Cardiomyopathies

Cardiomyopathies are a group of diseases (three major types) primarily involving the myocardium and characterized by myocardial dysfunction that is not the result of hypertension, coronary atherosclerosis, valvular dysfunction, or pericardial abnormalities.

Ejection Fraction (normal >55%)

Left Ventricular Diastolic Dimension (normal <55mm)

Left Ventricular Wall Thickness Atrial Size Valvular Regurgitation

Common First Symptoms Congestive Symptoms

Risk for Arrhythmia

<30%

≥60 mm Decreased Increased Mitral first during decompensation;

tricuspid regurgitation in late stages

Exertional intolerance Left before right, except right prominent in

young adults

Ventricular tachyarrhythmia; conduction block in Chagas' disease, giant cell myocarditis, and some families; atrial fibrillation

Dilated

Ejection Fraction (normal >55%)---------------------------------------------- Left Ventricular Diastolic----------------------------------------------- Dimension (normal <55mm)------------------------------------------------ Left Ventricular Wall Thickness-------------------------------------------- Atrial Size-------------------------------------------------------------- Valvular Regurgitation

-------------------------------------------------------------- Common First Symptoms--------------------------------------------------------------

Congestive Symptoms

Risk for Arrhythmia

25%-50%--------------------------------------------------- <60 mm---------------------------------------------------- Normal or increased---------------------------------------------------- Increased; may be massive-------------------------------------------------------- Frequent mitral and tricuspid regurgitation----------------------------------------------------- Exertional intolerance------------------------------------------------------- Right often exceeds left

Ventricular uncommon except in sarcoidosis; conduction block in sarcoidosis and amyloidosis; atrial fibrillation

Restrictive

Hypertrophic

Ejection Fraction (normal >55%)

>60%

Left Ventricular Diastolic Dimension (normal <55mm

Often decreased

Left Ventricular Wall Thickness Markedly increased

Atrial Size Increased

Valvular Regurgitation Mitral regurgitation

Common First Symptoms* Exertional intolerance; may have chest pain

Congestive Symptoms* Primary exertional dyspnea

Risk for Arrhythmia Ventricular tachyarrhythmiasAtrial fibrillation

DILATED (CONGESTIVE) CARDIOMYOPATHY

Definition

dilated cardiomyopathy, the heart is enlarged, and both ventricles are dilated. Myocardial contractility is diminished, and cardiac output is usually reduced

Etiology

Idiopathic Familial Alcoholism (accounts for 15 to 40% of

all cases in Western countries) Collagen vascular disease (SLE,

rheumatoid arthritis, polyarteritis), dermatomyositis

Postmyocarditis Peripartum (last trimester of

pregnancy or 6 months postpartum) Heredofamilial neuromuscular disease Toxins (cobalt, lead, phosphorus,

carbon monoxide, mercury, doxorubicin, daunorubicin) and possibly other trace elements (mercury, antimony, gold, chromium)

Nutritional (beri-beri, selenium deficiency, carnitine deficiency, thiamine deficiency)

Cocaine, heroin, organic solvents ("glue sniffer's heart")

Irradiation Acromegaly, osteogenesis imperfecta,

myxedema, thyrotoxicosis, diabetes

Hypocalcemia Antiretroviral agents (zidovudine,

didanosine, zalcitabine) Phenothiazines Infections: viral (human

immunodeficiency virus, coxsackievirus B), rickettsial, mycobacterial, toxoplasmosis, trichinosis, Chagas' disease, bacterial

Hematologic (e.g., sickle cell anemia, hemochromatosis)

Ischemic Heat stroke Amyloid End-stage renal disease on

hemodialysis Prolonged tachycardia Takotsubo cardiomyopathy (secondary

to severe stress or vigorous exercise)

Idiopathic dilated cardiomyopathy is often familial, and apparently healthy relatives may have latent, early, or undiagnosed established disease. Echocardiographic evaluation of family members is recommended.

Prognosis

Annual mortality rate is 20% in patients with moderate heart failure, and it exceeds 50% in patients with severe heart failure. Patients with peripartum cardiomyopathy have a better prognosis than do those with cardiomyopathy due to infiltrative myocardial disease, HIV infection, or doxorubicin therapy.

Symptoms

Dyspnea on exertion, orthopnea, paroxysmal nocturnal dyspnea

Fatigue Palpitations Systemic and pulmonary embolism Chest pain Resting tachycardia

Physical Findings

Resting tachycardia Increased jugular venous pressure Small pulse pressure Pulmonary rales, hepatomegaly, peripheral

edema S3, S4 Mitral regurgitation, tricuspid regurgitation

(less common)

Diagnostic Studies

Chest x-ray: Massive cardiac enlargement Interstitial pulmonary edema

ECG: Left ventricular hypertrophy with ST-T wave changes Right bundle branch block (RBBB) or LBBB P wave changes indicative of left atrial abnormalities,

first-degree AV block Arrhythmias (sinus tachycardia, atrial fibrillation,

PVC, premature atrial contraction, ventricular tachycardia)

Diagnostic Studies

Echocardiogram: chamber enlargement, low EF with global akinesia

Cardiac catheterization: elevation of left or right ventricular end-diastolic pressures; cardiac output is generally normal or reduced and does not rise significantly with exercise. Biopsy is helpful in dilated cardiomyopathy to look for potentially treatable causes (e.g., sarcoidosis, hemochromatosis) and to establish a definitive diagnosis (e.g., amyloidosis).

Diagnostic Studies

The role of endomyocardial biopsy in patients with dilated cardiomyopathy is not well defined. Diagnostic yield is generally low, and the risks of occasional perforation and death further limit its use.

Therapy

Treat underlying disease (SLE, alcoholism, hemochromatosis).

Treat CHF (cause of death in 70% of patients) with sodium restriction, diuretics, ACE inhibitors, β-blockers, spironolactone, and digitalis .

Limit activity when CHF is present.

Therapy

Vasodilators (combined with nitrates and ACE inhibitors) are effective on all symptomatic patients with left ventricular dysfunction.

Prevent thromboembolism with oral anticoagulants in all patients with atrial fibrillation and in patients with moderate or severe failure.

Therapy

Low-dose β-blockade with carvedilol or other β-blockers may improve ventricular function by interrupting the cycle of reflux sympathetic activity and controlling tachycardia.

Therapy

Diltiazem and ACE inhibitors have been reported to have a long-term beneficial effect in patients with idiopathic dilated cardiomyopathy.

Therapy

Use antiarrhythmic treatment as appropriate. Empiric pharmacologic suppression of asymptomatic ventricular ectopy does not reduce risk for sudden death or improve long-term survival. In patients with severe left ventricular dysfunction and/or symptomatic and sustained ventricular tachycardia, the use of an automatic, implantable cardioverter-defibrillator should be considered.

Therapy

Growth hormone administration has been shown to increase myocardial mass and reduce the size of the left ventricular chamber, resulting in improvement in hemodynamics and clinical status. This therapeutic approach remains controversial.

Therapy

Patients with dilated cardiomyopathy (left ventricular EF <25%) and associated coronary atherosclerosis (angina, ECG changes, reversible defects on thallium scan) may benefit from surgical revascularization.

Consider heart transplant for young patients (younger than 60 years of age) who are no longer responsive to medical therapy.

RESTRICTIVE CARDIOMYOPATHY

Definition

Restrictive cardiomyopathy is characterized by decreased ventricular compliance, usually secondary to infiltration of the myocardium. These patients have impaired ventricular filling and reduced diastolic volume, normal systolic function, and normal or near-normal myocardial thickness.

Etiology

Infiltrative and storage disorders (glycogen storage disease, amyloidosis, sarcoidosis, hemochromatosis)

Scleroderma Radiation Endocardial fibroelastosis Endomyocardial fibrosis Idiopathic: many patients classified as having "idiopathic"

restrictive cardiomiopathy may have mutations in the gene for cardiac troponin I and restrictive cardiomyopathy may represent an overlap with hypertrophic cardiomyopathy in many familial cases.

Toxic effects of anthracycline Carcinoid heart disease, metastatic cancers Diabetic cardiomyopathy Eosinophilic cardiomyopathy (Löffler's endocarditis)

Symptoms and Physical

Restrictive cardiomyopathy presents with symptoms of progressive left-sided and right-sided heart failure: Edema, ascites, hepatomegaly, distended neck veins

may be present. Fatigue, weakness (secondary to low output) are

common. Kussmaul's sign may be present. Regurgitant murmurs are common. Apical impulse may be prominent. An early diastolic third heart sound is often heard.

Diagnostic Studies

Chest x-ray: Moderate cardiomegaly Possible evidence of CHF (pulmonary vascular congestion, pleural effusions)

ECG: Low voltage with ST-T wave changes. Frequent arrhythmias, left-axis deviation, and atrial fibrillation may be present.

Echocardiogram reveals increased wall thickness and thickened cardiac valves (especially in patients with amyloidosis).

Cardiac catheterization: to distinguish restrictive cardiomyopathy from constrictive pericarditis. Constrictive pericarditis: usually involves both ventricles and produces a plateau of elevated filling

pressures. PCWP equal to right atrial pressure and right ventricular end-diastolic pressure. Pulmonary artery systolic pressure <50 mm Hg. Right ventricular end-diastolic pressure greater than one third the right ventricular systolic pressure.

Restrictive cardiomyopathy: impairs the left ventricle more than the right. PCWP greater than right atrial pressure. Pulmonary artery systolic pressure > 50 mm Hg.

Magnetic resonance imaging (MRI) can assess the extent of pericardial thickening and may be useful in distinguishing restrictive cardiomyopathy from constrictive pericarditis (thickness of the pericardium is ≥ 5 mm in the latter).

Therapy

Cardiomyopathy caused by hemochromatosis may respond to repeated phlebotomies to decrease iron deposition in the heart.

Sarcoidosis may respond to corticosteroid therapy. Corticosteroid and cytotoxic drugs may improve

survival in patients with eosinophilic cardiomyopathy. There is no effective therapy for other causes of

restrictive cardiomyopathy. Death usually results from CHF or arrhythmias; therefore, therapy should be aimed at controlling CHF by restricting salt, administering diuretics, and treating potentially lethal arrhythmias. Cardiac transplantation can be considered in patients with refractory symptoms in idiopathic or familial restrictive cardiomyopathies.

HYPERTROPHIC CARDIOMYOPATHY

In hypertrophic cardiomyopathy (HCM), there is marked hypertrophy of the myocardium and disproportionately greater thickening of the interventricular septum than that of the free wall of the left ventricle (asymmetric septal hypertrophy).

Pathophysiology

During midsystole, the apposition of the anterior mitral valve leaflet against the hypertrophied septum can cause narrowing of the subaortic area and result in left ventricular outflow obstruction; because of this, the disease has been called idiopathic hypertrophic subaortic stenosis or hypertrophic obstructive cardiomyopathy. Patients with hypertrophic cardiomyopathy also have limited ability to dilate the coronary arteries in response to increased myocardial oxygen demand.

Epidemiology

The disease occurs in two major forms: A familial form, usually diagnosed in young patients and gene-mapped to chromosome 14q. Autosomal dominant trait with variable penetrance caused by mutations in any of 1 to 10 genes, each encoding proteins of cardiac sarcomere

A sporadic form, usually found in elderly patients.

Factors Influencing Obstruction

Increase Obstruction _: Drugs: digitalis, β-adrenergic stimulators (isoproterenol,

dopamine, epinephrine), nitroglycerin, vasodilators, diuretics, and alcohol

Hypovolemia Tachycardia Valsalva maneuver Standing position

Decrease Obstruction Drugs: β-adrenergic blockers, calcium channel blockers,

disopyramide, α-adrenergic stimulators (phenylephrine) Volume expansion Bradycardia Handgrip exercise Squatting position

Symptoms

Hypertrophic cardiomyopathy may be suspected on the basis of abnormalities found on physical examination.

Classic findings include: Dyspnea Syncope (usually seen with exercise) Angina (decreased angina in recumbent position) Palpitations Sudden death: may be the only manifestation (usually

seen in young adults during physical exercise)

Physical Findings

Harsh, systolic, diamond-shaped murmur at the left sternal border or apex that increases with Valsalva maneuver and decreases with squatting

Paradoxic splitting of S2 (if left ventricular obstruction is present)

S4 Double or triple apical impulse Very rapid and forceful carotid upstroke

(percussion wave)

Diagnostic Studies

Chest x-ray: normal or cardiomegaly ECG is abnormal in 75% to 95% of patients

Left ventricular hypertrophy Abnormal Q waves may be seen in anterolateral and inferior leads

Two-dimensional echocardiography is used to establish the diagnosis. Findings include: Ventricular hypertrophy Ratio of septum thickness to left ventricular wall thickness greater than 1.3:1 Increased EF Mitral regurgitation

MRI may be of diagnostic value when echocardiographic studies are technically inadequate. MRI is also useful in identifying segmental LVH undetectable by echocardiography.

Cardiac catheterization: Elevated left ventricular end-diastolic pressure Increased height of left atrial A wave Pressure gradient between left ventricle and aorta Small hyperdynamic left ventricle Mitral regurgitation

Treatment

Therapy for hypertrophic cardiomyopathy is directed at blocking the effect of catecholamines that can exacerbate dynamic left ventricualr outflow tract obstruction and avoidance of certain agents (e.g., vasodilators or diuretic agents), which can worsen the obstruction.

Propranolol 160 to 320 mg/d. The beneficial effects of β-blockers on symptoms (principally dyspnea and chest pain) and exercise tolerance appear to be due largely to a decrease in the heart rate with consequent prolongation of diastole and increased passive ventricular filling. By reducing the inotropic response, β-blockers may also lessen myocardial oxygen demand and decrease the outflow gradient during exercise, when sympathetic tone is increased.

Verapamil also decreases left ventricular outflow obstruction by improving filling and probably reducing myocardial ischemia.

Intravenous saline solution infusion in addition to propranolol or verapamil is indicated in patients with CHF.

24-hour Holter monitoring is used to screen for potentially lethal arrhythmias (principal cause of syncope or sudden death in obstructive cardiomyopathy). Implantable defibrillator is a safe and effective

therapy in patients who are prone to ventricular arrhythmias.

Electrophysiologic studies may be used to select prophylactic therapy.

Disopyramide is a useful antiarrhythmic, because it is also a negative inotrope.

Surgical treatment (myotomy-myectomy) is reserved for patients who have both a large outflow gradient (≥ 50 mm Hg) and severe symptoms of heart failure that are unresponsive to medical therapy. The risk for sudden death from arrhythmias is not altered by surgery.

Implantable defibrillators are a safe and effective therapy in HCM patients prone to ventricular arrhythmias. Their use is strongly warranted for patients with previous cardiac arrest or sustained spontaneous ventricular tachycardia. Implantation of a dual chamber pacemaker has not been shown to result in significant improvement in objective measures of exercise capacity.

Antibiotic prophylaxis for bacterial endocarditis for surgical procedures.

Screening of first-degree relatives with two-dimensional echocardiography is indicated.

Avoid use of digitalis, diuretics, nitrates, and vasodilators.

Avoidance of alcohol; alcohol use (even in small amounts) results in increased obstruction of the left ventricular outflow tract.

Encouraging results have been reported on the use of pacing for hemodynamic and symptomatic benefit in patients with drug-resistant hypertrophic obstructive cardiomyopathy.

Prognosis

Patients with HCM are at increased risk for sudden death, especially if the onset of symptoms is during childhood. Ventricular tachycardia or fibrillation appears to be the principal mechanism of sudden death in these patients. In high-risk patients with hypertrophic cardiomyopathy, implantable defibrillators are highly effective in terminating such arrhythmias and may have a significant role in the primary and secondary prevention of sudden death.

Prognosis

Adult patients can be considered low risk if they have no symptoms or mild symptoms and also if they have none of the following: A family history of premature death due to HCM Nonsustained ventricular tachycardia during Holter

monitoring A marked outflow tract gradient Substantial left ventricular hypertrophy (>20 mm) Marked left atrial enlargement Abnormal blood-pressure response during exercise Recurrent syncope

Left ventricular outflow tract obstruction at rest is a strong, independent predictor of progression to severe symptoms of heart failure and of death.

Screening

Screening of first-degree relatives with two-dimensional echocardiography and electrocardiography is indicated, particularly if adverse HCM-related events have occurred in the family. Annual screening is recommended for all adolescents aged 12 to 18. Periodic screening of all first-degree adult family members at 5-year intervals is recommended because hypertrophy may not be detected until the sixth decade of life. It is advisable to have a trained clinical genetic counselor see the patient and obtain consent before genetic testing.

Screening

Future screening techniques may involve identification of mutations in the gene encoding the sarcomeric proteins. The most common sarcomeric subtype is MYBPC3-HCM, affecting one in five patients. Clinical predictors of positive genotype, such as the need for an implantable cardioverter-defibrillator, young age at diagnosis, high degree of left ventricular wall hypertrophy, and family history of HCM, may aid in patient selection for genetic testing and increase the yield of cardiac sarcomere gene screening.