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A 62-year-old white man presents to the physician because of worsening lower-extremity edema. He also reports feeling increasingly fatigued over the past 2 months and is lacking energy for normal activities. He has a history of hypertension and takes hydrochlorothiazide, which was increased recently because of his lower extremity edema. He also takes a daily aspirin and simvastatin for his hypercholesterolemia. Otherwise he is healthy and had a recent colonoscopy that he thinks was normal. His wife is with him and says she is worried because he has been feeling particularly light-headed lately. He denies having chest pain, fever, chills, or nausea. He also denies orthopnea or paroxysmal nocturnal dyspnea, but notes having occasional jaw pain. Physical examination is remarkable for a heart rate of 55/min and a blood pressure of 130/45 mm Hg that drops to 100/40 mm Hg when standing, at which point he reports feeling dizzy. He has elevated jugular venous pressure to 10-12 cm, and his cardiac examination is significant for bradycardia with a loud S4 gallop. He has hepatomegaly and 2+ lower-extremity edema to the knees that is pitting. Urinalysis shows 3+ protein but is negative for leukocyte esterase and blood. A basic metabolic panel is normal. A subcutaneous fat biopsy shows immunofluoresence with Congo-red staining.
Deposition of which of the following proteins most likely caused his symptoms?
A. A amyloid
B. Kerato-epithelin
C. Light chain immunoglobulins
D. Medin
E. Transthyretin
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The correct answer is C. 28% chose this.
Low voltages on an ECG can be due to an increase in the distance between the heart and ECG leads due to pericardiac effusions, large body habitus, infiltration of the heart muscle with proteins, or metabolic abnormalities. Amyloidosis has immunofluoresecence when stained with Congo-red, and the presence of amyloid proteins in his subcutaneous tissues makes the findings on this ECG a sign of an infiltrative cardiomyopathy. One of the most common causes of restrictive/infiltrative cardiomyopathy is cardiac amyloidosis due to AL amyloidosis (light chain amyloid). Patients with cardiac amyloid typically present with right heart failure. Amyloidosis is also associated with atrioventricular conduction delay. Presyncope and orthostasis are common in cardiac amyloidosis due to autonomic dysfunction and arrhythmias. Other findings of cardiac amyloid include low-voltage QRS on ECG, ventricular wall thickening, and other physical signs of a restrictive cardiomyopathy.
A is not correct. 61% chose this.
A amyloid produces a systemic type of amyloidosis that is almost never associated with cardiac amyloidosis, and therefore would not lead to ECG changes. A amyloid is associated with a number of rheumatologic diseases including rheumatoid arthritis and ankylosing spondylitis.
B is not correct. 3% chose this.
Kerato-epithelin is a protein associated with the development of localized corneal amyloid. It would not result in ECG changes
D is not correct. 2% chose this.
Medin, if mutated, can deposit in the aortic wall and is found in people >60 years old. It does not lead to cardiac amyloidosis and therefore would not generate these ECG findings.
E is not correct. 6% chose this.
Transthyretin is a protein produced by the liver that can mutate and result in amyloidosis. It is associated with both neurologic and cardiac amyloidosis, but transthyretin-caused amyloidosis is less common than that caused by light chain immunoglobulins. Transthyretin can cause isolated cardiac amyloidosis in African-Americans, but this man is white.
