Clinical Trajectory and Risk Stratification for Heart Failure with Preserved Ejection Fraction in a Real-World Cohort of Patients with Suspected Coronary Artery Disease

Abstract

Background: Heart failure with preserved ejection fraction (HFpEF) is a widespread condition with significant morbidity and mortality. Its clinical heterogeneity may delay the diagnosis. Aim: To identify predictors of HFpEF-related hospitalizations in ambulatory patients presenting with elevated cardiovascular risk, suspected coronary artery diseases (CADs), and positive HFpEF screenings. Methods: Consecutive patients presenting with suspected CAD, enrolled in the observational LIFE-Heart study (2006-2014, NCT00497887), and meeting HFpEF criteria per the 2016 European Society of Cardiology (ESC) guidelines were categorized according to the presence of "overlapping conditions" potentially masking or contributing to their symptoms. Additional stratification using the H₂FPEF score (<2: low risk, 2-5: intermediate risk, and ≥6 high risk) was performed. Follow-up for hospitalizations, reasons of hospitalization, and death spanned a median of 6 years. Results: Of 1054 patients (66 ± 10 years, 60% male, NT-pro-BNP 286, IQR 183-574 pg/mL), 53% had overlapping conditions, while 47% had "isolated HFpEF". The H₂FPEF scores classified 23%, 57%, and 20% as low-, intermediate-, and high-risk, respectively, with consistent proportions across patients with and without overlapping conditions (p = 0.91). During the follow-up observational phase, 54% were rehospitalized, 22% experienced heart failure (HF) rehospitalizations, and 11% of patients died. Multivariable logistic regression revealed a high-risk H₂FPEF category as an independent predictor of HF rehospitalization in the overall cohort (odds ratio: 3.4, CI: 2.4-4.9, p < 0.01) as well as in patients with and without overlapping conditions. Furthermore, a H₂FPEF score ≥ 6 was independently associated with higher mortality rates (hazard ratio: 1.8, CI: 1.2-2.6, p < 0.01) in the Cox regression analysis. Conclusions: Ambulatory patients presenting for suspected CAD and meeting HFpEF screening criteria face elevated risks for rehospitalizations over six years. Regardless of concomitant diagnoses, quantifying cardiac damage with the H₂FPEF score helps in risk-stratifying patients for HF hospitalization and mortality.

Keywords: H2FPEF score; coronary artery disease; heart failure hospitalization; heart failure with preserved ejection fraction.

Figure 1

Flowchart with study design and follow-up. Legend: CAD = coronary artery disease; ESC = European Society of Cardiology; FU = follow-up, HFpEF = heart failure with preserved ejection fraction; H₂FPEF = scoring system based on age, BMI, atrial fibrillation, pulmonary hypertension, elevated filling pressures, and arterial hypertension; HR = hazard ratio; IQR = interquartile range; OR = odds ratio; PE = pulmonary embolism; LV-Function = left ventricular systolic function; valve disease = moderate or severe valve disease.

Figure 2

Overall rehospitalizations according to H₂FPEF category (upper), percentage of patients with a HFpEF-related rehospitalization (middle), and percentage of coronary hospitalizations (lower left corner). CAD = coronary artery disease; CABG = coronary artery bypass graft; HFpEF = heart failure with preserved ejection fraction; H₂FPEF = scoring system based on age, BMI, atrial fibrillation, pulmonary hypertension, elevated filling pressures, and arterial hypertension. Risk classes are defined as low-risk for 0–1, intermediate-risk for 2–5, and high-risk for ≥6, respectively.

Figure 3

Kaplan–Meier estimates for patients according to H₂FPEF category. Ticks represent censored data. Legend: H₂FPEF = scoring system based on age, BMI, atrial fibrillation, pulmonary hypertension, elevated filling pressures, and arterial hypertension. Risk classes are defined as low risk for 0–1, intermediate or middle risk for 2–5, and high-risk for ≥6, respectively.