Heart Failure Duration, Cardiac Remodeling, Dysfunction, and Hemodynamic Severity in HFpEF and HFmrEF

BACKGROUND: Pathophysiologic features associated with increased risk in heart failure with preserved ejection fraction (HFpEF) may reflect distinct phenotypes or disease stages related to heart failure (HF) duration. OBJECTIVES: This study aims to determine how duration of HF diagnosis influences cardiac structure and function, hemodynamics, risk for worsening HF, and treatment response. METHODS: Baseline cardiac structure and function, hemodynamics, and outcomes following randomization were evaluated among individuals participating in the REDUCE LAP-HF II trial (N = 626): patients with HF, left ventricular ejection fraction ≥40%, and exercise pulmonary capillary wedge pressure ≥25 mm Hg, categorized by HF duration: <1 year, 1-3 years, and >3 years. RESULTS: Longer HF duration was associated with greater cardiac remodeling and dysfunction, including lower left ventricular global longitudinal strain (16.4% [Q1-Q3: 14.3%-18.6%] vs 17.7% [Q1-Q3: 15.4%-20.0%] vs 18.4% [Q1-Q3: 16.3%-20.5%]; P < 0.0001) and right ventricular free wall strain (20.8% [Q1-Q3: 16.7%-24.6%] vs 22.2% [Q1-Q3: 17.6%-26.1%] vs 24.4% [Q1-Q3: 19.2%-27.2%]; P < 0.0001), and more biatrial myopathy (48.8% vs 40.8% vs 28.2%; P < 0.0001). Resting pulmonary capillary wedge pressure elevation was more common with longer duration (75.8% vs 70.7% vs 64.9%; P = 0.024). These findings were confirmed in an independent sample of patients with HFpEF undergoing evaluation at Mayo Clinic. HF event risk increased with longer duration (HR: 1.70 [95% CI: 1.17-2.48]; P = 0.006 for >3 years vs <1 year). No significant heterogeneity in atrial shunt response was observed across duration groups. CONCLUSIONS: Longer duration of HFpEF diagnosis is associated with more advanced cardiac remodeling and dysfunction and higher risk of worsening HF, underlining the priority for earlier diagnosis to improve outcomes. (A Study to Evaluate the Corvia Medical, Inc IASD System II to Reduce Elevated Left Atrial Pressure in Patients with Heart Failure [REDUCE LAP-HF TRIAL II]; NCT03088033).