Pathophysiology and Management of Cardiovascular Manifestations in Marfan and Loeys–Dietz Syndromes

Abstract

SummaryMarfan syndrome (MFS) is an autosomal dominant heritable disorder of connective tissue that affects the cardiovascular, skeletal, ocular, pulmonary, and nervous systems and is usually caused by mutations in the FBN1 gene, which encodes fibrillin-1. MFS is traditionally considered to result from the structural weakness of connective tissue. However, recent investigations on molecular mechanisms indicate that increased transforming growth factor-β (TGF-β) activity plays a crucial role in the pathogenesis of MFS and related disorders, such as Loeys-Dietz syndrome (LDS), which is caused by mutation in TGF-β signaling-related genes. In addition, recent studies show that angiotensin II type 1 receptor (AT1R) signaling enhances cardiovascular pathologies in MFS, and the angiotensin II receptor blocker losartan has the potential to inhibit aortic aneurysm formation. However, the relationship between TGF-β and AT1R signaling pathways remains poorly characterized. In this review, we discuss the recent studies on the molecular mechanisms underlying cardiovascular manifestations of MFS and LDS and the ensuing strategies for management. (Int Heart J 2016; 57: 271-277)

Differences in manifestations of Marfan syndrome, Ehlers-Danlos syndrome, and Loeys-Dietz syndrome

“…However, in a subgroup of patients without significant valvular dysfunction, subclinical cardiac dysfunction is described. Indeed, in some patients, dilated cardiomyopathy-like features were observed, that did not correspond to the aneurysmal aortopathy and/or valvulopathy (19). A combination of increased aortic wall stiffness and ECM abnormalities might be underlying these features (19).…”

“…Indeed, in some patients, dilated cardiomyopathy-like features were observed, that did not correspond to the aneurysmal aortopathy and/or valvulopathy (19). A combination of increased aortic wall stiffness and ECM abnormalities might be underlying these features (19). Additionally, in a minority of patients arrhythmias can be observed in the presence or absence of ventricular dysfunction (5,12).…”

“…However, in LDS the incidence is even higher. The increased risk is related to a combination of hemodynamic changes, hormonal influences, and the change of elastic fiber organization during pregnancy (19).…”

“…Compared to MFS, the incidence of complications might be even higher in LDS (19,29). With regard to surgical outcome, LDS can be distinguished from EDS by the low rate of intraoperative mortality, due to less fragile soft tissues (28,31,39).…”

Peripartum type B aortic dissection in patients with Marfan syndrome who underwent aortic root replacement: a case series study

“…Diagnostic criteria of MFS were revised in 2010 (revised Ghent nosology) to place more emphasis on causative genetic analyses, aortic root aneurysm/dissection, and ectopia lentis (EL) . Since the release of the revised Ghent nosology, there have been two cohort studies on pregnancy outcomes of MFS patients collected from multiple institutions and five case series .…”