Future Directions for RDN | From Hypertension to AFib and Beyond: 2026 Update

Renal denervation (RDN) is re-emerging as a mechanistically compelling therapy that extends well beyond hypertension control. In his Sunday morning session at the 2026 Cardiovascular Research Technologies (CRT) conference in Washington, DC, Dr Eric Secemsky reviewed contemporary data linking sympathetic overactivity to heart failure (HF), atrial fibrillation (AFib), and cardiometabolic disease, and examined how renal and multi-organ denervation may modify these pathways.

Progressive HF is characterized by rising norepinephrine spillover in both cardiac and renal tissue, reflecting overactivity of the sympathetic system. Importantly, RDN appears to interrupt this cascade independent of blood pressure (BP) reduction.

Presented data emphasized improvements in structural and functional surrogates: in resistant hypertension cohorts, RDN was associated with reduced BNP and left ventricular mass index (LVMI) and improved ejection fraction (EF) and circumferential strain. Retrospective analyses also linked RDN with reverse LV remodeling, including reports suggesting effects that may not be fully explained by BP reduction alone.

Hypertension and sympathetic overdrive contribute to left atrial (LA) dilation, fibrosis, and AFib substrate propagation. The use of RDN has demonstrated improvement in both LA diameter and remodeling parameters, as well as enhancement of AFib ablation durability.

The ERADICATE-AF trial, a prospective randomized study of 302 patients conducted outside the US, showed that adding RDN to pulmonary vein isolation (PVI) significantly reduced recurrent AFib—as well as atrial flutter and/or tachycardia—at 1 year compared with PVI alone.¹

Additionally, meta-analytic data suggest an approximately 40% relative reduction in AFib recurrence when RDN is combined with AFib ablation strategies.²

Emerging evidence suggests that hepatic sympathetic innervation plays a clinically relevant role in cardiometabolic regulation, influencing sodium handling, gluconeogenesis, and pathways involved in hepatic steatosis and steatohepatitis—inspiring Dr Secemsky’s description of the system as a “procedural GLP-1 agonist.” Preclinical data demonstrate that multi-organ (renal and hepatic) denervation produced large tissue-level NE reductions at 7 days in normotensive swine.

To this end, the ongoing SPYRAL GEMINI Pilot Study (US) is evaluating 2 parallel cohorts:

1. Off-medication patients with uncontrolled hypertension with the aim to augment BP response
2. On-medication patients with hypertension and type 2 diabetes to assess cardiometabolic benefits including glucose and fatty liver management

Completion of the study is estimated for December, 2029.³

Renal denervation is evolving from a hypertension device therapy to a broader platform for sympathetic modulation. As data mature, RDN—alone or combined with AFib ablation—may influence heart failure progression, atrial remodeling, arrhythmia recurrence, and cardiometabolic risk.

Eric A. Secemsky, MD, MSc, RPVI, FACC, FAHA, FSCAI, is the Director of Vascular Intervention in the Cardiovascular Institute at Beth Israel Deaconess Medical Center, Section Head of Interventional Cardiology and Vascular Research at the Smith Center for Outcomes Research, and an Associate Professor of Medicine at Harvard Medical School.

1. Steinberg JS, Shabanov V, Ponomarev D, et al. Effect of renal denervation and catheter ablation vs catheter ablation alone on atrial fibrillation recurrence among patients with paroxysmal atrial fibrillation and hypertension: the ERADICATE-AF randomized clinical trial. JAMA. 2020;323(3):248-255. doi:10.1001/jama.2019.21187
2. Mujer MT, Al-Abcha A, Saleh Y, et al. Effect of combined renal denervation and pulmonary vein isolation in atrial fibrillation recurrence in hypertensive patients: a meta-analysis. Pacing Clin Electrophysiol. 2020;43(8):866-874. doi:10.1111/pace.14009
3. SPYRAL GEMINI Pilot Study (SPYRAL GEMINI). ClinicalTrials.gov identifier: NCT06907147. Updated March 2, 2026. Accessed March 11, 2026. https://clinicaltrials.gov/study/NCT06907147