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Abstract
Aortic Stenosis (AS) is the most frequent valvulopathy in the western world. Traditionally aortic valve replacement (AVR) has been recommended immediately after the onset of heart failure (HF) symptoms. However, recent evidence suggests that AVR outcome can be improved if performed earlier. After AVR, the process of left ventricle (LV) reverse remodelling (RR) is variable and frequently incomplete. In this study, we aimed at detecting mechanism underlying the process of LV RR regarding myocardial structural, functional and molecular changes before the onset of HF symptoms. Wistar-Han rats were subjected to 7-weeks of ascending aortic-banding followed by a 2-week period of debanding to resemble AS-induced LV remodelling and the early events of AVR-induced RR, respectively. This resulted in 3 groups: Sham (n = 10), Banding (Ba, n = 15) and Debanding (Deb, n = 10). Concentric hypertrophy and diastolic dysfunction (DD) were patent in the Ba group. Aortic-debanding induced RR, which promoted LV functional recovery, while cardiac structure did not normalise. Cardiac parameters of RV dysfunction, assessed by echocardiography and at the cardiomyocyte level prevailed altered after debanding. After debanding, these alterations were accompanied by persistent changes in pathways associated to myocardial hypertrophy, fibrosis and LV inflammation. Aortic banding induced pulmonary arterial wall thickness to increase and correlates negatively with effort intolerance and positively with E/e′ and left atrial area. We described dysregulated pathways in LV and RV remodelling and RR after AVR. Importantly we showed important RV-side effects of aortic constriction, highlighting the impact that LV-reverse remodelling has on both ventricles.
Highlights
Ventricular remodelling includes structural and functional changes taking place in the ventricle in response to chronic pressure overload
In response to left ventricle (LV) overload, hypertrophy was associated with increased systolic and diastolic www.nature.com/scientificreports
Diastolic dysfunction was evident by the significant decrease of E/A, increased E/E, LVEDP, Tau, EDPVR and left atrial dilatation
Summary
Ventricular remodelling includes structural and functional changes taking place in the ventricle in response to chronic pressure overload. LV overload activates several molecular and cellular pathways that trigger remodelling through morphological and functional alterations[1,2]. One of these changes is ventricular hypertrophy, which is perceived as an initial compensatory mechanism to normalise increased wall stress. The process of RR is frequently incomplete, and the underlying mechanisms remain to be clarified as patients show an extremely variable myocardial response during RR, ranging from partial to total recovery of cardiac function and structure. Several studies showed improvement of diastolic function[6,7] including active relaxation early after AVR8, the percentage of patients with moderate to severe DD increases 10-years after AVR9. Knowledge about RV function and structure in this context remains scarce, especially in a modulable experimental context
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