Impact of myocardial fibrosis on left ventricular remodelling, recovery, and outcome after transcatheter aortic valve implantation in different haemodynamic subtypes of severe aortic stenosis

Abstract

Aims Myocardial fibrosis (MF) might represent a key player in pathophysiology of heart failure in aortic stenosis (AS). We aimed to assess its impact on left ventricular (LV) remodelling, recovery, and mortality after transcatheter aortic valve implantation (TAVI) in different AS subtypes. Methods and results One hundred patients with severe AS were prospectively characterized clinically and echocardiographically at baseline (BL), 6 months, 1 year, and 2 years following TAVI. Left ventricular biopsies were harvested after valve deployment. Myocardial fibrosis was assessed after Masson’s trichrome staining, and fibrotic area was calculated as percentage of total tissue area. Patients were stratified according to MF above (MF+) or below (MF−) median percentage MF (≥11% or <11%). Myocardial fibrosis burden differed significantly between AS subtypes, with highest levels in low ejection fraction (EF), low-gradient AS and lowest levels in normal EF, high-gradient AS (29.5 ± 26.4% vs. 13.5 ± 16.1%, P = 0.003). In the entire cohort, MF+ was significantly associated with poorer LV function, higher extent of pathological LV remodelling, and more pronounced clinical heart failure at BL. After TAVI, MF+ was associated with a delay in normalization of LV geometry and function but not per se with absence of reverse remodelling and clinical improvement. However, 22 patients died during follow-up (mean, 11 months), and 14 deaths were classified as cardiovascular (CV) (n = 9 arrhythmia-associated). Importantly, 13 of 14 CV deaths occurred in MF+ patients (CV mortality 26.5% in MF+ vs. 2% in MF− patients, P = 0.0003). Multivariate analysis identified MF+ as independent predictor of CV mortality [hazard ratio (HR) 27.4 (2.0–369), P = 0.01]. Conclusion Histological MF is associated with AS-related pathological LV remodelling and independently predicts CV mortality after TAVI.

Distribution and prognostic value of left ventricular global longitudinal strain in elderly patients with symptomatic severe aortic stenosis undergoing transcatheter aortic valve replacement

“…Late gadolinium enhancement (LGE) by cardiac magnetic resonance (CMR) imaging detects myocardial fibrosis and a positive LGE-CMR has been shown to be present in 49% of patients with AS. Myocardial fibrosis identified by LV biopsy staining or LGE-CMR independently predicts mortality [20][21][22]. Recently, co-existing transthyretin wild type cardiac amyloidosis (ATTRwt) has been demonstrated in AS patients undergoing TAVR with a prevalence of 16% [23].…”

Distribution and Prognostic Value of Left Ventricular Global Longitudinal Strain in Elderly Patients with Symptomatic Severe Aortic Stenosis Undergoing Transcatheter Aortic Valve Replacement

“…Increased interstitial myocardial brosis has been reported in AS with preserved LVEF but with impaired longitudinal systolic function [19]. Presence of increased myocardial brosis detected by staining of LV biopsies taken during SAVR operation was associated with signi cantly higher serum Nt-pro-brain natriuretic peptide (NT-pro-BNP), higher LV mass index and impaired LVGLS [20]. Late gadolinium enhancement (LGE) by cardiac magnetic resonance (CMR) imaging detects myocardial brosis and a positive LGE-CMR has been shown to be present in 49% of patients with AS.…”

“…Late gadolinium enhancement (LGE) by cardiac magnetic resonance (CMR) imaging detects myocardial brosis and a positive LGE-CMR has been shown to be present in 49% of patients with AS. Myocardial brosis identi ed by LV biopsy staining or LGE-CMR independently predicts mortality [20][21][22]. Recently, co-existing transthyretin wild type cardiac amyloidosis (ATTRwt) has been demonstrated in AS patients undergoing TAVR with a prevalence of 16% [23].…”

Non-Coding RNAs as Blood-Based Biomarkers in Cardiovascular Disease

“…Cardiac pathological remodeling associated with the above-mentioned different cardiovascular diseases can lead to HF and, eventually, death. The severity of cardiac pathological remodeling frequently predicts treatment outcome and patient response [98]. In light of the current findings, such remodeling can be reversed and result in improved of cardiac function and, consequently, better patient prognosis and survival [99][100][101].…”