Incidental findings from the first prospective systematic screening of cardiac amyloidosis in the elderly

Abstract Background Amyloid transthyretin (ATTR) amyloidosis results from the deposition of misfolded transthyretin (TTR) in the heart. Despite its growing recognition, no systematic screening of ATTR cardiac amyloidosis (CA) has been conducted until recently. In the first screening study, we reported a prevalence of 0.4% of wild-type ATTR-CA in unselected elderly individuals from the general population. Here, we report on the collateral findings that emerged from this effort, underscoring the broader clinical value of systematic screening in elderly adults. Methods General practitioners working in an area of the Italian Tuscany region enrolled 1,000 individuals aged 65-90 years. Participants underwent a Cardiology visit, 12-lead electrocardiogram (ECG), transthoracic echocardiography, and blood sampling for cardiac biomarkers. Red flags for CA included interventricular septal thickness ≥12 mm, echocardiographic/ECG/clinical signs of CA, or high-sensitivity troponin T ≥14 ng/L. Patients with red flags underwent further evaluations, including monoclonal protein testing and bone scintigraphy. Additional cardiac conditions were documented, including left ventricular (LV) and right ventricular (RV) dysfunction, valvular disease, atrial fibrillation (AF), conduction abnormalities, and aortic pathology. Results Among 1,000 participants (51% males, aged 74±9 years), the prevalence of ATTRwt-CA was 0.46%, and 26.2% had a history of cardiac disease. Newly diagnosed abnormalities included LV diastolic dysfunction (3.1%), LV systolic dysfunction (1.4%), RV dysfunction (1.5%), regional wall motion abnormalities (0.7%), moderate-to-severe aortic stenosis (0.3%), moderate-to-severe mitral regurgitation (0.9%), and pericardial effusion (1.9%). The bicuspid aortic valve was detected in 0.1%, while aortic root (6.6%) and ascending aorta (8.9%) dilation were also identified. Two cases of cardiac masses were detected. Conduction abnormalities included left bundle branch block (0.6%) and new-onset AF (0.3%). Patients with valvular disease, aortic pathology, or coronary artery disease underwent specialist consultation, with one patient receiving surgical aortic valve replacement and another undergoing pacemaker implantation. Aortic ulceration was managed conservatively, while a case of mitral annular calcification was diagnosed via MRI. As an additional finding, we detected stage 3-5 chronic kidney disease in 15.6% of patients, who were referred to Nephrology evaluation. Conclusions The first systematic screening for CA in an elderly population revealed a range of previously undiagnosed cardiac conditions (Figure). These findings indicate that a screening program encompassing clinical examination, ECG, echocardiography, cardiac biomarkers, and plasma creatinine has diagnostic value beyond the detection of CA. Cost-effectiveness analyses evaluating the feasibility of such screening programs should consider this "collateral" benefits.Figure