1. Cardiomyopathies Faculty of Medicine University of Brawijaya Malang

2. Definition “A heart muscle disease, often of unknown cause …”

3. Cardiomyopathy Greek “kardia” heart + “myo” muscle “patheia” suffering/disease 1980 WHO: “heart muscle disease of unknown cause” 1995 WHO/Task force: “diseases of the myocardium associated with cardiac dysfunction”

4. Classification etiology gross anatomy histology genetics biochemistry immunology hemodynamics functional prognosis treatment

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

6. Functional Classification Dilatated (congestive, DCM, IDC) –ventricular enlargement and syst dysfunction Hypertrophic (IHSS, HCM, HOCM) –inappropriate myocardial hypertrophy in the absence of HTN (hypertension) or aortic stenosis Restrictive (infiltrative) –abnormal filling and diastolic function

7. Cardiomyopathies Idiopathic Dilated Konstam MA. J Card Failure. 2003. HF-Dilated HypertensiveIschemic HF-Non Dilated Hypertrophic CM

9. Characteristics of the three types of cardiomyopathy TypesLV wallLV cavitySystolic contrac-tility Diastolic Compli-ance Prognosis 10 year survival rate Dilated Cardiomyo- pathy ThinLarge↓Normal to ↓*30-40% Hypertro-phic Cardio- myopathy ThickSmall↑↓70% Restrictive Cardiomyo- pathy Normal to ↑NormalNormal to ↓↓↓50% (idio- pathic type) Contractility or compliance may be normal early in the disease state but may become abnormal subsequently

10. General approach to a patient with Cardiomyopathy Define the problem: –1. Failure? – due to a low cardiac output state (Dilated CM) or obstruction to LV filling (restrictive CM) –2. Arrhythmia? – due to supraventricular or ventricular arrhythmias. –3. Syncope?- due to obstruction in LV outflow tract (HOCM) and/or arrhythmias especially slow rates.

11. Dilated Cardiomyopathy

12. The heart is dilated and has impaired function The coronary arteries are normal.

13. Idiopathic Dilated Cardiomyopathy Observed Survival of 104 Patients Years Am J Cardiol 1981; 47:525

14. Incidence and Prognosis 3-10 cases per 100,000 20,000 new cases per year in the U.S.A. death from progressive pump failure 1-year25% 2-year35-40% 5-year40-80% stabilization observed in 20-50% of patient complete recovery is rare

15. Features for Diagnosis of Dilated Cardiomypathy Signs and symptoms of systolic heart failure Echocardiography shows dilated LV with global hypokinesia Normal coronary artery by angiography Presence of predisposing factors such as alcoholism, malnutrition etc

16. Etiologic classification of the Dilated Cardiomyopathy I.Idiopathic II.Inflammatory A.Infectious A.Viral B.Bacterial C.Mycobacterial D.Others: Parasitic, Rickettsial, Fungal B.Non-infectious A.Peripartal cardiomyopathy B.Autoimmune disease C.Hypersensitivity reaction D.Tranplantation rejection

17. Etiologic classification of the Dilated Cardiomyopathy III. Toxic agents A. Alcohol B. Methamphetamines/ Cocaine C. Chemotherapeutic agents (Doxorubicin) D. Cigarette smoking E. Elemental compounds D. Cathecolamines

18. Etiologic classification of the Dilated Cardiomyopathy IV. Metabolic A. Malnutrition B. Endocrinologic: Thyrotoxicosis C. Electrolyte abnormalities D. Cigarette smoking E. Elemental compounds F. Cathecolamines

19. Etiologic classification of the Dilated Cardiomyopathy V. Familial cardiomyopathy A. Neuromyopathic 1. Progressive muscular dystrophy 2. Myotonic muscular dystrophy 3. Friedrich’s ataxia B. Hereditary dilated Cardiomyopathy

20. Clinical features Progressive biventricular heart failure leads to symptoms –Fatigue –Paroxysmal nocturnal dyspnea, orthopnea, dyspnea –Peripheral edema –Ascites

21. Clinical history History of specific exposure to etiologic agents (e.g alcohol, methamphetamine) Symptoms of left sided failure, then right sided heart failure Chest pain may be present in the absence of ischemic heart disease

22. Physical examination Similar to those of congestive heart failure Dilated heart, distended neck veins with functional MR murmur due mitral annular dilatation

23. History and Physical Examination Symptoms of heart failure –pulmonary congestion (left HF) dyspnea (rest, exertional, nocturnal), orthpnea –systemic congestion (right HF) edema, nausea, abdominal pain, nocturia –low cardiac output fatigue and weakness hypotension, tachycardia, tachypnea, JVD (jugular venous distention)

24. Clinical features Other complications secondary to the progressive dilatation of the ventricles include: –Mural thrombi with systemic or pulmonary embolization –Dilatation of the tricuspid and mitral valve rings leading to functional valve regurgitation –Atrial fibrillation and other arrhythmias –Ventricular tachyarrhythmias and sudden death

25. Diagnostic tests 1. ECG: non-specific changes; may show LVH, occasionally LBBB 2. Chest X-ray: multichamber dilatation with congestive features 3. Echocardiography: multichamber dilatation, LV wall motion abnormalities usually global hypokinesia 4. Coronary angiography: normal coronary arteries 5. Angiography indicated only to rule out ischemic heart disease (“ischemic” cardiomyopathy)

26. Echocardiography Evaluation of dilated ventricles Evaluation of regurgitant valves Evaluation of thrombus

28. Normal echo 

31. Management Search and treat any underlying cause ( e.g stop alcohol) Treat heart failure (diuretics, ACE-inhibitor, nitrates/hydralazine combination) Treat any arrhythmias Prevention of sudden death with placement of implantable cardioverter defibrillator (ICD) is not recommended Anticoagulate with warfarin to prevent mural thrombi If cardiac failure does not respond to the above steps  if suitable candidate  cardiac transplantation

32. Predicting Prognosis in IDC PredictivePossibleNot Predictive Clinical factorssymptomsalcoholismage peripartumduration family historyviral illness HemodynamicsLVEFLV size Cardiac indexatrial pressure DysarrhythmiaLV cond delayAV blocksimple VPC complex VPCatrial fibrillation Histologymyofibril volumeother findings Neuroendocrinehyponatremia plasma norepinephrine atrial natriuretic factor VPC: ventricular premature contraction

33. Clinical Indications for Endomyocardial Biopsy Definite –monitoring of cardiac allograft rejection –monitoring of anthracycline cardiotoxicity Possible –detection and monitoring of myocarditis –diagnosis of secondary cardiomyopathies –differentiation between restrictive and constrictive heart disease

34. Hypertrophic cardiomyopathy

35. Types of hypertrophic cardiomyopathy 1. Obstructive type. Synonym: idiopatthic hypertrophic subaortic stenosis 2. Non obstructive type

36. Features for diagnosis Dyspne or syncope May have a family history of hypertrophic cardiomyopathy in 50% of cases Characteristic systolic ejection murmur at the left sternal area which increases with valsalva maneuver (in obstructive type)

37. Features for diagnosis (continued) Marked hypertrophy of the left ventricle involving the interventricular septum and the LV outflow tract in the absence of other causes of hypertrophy Echocardiography shows interventricular septum to posterior LV wall ratio > 1.3:1.

38. Hypertrophic obstructive cardiomyopathy Characterized by asymmetrical hypertrophy of the cardiac septum – the cardiac septum is hypertrophied compared to the free wall of the left ventricle. The most common cause of heart-related sudden death in those under 30 years old. HOCM is inherited as an autosomally dominant trait with equal sex incidence The genetic abnormality is the subject of much current research, and it seems that different genes may be involved in different families

39. Hypertrophic obstructive cardiomyopathy The myocytes of the left ventricle are abnormally thick when examined microscopically  left ventricular filling more difficult than normal and grossly disordered

40. 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

41. 65% 35% 10% www.kanter.com/hcm

44. Natural History annual mortality 3% in referral centers probably closer to 1% for all patients risk of SCD higher in children may be as high as 6% per year majority have progressive hypertrophy clinical deterioration usually is slow progression to DCM occurs in 10-15%

45. Risk Factors for SCD (sudden cardiac death) Young age (<30 years) “Malignant” family history of sudden death Gene mutations prone to SCD (ex. Arg403Gln) Aborted sudden cardiac death Sustained VT or SVT Recurrent syncope in the young Nonsustained VT (Holter Monitoring) Brady arrhythmias (occult conduction disease) Br Heart J 1994; 72:S13

46. Clinical features Symptoms usually begins in the third and fourth decades of life. Four main symptoms: –Angina – due to the increased oxygen demands of the hypertrophied muscle –Palpitations- atrial fibrillations and/or ventricular arrhythmias –Syncope and sudden death – due to LVOT obstruction by the hypertrophied septum or to ventricular arrhythmia –Orthopnea/paroxysmal nocturnal dyspnea/dyspnea – due to high end diastolic pressure  pulmonary edema

47. Clinical features The signs to watch for are: –Jerky peripheral pulse –Double apical beat (bisferiens pulse) –Prominent “a” wave in jugular –Systolic thrill –Systolic murmur

48. Diagnosis and investigations Electrocardiography Continuous ambulatory electrocardiography (Holter) Echocardiography

49. Electrocardiography The EKG is usually abnormal T wave and ST segment abnormalities LVH (Left ventricular hypertrophy)

50. Holter Ventricular arrhythmias

51. Echocardiography The most useful investigation Characteristic echocardiography findings: –Increased mass of the left ventricle with asymmetric hypertrophy of the septum –Abnormal systolic anterior motion of the anterior leaflet of the mitral valve –Calcification of the mitral valve –Left ventricular outflow tract obstruction

53. Prognosis Children who are diagnosed at less than 14 years of age  poor prognosis and high incidence of sudden death; 71% are asymptomatic Adults : better prognosis but have a higher mortality rate than general population Progressive cardiac failure with cardiac dilatation

54. Management Drug management –Avoid vasodilators because it worsen the gradient obstruction. HOCM patient should not receive nitrates –Avoid drugs for systolic heart failure (3 D’s): Digoxin, Ace-inhibitors (vaso-Dilators) and Diuretics are contra-indicated for the obstructive type of hypertrophic cardiomyopathy –Beta-blockers are used, negative inotropic effect acts to decrease the contractility of the hypertrophied septum and reduce the outflow tract obstruction

55. Management Drug management –Anti-arrhythmia is given for ventricular and atrial arrhythmias. –ICD (implantable cardioverter defibrillator) should be placed for any patient at risk for sudden death

56. Management Dual chamber pacing –This reduces the outflow tract gradient by pacing the RV apex and therefore altering the pattern of septal motion Surgery –Only used when all other treatments have failed –Myomectomy on the abnormal septum –Occluding the septal artery (new catheter technique to infarct the septum) –Injecting a small amount of alcohol

57. Recommendations for Athletic Activity Avoid most competitive sports (whether or not symptoms and/or outflow gradient are present) Low-risk older patients (>30 yrs) may participate in athletic activity if all of the following are absent

58. Recommendations for Athletic Activity Low-risk older patients (>30 yrs) may participate in athletic activity if all of the following are absent –ventricular tachycardia on Holter monitoring –family history of sudden death due to HCM –history of syncope or episode of impaired consciousness –severe hemodynamic abnormalities, gradient  50 mmHg –exercise induced hypotension –moderate or severe mitral regurgitation –enlarged left atrium (  50 mm) –paroxysmal atrial fibrillation –abnormal myocardial perfusion

59. Restrictive cardiomyopathy

60. Restrictive Cardiomyopathy Least common in developed countries Much more common in third world countries in Africa and South East Asia due to increased fibrosis of the endocardium secondary to infection The ventricular walls are excessively stiff and impede ventricular filling  increased end diastolic pressure. The systolic function on the ventricle is often normal

61. Possible causes of restrictive cardiomyopathy I.Infiltrative diseases A. Amyloidosis B. Hemochromatosis C. Sarcoidosis D. Glycogen storage disease (in pediatric age group) I.Endocardial – Obliterative disease A. Endomyocardial B. Fibrosis With eosinophilia (Loeffler’s syndrome) With eosinophilia

62. Possible causes of restrictive cardiomyopathy III. Interstitial disease A. Idiopathic B. Familial C. Radiation-induced D. Chronic allograft rejection

63. Clinical features of restrictive cardiomyopathy Most commonly present as right sided heart failure symptoms –Dyspnea, paroxysmal nocturnal dyspnea, and fatigue due to poor cardiac output –Peripheral edema and ascites –Elevated jugular venous pressure with a positive Kussmaul’s sign (increase in jugular venous pressure during inspiration) –Up to one-third of patients: thromboembolic complications or conduction disturbances

64. Pathophysiology Diastolic dysfunction in diastolic heart failure: increasing stiffness of the myocardium causes severe diastolic non-compliance of both ventricles. Thus, LV and RV filling pressure are above normal causing pulmonary congestion and right-sided failure As the disease progresses, systolic function is also compromised

65. Restriction vs Constriction History can provide important clues Constrictive pericarditis –history of TB, trauma, pericarditis, collagen vascular disorders Restrictive cardiomyopathy –amyloidosis, hemochromatosis Mixed –mediastinal radiation, cardiac surgery

66. Diagnostic tests 1. ECG: non specific changes, QRS voltages may be low because of the infiltrative process 2. Chest X-ray: may show dilated left atrium and right atrium; pulmonary venous congestion, pleural effusion

67. Diagnostic tests 3. Echocardiography: May show LV hypertrophy and RV hypertrophy but with no dilatation of the ventricles. Both atria are frequently dilated due to increase stiffness in the ventricles. Doppler signs of diastolic dysfunction suggestive of reduced ventricular compliance

68. Diagnostic tests 4. Cardiac catheterization: frequently not necessary 5. Cardiac biopsy: Low yield but may be useful in selected diseases with specific treatment (e.g hemochromatosis, sarcoidosis) Low voltage ECG’s with LV hypertrophy by echocardiography is suggestive of restrictive cardiomyopathy

69. Management Presentation is similar to that of constrictive pericarditis. Often a history of pericarditis, TB, radiation or surgery will favor constrictive pericarditis. The condition usually progresses towards death relatively quickly Most patients do not survive 10 years after diagnosis.

70. Treatment No satisfactory medical therapy Drug therapy must be used with caution –diuretics for extremely high filling prssures –vasodilators may decrease filling pressure –Ace-inhibitors and calcium channel blockers are of uncertain benefit. –? Calcium channel blockers to improve diastolic compliance –digitalis and other inotropic agents are not indicated

71. Prognosis Poor prognosis for patients with amyloidosis Generally declining to zero survival at 4 years. For idiopathic restrictive cardiomyopathy, 10 year survival is about 50%