Mechanistic Basis for Differential Effects of Interatrial Shunt Treatment in HFrEF vs HFpEF: The RELIEVE-HF Trial

The RELIEVE-HF (REducing Lung congestion symptoms using the v-wavE shunt in adVancEd Heart Failure) trial randomized 508 patients with heart failure (HF) to interatrial shunt treatment vs placebo procedure. Randomization was stratified into 2 patient groups: heart failure with reduced ejection fraction (HFrEF) (left ventricular ejection fraction [LVEF] ≤40%); and heart failure with preserved ejection fraction (HFpEF) (LVEF >40%). HF event rates (all-cause death, transplantation or left ventricular (LV) assist device, HF hospitalization or outpatient worsening) after shunt treatment during 2-year follow-up were directionally opposite: decreased by 51% in HFrEF, increased by 69% in HFpEF.

This study aims to examine differences in cardiac structure and function before and after interatrial shunt placement in patients with HFrEF vs HFpEF that could underlie these discordant clinical outcomes.

Serial changes from baseline to 12 months in 17 transthoracic echocardiographic parameters in shunt-treated vs control patients in HFrEF vs HFpEF were assessed and compared by ANCOVA (analysis of covariance).

In shunt-treated vs control patients with HFrEF, there were reductions in median LV end-diastolic volumes (-11.9 mL/m² [Q1-Q3: -21.3 to -2.5 mL/m²]; P = 0.01) and LV end-systolic volumes (-8.9 mL/m² [Q1-Q3: -17.2 to -20.7 mL/m²]; P = 0.01) indicative of reverse LV remodeling. There were no significant changes in right ventricular (RV), right atrial, or inferior vena cava sizes or pulmonary artery systolic pressure (PASP). In contrast, shunt-treated vs control patients with HFpEF did not have LV remodeling, but they had increased RV, right atrial, and inferior vena cava dimensions, and PASP also increased (4.7 mm Hg [Q1-Q3: 0.9-8.5 mm Hg]; P = 0.02). LV and RV diastolic compliance were decreased in HFpEF vs HFrEF at baseline and decreased further after shunt treatment in HFpEF.

Differential changes in left-sided and right-sided heart remodeling and PASP following interatrial shunt placement in patients with HFrEF vs HFpEF provide a mechanistic basis for the variable effects on clinical outcomes observed in RELIEVE-HF. (REducing Lung congestion symptoms using the v-wavE shunt in adVancEd Heart Failure [RELIEVE-HF]; NCT03499236).