Cardiomyopathy in Genetic Aortic Diseases

Abstract

Genetic aortic diseases are a group of illnesses characterized by aortic aneurysms or dissection in the presence of an underlying genetic defect. They are part of the broader spectrum of heritable thoracic aortic disease, which also includes those cases of aortic aneurysm or dissection with a positive family history but in whom no genetic cause is identified. Aortic disease in these conditions is a major cause of mortality, justifying clinical and scientific emphasis on the aorta. Aortic valve disease and atrioventricular valve abnormalities are known as important additional manifestations that require careful follow-up and management. The archetype of genetic aortic disease is Marfan syndrome, caused by pathogenic variants in the Fibrillin-1 gene. Given the presence of fibrillin-1 microfibers in the myocardium, myocardial dysfunction and associated arrhythmia are conceivable and have been shown to contribute to morbidity and mortality in patients with Marfan syndrome. In this review, we will discuss data on myocardial disease from human studies as well as insights obtained from the study of mouse models of Marfan syndrome. We will elaborate on the various phenotypic presentations in childhood and in adults and on the topic of arrhythmia. We will also briefly discuss the limited data available on other genetic forms of aortic disease.

Keywords: FBN1 gene; HTAD; Marfan syndrome; arrhythmia; cardiomyopathy; myocardial disease.

Figure 1

Typical manifestations of neonatal Marfan syndrome. (A) Child with neonatal MFS showing arachnodactyly, long feet, crumpled ears, lipodystrophy and mild pectus excavatum. (B) Chest X-ray showing cardiomegaly and mild scoliosis. (C) Echocardiographic four-chamber view showing mitral and tricuspid valve prolapse (white arrows). (D) Echocardiographic apical four-chamber color doppler view showing moderate-severe mitral and tricuspid valve regurgitation. (E) Echocardiographic parasternal long axis view showing enlargement of the sinus of Valsalva. Ao, aorta; LA, left atrium; LV, left ventricle; RV, right ventricle; RA, right atrium.

Figure 2

Different manifestations of myocardial disease in classical Marfan syndrome. (A) Echocardiographic image (2D TTE PSLAX view) in a 16 yr old male showing severe dilatation of the left ventricle. (B) Echocardiographic image (2D TTE PSLAX view) showing mitral annular disjunction. (C) ECG recordings in 28 yr old male showing ventricular tachycardia followed by presyncope during exercise test 6 m after mitral valve surgery and aortic root replacement (D) ambulatory electrocardiogram recording in a 57 yr old female with frequent episodes of non-sustained ventricular tachycardia. Ao, aorta; LA, left atrium; LV, left ventricle; LVEDD, left ventricular end-diastolic diameter; MAD, mitral annular disjunction.