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

Steven A Muller, Belén Peiró-Aventin, 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 G Varrà, Alberto Ponziani, Alexander Hirsch, Aldostefano Porcari, Manon G van der Meer, Mattia Zampieri, Pim van der Harst, Andreas Kammerlander, Elena BiaginiJ 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 Garcia-Pavia, Marish I F J Oerlemans

Research output: Contribution to journalArticleAcademicpeer-review

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.

Original languageEnglish
Pages (from-to)2025-2034
Number of pages10
JournalEuropean Journal of Heart Failure
Volume26
Issue number9
Early online date17 Jun 2024
DOIs
Publication statusPublished - Sept 2024

Keywords

  • ATTRv
  • Amyloidosis
  • Cascade screening
  • Repeat evaluation

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