic picture

13. Etiologic Classification of Cardiomyopathies Cardiomyopathies of Known Etiology Nutritional Beriberi*Selenium deficiency*Kwashiorkor * Is potentially reversible

14. Etiologic Classification of Cardiomyopathies Cardiomyopathies of Known Etiology Ischemic * * Is potentially reversible !!!

15. Idiopathic Dilated Cardiomyopathy

16. Congestive (Dilated) Cardiomyopathy- Definition • a disease of unknown etiology that principally affects the myocardium • LV dilatation and systolic dysfunction • pathology • increased heart size and weight • ventricular dilatation, normal wall thickness • heart dysfunction out of portion to fibrosis

17. Secondary Congestive (Dilated) Cardiomyopathy • Infectious and Autoimmune processes (Myocarditis) • Coxsackie virus B e.t. • Autoimmune processes • Acute Myocarditis vs. Congestive Cardiomyopathy • Fever with CHF • Pericarditis • Elevated CPK – MB , TnT ( less than 30% of myocarditos)

18. Dilated (Congestive) Cardiomyopathy • A familial form may be present in 10 – 30% • Characterized by diminished myocardial contractility • Reflected in reduction of systolic function. ( EF , LV EDP , SV , C.O  ) • RV dysplasia characterized by RV failure and VT

19. Dilated (Congestive)CardiomyopathyClinical Manifestations • Highest incidence in middle age • blacks 2x more frequent than whites • men 3x more frequent than women • symptoms may be gradual in onset • acute presentation • misdiagnosed as viral URI in young adults • uncommon to find specific myocardial disease on endomyocardial biopsy

20. Dilated (Congestive) Cardiomyopathy • Clinical Features • Dyspnea and fatigue • Palpitation, occasionally syncope • Systemic and pulmonary emboli (+4 % / year) • Chest pain ( 1/3 of patients)-atypical • Physical Finding • Reflects the variable severity of CHF • Diagnostic Studies • CXR, EKG, Echocardiogram (segmental vs global asynergy) • MRI (Dysplastic RV Cardiomyopathy) • Gallium 67 ( sarcoidosis, myocarditis) • Cardiac Catheterization

21. Posteroanterior CXR of a 52 y.o man with idiopathic dilated cardiomyopathy exhibit diffuse cardiomegaly. The LA can be seen as a faint double density.

22. Lateral view of the same patient

23. Echocardiogram: Severe Dilated Cardiomyopathy Apical four-chamber echocardiographic view of a patient with severe dilated cardiomyopathy. All four cardiac chambers are markedly enlarged. The left ventricular ejection fraction was 22%, and the left ventricular end-diastolic diameter was 74 mm.

24. Dilated (Congestive) Cardiomyopathy • Endomyocardial Biopsy • Low diagnostic yield • Uncertainty regarding role of immunosuppressive therapy • Led most investigators to abandon it routine use

25. Endomyocardial Biopsy: Myocarditis A 19y.o. man; presented with DCM and VPCs. The findings of focal lymphocytic infiltrates, interstitial edema, and myocyte degeneration are typical of myocarditis. The patient responded to prednisone.

26. Biopsy: End-Stage Dilated Cardiomyopathy An 80 y.o. man with end-stage CM. There is marked hypertrophy of myocytes, interstitial and focal fibrosis,and no evidence of interstitial inflammation. Immunosuppressive therapy was not indicated.

27. Dilated Cardiomyopathy (DCM)Course and Prognosis • The most common complication of DCM is progressive CHF – the cause of death in 50 – 75% • Sudden death (SD) by arrhythmia is common especially in patients with complex ventricular ectopy and severe LV dysfunction. • Systemic / pulmonary embolism is found at autopsy in 50% of patients with DCM – emboli can cause catastrophic complications but rarely death. • Prognosis varies considerably from fulminent cases that result in death within a few weeks, or conversely some patients do remarkably well for years. Most death within 5 years. • Spontaneous improvement in LV function occurs in 20 – 40%, most frequently within 6 months. • A peak 02 uptake less than 14 ml/kg /min predicts 1 year survival of 70%.

28. Survival in Symptomatic Idiopathic Dilated Cardiomyopathy Survival symptomatic IDC in seven reported series. Study A, 1986-89 (basis for selection unspecified); study B, 1975-84 (population based); study C, 1973-87 (referral based); study D, 1962-82 (referral based); study E, 1960-73 (referral based); study F, 1972-82 (referral based); study G, 1965-86 (autopsy series). (N number of patients)

29. Dilates Cardiomyopathy Medical Treatment • Limit activity based on functional status • salt restriction of a 2-g Na+ (5g NaCl) diet • fluid restriction for significant low Na+ • initiate medical therapy • ACE inhibitors, diuretics • digoxin, carvedilol • hydralazine / nitrate combination

30. Dilates Cardiomyopathy Medical Treatment • Principally standard CHF therapy • Anticoagulation therapy is controversial some arthritis recommend with marked right sided failure and/or BF < 30 • Antiarrhythmics: arrhythmias are common Empirical suppression in symptomatic patient is contraindicated (CAST) due to proarrhythmic effect. In symptomatic patients – amiodarone (GESICA 26% reduced mortality vs. STAT – CHF) • Defibriallation: SAEKG and EP are not reliable in assessing prognosis or guide antiarrhythimic therapy in patients with DCM. ICD is indicated in patients with sustained V.T. In NSVT the MADIT trail demonstrated an advantage for ICD those were IHD (inducible ) patient, MADIT doesn’t apply. Trial results pending.

32. Hypertrophic Cardiomyopathy

33. Hypertrophic Cardiomyopathy • The hallmark of the disease is unexplained myocardial hypertrophy • In the obstructive form: ASH, SAM. MR • Obstruction may be fixed or labile • Hyper-contractile LV (EF 80 – 90%) with reduced ESV. • Reduced LV compliance (if patient in CHF – diastolic) • Factor that provoke or increase/decrease obstruction: • Change in contractile stale • Change chamber – size (preload and after load)

34. Coronal Section in Hypertrophic Cardiomyopathy The thickening of the IVS is disproportionately greater than that of the LV wall behind the posterior mitral leaflet. The LV chamber is small and elongated.

35. Myofibrillar Pattern in HCM vs. HTN Different myofibrillar patterns in tissue taken from the septum of a patient with HCM (left) and from the hypertrophied LV of a patient with HTN (right). Note the chaotic arrangement of the cells of septal myocardium taken from the HCM.In contrast, note the orderly parallel arrangement of myofibrils in ventricular myocardium in the HTN patient.

36. Morphologic and Hemodynamic Characteristics of the Cardiomyopathies Dilated Hypertrophic Restrictive Obliterative(Restrictive-Obliterative) Morphologic Biventricular dilatation Marked hypertrophy of leftventricle and occasionallyof right ventricle; usuallybut not always,disproportionatehypertrophy of septum Reduced ventricularcompliance; usuallycaused by infiltrationof myocardium (e.g., byamyloid, hemosiderin,or glycogen deposits) Thickened endocardiumor mural thrombi, or both,act as space-occupyinglesions Hemodynamic Cardiac output   Normal Normal to  Normal or  Stroke volume   Normal or ↑ Normal or  Normal or  Ventricular fillingpressure ↑↑ Normal or ↑ ↑↑ Usually ↑ Chamber size ↑↑ Normal or  Normal or ↑ Typically  Ejection fraction   ↑↑ Normal to  Normal to  Diastolic compliance Normal or        Other findings May have associatedfunctional mitral ortricuspid regurgitation Obstruction may developbetween interventricularseptum and septal leafletof mitral valveMitral regurgitation maybe present Characteristic ventricularpressure tracings thatresemble those recordedin constrictive pericarditis,with early diastolic dip-and-plateau configuration May be seen as a featureof the hypereosinophilicsyndromesSome investigators considerit a form of restrictivecardiomyopathy

37. Hypertrophic Cardiomyopath Pathophysiology • Systole • dynamic outflow tract gradient • Diastole • impaired diastolic filling,  filling pressure • Myocardial ischemia •  muscle mass, filling pressure, O2 demand •  vasodilator reserve, capillary density • abnormal intramural coronary arteries • systolic compression of arteries

38. Obstructive (fixed, Rabile) Non Obstructive Concentric Mid ventricular Apical Hypertrophic Cardiomyopath* * The vast majority of cases of hypertrophic cardiomyopathy result from specific defects in the genes regulating the formation of cardiac muscle This defect is either sporadic or hereditary in 50% of cases (autosomal dominant).

39. 35% 65% 10%

40. Survival Curves in Hypertrophic Cardiomyopathy The surviv al of patients with hypertrophic cardiomyopathy caused by different mutations: cardiac troponin T mutations (introns 15 G1(r) A, Ile79Asn, DGlu160, and Arg92Gln) is similar to that in persons with a malignant b-myosin heavy-chain mutation (Arg403Gln) but significantly shorter than that observed in persons with a benign myosin mutation (Val606Met).

41. Factors That Increase Obstruction Factors That Decrease Obstruction Mechanism Physiologic or Pharmacologic Factor Mechanism Physiologic or Pharmacologic Factor Increase incontractility Digitalis glycosidesBeta-adrenergic stimulation (e.g., isoproterenol,epinephrine)TachycardiaPremature beats Decrease incontractility Beta-adrenergic blockade (e.g., propranolol)Heavy sedation and general anesthesiaCalcium channel blockers, disopyramide, and otherdrugs that depress myocardial function Reduction inpreload Valsalva maneuver†Decrease in intravascular volume (e.g., from hemorrhage,diuresis, GI losses)Standing†Nitroglycerin and related drugs†Vasodilator drugsTachycardia Increase inpreload Intravascular volume expansionSquatting†BradycardiaBeta-adrenergic blockade Reduction inafterload HypovolemiaNitroglycerin and related drugs†Vasodilator drugs Increase inafterload Intravascular volume expansionSquatting†Alpha-adrenergic stimulation (e.g., phenylephrine,mephentermine)Handgrip exercise† Factors That Influence the Degree of Obstruction in Hypertrophic Cardiomyopathy* *In general, anything that increases obstruction will increase the intensity of the associated murmurs, whereas factors that reduce obstruction will diminish murmur intensity.†May assist in diagnosis at the bedside.

42. Hypertrophic Cardiomyopathic Diagnosis • Symptoms • Angina (recumbent position) • Syncope (after exercise, arrhythmia) • Palpitations (A.F, VT) • CHF (atrail contraction, AF with fast response) • Systemic embolism • S.D. (even in asymptomatics) lethal arrhythmia more likely in young • Physical examination • EKG, Echocardiography, Cardiac Cath

43. Changes of Murmer in Obstructive Hypertrophic Cardiomyopathy Variations in the quality of the murmur associated with HOCM are observed before (a), during (b), and after (c) the Valsalva maneuver. Before the Valsalva maneuver, a soft systolic murmur is recorded at the apex. The arterial pulse contour is normal. During the Valsalva maneuver, there is a dramatic increase in the intensity of the murmur. After Valsalva release, the murmur becomes softer, but the carotid pulse exhibits the classic spike-and-dome configuration characteristic of obstructive hypertrophic cardiomyopathy.

44. Hypertrophic Cardiomyopathic Change in Gradient and Murmur Contractility Preload Afterload valsalva (strain)  -- standing --postextrasystole   -- isoproterenol  digitalis  --amyl nitrite  nitroglycerine  exercise tachycardia  --hypovolemia   

45. Hypertrophic Cardiomyopathic Change in Gradient and Murmur Contractility Preload Afterloadvalsalva (overshoot)--squatting ---passive leg elevation   __--phenylephrine  -- beta-blocker -- -- general anesthesia  -- --isometric grip  -- 

46. Hypertrophic CardiomyopathyHCM vs Aortic Stenosis HCM Fixed Obstructioncarotid pulse spike and dome parvus et tardus murmur radiate to carotids valsalva, standing  squatting, handgrip  passive leg elevation systolic thrill 4th left interspace 2nd right interspacesystolic click absent present

47. ECG in Obstructive Hypertrophic Cardiomyopathy Abnormal Q waves suggestive of an old anterior myocardial infarct are observed in leads V3 through V6 in an ECG recorded in a 45-year-old woman with obstructive hypertrophic cardiomyopathy.

48. Hypertrophic Cardiomyopathy -Echocardiography

49. Hypertrophic Cardiomyopathy -Echocardiography