A 74-year-old man presents to the cardiology clinic because of progressive exertional dyspnea, abdominal fullness, and swelling of both legs. During the past year, he has also developed numbness and burning discomfort in both feet. His medical history includes hypertension and monoclonal gammopathy of undetermined significance. Medications include lisinopril and furosemide. He underwent bilateral carpal tunnel release several years ago. Temperature is 36.7°C (98.1°F), blood pressure is 102/66 mm Hg, pulse is 88/min, and respiratory rate is 18/min. Oxygen saturation is 96% on room air. Physical examination demonstrates elevated jugular venous pressure that increases with inspiration, hepatomegaly, ascites, and bilateral pitting edema. Heart sounds are normal without a pericardial knock. The lungs are clear. ECG demonstrates low-voltage QRS complexes despite increased ventricular wall thickness on echocardiography. Transthoracic echocardiography shows biatrial enlargement, concentric thickening of both ventricular walls, preserved left ventricular ejection fraction, and impaired diastolic filling. Cardiac magnetic resonance imaging demonstrates diffuse subendocardial late gadolinium enhancement. Right-heart catheterization reveals elevated right- and left-sided filling pressures.
Which of the following is the most likely underlying cause of this patient’s cardiac dysfunction?
The correct answer is:
A) Amyloid deposition within the myocardium
This patient has restrictive cardiomyopathy due to cardiac amyloidosis. The combination of right-sided heart failure, preserved systolic function, impaired ventricular filling, biatrial enlargement, and increased ventricular wall thickness suggests an infiltrative myocardial process. The ECG finding of low QRS voltage despite markedly thickened ventricular walls is particularly characteristic of cardiac amyloidosis because the apparent hypertrophy is caused by extracellular protein deposition rather than enlargement of functioning cardiac myocytes.
The extracardiac findings further support the diagnosis. Peripheral neuropathy, bilateral carpal tunnel syndrome, and a monoclonal gammopathy may accompany systemic amyloidosis. Cardiac magnetic resonance imaging commonly demonstrates diffuse subendocardial or transmural late gadolinium enhancement due to expansion of the myocardial extracellular space.
This case is designed to distinguish restrictive cardiomyopathy from constrictive pericarditis. Both conditions can cause elevated jugular venous pressure, Kussmaul sign, ascites, peripheral edema, preserved ejection fraction, and elevated diastolic filling pressures. In restrictive cardiomyopathy, however, the pathology is located within the myocardium. Ventricular contraction remains coupled during respiration, producing concordant changes in right- and left-ventricular systolic pressures. Constrictive pericarditis causes exaggerated ventricular interdependence and discordant respiratory changes because the rigid pericardium fixes total intrapericardial volume.
Treatment depends on the amyloid subtype and the severity of cardiac involvement. Diuretics may reduce congestion, but patients are often preload dependent and can develop hypotension with excessive diuresis. Disease-specific treatment is required to limit additional amyloid deposition.
Answer choice B: Calcification and fibrosis of the pericardium, is incorrect.
This describes constrictive pericarditis, the most important near-miss diagnosis. Constrictive pericarditis also causes impaired diastolic filling, right-sided congestion, Kussmaul sign, and preserved ejection fraction. However, a pericardial knock, normal myocardial wall thickness, and septal bounce, would be more characteristic. The low-voltage ECG despite thick ventricular walls, extracardiac neuropathy, and diffuse myocardial enhancement favor amyloidosis.
Answer choice C: Chronic pressure overload from aortic stenosis, is incorrect.
Severe aortic stenosis causes true left ventricular myocyte hypertrophy and diastolic dysfunction. Patients generally have a harsh systolic ejection murmur radiating to the carotids, delayed carotid upstrokes, and increased rather than disproportionately low ECG voltage. Aortic stenosis would not explain bilateral carpal tunnel syndrome, peripheral neuropathy, or diffuse subendocardial enhancement.
Answer choice D: Iron deposition within cardiac myocytes, is incorrect.
Cardiac hemochromatosis can produce restrictive physiology early and dilated cardiomyopathy later. However, systemic iron overload is more commonly associated with liver disease, diabetes mellitus, skin hyperpigmentation, hypogonadism, and elevated ferritin and transferrin saturation. The clinical findings in this patient are more characteristic of amyloid deposition.
Answer choice E: Sarcomere mutation causing asymmetric septal hypertrophy, is incorrect.
Hypertrophic cardiomyopathy causes unexplained myocardial hypertrophy, often with asymmetric septal thickening and dynamic left ventricular outflow obstruction. The murmur typically increases with reduced preload, such as during Valsalva or standing. It does not usually cause low ECG voltage, diffuse subendocardial enhancement, peripheral neuropathy, or bilateral carpal tunnel syndrome.
Key Learning Point
Cardiac amyloidosis causes restrictive cardiomyopathy with preserved ejection fraction, biatrial enlargement, thickened ventricular walls, and paradoxically low ECG voltage.
