Sex Dimorphism in the Myocardial Response to Aortic Stenosis

Abstract

ObjectivesThe goal of this study was to explore sex differences in myocardial remodeling in aortic stenosis (AS) by using echocardiography, cardiac magnetic resonance (CMR), and biomarkers.BackgroundAS is a disease of both valve and left ventricle (LV). Sex differences in LV remodeling are reported in AS and may play a role in disease phenotyping.MethodsThis study was a prospective assessment of patients awaiting surgical valve replacement for severe AS using echocardiography, the 6-min walking test, biomarkers (high-sensitivity troponin T and N-terminal pro–brain natriuretic peptide), and CMR with late gadolinium enhancement and extracellular volume fraction, which dichotomizes the myocardium into matrix and cell volumes. LV remodeling was categorized into normal geometry, concentric remodeling, concentric hypertrophy, and eccentric hypertrophy.ResultsIn 168 patients (age 70 ± 10 years, 55% male, indexed aortic valve area 0.40 ± 0.13 cm2/m2, mean gradient 47 ± 4 mm Hg), no sex or age differences in AS severity or functional capacity (6-min walking test) were found. CMR captured sex dimorphism in LV remodeling not apparent by using 2-dimensional echocardiography. Normal geometry (82% female) and concentric remodeling (60% female) dominated in women; concentric hypertrophy (71% male) and eccentric hypertrophy (76% male) dominated in men. Men also had more evidence of LV decompensation (pleural effusions), lower left ventricular ejection fraction (67 ± 16% vs. 74 ± 13%; p < 0.001), and higher levels of N-terminal pro–brain natriuretic peptide (p = 0.04) and high-sensitivity troponin T (p = 0.01). Myocardial fibrosis was higher in men, with higher focal fibrosis (late gadolinium enhancement 16.5 ± 11.2 g vs. 10.5 ± 8.9 g; p < 0.001) and extracellular expansion (matrix volume 28.5 ± 8.8 ml/m2 vs. 21.4 ± 6.3 ml/m2; p < 0.001).ConclusionsCMR revealed sex differences in associations between AS and myocardial remodeling not evident from echocardiography. Given equal valve severity, the myocardial response to AS seems more maladaptive in men than previously reported. (Regression of Myocardial Fibrosis After Aortic Valve Replacement [RELIEF-AS]; NCT02174471)

Sex‐ and age‐based differences in the natural history and outcome of dilated cardiomyopathy

“…Myocyte death is central to the development of replacement fibrosis and it is possible that the different impact of these sex hormones on myocyte survival contributes to a higher prevalence of replacement fibrosis in men. A sex disparity in the prevalence of replacement fibrosis in DCM is consistent with other studies and has also been demonstrated in acute myocarditis and aortic stenosis . Other studies have demonstrated sex differences in gene expression in patients presenting with HF secondary to DCM and these may be responsible for differences in phenotype and outcome …”

Mass Regression after Aortic Valve Replacement in Aortic Stenosis: A Comparison between "Appropriate" and "Inappropriate" Left Ventricular Hypertrophy

“…In our study, gender and diabetes were unevenly distributed between the groups, while for the BMI there was a trend in being higher in the group with "inappropriate" hypertrophy ( Table 1). The gender issue was in line with other studies in which was demonstrated that male gender easily develops a higher LVM, fibrosis deposition and LV dysfunction than females [34][35][36].…”

“…Hypertension is one of the most frequent factor that may be responsible for the persistence of LV hypertrophy [6] along with the high stiffness of the vascular system, resulting in a high arterial impedance or Zva [37]. These two conditions hamper LV mass regression both pre-operatively, with the deposition of irreversible fibrosis [11,20,23], and post-operatively if the hypertension is not adequately treated or a high LV impedance persists [6,36]. Apparently, this was not the case in our study, because both hypertension incidence and the level of the Zva and arterial compliance were similar in the two groups.…”

Remodeling classification system considering left ventricular volume in patients with aortic valve stenosis: Association with adverse cardiovascular outcomes

“…Conventional wisdom holds that women more often present higher RWT and lower LV sizes when compared to men . However, more recent studies using cardiac magnetic resonance revealed that in AS women tolerate pressure overload with less concentric remodeling …”