Abstract
BackgroundIncreased myocardial fibrosis may play a key role in heart failure with preserved ejection fraction (HFpEF) pathophysiology. The study aim was to evaluate the presence, associations, and prognostic significance of diffuse fibrosis in HFpEF patients compared to age- and sex-matched controls.MethodsWe prospectively included 118 consecutive HFpEF patients. Diffuse myocardial fibrosis was estimated by extracellular volume (ECV) quantified by cardiovascular magnetic resonance with the modified Look-Locker inversion recovery sequence. We determined an ECV age- and sex-adjusted cutoff value (33%) in 26 controls.ResultsMean ECV was significantly higher in HFpEF patients versus healthy controls (32.9 ± 4.8% vs 28.2 ± 2.4%, P < 0.001). Multivariate logistic regression showed that body mass index (BMI) (odds ratio (OR) =0.92 [0.86–0.98], P = 0.011), diabetes (OR = 2.62 [1.11–6.18], P = 0.028), and transmitral peak E wave velocity (OR = 1.02 [1.00–1.03], P = 0.022) were significantly associated with abnormal ECV value. During a median follow-up of 11 ± 6 months, the primary outcome (all-cause mortality or first heart failure hospitalization) occurred in 38 patients. In multivariate Cox regression analysis, diabetes (hazard ratio (HR) =1.98 [1.04; 3.76], P = 0.038) and hemoglobin level (HR = 0.81 [0.67; 0.98], P = 0.028) were significant predictors of composite outcome. The ECV ability to improve this model added significant prognostic information. We then developed a risk score including diabetes, hemoglobin and ECV > 33% demonstrating significant prediction of risk and validated this score in a validation cohort of 53 patients. Kaplan–Meier curves showed a significant difference according to tertiles of the probability score (P < 0.001).ConclusionAmong HFpEF patients, high ECV, likely reflecting abnormal diffuse myocardial fibrosis, was associated with a higher rate of all-cause death and first HF hospitalization in short term follow up.Trial registrationCharacterization of Heart Failure With Preserved Ejection Fraction. Trial registration number: NCT03197350. Date of registration: 20/06/2017. This trial was retrospectively registered.
Highlights
Increased myocardial fibrosis may play a key role in heart failure with preserved ejection fraction (HFpEF) pathophysiology
Several studies using autopsies or myocardial biopsies have highlighted the key role of myocardial extracellular matrix abnormalities and myocardial structural changes such as altered cardiomyocyte function, systemic and coronary microvascular inflammation, and endothelial dysfunction as all being involved in myocardial stiffness and diastolic dysfunction [10, 11]
We observed a high prevalence of established cardiovascular risk factors in our HFpEF population; including arterial hypertension (93%), diabetes (39%), hypercholesterolemia (67%), and higher body mass index (BMI)
Summary
Increased myocardial fibrosis may play a key role in heart failure with preserved ejection fraction (HFpEF) pathophysiology. The study aim was to evaluate the presence, associations, and prognostic significance of diffuse fibrosis in HFpEF patients compared to age- and sex-matched controls. Heart failure (HF) with preserved ejection fraction (HFpEF) has been established as a major cause of cardiovascular morbidity and mortality, especially among the elderly [1, 2]. Compared to HF with reduced ejection fraction (HFrEF), survival in HFpEF has not improved over time, and to date, no treatment effectively improves outcomes, probably because of the phenotypic heterogeneity of this syndrome [4]. Several studies using autopsies or myocardial biopsies have highlighted the key role of myocardial extracellular matrix abnormalities (fibrosis [7,8,9]) and myocardial structural changes such as altered cardiomyocyte function (hypertrophy [7]), systemic and coronary microvascular inflammation, and endothelial dysfunction (oxidative stress) as all being involved in myocardial stiffness and diastolic dysfunction [10, 11]
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