Device-Based Neuromodulation for Resistant Hypertension Therapy

Abstract

Despite availability of effective drugs for hypertension therapy, significant numbers of hypertensive patients fail to achieve recommended blood pressure (BP) levels while on ≥3 antihypertensive drugs of different classes. These individuals have a high prevalence of adverse cardiovascular events and are defined as having resistant hypertension (RHT) although nonadherence to prescribed antihypertensive medications is common in patients with apparent RHT. Furthermore, apparent and true RHT often display increased sympathetic activity. Based on these findings, technology was developed to treat RHT by suppressing sympathetic activity with electrical stimulation of the carotid baroreflex and catheter-based renal denervation (RDN). Over the last 15 years, experimental and clinical studies have provided better understanding of the physiological mechanisms that account for BP lowering with baroreflex activation (BA) and RDN and, in so doing, have provided insight into which patients in this heterogeneous hypertensive population are most likely to respond favorably to these device-based therapies. Experimental studies have also played a role in modifying device technology after early clinical trials failed to meet key endpoints for safety and efficacy. At the same time, these studies have exposed potential differences between BA and RDN and common challenges that will likely impact antihypertensive treatment and clinical outcomes in patients with RHT. In this review, we emphasize physiological studies that provide mechanistic insights into BP lowering with BA and RDN in the context of progression of clinical studies, which are now at a critical point in determining their fate in RHT management.

Sodium glucose cotransporter (SGLT)-2 inhibitors alleviate the renal stress responsible for sympathetic activation

“…Based on the results of animal studies, renal denervation and baroreflex activation therapy, which suppresses the increase in central sympathetic activity, has been attempted as a treatment for treatment-resistant hypertension in humans, and both have been reported to lower blood pressure and, in addition, to exert therapeutic effects on heart failure. 12,13 SGLT2 inhibitors inhibit overactivation of the sympathetic nervous system Sympathetic nervous system activation is associated with hospitalization and death in heart failure. 14 It has been shown that in diabetic patients, as in hypertensive patients, there is an overactivation of the systemic sympathetic nervous system.…”

“…Based on the results of animal studies, renal denervation and baroreflex activation therapy, which suppresses the increase in central sympathetic activity, has been attempted as a treatment for treatment-resistant hypertension in humans, and both have been reported to lower blood pressure and, in addition, to exert therapeutic effects on heart failure. 12 , 13 …”

Implant-Mediated Therapy of Arterial Hypertension

“…The BAROSTIM NEO® Pivotal Trial (NCT01679132) was designed as a single-group open-label trial including 10 participants. However, this trial was suspended, since the company focused on other studies [35]. Currently, two large randomized controlled trials for baroreceptor activation therapy are carried out, investigating the unilateral BAROSTIM NEO® System.…”

Baroreflex Activation Therapy for Resistant Hypertension and Heart Failure

“…40 Although BAT received little or no attention for decades thereafter, primarily due to successful drug development, an increasing need for alternative treatment approaches for resistant hypertension and heart failure has prompted renewed research in this area. 35,[41][42][43]…”