Left Ventricular Systolic Dysfunction in Asymptomatic Marfan Syndrome Patients Is Related to the Severity of Gene Mutation: Insights from the Novel Three Dimensional Speckle Tracking Echocardiography

Rahman, Mohamed Abdel; Haase, Denise; Rentzsch, Axel; Olchvary, Julia; Schäfers, Hans‐Joachim; Henn, Wolfram; Wagenpfeil, Stefan; Abdul‐Khaliq, Hashim

doi:10.1371/journal.pone.0124112

Cited by 16 publications

(9 citation statements)

References 40 publications

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“…Interestingly, there appears to be familial clustering of individuals with abnormal VVI. A correlation between non‐missense FBN1 mutations and impaired LV function has been described, although such a pattern was not evident in the present MFS group. Thus, the VVI may be useful as a novel risk stratifier for individuals with MFS.…”

Section: Discussioncontrasting

confidence: 70%

Ventricular‐Vascular Coupling in Marfan and Non‐Marfan Aortopathies

Loeper

Oosterhof

Linde

et al. 2016

JAHA

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BackgroundMarfan syndrome (MFS) and familial non–syndromal thoracic aortic aneurysm and dissection (ns‐TAAD) are genetic aortopathies causing aortic dilatation with increased aortic stiffness. Left ventricular (LV) contractility and ventricular‐vascular coupling index (VVI) were compared between MFS and ns‐TAAD and determinants of VVI were investigated.Methods and ResultsPatients with MFS (M 57, F 47) and ns‐TAAD (M 72, F 39) were studied by echocardiography and compared with controls (M 77, F 71). Aortic geometry, hemodynamics, LV work, LV contractility (end‐systolic elastance [Ees]), and VVI were documented. Aortic sinuses were equally dilated in MFS (19.7±2.4) and ns‐TAAD (19.8±1.8) compared to controls (16.2±1.4 mm·m−2, P<0.001). Aortic stiffness index was increased in MFS (9.7±5.1) and ns‐TAAD (10.8±4.7) versus controls (5.4±2.0, P<0.01); LV stroke work was unchanged in MFS (436±74) compared to controls (435±60) but increased in ns‐TAAD (492±109 mJ·m−2 P<0.01). The LV Ees was reduced in MFS (1.32±0.19) compared to controls (1.65±0.29 mm Hg·mL−1, P<0.01) but increased in ns‐TAAD (1.83±0.30, P<0.01) and VVI was abnormal in MFS (0.71±0.11) compared to controls (0.62±0.07, P<0.01) and ns‐TAAD (0.62±0.09). Treatment with β‐blockers was associated with partial normalization of VVI in MFS. A VVI ≥0.8 was associated with increased risk of death and heart failure in MFS.ConclusionsLeft ventricular contractility and ventricular‐vascular coupling are abnormal in MFS but preserved in ns‐TAAD, and are independent of aortic stiffness, consistent with intrinsic impairment of myocardial contractility in MFS.

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Section: Discussioncontrasting

confidence: 70%

Ventricular‐Vascular Coupling in Marfan and Non‐Marfan Aortopathies

Loeper

Oosterhof

Linde

et al. 2016

JAHA

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“…Similar findings were observed in the CMR studies by de Witte et al and by Winther et al, confirming that the reduced LV EF, is mostly mild but might affect a subgroup of patients in a more severe way [ 29 , 30 ]. By extending the detection prowess of conventional echocardiography, studies utilizing strain and strain rate imaging to assess and quantify changes in global and regional contractile function have confirmed the findings obtained from CMR [ 30 , 31 , 32 , 33 ].…”

Section: Myocardial Involvementmentioning

confidence: 73%

“…Patients carrying non-missense variants (predicted to result in HI) more often demonstrated LV dilatation than those carrying missense variants (predicted to result in DN effect) [ 68 ]. Similarly, in a smaller study by Rahman et al using three-dimensional speckle tracking echocardiography, LV EF, global LV circumferential strain and global LV area strain were all significantly lower in patients with variants predicted to result in HI than in those variants predicted to result in DN effect ( p < 0.05) [ 33 ]. Different types of FBN1 gene variants may also have a different effect on aortic elasticity [ 67 ], thereby potentially further contributing to impairment of myocardial function, but this has not been studied yet.…”

Section: Pathophysiology Of Marfan Cardiomyopathymentioning

confidence: 96%

“…In the same vein, a genotype-phenotype relationship in the myocardium can be suspected. Two studies have indicated a genotype-phenotype relation between myocardial impairment and underlying FBN1 gene variants [ 33 , 68 ]. Aalberts et al have shown an association between the type of underlying pathogenic FBN1 variant and the development of LV dilatation in MFS [ 68 ].…”

Section: Pathophysiology Of Marfan Cardiomyopathymentioning

confidence: 99%

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Myocardial Function, Heart Failure and Arrhythmia in Marfan Syndrome: A Systematic Literature Review

Demolder

Kodolitsch²,

Muiño-Mosquera

et al. 2020

Diagnostics

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Marfan syndrome (MFS) is a heritable systemic connective tissue disease with important cardiovascular involvement, including aortic root dilatation and mitral valve prolapse. Life expectancy in patients with MFS is mainly determined by cardiovascular complications, among which aortic dissection or rupture are most dreaded. In recent years, heart failure and ventricular arrhythmia have drawn attention as extra-aortic cardiovascular manifestations and as additional reported causes of death. Imaging studies have provided data supporting a primary myocardial impairment in the absence of valvular disease or cardiovascular surgery, while studies using ambulatory ECG have demonstrated an increased susceptibility to ventricular arrhythmia. In this paper, current literature was reviewed in order to provide insights in characteristics, pathophysiology and evolution of myocardial function, heart failure and ventricular arrhythmia in MFS.

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“…In asymptomatic patients with MF syndrome, early primary LV dysfunction can be detected by new echo techniques. 38 The LV dysfunction has been found to be related to the severity of gene mutation, suggesting possible primary cardiomyopathy in patients with MF syndrome. Follow-up studies with regard to the prognostic value of these observations are warranted.…”

Section: Cardiovascular Manifestationsmentioning

confidence: 99%

Marfan syndrome: current perspectives

Pepe¹,

Giusti²,

Sticchi³

et al. 2016

TACG

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Marfan syndrome (MFS) is a pleiotropic connective tissue disease inherited as an autosomal dominant trait, due to mutations in the FBN1 gene encoding fibrillin 1. It is an important protein of the extracellular matrix that contributes to the final structure of a microfibril. Few cases displaying an autosomal recessive transmission are reported in the world. The FBN1 gene, which is made of 66 exons, is located on chromosome 15q21.1. This review, after an introduction on the clinical manifestations that leads to the diagnosis of MFS, focuses on cardiovascular manifestations, pharmacological and surgical therapies of thoracic aortic aneurysm and/or dissection (TAAD), mechanisms underlying the progression of aneurysm or of acute dissection, and biomarkers associated with progression of TAADs. A Dutch group compared treatment with losartan, an angiotensin II receptor-1 blocker, vs no other additional treatment (COMPARE clinical trial). They observed that losartan reduces the aortic dilatation rate in patients with Marfan syndrome. Later on, they also reported that losartan exerts a beneficial effect on patients with Marfan syndrome carrying an FBN1 mutation that causes haploinsufficiency (quantitative mutation), while it has no significant effect on patients displaying dominant negative (qualitative) mutations. Moreover, a French group in a 3-year trial compared the administration of losartan vs placebo in patients with Marfan syndrome under treatment with beta-receptor blockers. They observed that losartan decreases blood pressure but has no effect on aortic diameter progression. Thus, beta-receptor blockers remain the gold standard therapy in patients with Marfan syndrome. Three potential biochemical markers are mentioned in this review: total homocysteine, serum transforming growth factor beta, and lysyl oxidase. Moreover, markers of oxidative stress measured in plasma, previously correlated with clinical features of Marfan syndrome, may be explored as potential biomarkers of clinical severity.

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Left Ventricular Systolic Dysfunction in Asymptomatic Marfan Syndrome Patients Is Related to the Severity of Gene Mutation: Insights from the Novel Three Dimensional Speckle Tracking Echocardiography

Cited by 16 publications

References 40 publications

Ventricular‐Vascular Coupling in Marfan and Non‐Marfan Aortopathies

Ventricular‐Vascular Coupling in Marfan and Non‐Marfan Aortopathies

Myocardial Function, Heart Failure and Arrhythmia in Marfan Syndrome: A Systematic Literature Review

Marfan syndrome: current perspectives

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