Evaluation of the 2021 ESC Recommendations for Family Screening in Hereditary Transthyretin Cardiac Amyloidosis
Steven A. Muller, Belén Peiró-Aventín, Giulia Biagioni, Giacomo Tini, Giulia Saturi, Christina Kronberger, Anouk Achten, Stephan Dobner, Wouter P. te Rijdt, Alessio Gasperetti, Anneline S.J.M. te Riele, Guerino Giuseppe Varrà, Alberto Ponziani, Alexander Hirsch, Aldostefano Porcari, Manon G. van der Meer, Mattia Zampieri, Pim van der Harst, Andreas A. Kammerlander, Elena Biagini, J. Peter van Tintelen, Emanuele Barbato, Folkert W. Asselbergs, Silvia Menale, Christoph Gräni, Marco Merlo, Michelle Michels, Christian Knackstedt, Christian Nitsche, Simone Longhi, Beatrice Musumeci, Francesco Cappelli, Pablo García‐Pavía, Marish I.F.J. Oerlemans
Abstract
AIMS: The 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 RESULTS: We 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%. CONCLUSIONS: Screening 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.