Novel device-based and catheter-directed therapies for heart failure with preserved ejection fraction

Heart failure with preserved ejection fraction (HFpEF) presents a major clinical and therapeutic challenge owing to its complex pathophysiology and pronounced clinical heterogeneity. While traditional empirical strategies targeting comorbidities offered limited success, recent advances in molecular, hemodynamic, and autonomic profiling have catalyzed a fundamental shift toward phenotype-guided, personalized management. Clinical trial insights underscore that precise patient selection is paramount for therapeutic efficacy; for example, interatrial shunt interventions demonstrate clinical benefits primarily in patients without elevated exercise pulmonary vascular resistance, whereas improper application risks right ventricular decompensation. Simultaneously, novel device-based modalities, including transcutaneous vagal nerve stimulation, cardiac contractility modulation, splanchnic nerve ablation, and adjustable interatrial shunts, are emerging as promising avenues to directly address underlying mechanisms such as systemic inflammation, impaired calcium handling, and volume redistribution. Moving forward, the management paradigm of HFpEF will increasingly shift from monotherapy to synergistic multimodal approaches. Combining established foundational pharmacotherapies, such as sodium-glucose cotransporter 2 inhibitors and glucagon-like peptide-1 receptor agonists, with continuous pulmonary artery pressure monitoring and targeted interventional devices holds immense potential to establish closed-loop, individualized treatment strategies. In this review, we synthesize current clinical evidence, highlight key anatomical and hemodynamic considerations, evaluate emerging device platforms, and discuss future strategic perspectives aimed at optimizing precision medicine for patients with HFpEF. Phenotype-Guided Non-Pharmacological and Device Therapies in HFpEF. LAP: left atrial pressure, PCWP: pulmonary capillary wedge pressure, PH: pulmonary hypertension, HFpEF: heart failure with preserved ejection fraction, PVR pulmonary vascular resistance, RV: right ventricular, LV: left ventricular, IASD: atrial septal shunt device, RDN: renal denervation, GSN: greater splanchnic nerve, BAT: baroreflex activation therapy, PADN: percutaneous pulmonary artery denervation, CCM: cardiac contractility modulation, LA: left atrial, VNS; vagus nerve stimulation.