A diagnostic screening algorithm for the identification of transthyretin amyloid cardiomyopathy in high-risk patient populations: updated results

Transthyretin amyloid cardiomyopathy (ATTR-CM) is an underdiagnosed disease, resulting in heart failure, arrhythmias, and valvular disease. Effective screening methods are needed to identify ATTR-CM at a treatable stage and to improve outcomes for this complex population. We designed pragmatic screening criteria to identify high-risk patients in heart failure (HFC), atrial fibrillation (AFC), transcatheter valve (TAVR), and amyloid (AC) clinics and in cardiologist’s offices from January 2019-December 2022. Patients >60 years old were included if one of several broad screening criteria was met and if ATTR evaluation was felt appropriate by the physician. Patients were screened with nuclear scintigraphy (PYP) and monoclonal protein. Baseline demographic, laboratory, and imaging data were collected, and patients are followed for 3 years. 200 patients were screened: 49% in HFC, 26% in cardiologists’ offices, 15% in AFC, 7% in AC. The mean age was 78 years and 56% were male. Positive PYP scans were identified in 22% HFC, 31% cardiologist office, 7% AFC, and none in TAVR clinic. Excluding 14 patients screened in AC, 39 (21%) had positive PYP scans. 37 patients (20%) were diagnosed with ATTR-CM, including 8 (4%) with monoclonal protein, and 2 (1%) had false positive tests. 3 (2%) screened were diagnosed with AL amyloidosis, none of whom had a positive PYP. The positive predictive value (PPV) for ATTR-CM screening criteria ranged from 16-38% (Table 1) and was highest for age >70 years and new HF (PPV 38%), moderate-severe diastolic dysfunction (PPV 34%), and left ventricular septal thickness >12 mm (IVSD12; PPV 32%). The negative predictive value (NPV) was highest for age >70 and new onset HF (NPV 95%), followed by HFpEF and IVSD12 (NPV 89%). Of those with positive PYP scans, 98% were >70 years or had a history of HF, 94% had relative wall thickness >0.42, 66% had AF, and none had AF without HF. Only 6% had dilated left ventricle. They were less likely to be on beta-blocker (p < 0.001) and renin-angiotensin blocker drugs (p=0.01), and more likely to be diuretics (p=0.02) and amiodarone (p=0.02). Troponin was more likely to be elevated (OR 6.8, p< 0.001) and NT-pro BNP was more elevated (3633 vs. 2018; p=0.01). Broad screening criteria applied to high-risk patient populations yield new ATTR-CM diagnoses in up to 30% of patients screened. Further refinement of these criteria may lead to even greater diagnostic yield allowing earlier diagnosis and therapeutic interventions.