Long-Term Safety and Procedural Performance of an Interatrial Shunt for Heart Failure According to Ejection Fraction

BACKGROUND: Long-term device durability and phenotype-specific safety outcomes after interatrial shunting require further characterization. OBJECTIVES: This study aimed to evaluate the procedural success, device durability, and heart failure (HF) phenotype-specific safety outcomes of an interatrial shunt in the RELIEVE-HF trial. METHODS: Randomized patients were assigned 1:1 to shunt or sham control with prespecified stratification by left ventricular ejection fraction (LVEF) into heart failure with reduced ejection fraction (HFrEF) (LVEF ≤40%) and heart failure with preserved ejection fraction (HFpEF) (LVEF >40%). Procedural performance, device durability, serious adverse events (SAEs), major adverse cardiovascular or neurological events (MACNE), major bleeding, and renal outcomes were assessed through 2 years. RESULTS: Among 605 enrolled patients (508 randomized; 97 roll-in), shunt implantation was attempted in 370 and was successful in 369 (99.7%). Among implanted patients with follow-up (n = 348), no device- or procedure-related MACNE occurred through 2 years (0%; 95% CI: 0%-0.9%), and shunt patency was 99.4% (95% CI: 97.9%-99.9%). Prespecified LVEF-stratified analyses demonstrated divergent safety profiles. In HFrEF, shunt therapy was not associated with excess all-cause MACNE, major bleeding, or renal decline and was associated with lower SAE burden. In HFpEF, shunt therapy was associated with higher all-cause MACNE, greater SAE burden, increased major bleeding, and greater renal decline. CONCLUSIONS: Interatrial shunt implantation was mechanically reliable and durable through 2 years. Safety outcomes differed by HF phenotype, with no evidence of excess clinical safety events in HFrEF but increased adverse events in HFpEF. These findings support phenotype-specific evaluation of interatrial shunt therapy. (REducing Lung congestion symptoms using the v-wavE shunt in adVancEd Heart Failure [RELIEVE-HF]; NCT03499236).