Clinical Disease Beyond the Heart: Diagnosis of Patients with Wild-Type ATTR Cardiomyopathy

Especially in older males, wild-type transthyretin-mediated amyloidosis (ATTR)-induced cardiomyopathy (CM) is recognized as a common cause of restrictive CM. The diagnosis is often missed and therefore underdiagnosed, despite recent diagnostic improvements and the use of scintigraphy. Transthyretin (TTR)-stabilizing drugs have been shown to potentially improve outcomes in this patient population, and new TTR-targeting therapies are being explored. To define diagnostic algorithms and efficacy benchmarks and evaluate the cost-effectiveness of new therapies, it is important to have a detailed description of each patient’s characteristics, and the natural history of this disease, in the real-world setting.

From a single center located in Greece, data were collected about the diagnostic approach, clinical characteristics, and outcomes of patients with ATTR-CM.

Fifty patients who were diagnosed with ATTR-CM after January 2015 were included in the analysis. Rates of ATTR-CM diagnosis doubled each year. The median age was 81 years, and 85% of the patients were male. The median heart-to-contralateral ratio was 1.7. All patients had positive pyrophosphate technetium-99m scans. Researchers performed a fat aspirate in 60% of biopsy samples, 35% of which were Congo red–positive. In the 8% of patients who underwent endomyocardial biopsy, all cases were positive; a monoclonal protein was found in 9% of patients. In 12% of patients, typing was performed by immunohistochemistry, immunoelectron microscopy, or mass spectrometry. In all patients, genetic testing was performed, and in 6% of patients (N = 2, with 1 female) a TTR mutation was found; however, these 2 patients did not have neuropathy. Median estimated glomerular filtration rate was 65 mL/min/1.73 m2 and median serum creatinine was 1.12 mg/dL.

Restrictive cardiomyopathy was a symptom in all patients; median New York Heart Association (NYHA) stage was II and 20% were NYHA stage ≥III Echocardiography showed the median interventricular septum was 15.5 mm, posterior wall was 15 mm, median ejection fraction was 50%, and median global longitudinal strain was –9.6%. Median N-terminal-pro hormone B-type natriuretic peptide was 4541 pg/mL. Approximately 23% of patients had a pacemaker, 58% had atrial fibrillation, and 25% had a history of coronary artery disease. Nearly all patients (98%) were receiving diuretics, 45% received an angiotensin-converting enzyme inhibitor or angiotensin II receptor blocker, and 72% received a beta-blocker. Other findings and symptoms at the time of diagnosis included carpal tunnel syndrome in 36% of patients, weight loss in 36%, purpura in 10%, history of spinal stenosis in 4%, tendon rupture in 14%, peripheral edema in 38%, peripheral neuropathy symptoms in 34%, and autonomic neuropathy in 16%. Doxycycline was prescribed to 42% of patients. The overall survival rate was 92%, while the median follow-up was 24 months.

The researchers concluded that the symptoms of severe heart failure dominate the clinical presentation of patients with ATTR-CM; however, other organ system symptoms indicate that ATTR is a systemic disease. While a small number of patients carry TTR mutations, in all patients with ATTR-CM, genetic testing should be considered.

Source: Kastritis E, Dialoupi I, Theodorakakou F, et al. Diagnosis and clinical characteristics of patients with wtATTR cardiomyopathy: a systemic disease beyond the heart. Presented at: XVII International Symposium on Amyloidosis 2020; September 14-18, 2020. Abstract PW092.

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