Extracellular volume fraction associates with long-term outcome in patients with severe symptomatic aortic stenosis: 10-year outcomes of the Regression of Myocardial Fibrosis After Aortic Valve Replacement study.

BACKGROUND: Diffuse fibrosis is central to the pathophysiology of aortic stenosis (AS), can be assessed using cardiovascular magnetic resonance (CMR) with extracellular volume fraction (ECV%), and is associated with mortality. The relevance of this signal to long-term prognosis remains unclear. We aim to assess predictors of long-term mortality with focus on diffuse fibrosis.

METHODS: Single-center prospective observational cohort study of patients with severe, symptomatic AS undergoing aortic valve replacement (AVR). Patients were assessed using echocardiography, high-sensitivity cardiac troponin T (hs-cTnT), N-terminal pro-B-type natriuretic peptide (NT-proBNP), and CMR, including T1 mapping for ECV% quantification. All-cause mortality was identified using the NHS National Spine Database. Univariable and multivariable Cox regression models were fitted to assess all-cause mortality associations.

RESULT: One hundred and sixty-eight patients (age 72 [65-77] years, 55% [92/168] male) underwent CMR. Over a follow-up period of 9.7 (6.8-10.9) years, 76 deaths occurred. Patients who died had higher ECV% (29.9% vs 27.6%, p = 0.014) and greater late gadolinium enhancement (3.9% vs 2.0%, p = 0.013). Univariable predictors of mortality were age, atrial fibrillation (AF), left atrial area, left atrial volume, total cholesterol, triglycerides, HDL:LDL ratio, non-bicuspid aortic valve, hs-cTnT, NT-proBNP, EuroSCORE II and ECV%. On multivariable regression, age, AF and ECV% remained significant predictors of mortality, independently of sex. AIC indicated that the model with four covariates was preferable to the one also including EuroSCORE II and coronary artery disease, and this result was confirmed by a likelihood ratio test (p=0.387).

CONCLUSIONS: In the longest follow-up cohort of T1 mapping in severe AS, we demonstrate diffuse fibrosis remains an independent predictor of long-term mortality. Integration of ECV% in baseline risk stratification should be explored further in patients with AS undergoing AVR.