Cardiomyopathy 2008 채성철

Transcription

1 Cardiomyopathy 2008 채성철

2 Definition A group of heart disorders in which the major structural abnormality is limited to the myocardium Excluded; heart muscle impairment resulting from other known cardiac conditions, e.g. hypertension, valvular disorders, or CAD

3 Classification on an etiologic basis Primary type Heart muscle disease of unknown cause Secondary type Myocardial disease of known cause Associated with a disease involving other organ system Specific cardiomyopathy by WHO

4 Etiologic classification of CMP Primary myocardial involvement Idiopathic (D,R,H) Familial (D,R,H) Eosinophilic endomyocardial disease (R) Endomyocardial fibrosis (R) Secondary myocardial involvement Infective (D) Viral myocarditis Bacterial myocarditis Fungal myocarditis Protozoal myocarditis Metazoal myocarditis Spirochetal Rickettsial Metabolic (D) Familial storage disease (D,R) Glycogen storage disease Mucopolysaccharidoses Hemochromatosis Fabry s disease Deficiency (D) Electrolytes Nutritional Connective tissue disorders (D) Systemic lupus erythematosus Polyarteritis nodosa Rheumatoid arthritis Progressive systemic sclerosis Dermatomyositis Infiltrations and Granulomas (R,D) Amyloidosis Sarcoidosis Malignancy Neuromuscular (D) Muscular dystrophy Myotonic dystrophy Friedreich s ataxia (H,D) Sensitivity and toxic reactions (D) Alcohol Radiation Drugs Peripartum heart disease (D)

5 Classification on the basis of pathophysiology and clinical presentation Dilated CMP Left &/or right ventricular enlargement Impaired systolic function Hypertrophic CMP Disproportionate left ventricular hypertrophy Typically involving septum more than free wall (asymmetric) Restrictive CMP Endomyocardial scarring or myocardial infiltration resulting in restriction to left &/or right ventricular filling (restrictive filling) Harrison T221-2, p1408

6 Classification on the basis of pathophysiology and clinical presentation Arrhythmogenic right ventricular cardiomyopathy/dysplasia Progressive fibrofatty replacement of right ventricular myocardium and some left ventricular involvement Unclassified cardiomyopathy Fibroelastosis Noncompacted myocardium Systolic dysfunction with minimal dilatation Mitochondrial involvement Harrison T221-2, p1408

7 Specific cardiomyopathy by WHO Heart muscle diseases associated with specific cardiac or systemic disorders Ischemic cardiomyopathy Valvular cardiomyopathy Hypertensive cardiomyopathy Inflammatory cardiomyopathy Myocarditis in association with cardiac dysfunction Idiopathic, autoimmune, infectious forms

8 Dilated CM

9 Dilated CM-Etiology Idiopathic Familial (genetic) Inflammatory Infectious (esp, viral) Noninfectious; connective tissue diseases, peripartum cardiomyopathy, sarcoidosis Toxic; chronic alcohol ingestion, chemotherapeutic agents Metabolic; hypothyroidism, chronic hypocalcemia or hypophosphatemia Neuromuscular; Muscular or myotonic dystrophy

10 Pathogenesis of DCMP Acute viral myocarditis Subacute viral myocarditis altered immunity deficient NK cell activity altered T-cell activity Viral clearing altered immunity altered T-cell activity molecular mimicry Viral persistence (10-40%) Persistent cell-mediated & humoral autoimmunity Virus-induced cytotoxicity (dystophin etc) Apoptosis Recovery (40-50%) Persistent inflammation Inflammatory cardiomyopathy DCM

11 Reversible form of DCMP Alcohol abuse Pregnancy Thyroid disease Cocaine use Chronic uncontrolled tachycardia Selenium deficiency Hypophsphatemia hypocalcemia

12 DCM-pathology Marked enlargement of all 4 chambers sometimes limited to left or right LV wall thickness may be increased, dilatation is out of proportion to hypertrophy Microscopically myocyte degeneration with irregular hypertrophy and atrophy of myofibers Ineterstitial and perivascular fibrosis

13 DCM- Pathophysiology Ventricular dilatation with decreased contractile function Compensatory mechanism Frank-Starling mechanism Nuerohormonal activation Development of clinical symptoms of heart failure Development of functional valvular regurgitation Volume and pressure load to atrium dilation, AF Further decrease in forward SV Further volume load to LV

14 DCM Clinical findings Congestive heart failure

15 DCM- PE Signs of decreased CO Pulmonary congestion Enlarged heart with leftward displacement of apical impulse S3 Murmur of MR Signs of RV failure

16 DCM-Diagnostic Chest X-ray ECG Echocardiography Cardiac catherization

17 Laboratory examinations Chest x-ray Enlargement of the cardiac silhouette Evidence of pulmonary venous hypertension Interstitial or alveolar edema

18 ECG Sinus tachycardia Atrial fibrillation Ventricular arrhythmias Left atrial abnormality Diffuse nonspecific ST-T wave abnormalities Intraventricular conduction defects Low voltage

19 Echocardiography Left ventricular dilatation Systolic dysfunction Reduced ejection fraction Wall thickness Normal, minimally thickened, or thinned

20 Elevated level of BNP Brain natriuretic peptide (BNP) DDX of heart failure from pulmonary disease Increased risk of sudden death Therapeutic monitoring

21 Cardiac catheterization Dilated, diffusely hypokinetic left ventricle Some degree of mitral regurgitation Endomyocardial biopsy Recognition of secondary cardiomyopathies Amyloidosis Acute myocarditis Inflammatory cardiomyopathy

22 DCM- Treatment Relieve symptoms Prevent complications Improve long-term survival

23 DCM- prevention and treatment of arrhythmias 40% of deaths; VT or VF Maintain serum electrolytes (K, Mg) Amiodarone is the safest drug for AF and other supraventricular arrhythmias; No convincing evidence to reduce mortality from ventricular arrhythmias in DCM ICD reduce arrhythmic deaths (for chronic symptomatic DCN and at least moderately reduced systolic function (eg, LVEF < 35%)

24 DCM - Treatment Cardiac resynchronization therapy Improved quality of life Improved exercise tolerance Decreased hospitalizations for heart failure Reduced mortality Particularly in pretreatment LBBB or other conduction abnormalities with markedly prolonged QRS duration

25 DCM Increased risk of thromboembolic complications Stasis in the ventricles (poor systolic function) Stasis in atria (LAE, AF) An abnormally thrombogenic endocardial surface Venous stasis

26 DCM - prevention of thromboembolic events Indication for systemic anticoagulation AF A previous thromboembolic event An LV thrombus? Severe depression of LV function; often anticoagulated, but prospective studies lacking

27 DCM Cardiac transplantation Better prognosis than the standard therapies in suitable patients Scarcity of donor hearts Mechanical devices (Ventricular assist device, artificial hearts, )

28 DCM - Prognosis Average 5-year survival; < 50%

29 Specific cardiomyopathy

30 Alcoholic cardiotoxicity Alcoholic cardiomyopathy Recurrent supraventricular or ventricular tachyarrhythmias Holiday heart syndrome After a drinking binge AF, atrial flutter, VPC

31 Alcoholic cardiomyopathy Large quantities of alcohol over many years > 80 g/day male, > 40 g/day female Partially genetically determined Reducing or ceasing alcohol consumption before severe heart failure has developed halt the progression even reverse the course of the disease Alcoholic CMP with advanced HF Poor prognosis Particularly if continue to drink Fewer than one-quarter survive 3 years

32 Peripartum cardiomyopathy Last trimester or within 6 months after delivery Mostly in the month before or immediately after delivery Risk factors Multiparous African American Over the age of 30 Mortality rate : 10 20% Prognostic factor Whether the heart size returns to normal after the first episode of CHF

33 Hypertrophic CM

34 Hypertrophic cardiomyopathy The most common cardiac abnormality in young athletes who die suddenly during vigorous physical exertion Incidence; 1/500 Septal or LV hypertrophy not caused by chronic pressure overload Systolic LV contraction is vigorous Impaired ventricular relaxation and high diastolic pressure; thickened muscle is stiff

35 HCM - Etiology A familial disease; autosomal dominant pattern with variable penetrance and a large variety of mutations in at least 10 different genes Encoded proteins; beta-myosin heavy chain, cardiac troponin T, myosin-binding protein C Incorporation into the sarcomere Impaired contractile function Increase in myocyte stress Compensatory hypertrophy and proliferation of fibroblasts

36 HCM -Etiology Pathophysiology and natural history related to particular mutations within the gene, rather than the actual gene involved The age of onset of hypertrophy The extent and pattern of cardiac remodeling The person s risk of developing symptomatic heart failure or sudden death

37 HCM - Pathology Hypertrophy; any portion of the ventricles; 90% asymmetric hypertrophy of ventricular septum Myocardial fibers; extensive disarray Short, wide, hypertrophied fibers oriented in chaotic directions and surrounded by numerous cardiac fibroblasts and extracelluar matrix?abnormal diastolic stiffness and arrhythmias

38 Patterns of Hypertrophy Basal to entire septum Isolated lateral free wall Concentric Apical Midventricular

39

40 Apical hypertrophy Giant negative T-waves on ECG Spade-shaped LV cavity Benign clinical course

41 HCM - Pathophysiology Marked ventricular hypertrophy Reduced compliance and relaxation Transient LVOT obstruction during systole (Asymmetric hypertrophy of prox. septum)

42 HCM without outflow obstruction Rise in diastolic filling pressure Elevation of LA, pulmonary venous, pulmonary capillary pressure Exertional dyspnea

43 HCM with outflow obstruction Elevated ventricular systolic pressure Increase wall stress and myoc O 2 consumption Mitral regurgitation (SAM may hinder MV closure) increase Lap, PVp. AF Dynamic systolic pressure gradient; depends on LV cavity size and contractility Symptoms; primarily stems from increased LV stiffness and diastolic dysfunction

44 HCM Clinical findings Dyspnea Angina (High O2 demand, narrowed small branches of coronary arteries within hypertrophied ventricular wall) Syncope; arrhythmias, transient fall in CO Orthostatic lightheadedness Pooling of venous return LV size LV obstruction - CO Development of arrhythmias exacerbates symptoms First manifestation may be VF and sudden cardiac death (particularly during strenuous exertion) Risk factors for sudden death; hx of syncope, family hx of sudden death, certain high-risk mutations, extreme hypertrophy of LV wall (>30 mm)

45 HCM - PE S4 Palpable presystolic impulse (double apical impulse) Carotid pulse; brisk rise and quick decline Systolic murmur at left LSB Holosytolic murmur at apex (MR)

46 HCM - PE Valsalva maneuver; intrathoracic pressure venous return LV size Squatting position; venous return, systemic vascular resistance Standing; venous return, systemic vascular resistance Valsalva Squatting Standing HCM murmur AS murmur

47 HCM Diagnostic studies ECG; LVH, LAE, prominent Q waves, diffuse T wave inversions, arrhythmias, Echocardiography; most helpful Cardiac catheterization; percutaneous septal ablation? Genetic testing

48 HCM with SAM

49 HCM - treatment Beta-blockers Reduce myocardial O2 demand Lessen LV outflow gradient during exercise Increase passive diastolic ventricular filling time Decrease ventricular ectopic beats But, have not shown to prevent sudden arrhythmic death

50 HCM - treatment CCB s Can reduce vent stiffness Diuretics; in pulmonary congestion (cautiously to avoid volume depletion) Vasodilators should be avoided Amiodarone and disopyramide for AF Digitalis should be avoided Strenuous exercise and competitive sports should be avoided ICD for high risk of sudden cardiac death Prophylaxis for infective endocarditis?dual chamber (RA and RV) pacing; alter normal sequence of ventricular contraction Myomectomy; no response to pharmacologic therapy; current procedure of choice Percutaneous septal ablation Genetic counseling

51 Percutaneous septal ablation

52 Percutaneous septal ablation

53 Surgical septal myectomy

54 Dual-chamber permanent pacing With a short PR interval Patients with severe symptoms Altering the pattern of ventricular depolarization and contraction Effects Improving symptoms Reducing the outflow gradient

55 HCM -Prognosis Sudden death Adults; 2-4% /year Children and adolescents; 4-6%

56 Restrictive CM

57 Restrictive cardiomyopathy Less common Abnormally rigid ventricles (not necessarily thickened) Impaired diastolic filling Usually normal or near-normal systolic function Fibrosis or scarring of the endomyocardium or Infiltration of the myocardium by an abnormal substance

58 Classification Myocardial Noninfiltrative Idiopathic cardiomyopathy Familial cardiomyopathy Hypertrophic CMP Scleroderma Pseudoxanthoma elasticum Diabetic cardiomyopathy Infiltrative Amyloidosis Sarcoidosis Gaucher s disease Hurler s disease Fatty infiltration Storage disease Hemochromatosis Fabry s disease Glycogen storage disease Endomyocardial Endomyocardial fibrosis Eosinophilic endomyocardial disease (Hypereosinophilic syndrome) Carcinoid heart disease Metastatic cancer Mediastinal irradiation Anthracycline toxicity Drugs causing fibrous endocarditis Serotonin Methysergide Ergotamine Mercurial agent Busulfan

59 RCM - Amyloidosis primary, secondary, hereditary, senile forms; deposition of extracellular amyloid between myocardial fibers in the atria and ventricles, in coronary arteries and veins, and valves Clinical manifestation of cardiac involvement are most common in the primary form; less frequently systolic dysfunction Orthostatic hypotension in 10%; amyloid deposition in ANS and peripheral blood vessels Arrhythmias and conduction impairment; syncope and sudden death

60 Echocardiography Thickened myocardial wall speckled appearance patch amorphous, high-intensity echoes

61 Diagnosis Aspiration of abdominal fat Biopsy of the myocardium or other organs Skin, rectum, bone marrow Amyloid material stained red within the cardiac muscle cells with Congo red stain Typical yellow-green birefringence after Congo red stain under polarizing microscopic examination Positive reaction of amyloid material between atrophic cardiac muscle cells with monoclonal murine antibody of amyloid associated protein

62 RCM - Pathophysiology Elevation of diastolic LV pressure Elevation of systemic and pulmonary venous pressures; right- and left-sided vascular congestion Reduced ventricular cavity size with decreased SV and CO

63 RCM Clinical findings Signs of left- and right-sided HF Fatigue and decreased exercise tolerance due to decreased CO Systemic congestion jugular venous distension, peripheral edema, ascites with a large, tender liver Arrhythmias; AF and various types of heart block

64 RCM Physical examination Signs of congestive heart failure Kussmaul sign

65 RCM Diagnostic studies Chest X-ray; normal sized heart with signs of pulmonary congestion ECG; ST-T wave abnormalities, conduction disturbances

66 ECG Low-voltage Nonspecific ST-T-wave changes Various arrhythmias

67 Echocardiography Symmetrically thickened LV walls Normal or slightly reduced ventricular volumes & systolic function Biatrial enlargement LV RV RA LA

68 RCM - DDX DDX; constrictive pericarditis correctable RCM only rarely treatable Transvenous endomyocardial biopsy, CT, MRI

69 RCM Treatment Very poor prognosis Hemochromatosis; phlebotomy, iron chelation therapy Primary amyloidosis; Chemotherapy followed by BMT Symptomatic treatment; digitalis and vasodilators not helpful

70 Myocarditis

71 Myocarditis Cardiac inflammation Etiology Infective : most common cause Virus : coxsackievirus B, adenovirus, HIV Hypersensitivity to drugs Radiation Chemicals Physical agents

72 Etiologies of myocarditis

73 Clinical manifestations Asymptomatic Transient electrocardiographic ST-T wave abnormalities Fulminant myocarditis Arrhythmias, heart failure, death Chest pain Acute myocardial infarction mimicking myocarditis Heart failure Arrhythmia

74 Preceding upper respiratory febrile illness or a flu-like syndrome Viral nasopharyngitis or tonsillitis

75 Physical examination Often normal Severe form Muffled S 1 S 3 Murmur of mitral regurgitation Pericarditis 동반 Pericardial friction rub

76 Diagnosis Isolation of virus Stool, pharyngeal washings, or other body fluids Changes in specific antibody titers Endomyocardial biopsy Round-cell infiltration Necrosis of adjacent myocytes

77 Clinical presentation & Evolution of acute viral myocarditis

78 Progress to chronic or DCM

79 Prognosis Myocarditis with pulmonary hypertension High risk of death

80 Treatment Exercise Deleterious in patients with viral myocarditis Avoid strenuous activity until ECG has returned to normal Patients with CHF ACE inhibitor, diuretics, salt restriciton Unusually sensitive to digitalis Fulminant myocarditis Mechanical cardiopulmonary support Cardiac transplantation Majority survive & demonstrate substantial recovery of ventricular function