Supplementary Material for: Effects of Renal Denervation on Cardiac Remodeling, Cardiac Function, and Cardiovascular Neurohormones in Heart Failure with Reduced Ejection Fraction Patients: A Meta-Analysis and Systematic Review

Objective: To evaluate the effects of Renal Denervation (RDN) on cardiac remodeling, cardiac function, and cardiovascular (CV) neurohormones in heart failure patients with reduced ejection fraction (HFrEF).
Methods: We searched PubMed, Embase, Web of Science, and China National Knowledge Infrastructure (CNKI), identifying 6 randomized controlled trials (RCTs) and 9 single-arm studies, totaling 352 participants. Meta-analyses for RCTs and single-arm studies were conducted using STATA 17 software and the metafor package in R, respectively.
Results: In RCTs, RDN significantly reduced left ventricular end-diastolic diameter (LVEDD) (WMD=-3.55 mm, 95% CI [-5.51, -1.59], P<0.01), left ventricular end-systolic diameter (LVESD) (WMD=-4.13 mm, 95% CI [-6.08, -2.18], P<0.01), and significantly increased left ventricular ejection fraction (LVEF) (WMD=6.30%, 95% CI [4.64, 7.96], P<0.01) and 6-minute walk test (6MWT) distance (WMD=51.25 m, 95% CI [8.30, 94.20], P<0.05). brain natriuretic peptide (BNP) or N-terminal pro-B-type natriuretic peptide (NT-proBNP) levels were significantly reduced (SMD=-1.24, 95% CI [-1.57, -0.90], P<0.01). In single-arm studies, RDN significantly reduced LVEDD (MC=−2.41 mm, 95% CI [-3.74, -1.09], P<0.01), LVESD (MC=−1.72 mm, 95% CI [-2.77, -0.67], P<0.01), LAD (MC=−1.62 mm, 95% CI [-3.16, -0.08], P<0.01), and interventricular septal thickness (IVST) (MC=−0.76mm, 95% CI [-1.05, −0.47], P<0.01). RDN significantly increased LVEF（MC=29.52%, 95% CI [ 12.74, 46.31], P<0.01）and 6MWT distance (MC=100.49 m, 95% CI [49.12, 151.86], P<0.05). RDN significantly reduced BNP or NT-proBNP levels (SMC=−0.57, 95% CI [-0.83, −0.31], P<0.01). Our study also found that RDN had varying degrees of reduction on Renin, Angiotensin II, Aldosterone, and Norepinephrine (NE) in HFrEF patients. Additionally, we found that RDN had no significant effect on SBP/DBP in HFrEF patients, but reduced heart rate (WMD=-7.22 bpm, 95% CI [-9.84, -4.60], P<0.01).
Conclusion: Our meta-analysis demonstrates that RDN can improve cardiac remodeling, enhance cardiac function, reduce CV neurohormones and has no significant effect on blood pressure in patients with HFrEF.