@article{8749826,
  abstract     = {{Background: Heritable thoracic aortic diseases (HTAD), typically entailing aortic complications, can be caused by pathogenic variants or likely pathogenic variants (PV/LPVs) in several genes, including fibrillin1 (FBN1), Actin Alpha2 (ACTA2) and genes encoding components of the transforming growth factor (TGF)-beta signaling pathway. In addition to aortic complications, non-aortic cardiac disease such as impaired myocardial function and/or arrhythmia have been increasingly reported, mainly in Marfan syndrome with underlying FBN1 PV/LPVs and are acknowledged as additional causes of morbidity and mortality. The prevalence of these manifestations in the various HTAD entities is largely unknown.

Methods: This international multicentre retrospective study collected data on patients with HTAD presenting non-aortic cardiac disease. A total of 9 centers from 7 different countries participated. Patients 12 years or older carrying a PV/LPV in one of the following genes: FBN1, TGFBR1, TGFBR2, TGFB2, TGFB3, SMAD3 and ACTA2 were screened. Non-aortic cardiac disease included impaired myocardial function and/or arrhythmia. Impaired myocardial function was defined as (a)symptomatic reduced ejection fraction (EF<50%). Arrhythmias included atrial fibrillation (AF), atrial flutter (AFL), ventricular tachycardia (VT), ventricular fibrillation (VF) and (aborted) sudden cardiac death (presumed arrhythmogenic) (SCD).

Results: Medical records of 3219 patients with HTAD were screened (2761, 385 and 73 carrying a PV/LPV in FBN1, in a TGF-beta signaling gene and in ACTA2 respectively). Non-aortic cardiac disease was reported 142 times in 101 patients (3.1%) (age 37 [range 12-77] years, 39% female): 88 patients carrying an FBN1 PV/LPV and 13 carrying a PV/LPV in one of the TGF-beta signaling genes. Neither impaired myocardial function nor arrhythmia was reported in screened patients carrying a PV/LPV in ACTA2. Among the 142 reported non-aortic cardiac diseases, 68 (48%) were impaired myocardial function, 47 (33%) were AF/AFL and 27 (19%) were VT/VF/SCD. Among the patients with non-aortic cardiac disease, prior cardiac surgery was noted in 80% and severe valvular disease (valvular surgery or severe valvular regurgitation) in 58%, while 18% of the patients developed non-aortic cardiac disease in the absence of any of the latter.

Conclusions: In patients with HTAD, arrhythmia and impaired myocardial function was reported in patients with PV/LPVs in FBN1 and in the TGF-beta signaling genes and not in patients harboring PV/LPVs in ACTA2. Though infrequent, non-aortic cardiac disease should be acknowledged as potentially severe, also occurring in young patients with no underlying significant valvular or aortic disease.}},
  articleno    = {{104503}},
  author       = {{Demolder, Anthony and Bianco, Lisa and Caruana, Maryanne and Cervi, Elena and Evangelista, Arturo and Jondeau, Guillaume and Buttigieg, Lisa Lauren and López-Sainz, Ángela and Delmás, Elena Montañés and Pini, Alessandro and Sabaté-Rotés, Anna and Szöcs, Katalin and Tchitchinadze, Maria and Teixidó-Tura, Gisela and von Kodolitsch, Yskert and Muiño Mosquera, Laura and De Backer, Julie}},
  issn         = {{1769-7212}},
  journal      = {{EUROPEAN JOURNAL OF MEDICAL GENETICS}},
  keywords     = {{Genetics (clinical),Genetics,General Medicine,SUDDEN CARDIAC DEATH,MARFAN-SYNDROME,ANEURYSMS,ASSOCIATION,GUIDELINES,SOCIETY}},
  language     = {{eng}},
  number       = {{6}},
  pages        = {{8}},
  title        = {{Arrhythmia and impaired myocardial function in heritable thoracic aortic disease : an international retrospective cohort study}},
  url          = {{http://doi.org/10.1016/j.ejmg.2022.104503}},
  volume       = {{65}},
  year         = {{2022}},
}

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