Heart failure with preserved ejection fraction (HFpEF) is a complex and heterogeneous clinical syndrome characterized by signs and symptoms of heart failure despite normal or near-normal ejection fraction. It is a debilitating chronic disease that affects millions of people worldwide, and due to the paucity of evidence-based pharmacological treatments for HFpEF, nonpharmacological approaches as potential therapeutic alternatives are of growing interest. As a result, renal denervation (RDN), initially developed as a therapeutic tool for resistant hypertension, has become an area of active clinical interest. RDN is a catheter-based procedure that targets the renal sympathetic pathways, aiming to reduce neurohormonal activation and mitigate maladaptive cardiac remodeling. Preclinical studies in animal models have demonstrated that RDN can improve cardiac and vascular fibrosis, reduce renal inflammation, control hypertension, and alleviate endothelial dysfunction. Recent clinical studies have further highlighted the potential benefits of RDN in patients with HFpEF and uncontrolled hypertension. In this review, we aim to outline the pathophysiology of HFpEF and demonstrate the complex clinical interplay involved in how RDN impacts the heart. Moreover, we discuss the present status of clinical studies on RDN and explore its therapeutic potential as a viable treatment for HFpEF.

Severe pulmonary hypertension (PH) is a relative contraindication to left-sided valve replacement given elevated risk of decompensation. A 64-year-old woman with prior atrioventricular canal repair, bioprosthetic mitral valve replacement, and suprasystemic group II PH presented with recurrent heart failure admissions in the setting of severe bioprosthetic valve regurgitation. Considered at prohibitive risk for redo surgery, she underwent valve-in-valve transcatheter mitral valve replacement (TMVR) under intracardiac echocardiography (ICE) guidance and conscious sedation. Pulmonary artery systolic pressure decreased from the 110s to the 80s mm Hg postprocedure and to the 50s mm Hg with sildenafil optimization. At 9 months postprocedure, she had improved to NYHA functional class I-II status. This case illustrates the safety and feasibility of ICE-guided TMVR without general anesthesia in patients with severe PH. It highlights a "hyper-responder" physiology after correction of left-sided valve pathology and optimization of pulmonary vasodilators. ICE-guided TMVR under conscious sedation (in combination with pulmonary vasodilators) can be safe in select severe PH patients, achieving significantly lower pulmonary pressures with meaningful symptom improvement.