A 71-year-old man of African descent presented with intermittent chest discomfort and exertional dyspnea. His cardiovascular history was notable for a recent embolic left temporoparietal cerebrovascular accident with subsequent generalized tonic-clonic seizure disorder, hypertension, and diabetes mellitus.

Review of symptoms was positive for nonadherence to his anti-epiletic medications, progressive numbness and tingling in bilateral hands, erectile dysfunction, abdominal distension, decreased appetite, orthopnea, and lower extremity and facial edema. He noted that his mother had a similar complex of symptoms in advanced age.

On physical exam, he was tachycardic with mild respiratory distress with a temperature of 97.6 degrees Fahrenheit, heart rate of 87 bpm, blood pressure of 150/86 mm Hg, respiratory rate of 35 breaths per minute, and oxygen saturation of 100% on 2 L/min nasal cannula. His exam was significant for mild periorbital darkening, slight scalloping of the tongue, jugular venous distension of 14 cm H2O with Kussmaul's sign, a slightly laterally displaced point of maximal impulse with a regular rate and rhythm, a loud pulmonary component of the second heart sound, bibasilar pulmonary rales, a distended abdomen with a fluid wave and hepatomegaly, and 1+ lower extremity edema to his knees with bilateral biceps rupture. Laboratory data revealed normal renal and hepatic function with mild normocytic anemia and an elevated troponin T level of 0.08 ng/mL. His electrocardiogram showed normal sinus rhythm with nonspecific intraventricular conduction delay, left atrial abnormality, evidence of prior inferior and anteroseptal myocardial infarctions (MIs) and low voltage in the limb leads. Chest radiograph demonstrated cardiomegaly and decreased lung volumes.

Transthoracic echocardiogram (Figure 1) revealed severe concentric left ventricular hypertrophy (LVH) with interventricular septal thickness of 2.4 cm and posterior wall thickness of 2.2 cm, small left ventricle with impaired systolic function and diastolic function with ejection fraction of 45% with global hypokinesis, biatrial enlargement, and estimated right ventricular systolic pressure of 47 mm Hg.

Figure 1

Coronary angiography was negative for obstructive epicardial coronary disease.

Serum immunofixation and serum and urine protein electrophoresis were negative. Kappa light chain level was mildly elevated at 20.9 mg/L. A fat pad biopsy was negative for amyloid deposition. He was treated with intravenous furosemide, labetalol, and lisinopril. His course was complicated by paroxysms of atrial fibrillation, for which he was initiated on anticoagulants.

Cardiac magnetic resonance imaging (MRI) revealed severe concentric LVH with moderately increased left ventricular mass and globally decreased systolic function with ejection fraction of 44%, mildly dilated right ventricle with normal function, biatrial enlargement, and diffuse circumferential transmural late gadolinium enhancement of both ventricles and atria (Figure 2). These findings were consistent with cardiac amyloidosis.

Figure 2

A technetium-99m pyrophosphate single-photon emission computed tomography (SPECT) with computed tomography for attenuation correction was performed following intravenous administration of 20.8 m Ci of technetium-99m pyrophosphate at rest with imaging immediately and 60 minutes after administration. Cardiac and whole body images were obtained. These images demonstrated qualitatively uniform mild left and right ventricular uptake that was greater to the uptake in the ribs and sternum without evidence of extracardiac uptake aside from degenerative changes of bilateral, shoulders, and the right great toe (Figure 3). Cardiac uptake was also demonstrated in short axis images (Figure 4). These findings were all consistent with the diagnosis of TTR cardiac amyloidosis.

Figure 3

Figure 4

He was discharged on a beta-blocker, diuretics, and an angiotensin-converting enzyme inhibitor but continued to experience dyspnea on exertion.

In order to confirm the diagnosis and facilitate enrollment in a clinical trial, a right heart catheterization and endomyocardial biopsy were pursued with findings of elevated right atrial pressure of 14 mm Hg, elevated right ventricular pressures of 57/17 mm Hg, elevated pulmonary artery pressure of 56/17, and normal pulmonary capillary wedge pressure of 15 mm Hg. Six biopsy specimens were obtained from the right ventricle. Pathology was negative for active inflammation and MI but demonstrated amorphous, palely eosinophilic, extracellular material with positive Congo red and sulfated Alcian blue stains (Figure 5). Subsequent genetic assessment was positive for the isoleucine 122 variant of TTR amyloidosis, and the patient was thereafter enrolled in the trial. Since enrollment, he has remained clinically stable with symptoms of New York Heart Association Class II congestive heart failure.

Figure 5