MKSAP Quiz: 1-year history of progressive fatigue, dyspnea, edema
A 62-year-old man is evaluated for a 1-year history of progressive fatigue, dyspnea on exertion, and lower-extremity edema. He has been hospitalized twice in the past year for heart failure. Following a physical exam and electrocardiogram, what is the most likely diagnosis?
A 62-year-old man is evaluated for a 1-year history of progressive fatigue, dyspnea on exertion, and lower-extremity edema. He has been hospitalized twice in the past year for heart failure. Medical history is otherwise unremarkable. His current medications are furosemide, amlodipine, and spironolactone. He is Black.
On physical examination, temperature is normal, blood pressure is 106/68 mm Hg, pulse rate is 68/min, and respiration rate is 14/min. Oxygen saturation breathing ambient air is normal. Jugular venous distention is noted. No crackles are present. A grade 2/6 holosystolic murmur is heard at the left lower sternal border and increases with inspiration. There is no S3 or S4. The liver is enlarged. Pitting edema is present to the mid shin bilaterally.
An electrocardiogram reveals sinus rhythm, biatrial enlargement, and low voltage of the QRS complexes. Q waves are present in leads V1 through V3. Echocardiogram reveals severe concentric left ventricular hypertrophy with wall thickness of 16 mm, moderate biatrial dilatation, normal left ventricular cavity size, a left ventricular ejection fraction of 55%, and no regional wall motion abnormalities. Diastolic dysfunction is noted. Right ventricular size and systolic function are normal, and the right ventricular wall thickness is slightly increased. The estimated right ventricular systolic pressure is 68 mm Hg. Tricuspid regurgitation is present. There is no pericardial effusion.
Which of the following is the most likely diagnosis?
A. Cardiac amyloidosis
B. Constrictive pericarditis
C. Hypertensive heart disease
D. Hypertrophic cardiomyopathy
MKSAP Answer and Critique
The correct answer is A. Cardiac amyloidosis. This content is available to MKSAP 18 subscribers as Question 99 in the Cardiovascular Medicine section. More information about MKSAP is available online.
The most likely diagnosis is cardiac amyloidosis. This patient has heart failure, elevated right heart pressure, and severe concentric wall thickening with preserved systolic function and severe pulmonary hypertension. The electrocardiogram paradoxically demonstrates low QRS voltage and a “pseudoinfarct” pattern: Q waves in the anteroseptal leads without regional wall motion abnormalities on echocardiogram. The most likely diagnosis is cardiac amyloidosis, likely related to a Val122lle mutation in transthyretin (TTR), which is present in 3% to 4% of the Black population. Cardiac amyloidosis should be suspected in Black patients older than 50 years who have left ventricular wall thickening that is not explained by loading conditions (for example, hypertension or aortic stenosis) and present with heart failure or features of diastolic dysfunction. Although a monoclonal gammopathy is present in immunoglobulin light-chain (AL) amyloidosis, this is not a feature of TTR amyloidosis. Diagnosis is established by histopathology; endomyocardial biopsy is more sensitive than abdominal fat pad biopsy.
Patients with constrictive pericarditis usually have normal or only mildly increased left ventricular wall thickness. Severe pulmonary hypertension is usually not present.
Amyloidosis may be mistaken for hypertensive heart disease; however, the left ventricular wall thickness in this patient is greater than expected for a patient without hypertensive heart disease. Additionally, electrocardiographic features of left ventricular hypertrophy (increased voltage) would be expected.
Hypertrophic cardiomyopathy may be symmetric and nonobstructive and may demonstrate a restrictive filling pattern on echocardiogram. However, in most cases, the QRS voltage on electrocardiogram is congruent with the degree of hypertrophy.
Key Point
- Cardiac amyloidosis should be suspected in Black patients older than 50 years who have left ventricular wall thickening that is not explained by loading conditions (for example, hypertension or aortic stenosis) and present with heart failure or features of diastolic dysfunction.