Dataset Information

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.

SUBMITTER: Puls M

PROVIDER: S-EPMC7242071 | biostudies-literature | 2020 May

REPOSITORIES: biostudies-literature

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

Puls Miriam M Beuthner Bo Eric BE Topci Rodi R Vogelgesang Anja A Bleckmann Annalen A Sitte Maren M Lange Torben T Backhaus Sören Jan SJ Schuster Andreas A Seidler Tim T Kutschka Ingo I Toischer Karl K Zeisberg Elisabeth Maria EM Jacobshagen Claudius C Hasenfuß Gerd G

European heart journal 20200501 20

<h4>Aims</h4>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.<h4>Methods and results</h4>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 ...[more]

PMID: 32049275

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Project description:Importance:Clinical practice guidelines currently endorse a reliance on clinical symptoms of overt left ventricular (LV) failure to time aortic valve replacement for severe aortic stenosis; however, delayed aortic valve replacement can result in irreversible LV injury and adverse outcomes. Blood metabolomic signatures possess prognostic value in heart failure; this study assesses whether they are informative in aortic stenosis. Objective:To evaluate the value of metabolomic signatures in reflecting the extent of maladaptive LV remodeling in patients with end-stage aortic stenosis undergoing transcatheter aortic valve replacement, and to assess whether this procedure reverses metabolomic aberrations. Design, Setting, and Participants:This study of 44 patients with symptomatic severe aortic stenosis who underwent transfemoral transcatheter aortic valve replacement at a single-center tertiary care hospital. Liquid chromatography-mass spectrometry-based metabolomic profiling was performed on blood samples collected before and 24 hours after the procedure, and analyses were conducted to identify metabolites related to the measures of LV remodeling. Main Outcomes and Measures:We evaluated LV ejection fraction, LV mass index, and relative wall thickness, as well as levels of the acylcarnitines C16, C18:1, C18:2, C18, C26, choline, and kynurenine. Results:We enrolled 44 patients with severe aortic stenosis with a mean (SD) age of 81.9 (8.5) years, of whom 23 (52%) were women. The mean (SD) LV ejection fraction was 56.7% (18.2%), mean (SD) LV mass index was 117.3 (41.4) g/m2, and relative wall thickness was 0.53 (0.14). The mean ? values of acylcarnitines C16, C18:1, C18:2, C18, and C26 were independently associated with LV mass index (C16: mean, 19.24; 95% CI, 5.48-33.01; P?=?.008; C18:1: mean, 26.18; 95% CI, 14.04-38.32; P?<?1.0?×?10-4; C18:2: mean, 17.42; 95% CI, 3.40-31.43; P?=?.02; C18: mean, 25.25; 95% CI, 10.91-39.58; P?=?.001; C26: mean, 19.93; 95% CI, 4.41-35.45; P?=?.01), even after adjustments for age, sex, diabetes status, renal function, and B-type natriuretic peptide (BNP). Circulating levels of C18:2 acylcarnitine were associated with LV ejection fraction before and after multivariable adjustment (mean, -6.11; 95% CI, -10.88 to 1.34; P?=?.01). Blood metabolite levels did not independently relate to relative wall thickness. Within 24 hours of transcatheter aortic valve replacement, circulating levels of C16 decreased by 30.2% (P?=?7.3?×?10-6), C18:1 by 42.7% (P?=?3.7?×?10-8), C18:2 by 37.3% (P?=?5.1?×?10-6), and C18 by 38.3% (P?=?3.4?×?10-5). Conclusions and Relevance:In symptomatic patients with severe aortic stenosis undergoing transcatheter aortic valve replacement, circulating levels of long-chain acylcarnitines were independently associated with measures of maladaptive LV remodeling, and metabolic perturbations lessened after procedure completion. Further efforts are needed to determine the clinical applicability of these novel biomarkers.

Dataset Information

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

Publications

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

Similar Datasets

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