The effect of percutaneous renal denervation on muscle sympathetic nerve activity in hypertensive patients

Vink, Eva E.; Verloop, Wilhelmina L.; Siddiqi, Laima; Schelven, Leonard J. van; Oey, P. L.; Blankestijn, P J

doi:10.1016/j.ijcard.2014.06.021

Cited by 30 publications

(26 citation statements)

References 35 publications

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“…In a follow-up study in 25 obese patients with resistant hypertension, these same SYMPLICITY trial investigators reported that after 3 mo of renal nerve ablation, blood pressure lowering was associated with a much smaller 7-8% decrease in multiunit MSNA (34). In contrast, others have reported that reductions in MSNA and arterial pressure are not consistent responses to renal nerve ablation in patients with resistant hypertension, and, when blood pressure lowering is achieved, there has been no correlation between reductions in arterial pressure and MSNA (12,31,85).…”

Section: Other Potential Determinants Of the Antihypertensive Responsmentioning

confidence: 99%

Renal denervation for the treatment of resistant hypertension: review and clinical perspective

Iliescu

Lohmeier

Tudorancea

et al. 2015

American Journal of Physiology-Renal Physiology

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When introduced clinically 6 years ago, renal denervation was thought to be the solution for all patients whose blood pressure could not be controlled by medication. The initial two studies, SYMPLICITY HTN-1 and HTN-2, demonstrated great magnitudes of blood pressure reduction within 6 mo of the procedure and were based on a number of assumptions that may not have been true, including strict adherence to medication and absence of white-coat hypertension. The SYM-PLICITY HTN-3 trial controlled for all possible factors believed to influence the outcome, including the addition of a sham arm, and ultimately proved the demise of the initial overly optimistic expectations. This trial yielded a much lower blood pressure reduction compared with the previous SYMPLICITY trials. Since its publication in 2014, there have been many analyses to try and understand what accounted for the differences. Of all the variables examined that could influence blood pressure outcomes, the extent of the denervation procedure was determined to be inadequate. Beyond this, the physiological mechanisms that account for the heterogeneous fall in arterial pressure following renal denervation remain unclear, and experimental studies indicate dependence on more than simply reduced renal sympathetic activity. These and other related issues are discussed in this paper. Our perspective is that renal denervation works if done properly and used in the appropriate patient population. New studies with new approaches and catheters and appropriate controls will be starting later this year to reassess the efficacy and safety of renal denervation in humans. denervation; hypertension; pathophysiology; renal nerves; resistance RESISTANT HYPERTENSION IS defined as failure to achieve a guideline-driven blood pressure of less than 140/90 mmHg in patients who are adherent to maximally tolerated doses of at least three antihypertensive drugs, including a diuretic appropriate for kidney function (13). Population-based studies published over the last decade indicate that anywhere from 3 to 12% of hypertensive patients in the United States have resistant hypertension, despite the abundance of efficacious blood pressure-lowering agents belonging to over seven drug classes (11,20,68). Moreover, in addition to the cardiovascular mortality risk directly linked to the extent of blood pressure elevation, resistant hypertensive patients frequently have additional risk factors such as obesity, diabetes, chronic kidney disease, and age over 55 and are therefore more likely to die from stroke, myocardial infarction, heart failure, and end-stage renal disease (47, 76).Since increased sympathetic activity was believed to be present in many patients with resistant hypertension, renal denervation was thought to be the solution for all patients whose blood pressure could not be controlled by medication and was introduced for clinical use 6 years ago. In the open label, uncontrolled SYMPLICITY HTN-1 and SYMPLICITY HTN-2 trials, undertaken in patients with resistant hypertension, redu...

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Section: Other Potential Determinants Of the Antihypertensive Responsmentioning

confidence: 99%

Renal denervation for the treatment of resistant hypertension: review and clinical perspective

Iliescu

Lohmeier

Tudorancea

et al. 2015

American Journal of Physiology-Renal Physiology

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“…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.…”

Section: Protocol and Data Analysismentioning

confidence: 99%

“…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.…”

Section: Introductionmentioning

confidence: 99%

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

Seravalle

Trevano

Spaziani³

et al. 2015

Clinical Journal of the American Society of Nephrology

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Background and objectives The plasma concentration of the endogenous inhibitor of nitric oxide synthase asymmetric dimethylarginine (ADMA) associates with sympathetic activity in patients with CKD, but the driver of this association is unknown.Design, setting, participants, & measurements In this longitudinal study (follow-up: 2 weeks-6 months), repeated measurements over time of muscle sympathetic nerve activity corrected (MSNAC), plasma levels of ADMA and symmetric dimethylarginine (SDMA), and BP and heart rate were performed in 14 patients with drug-resistant hypertension who underwent bilateral renal denervation (enrolled in 2013 and followed-up until February 2014). Stability of ADMA, SDMA, BP, and MSNAC over time (6 months) was assessed in two historical control groups of patients maintained on stable antihypertensive treatment.Results Time-integrated changes in MSNAC after renal denervation ranged from -40.6% to 10% (average, -15.1%), and these changes were strongly associated with the corresponding changes in plasma ADMA (r= 0.62, P=0.02) and SDMA (r=0.72, P=0.004). Changes in MSNAC went along with simultaneous changes in standardized systolic (r=0.65, P=0.01) and diastolic BP (r=0.61, P=0.02). In the historical control groups, no change in ADMA, SDMA, BP, and MSNAC levels was recorded during a 6-month follow-up. ConclusionsIn patients with resistant hypertension, changes in sympathetic activity after renal denervation associate with simultaneous changes in plasma levels of the two major endogenous methylarginines, ADMA and SDMA. These observations are compatible with the hypothesis that the sympathetic nervous system exerts an important role in modulating circulating levels of ADMA and SDMA in this condition.

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“…• Vincristine was administered locally by accessing the renal artery trough a catheter into the periadventitial space [60] control [74]. Small sized studies have shown reduction in bursts [75], as well as no change [73,76]. The method is operator dependent, time demanding and not suited for large studies.…”

Section: Muscle Sympathetic Nerve Activitymentioning

confidence: 99%

Renal denervation

Olsen

Kamper

Svendsen

et al. 2015

European Journal of Internal Medicine

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Initial studies demonstrated that RDN in patients with resistant hypertension was both feasible and safe and indicated that RDN may lead to impressive reductions in BP. However, recent controlled studies question the BP lowering effect of RDN treatment. Large-scale registry data still supports the favorable BP reducing effect of RDN. We suggest that, in the near future, RDN should not be performed outside clinical studies. The degree of denervation between individual operators and between different catheters and techniques used should be clarified. The major challenge ahead is to identify which patients could benefit from RDN, to clarify the lack of an immediate procedural success parameter, and to establish further documentation of overall effect of treatment such as long-term cardiovascular morbidity and mortality.

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The effect of percutaneous renal denervation on muscle sympathetic nerve activity in hypertensive patients

Cited by 30 publications

References 35 publications

Renal denervation for the treatment of resistant hypertension: review and clinical perspective

Renal denervation for the treatment of resistant hypertension: review and clinical perspective

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

Renal denervation

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