Electrocardiographic heterogeneity of patients with variant transthyretin amyloid cardiomyopathy: Genotype-phenotype correlations

Domitilla Russo; Francesco Cappelli; Gianluca Di Bella; Giacomo Tini; Aldostefano Porcari; Alberto Cipriani; Marco Canepa; Marco Merlo; Roberto Licordari; Pier Filippo Vianello; Mattia Zampieri; Laura De Michieli; Riccardo Scirpa; Federico Perfetto; Gianfranco Sinagra; Camillo Autore; Claudio Rapezzi; Maria Beatrice Musumeci

doi:10.1016/j.ijcard.2023.131354

Electrocardiographic heterogeneity of patients with variant transthyretin amyloid cardiomyopathy: Genotype-phenotype correlations

Int J Cardiol. 2023 Dec 15:393:131354. doi: 10.1016/j.ijcard.2023.131354. Epub 2023 Sep 9.

Authors

Domitilla Russo¹, Francesco Cappelli², Gianluca Di Bella³, Giacomo Tini¹, Aldostefano Porcari⁴, Alberto Cipriani⁵, Marco Canepa⁶, Marco Merlo⁴, Roberto Licordari³, Pier Filippo Vianello⁷, Mattia Zampieri², Laura De Michieli⁵, Riccardo Scirpa¹, Federico Perfetto², Gianfranco Sinagra⁴, Camillo Autore¹, Claudio Rapezzi⁸, Maria Beatrice Musumeci⁹

Affiliations

¹ Cardiology Department, Clinical and Molecular Medicine Department, Sapienza University of Rome, Rome, Italy.
² Tuscan Regional Amyloidosis Centre, Careggi University Hospital, Florence, Italy.
³ Clinical and Experimental Department of Medicine and Pharmacology, University of Messina, Italy.
⁴ Center for Diagnosis and Treatment of Cardiomyopathies, Cardiovascular Department, Azienda Sanitaria Universitaria Giuliano-Isontina (ASUGI), University of Trieste, European Reference Network for Rare, Low Prevalence and Complex Diseases of the Heart-ERN GUARD-Heart, Trieste, Italy.
⁵ Department of Cardiac, Thoracic and Vascular Sciences and Public Health, University of Padua, Italy.
⁶ Cardiovascular Disease Unit, IRCCS Ospedale Policlinico San Martino, Genova, Italy; IRCCS Italian Cardiovascular Network & Department of Internal Medicine, University of Genova, Genova, Italy.
⁷ Cardiovascular Disease Unit, IRCCS Ospedale Policlinico San Martino, Genova, Italy.
⁸ Centro Cardiologico Universitario di Ferrara, University of Ferrara, Italy; Maria Cecilia Hospital, GVM Care & Research, Cotignola (RA), Italy.
⁹ Cardiology Department, Clinical and Molecular Medicine Department, Sapienza University of Rome, Rome, Italy. Electronic address: beatrice.musumeci@uniroma1.it.

PMID: 37696363
DOI: 10.1016/j.ijcard.2023.131354

Abstract

Backgorund: Hereditary transthyretin(vATTR) cardiac amyloidosis has extremely different features according to the type of transthyretin(TTR) mutation. Data about electrocardiographic findings(ECG) in vATTR are limited and not informative of genotype correlation. Aim of this study is to analyze ECG characteristics and their correlation to clinical and echocardiographic aspects in patients with vATTR, focusing on different TTR mutations.

Methods and results: This is a multicentric, retrospective, observational study performed in six Italian referral centres. We divided patients in two groups, according to the previously described phenotypic manifestations of the TTR mutation. Of 64 patients with vATTR, 23(36%) had prevalent cardiac(PC) TTR mutations and 41(64%) patients had a prevalent neurological(PN) TTR mutations. Patients with PC mutations were more frequently males and older, with advanced NAC staging. At baseline ECG, atrial fibrillation was more common in patients with PC, while pacemaker induced rhythm in PN mutations. PQ and QRS durations were longer and voltage to mass ratio was lower in PC mutations. Different TTR mutations tend to have distinctive ECG features.

Conclusions: ECG in vATTR is extremely heterogeneous and the specific mutations are associated with distinct instrumental and clinical features. The differences between PN and PC vATTR are only partially explained by the different degree of cardiac infiltration.

Keywords: Cardiac amyloidosis; ECG; Genotype phenotype correlations; Hereditary transthyretin.