Myocardial involvement in the Marfan syndrome.

Fujiseki, Y; Okuno, Keiko; Tanaka, Masaki; Shimada, Morimi; Takahashi, Masashi; Kawanishi, Katsuyuki

doi:10.1536/ihj.26.1043

Cited by 19 publications

(15 citation statements)

References 8 publications

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“…In 1985, a case report describing a 9-year-old girl with MFS with no significant valvular disease revealed left ventricular hypertrophy on an echocardiographic study. This finding was confirmed by an endomyocardial biopsy, which showed loss of elastic fibres and degeneration of collagen fibres and cardiomyocytes 18. These changes were probably related to the underlying MFS.…”

Section: Evidence For Primary Myocardial Dysfunction In Childrensupporting

confidence: 53%

The unravelling of primary myocardial impairment in Marfan syndrome by modern echocardiography

Kiotsekoglou

Sutherland

Moggridge

et al. 2009

Heart

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Use of echocardiography has dramatically changed the way in which patients with Marfan syndrome are diagnosed, monitored and treated. Owing to the lethal nature of aortic complications, priority has been given to the assessment of the aortic root. Echocardiographic studies on patients with Marfan syndrome have also provided data supporting primary myocardial involvement, although this evidence has remained controversial for several years. Use of more sensitive ultrasound techniques has demonstrated mild myocardial impairment in these patients. Biventricular function assessment should be added to the aortic root evaluation, so that appropriate treatment may be offered to support myocardial function.

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Section: Evidence For Primary Myocardial Dysfunction In Childrensupporting

confidence: 53%

The unravelling of primary myocardial impairment in Marfan syndrome by modern echocardiography

Kiotsekoglou

Sutherland

Moggridge

et al. 2009

Heart

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show abstract

“…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.…”

Section: Discussionmentioning

confidence: 99%

“…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).…”

Section: Introductionmentioning

confidence: 99%

Abnormal muscle mechanosignaling triggers cardiomyopathy in mice with Marfan syndrome

Cook¹,

Carta²,

Bénard³

et al. 2014

J. Clin. Invest.

121

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Patients with Marfan syndrome (MFS), a multisystem disorder caused by mutations in the gene encoding the extracellular matrix (ECM) protein fibrillin 1, are unusually vulnerable to stress-induced cardiac dysfunction. The prevailing view is that MFS-associated cardiac dysfunction is the result of aortic and/or valvular disease. Here, we determined that dilated cardiomyopathy (DCM) in fibrillin 1-deficient mice is a primary manifestation resulting from ECM-induced abnormal mechanosignaling by cardiomyocytes. MFS mice displayed spontaneous emergence of an enlarged and dysfunctional heart, altered physical properties of myocardial tissue, and biochemical evidence of chronic mechanical stress, including increased angiotensin II type I receptor (AT1R) signaling and abated focal adhesion kinase (FAK) activity. Partial fibrillin 1 gene inactivation in cardiomyocytes was sufficient to precipitate DCM in otherwise phenotypically normal mice. Consistent with abnormal mechanosignaling, normal cardiac size and function were restored in MFS mice treated with an AT1R antagonist and in MFS mice lacking AT1R or β-arrestin 2, but not in MFS mice treated with an angiotensin-converting enzyme inhibitor or lacking angiotensinogen. Conversely, DCM associated with abnormal AT1R and FAK signaling was the sole abnormality in mice that were haploinsufficient for both fibrillin 1 and β1 integrin. Collectively, these findings implicate fibrillin 1 in the physiological adaptation of cardiac muscle to elevated workload.

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“…Fujiseki and colleagues reported the first case of MFSassociated myocardial involvement in 1984 [47]. Since then both right and left ventricular dysfunction and a dilated cardiomyopathy phenotype have been described [48].…”

Section: Myocardial Involvementmentioning

confidence: 99%