Baroreceptor Dysregulation Mediated via Neurohormonal Mechanisms in Heart Failure and its Influence on Renal Function: Potential Role of Baroreflex Activation Therapy
Racha Ghoussaini, Aditi Patel, Brady Simpson, Kirollos Gabrah, Romani Wahba, Pramod Mohanty, Sriram Sriperumbuduri, Mohammad Al-Ani, Hamang Patel, Keyur B. Shah, Pengyang LiBaroreflex activation therapy (BAT), which electrically stimulates carotid sinus baroreceptors to modulate autonomic tone, has emerged as a novel adjunct to guideline-directed medical therapy for resistant hypertension and heart failure. Beyond its established cardiovascular benefits, emerging preclinical and early-phase clinical data suggest that BAT may favorably influence renal function and cardiorenal interactions. By suppressing sympathetic nervous system activity and downregulating the renin-angiotensin-aldosterone system, BAT improves renal hemodynamics and may counteract key mechanisms leading to diuretic resistance. The latter represents a common and clinically significant challenge in patients with advanced heart failure, in whom impaired renal perfusion, neurohormonal activation, and tubular remodeling all contribute to reduced diuretic responsiveness and worsening kidney function. Early evidence indicates that BAT may preserve glomerular filtration rate, reduce proteinuria and improve urinary sodium excretion, suggesting potential renoprotective effects and a therapeutic role in mitigating diuretic resistance. However, these findings remain limited by small sample sizes, short follow-up periods, and heterogenous study populations across diverse clinical settings. This review synthesizes key physiologic mechanisms linking baroreflex signal modulation to renal outcomes and evaluates available clinical data. While BAT offers established cardiovascular benefits in heart failure, its renoprotective and diuretic-sparing potential remains investigational and lacks validation from randomized clinical trials. Dedicated prospective large-scale randomized studies are essential to establish long-term renal efficacy across the cardiorenal disease spectrum.