Cardiomyopathy Dilated Cardiomyopathy
GENERAL PRINCIPLES
Definition
Dilated cardiomyopathy (DCM) is a disease of cardiac muscle characterized by dilation of the cardiac chambers and reduction in ventricular contractile function.
Epidemiology
DCM is the most common form of nonischemic cardiomyopathy and is responsible for approximately 10,000 deaths and 46,000 hospitalizations each year. The lifetime incidence of DCM is about 30 cases per 100,000 persons.
Pathophysiology
DCM may be secondary to progression of any process that affects the myocardium, and dilation is directly related to neurohormonal activation. Familial DCM accounts for up to 50% of cases and is likely underestimated.4,72
Dilation of the cardiac chambers and varying degrees of hypertrophy are anatomic hallmarks. Tricuspid and mitral regurgitation are common because of the effect of chamber dilation on the valvular apparatus.
Atrial and ventricular arrhythmias are present in as many as one-half of these patients and contribute to the high incidence of sudden death in this population.
DIAGNOSIS
Clinical Presentation
Patients most often present with typical features of heart failure.
Diagnostic Testing
IMAGING
Diagnosis of DCM can be confirmed with echocardiography or cardiac MRI.
DIAGNOSTIC PROCEDURES
Endomyocardial biopsy provides little information that affects treatment of patients with DCMs and is not routinely recommended.11 Endomyocardial biopsy for DCM is recommended in clinical scenarios that may result in the diagnosis of a treatable form of acute myocarditis, including:
New-onset HF of EXAMINATION
Coarse systolic outflow murmur localized along the left sternal border that is accentuated by maneuvers that decrease preload (e.g., standing, Valsalva maneuver) and may be associated with a
forceful double or triple apical impulse.
Bisferiens (double peak per cardiac cycle) carotid pulse may occur in the presence of obstruction.
Diagnostic Testing
ELECTROCARDIOGRAPHY
The ECG of HCM is usually abnormal and invariably so in symptomatic patients with LVOT obstruction. The most common abnormalities are ST-segment and T-wave abnormalities, followed by evidence of LV hypertrophy. The ECG in apical-variant HCM is characterized by large, inverted T waves across the precordial leads.
IMAGING
Two-dimensional echocardiography and Doppler flow studies can establish the presence of a significant LV outflow gradient at rest or with provocation.
Additional risk stratification should be pursued with 24- to 48-hour Holter monitoring and exercise testing.
Cardiac MRI is indicated in patients with suspected HCM in whom the diagnosis cannot be confirmed with echocardiography. Delayed gadolinium enhancement on MRI indicates increased risk of SCD.
GENETIC TESTING
Genetic testing for HCM is commercially available. Genetic testing can be used to confirm the diagnosis of HCM when the clinical presentation is unclear or to facilitate family screening to determine at-risk first-degree relatives of an index patient.78
TREATMENT
Management is directed toward relief of symptoms and prevention of sudden death.
Infective endocarditis prophylaxis remains controversial, and prophylactic antibiotics are no longer recommended by guidelines.
Treatment in asymptomatic individuals is controversial, and no conclusive evidence has been found that medical therapy is beneficial.
Mild- to moderate-intensity recreational exercise is beneficial.
Participation in high-intensity recreational activities or moderate- to high-intensity competitive sports may increase the risk of sudden death. These activities should only be considered after a comprehensive evaluation and shared discussion.
Medications
Nonvasodilating β-blockers are first-line agents to reduce symptoms of HCM by reducing myocardial contractility and heart rate.
Nondihydropyridine calcium channel antagonists (verapamil and diltiazem) may improve the symptoms of HCM by reducing myocardial contractility and heart rate. Therapy should be initiated at low doses, with careful titration in patients with outflow obstruction. The dose should be increased gradually over several days to weeks if symptoms persist.
Disopyramide, a negative inotropic agent that results in lowering of the LVOT gradient, may be added for HCM patients who remain symptomatic despite the use of β-blockers and calcium channel blockers (alone or in combination). Use requires monitoring of the QT interval, and concomitant use of other antiarrhythmic drugs should be avoided.
Diuretics may improve pulmonary congestive symptoms in patients with elevated pulmonary venous pressures. These agents should be used cautiously in patients with LVOT obstruction because excessive preload reduction worsens the obstruction.
Vasodilators should be avoided, due to the risk of increasing the LVOT gradient.
Atrial and ventricular arrhythmias occur commonly in patients with HCM. Supraventricular tachyarrhythmias are tolerated poorly. Cardioversion is indicated if hemodynamic compromise develops.
Digoxin is relatively contraindicated because of its positive inotropic properties and potential for exacerbating ventricular outflow obstruction.
AF should be converted to sinus rhythm when possible, and anticoagulation is recommended if paroxysmal or chronic AF develops.
Diltiazem, verapamil, or β-blockers can be used to control the ventricular response. Procainamide, disopyramide, or amiodarone (see Chapter 7, Cardiac Arrhythmias) may be effective in the chronic suppression of AF.
ICD implantation is recommended for patients with HCM and prior cardiac arrest, ventricular fibrillation, or hemodynamically significant ventricular tachycardia.
ICD implantation is reasonable in high-risk patients with the following:
๎ Prior cardiac arrest
๎ Unexplained syncope
๎ LV maximal wall thickness >30 mm
๎ Sudden death attributed to HCM in one or more first-degree relatives
๎ LV apical aneurysm
๎ LV systolic dysfunction with LVEF enzyme α-galactosidase A, resulting in lysosomal accumulation of globotriaosylceramide in tissues.
More than half of patients develop cardiomyopathy, typically with LV hypertrophy and RCM.DIAGNOSIS
Diagnostic Testing
ELECTROCARDIOGRAPHY
The classic ECG finding in amyloidosis is low voltage (despite echocardiographic evidence of ventricular thickening) with poor R-wave progression. In sarcoidosis, conduction disease is often
present.
IMAGING
In RCM, echocardiography with Doppler analysis often demonstrates thickened myocardium with normal or abnormal systolic function, abnormal diastolic filling patterns, and evidence of elevated intracardiac pressure. Compared with constrictive pericarditis, respiratory variation is less marked and tissue Doppler velocities are reduced.
Cardiac MRI and PET are useful diagnostic tools for patients with cardiac sarcoidosis because granulomas, inflammation, and edema may be seen, which appear to improve with therapy.81 Cardiac MRI is also useful in the diagnosis of amyloidosis.
Bone-seeking radiotracers have strong avidity for TTR-variant amyloid, and bone scintigraphy with 99m technetium-labeled pyrophosphate is highly sensitive and specific for TTR-cardiac amyloidosis.
DIAGNOSTIC PROCEDURES
On cardiac catheterization, elevated and equalized RV and LV filling pressures are seen with a classic dip-and-plateau pattern in the RV and LV pressure tracing. Although pericardial constriction may produce similar findings, absence of ventricular interdependence identifies RCM as opposed to constriction.82
RV endomyocardial biopsy should be considered in patients in whom a diagnosis is not established or where characterization of a protein species will alter therapy, as in cardiac amyloidosis.
TREATMENT
Specific therapy aimed at amelioration of the underlying cause should be initiated.
In patients with AL cardiac amyloidosis, chemotherapy to reduce AL production should be pursued in conjunction with a hematologist.
In patients with TTR amyloidosis, tafamidis has been shown to reduce all-cause mortality and HF hospitalizations and improve functional status and quality of life.83
Heart or heart-liver transplantation may be considered for treatment refractory cardiac amyloidosis.
Cardiac hemochromatosis may respond to reduction of total body iron stores via phlebotomy or chelation therapy with deferoxamine.84
Cardiac sarcoidosis may respond to glucocorticoid therapy or other immunomodulatory therapies.
Fabry disease may be treated with recombinant α-galactosidase A enzyme replacement therapy.85,86
Digoxin should be avoided in patients with AL cardiac amyloidosis because digoxin is bound extracellularly by amyloid fibrils and may cause hypersensitivity and toxicity.87 β-Blockers should be avoided in patients with cardiac amyloidosis.