RESUMO
Bicuspid aortic valve (BAV) is the most common congenital heart malformation in adults but can also cause childhood-onset complications. In multicenter study, we found that adults who experience significant complications of BAV disease before age 30 are distinguished from the majority of BAV cases that manifest after age 50 by a relatively severe clinical course, with higher rates of surgical interventions, more frequent second interventions, and a greater burden of congenital heart malformations. These observations highlight the need for prompt recognition, regular lifelong surveillance, and targeted interventions to address the significant health burdens of patients with early onset BAV complications.
RESUMO
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)-ß 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-ß 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-ß 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-ß 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.