Sustained Sympathetic and Blood Pressure Reduction 1 Year After Renal Denervation in Patients With Resistant Hypertension

Abstract

U ncontrolled blood pressure (BP) remains the leading cause of cardiovascular morbidity and mortality globally.1 Despite the availability of potent antihypertensive drugs, only 53% of patients with documented hypertension achieve target BP levels.2 Although determining the exact prevalence of patients with resistant hypertension (RH) remains complex, data available from United States and Europe have indicated that resistance to pharmacological treatment occurs in 13% of treated patients with elevated BP.3 Furthermore, the prevalence 3 and incidence of RH is projected to increase progressively. 4 Patients with true RH commonly display evidence of end organ damage 5 and are at high risk for cardiovascular events.6 Accordingly, even a mild reduction in BP has been demonstrated to reduce overall cardiovascular morbidity and mortality substantially. 7,8 As part of the complex and multifactorial pathophysiology of RH, 9 enhanced sympathetic activation is a critical contributor to BP elevation. [10][11][12] In fact, both low-risk subjects with high-normal BP 13 and high-risk patients with RH 14 have increased muscle sympathetic nerve activity (MSNA). Furthermore, patients with RH are characterized by persistent sympathetic activation as evidenced by increased single-and multiunit MSNA and augmented renal noradrenaline spillover. [14][15][16] In this context, catheter-based sympathetic renal denervation (RDN) provides a rational approach in patient management given that both efferent and afferent renal nerves are pivotal in the initiation and maintenance of elevated BP.17 Indeed, RDN has been associated with substantial and sustained BP reduction, decreased noradrenaline spillover, and postganglionic efferent single-and multiunit MSNA in RH. [14][15][16][18][19][20][21] Although the majority of currently available results with RDN are promising and the rationale for the use of this approach for other conditions characterized by sympathetic excitation is apparent, not all studies demonstrated a reduction in MSNA after RDN. 22 Furthermore, renal nerves have the capacity to regrow, which may affect the long-term effects of the procedure. At this stage, it is unclear whether any reinnervation that may occur is of functional relevance. 23 Likewise, the long-term effect of RDN on MSNA has not yet Abstract-Renal denervation (RDN) reduces muscle sympathetic nerve activity (MSNA) and blood pressure (BP) in resistant hypertension. Although a persistent BP-lowering effect has been demonstrated, the long-term effect on MSNA remains elusive. We investigated whether RDN influences MSNA over time. Office BP and MSNA were obtained at baseline, 3, 6, and 12 months after RDN in 35 patients with resistant hypertension. Office BP averaged 166±22/88±19 mm Hg, despite the use of an average of 4.8±2.1 antihypertensive drugs. Baseline MSNA was 51±11 bursts/min ≈2-to 3-fold higher than the level observed in healthy controls. Mean office systolic and diastolic BP significantly decreased by -12.6±18.3/-6.5±9.2, -16.1±25.6/-8.6±12.9, and -21.2±29....

Asymmetric and Symmetric Dimethylarginine and Sympathetic Nerve Traffic after Renal Denervation in Patients with Resistant Hypertension

“…First, our control groups are historical rather than synchronous, with the group of patients submitted to renal denervation, and the group we used to control for the effect of antihypertensive drugs on ADMA levels was composed of hypertensive CKD patients rather than patients with treatment-resistant hypertension. Long-term MSNAC remains unchanged over a 3-month interval in resistant hypertensive patients maintained on standard drug therapy (8). ADMA and SDMA are quite repeatable measurements (see Methods), and we documented in historical controls the constancy of both MSNAC and ADMA and SDMA over 6 months (i.e., the longest observation period postdenervation in patients included in this study).…”

“…Sympathetic nerve traffic was recorded together with finger BP, heart rate, and respiration rate during a 30-minute period in a quiet semidark room kept at a constant temperature of 22°C-24°C. Renal denervation was carried out by using a radiofrequency ablation catheter (Symplicity; Medtronic Ardian, Palo Alto, CA), following the protocol and sequence of interventions (which included renal angiograms) described in previous articles (8)(9)(10). Data were analyzed by a single investigator unaware of the experimental design and of the belonging of each patient to the different experimental sessions.…”

“…Observations in resistant hypertension show that renal denervation may result in a marked reduction in whole-body norepinephrine spillover (7) and into a sustained decrease in MSNAC (8), even though these findings were not replicated in all studies (9,10). Renal denervation in resistant hypertension represents a unique model to further examine the hypothesis that sympathetic activity modulates circulating ADMA and SDMA levels.…”

Reduced Effect of Percutaneous Renal Denervation on Blood Pressure in Patients With Isolated Systolic Hypertension

“…1 Catheter-based renal denervation (RDN) has been shown to reduce sympathetic activity 2 and thereby office and ambulatory blood pressure (BP) in certain but not all patients with resistant hypertension. [3][4][5] Data about the effectiveness of RDN in different types of hypertension are lacking.…”

123I-mIBG scintigraphy: Clinical tool for assessing renal sympathetic activity?

“…The most promising and best characterized are the measurements of muscle sympathetic nerve activity (MSNA), renal NE spillover rate, and assessment of sympathetically mediated responses to electrical stimulation of the renal artery before and after denervation. [6][7][8] Assessment of MSNA is minimally invasive and entails percutaneous insertion of a recording electrode into a superficial nerve (peroneal or radial), allowing direct recording of postganglionic sympathetic neural bursts. MSNA reflects moment-to-moment sympathetic outflow from the central nervous system to either skeletal muscle or skin, but does not provide direct information on sympathetic outflow to the kidney or heart.…”