Dilated Cardiomyopathy in a Patient with Marfan Syndrome Accompanied by Chronic Type A Aortic Dissection and Right Atrial Thrombus

Abstract

Marfan's syndrome (MFS) is an autosomal dominant disorder of connective tissue involving musculoskeletal, cardiovascular and ocular systems. Aortic disease is the leading cause of mortality in MFS. Among all, dilated cardiomyopathy in the absence of severe valvular dysfunction is a very rare cardiovascular feature of MFS. We report a case of biventricular heart failure in a patient with MFS, complicated by chronic type A aortic dissection and right atrial thrombus. This report clearly highlights the importance of close cardiovascular follow-up in patients with MFS.

Abnormal muscle mechanosignaling triggers cardiomyopathy in mice with Marfan syndrome

“…For example, a retrospective study of 143 MFS patients identified that the long-term mortality rate associated with aortic repair was 20% and that congestive heart failure was almost as great a risk factor as rupture/dissection of a secondary aneurysm (19% vs. 23%, respectively) (31). Since first described in a 1985 report (9), cardiomyopathy in MFS has been evaluated in several clinical studies totaling over 800 patients and collectively suggesting an average disease prevalence of approximately 20% with cohort-specific ranges from 0% to 68% (10)(11)(12)(13)(14)(15)(16)(17)(18)(19)(20). Different factors are likely to have contributed to this extreme variance; among others, they include the exclusion criteria used in the studies, the size and age of the cohorts examined, the medication status of individual patients, the parameters used to normalize cardiac measurements, and the accuracy and resolution across different imaging modalities.…”

“…While the prevailing view is that thoracic aortic aneurysm (TAA) and cardiac valve abnormalities overload the left ventricle (LV) by respectively stiffening the aortic wall and increasing valve regurgitation (6), several clinical studies of relatively small cohorts of MFS patients have reported LV pathology in the absence of severe valve regurgitation or aortic surgery, or that is out of proportion with aneurysm growth (9)(10)(11)(12)(13)(14)(15)(16)(17)(18)(19)(20). These findings have been used to argue that mutations in fibrillin 1 may cause ventricular dysfunction by altering the structural properties of myocardial tissue and/ or the local bioavailability of TGF-β signals (6,18).…”

“…Relevant to the former possibility, fibrillin 1 assemblies are broadly distributed in the myocardium, where they couple individual myocytes to the pericellular matrix, as basement membrane-associated (BM-associated) microfibrils, confer physical properties to cardiac tissue, as obligatory components of interstitial elastic fibers, and weave together adjoining clusters of myocytes, as molecular bridges between pericellular and interstitial matrices (5,7). By analogy to the medial layer of the aortic wall (19), the interconnected meshwork of fibrillin 1 assemblies in the myocardium may therefore represent a key component of the structural scaffold believed to support proper muscle function (5).…”

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

“…[57][58][59][60] Moreover, Das, et al reported that children and young adult MFS patients were predisposed to prolonged mitral deceleration times (DT) and mitral E/A ratios in echocardiography, suggesting impaired LV relaxation (diastolic dysfunction). 61) In other studies, some patients developed dilated cardiomyopathy (DCM)-like features that were not consistent with aortopathy and valvulopathy, 62,63) but these patients could receive heart transplantation under careful monitoring. 63,64) It has been speculated that increased aortic wall stiffness may lead to increased LV afterload and associated LV dilatation, 65) and abnormal ECM may result in altered cardiac performance.…”

In Vivo Measurements of Biophysical Properties of a Heart and Aorta in a Mouse Model of Marfan Syndrome

“…A study described a mouse model with fibrillin-1 mutation associated with hypertrophic cardiomyopathy (Siracusa, McGrath et al 1996). Despite the fact that most cases of heart failure were caused by heart valve incompetence instead of primary myocardial tissue dysfunction, some studies have reported that the Marfan patients had dilated cardiomyopathy in the absence of severe valvular dysfunction (Chatrath, Beauchesne et al 2003, Yetman, Bornemeier et al 2003, Kahveci, Erkol et al 2010. Moreover, some cases of Marfan patients have presented with ventricular connective tissue abnormality including elongation, abnormal insertion and spontaneous rupture of the chordae tendinae and dilation of the annulus fibrosus (el Habbal 1992).…”