Hereditary and wild type transthyretin amyloid cardiomyopathy in Bulgaria in patients suspected for cardiac amyloidosis

Introduction: Transthyretin amyloid cardiomyopathy (ATTR-CM) is a severe progressive disease, more common than previously expected. The main objectives were to evaluate hereditary and wild type ATTR-CM frequency and clinical manifestations. Material and methods: One hundred seventy-eight patients at mean age 68 13 years (129 males), referred by cardiologists with suspected cardiac amyloidosis (left ventricular wall thickness 12 mm and red flags) were evaluated. Pyrophosphate scintigraphy (99mTc-PYP) grade 2-3 myocardial uptake in the absence of monoclonal protein confirmed the diagnosis. Genetic test differentiated variant from wild type ATTR-CM. Endomyocardial biopsy with amyloid typing was performed in two patients. Results: Cardiac amyloidosis was diagnosed in 69 patients: light chain in 24 (13%) and ATTR-CM in 45 patients (25%). Wild type (ATTRwt) was found in 21 (12%) male patients at mean age 81 6 years and variant type (ATTRv) in 24 patients (13%) at mean age 58 7 years (15 males). In all ATTRv-CM patients some degree of peripheral polyneuropathy was found. The most common clinical red flags at diagnosis in both ATTRv and ATTRwt were heart failure in all patients, atrial fibrillation (16; 36%), pacemaker (5; 11%), and carpal tunnel syndrome (8; 18%). Severe aortic stenosis (4; 19%), spinal stenosis (2;10%), biceps tendon rupture (1; 5%) were characteristic for the wild type. At follow up, four patients needed a pacemaker for high degree AV block, six patients developed new onset atrial fibrillation, seventeen patients needed either initiation or an increase of the dose of loop diuretic, another 7 patients were hospitalized for heart failure exacerbation. Eight patients (18%) died, 7 (33%) with ATTRwt-CM and 1 (4%) with ATTRv-CM, all with advanced heart failure, 4 with concomitant severe aortic stenosis. Conclusions: This study provides the first nationwide estimates of the frequency and the clinical manifestations of ATTR-CM. Confirming the severity of the disease and poor prognosis, a low threshold for screening is needed for early diagnosis and timely treatment.