Evaluation of the 2021 ESC recommendations for family screening in hereditary transthyretin cardiac amyloidosis

Abstract

AimsThe 2021 European Society of Cardiology (ESC) screening recommendations for individuals carrying a pathogenic transthyretin amyloidosis variant (ATTRv) are based on expert opinion. We aimed to (i) determine the penetrance of ATTRv cardiomyopathy (ATTRv‐CM) at baseline; (ii) examine the value of serial evaluation; and (iii) establish the yield of first‐line diagnostic tests (i.e. electrocardiogram, echocardiogram, and laboratory tests) as per 2021 ESC position statement.Methods and resultsWe included 159 relatives (median age 55.6 [43.2–65.9] years, 52% male) at risk for ATTRv‐CM from 10 centres. The primary endpoint, ATTRv‐CM diagnosis, was defined as the presence of (i) cardiac tracer uptake in bone scintigraphy; or (ii) transthyretin‐positive cardiac biopsy. The secondary endpoint was a composite of heart failure (New York Heart Association class ≥II) and pacemaker‐requiring conduction disorders. At baseline, 40/159 (25%) relatives were diagnosed with ATTRv‐CM. Of those, 20 (50%) met the secondary endpoint. Indication to screen (≤10 years prior to predicted disease onset and absence of extracardiac amyloidosis) had an excellent negative predictive value (97%). Other pre‐screening predictors for ATTRv‐CM were infrequently identified variants and male sex. Importantly, 13% of relatives with ATTRv‐CM did not show any signs of cardiac involvement on first‐line diagnostic tests. The yield of serial evaluation (n = 41 relatives; follow‐up 3.1 [2.2–5.2] years) at 3‐year interval was 9.4%.ConclusionsScreening according to the 2021 ESC position statement performs well in daily clinical practice. Clinicians should adhere to repeating bone scintigraphy after 3 years, as progressing to ATTRv‐CM without signs of ATTRv‐CM on first‐line diagnostic tests or symptoms is common.