Cardiac amyloidosis mimicking hypertrophic cardiomyopathy with obstruction: treatment with disopyramide.

A 71-year old-man presented with 4 posturally related syncopal episodes. He carried a diagnosis of asymptomatic hypertrophic cardiomyopathy (HCM) without obstruction based on an echocardiogram 7 years earlier. Echocardiography at the time of syncope evaluation demonstrated a hyperdynamic left ventricle with a septal thickness of 20 mm (an increase of 4 mm from an earlier echocardiogram), newly present systolic anterior motion of the mitral valve, and a peak left ventricular (LV) outflow tract gradient of 42 mm Hg at rest and 120 mm Hg with Valsalva maneuver (Figure 1). He was referred for septal myectomy, and cardiac catheterization demonstrated nonobstructive coronary artery disease. An ECG showed low-voltage limb leads, unusual in HCM (Figure 2), and cardiac magnetic resonance imaging (MRI) revealed delayed gadolinium enhancement in the papillary muscles, transmural enhancement involving the basal lateral walls, and subendocardial enhancement of the basal, mid, and distal anterior walls. There was also extensive gadolinium uptake in the atrial walls (Figure 3). Because the cardiac MRI suggested an infiltrative process, a cardiac biopsy was performed. This demonstrated extensive amyloid infiltration (Figure 4). Immunohistochemistry was positive for transthyretin, but negative for amyloid A and / light chains. Genetic testing for common mutations associated with HCM was negative, and no transthyretin mutations were detected. A diagnosis of wild-type transthyretin cardiac amyloidosis (senile systemic amyloidosis) mimicking HCM with obstruction was made.1 In light of the diagnosis of cardiac amyloidosis, the risk of surgical myectomy was considered to be increased, with an unknown risk-benefit ratio, and alcohol septal ablation was thought unlikely to be successful. Based on disopyramide’s efficacy in reducing LV outflow tract gradient in HCM with obstruction,2 a trial of a single dose of disopyramide 300 mg was instituted under carefully monitored conditions. This resulted in a decrease in the murmur and a reduction in the peak LV outflow tract gradient, from 40/120 mm Hg at rest and Valsalva maneuver, respectively, to 6/10 mm Hg 1 hour after drug administration (Figure 5). He was continued on short-acting disopyramide 200 mg 3 times daily; the gradient