Ventricular‐Vascular Coupling in Marfan and Non‐Marfan Aortopathies

Abstract

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.

Heart failure and sudden cardiac death in heritable thoracic aortic disease caused by pathogenic variants in the SMAD3 gene

“…The notion of increased rates of heart failure/myocardial dysfunction and ventricular arrhythmias/sudden cardiac death in patients with Marfan syndrome (MFS) has been established for several decades, both in mortality registries (Gott et al, 1999;Murdoch et al, 1972) as in clinical studies (Alpendurada et al, 2010;Campens et al, 2015;Cook et al, 2014;Hoffmann et al, 2012;Kiotsekoglou et al, 2008Kiotsekoglou et al, , 2009Loeper et al, 2016;Rouf et al, 2017;Rybczynski et al, 2007;Tae et al, 2016). The exact nature of these abnormalities is largely unknown.…”

“…From a clinical cardiovascular perspective, the spectrum broadened as well with attention also being paid to extra‐aortic cardiovascular manifestations. There has been growing evidence of intrinsic myocardial dysfunction in patients with Marfan syndrome (MFS) caused by pathogenic variants in the FBN1 gene (Alpendurada et al., ; de Backer et al., ; Kiotsekoglou et al., ; Loeper et al., ; Rybczynski et al., ). Clinically overt heart failure, even necessitating cardiac transplantation has been reported in some cases and small series (Audenaert, de Pauw, François, & De Backer, ; Kesler et al., ; Knosalla et al., ) but the majority of patients will present subclinical forms of myocardial dysfunction, the clinical impact of which is not entirely understood yet.…”

Identification of Novel Causal FBN1 Mutations in Pedigrees of Marfan Syndrome

“…Alternatively, Wang et al likewise observed an association with truncating mutations in MFs with cardiovascular defects [ 22 ]. For a severe ventricular phenotype, like LV dilatation, it has been reported to be related with the disorder of microfibril assembly by in-frame deletions or non-missense mutations [ 23 , 24 ]. Likewise, the present study also identified similar results as in previous studies in 3 MFS pedigrees with frameshift mutations, thereby contributing to the extension of the known mutational spectrum of frameshift, for understanding the genotype–phenotype correlations in cardiovascular involvement.…”

Angiotensin, transforming growth factor β and aortic dilatation in Marfan syndrome: Of mice and humans

“…Amongst patients with MFS, arterial function is abnormal, with increased vascular stiffness, increased systemic pulse wave velocity and abnormal ventricular-vascular coupling [ 63 ]. The role of AngII in mediating these changes is now supported by experimental evidence.…”