Related Experiment Video
Updated: Sep 27, 2025
Estimating Bilateral Atrial Function by Cardiovascular Magnetic Resonance Feature Tracking in Patients with Paroxysmal Atrial Fibrillation
Published on: July 20, 2022
Arrhythmia and impaired myocardial function in heritable thoracic aortic disease: An international retrospective
Anthony Demolder1, Lisa Bianco2, Maryanne Caruana3
1Centre for Medical Genetics, Ghent University Hospital, Ghent, Belgium; Department of Cardiology, Ghent University Hospital, Ghent, Belgium.
Insights
Non-aortic cardiac conditions like impaired heart function and arrhythmias occur in some patients with heritable thoracic aortic diseases (HTAD) linked to FBN1 and TGF-β pathway genes, but not ACTA2.
Area of Science:
- Cardiovascular Genetics
- Thoracic Aortic Disease
- Genetic Cardiology
Background:
- Heritable thoracic aortic diseases (HTAD) are linked to genetic variants (PV/LPVs) in genes like FBN1, ACTA2, and TGF-β pathway genes.
- Non-aortic cardiac conditions, including impaired myocardial function and arrhythmias, are increasingly recognized in HTAD, particularly Marfan syndrome (FBN1 PV/LPVs).
- The prevalence of these non-aortic cardiac manifestations across different HTAD types is not well understood.
Purpose of the Study:
- To investigate the prevalence and characteristics of non-aortic cardiac disease in patients with HTAD.
- To identify specific genetic variants associated with non-aortic cardiac manifestations in HTAD.
- To understand the clinical significance of non-aortic cardiac disease in the context of HTAD.
Main Methods:
- An international, multicenter, retrospective study screened 3219 HTAD patients from 9 centers in 7 countries.
- Patients aged 12+ with PV/LPVs in FBN1, TGF-β signaling genes (TGFBR1, TGFBR2, TGFB2, TGFB3, SMAD3), or ACTA2 were included.
- Non-aortic cardiac disease was defined as impaired myocardial function (EF<50%) and/or arrhythmias (AF, AFL, VT, VF, SCD).
Main Results:
- Non-aortic cardiac disease occurred in 101 patients (3.1%), primarily those with FBN1 (88 patients) or TGF-β pathway gene (13 patients) PV/LPVs.
- No non-aortic cardiac disease was observed in patients with ACTA2 PV/LPVs.
- Impaired myocardial function (48%), atrial fibrillation/flutter (33%), and ventricular arrhythmias/sudden cardiac death (19%) were the main non-aortic cardiac conditions. Prior cardiac surgery (80%) and severe valvular disease (58%) were common comorbidities.
Conclusions:
- Arrhythmia and impaired myocardial function in HTAD are associated with PV/LPVs in FBN1 and TGF-β signaling genes, but not ACTA2.
- Non-aortic cardiac disease, though infrequent, can be severe in HTAD patients, including younger individuals without significant prior aortic or valvular disease.
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)-β 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-β 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-β 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-β 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.
Related Concept Videos
01:15Aortic Regurgitation I: Introduction
01:22Aortic Regurgitation II: Clinical Features and Diagnostic Tests
01:25Aortic Regurgitation III: Medical Management
01:28Mechanism of Cardiac Arrhythmias
01:29Cardiomyopathy III: Hypertrophic Cardiomyopathy
01:22Rheumatic Heart Disease II: Clinical Manifestations and Diagnostic Studies