Effect Of Catheter-based Renal Denervation Research Articles

Reinnervation following catheter-based radio-frequency renal denervation.

What is the topic of this review? Does catheter-based renal denervation effectively denervate the afferent and efferent renal nerves and does reinnervation occur? What advances does it highlight? Following catheter-based renal denervation, the afferent and efferent responses to electrical stimulation were abolished, renal sympathetic nerve activity was absent, and levels of renal noradrenaline and immunohistochemistry for tyrosine hydroxylase and calcitonin gene-related peptide were significantly reduced. By 11months after renal denervation, both the functional responses and anatomical markers of afferent and efferent renal nerves had returned to normal, indicating reinnervation. Renal denervation reduces blood pressure in animals with experimental hypertension and, recently, catheter-based renal denervation was shown to cause a prolonged decrease in blood pressure in patients with resistant hypertension. The randomized, sham-controlled Symplicity HTN-3 trial failed to meet its primary efficacy end-point, but there is evidence that renal denervation was incomplete in many patients. Currently, there is little information regarding the effectiveness of catheter-based renal denervation and the extent of reinnervation. We assessed the effectiveness of renal nerve denervation with the Symplicity Flex catheter and the functional and anatomical reinnervation at 5.5 and 11months postdenervation. In anaesthetized, non-denervated sheep, there was a high level of renal sympathetic nerve activity, and electrical stimulation of the renal nerve increased blood pressure and reduced heart rate (afferent response) and caused renal vasoconstriction and reduced renal blood flow (efferent response). Immediately after renal denervation, renal sympathetic nerve activity and the responses to electrical stimulation were absent, indicating effective denervation. By 11months after denervation, renal sympathetic nerve activity was present and the responses to electrical stimulation were normal, indicating reinnervation. Anatomical measures of renal innervation by sympathetic efferent nerves (tissue noradrenaline and tyrosine hydroxylase) and afferent sensory nerves (calcitonin gene-related peptide) demonstrated large decreases at 1week postdenervation, but normal levels at 11months postdenervation. In summary, catheter-based renal denervation is effective, but reinnervation occurs. Studies of central and renal changes postdenervation are required to understand the causes of the prolonged hypotensive response to catheter-based renal denervation in human hypertension.

Reinnervation of renal afferent and efferent nerves at 5.5 and 11 months after catheter-based radiofrequency renal denervation in sheep.

Previous studies indicate that catheter-based renal denervation reduces blood pressure and renal norepinephrine spillover in human resistant hypertension. The effects of this procedure on afferent sensory and efferent sympathetic renal nerves, and the subsequent degree of reinnervation, have not been investigated. We therefore examined the level of functional and anatomic reinnervation at 5.5 and 11 months after renal denervation using the Symplicity Flex catheter. In normotensive anesthetized sheep (n=6), electric stimulation of intact renal nerves increased arterial pressure from 99±3 to 107±3 mm Hg (afferent response) and reduced renal blood flow from 198±16 to 85±20 mL/min (efferent response). In a further group (n=6), immediately after denervation, renal sympathetic nerve activity was absent and the responses to electric stimulation were abolished. At 11 months after denervation (n=5), renal sympathetic nerve activity and the responses to electric stimulation were at normal levels. Immunohistochemical staining for renal efferent (tyrosine hydroxylase) and renal afferent nerves (calcitonin gene-related peptide), as well as renal norepinephrine levels, was normal 11 months after denervation. Findings at 5.5 months after denervation were similar (n=5). In summary, catheter-based renal denervation effectively ablated the renal afferent and efferent nerves in normotensive sheep. By 11 months after denervation the functional afferent and efferent responses to electric stimulation were normal. Reinnervation at 11 months after denervation was supported by normal anatomic distribution of afferent and efferent renal nerves. In view of this evidence, the mechanisms underlying the prolonged hypotensive effect of catheter-based renal denervation in human resistant hypertension need to be reassessed.

Cost Effectiveness of Catheter-Based Renal Denervation for Treatment Resistant Hypertension - an Australian Payer Perspective.

Cost Effectiveness of Catheter-Based Renal Denervation for Treatment Resistant Hypertension - an Australian Payer Perspective.

Effectiveness of Catheter-Based Renal Denervation for Treatment Resistant Hypertension - Results of a Systematic Review and Meta-Analysis.

Effectiveness of Catheter-Based Renal Denervation for Treatment Resistant Hypertension - Results of a Systematic Review and Meta-Analysis.

The link between renal denervation and reduction of cardiovascular risks: Simplicity or not?

It has been demonstrated that abnormalities of the sympathetic nervous system strongly contribute to the development and/or maintenance of multiple disease states such as hypertension, heart failure, diabetes mellitus, sleep apnea, kidney disease and arrhythmias [1]. When we look through the window of hypertension, the renal nerves have been identified as important contributors in both development and maintenance of hypertension [2]. We read with great enthusiasm the article written by Ott and colleagues evaluating the effect of renal denervation (RDN) on elevated urinary albumin-to-creatinine ratio (UACR) in patients with resistant hypertension [3]. They have subdivided the patients according to their UACR at baseline into micro(30–300 mg/g, n = 37) and macroalbuminuria (300–2200 mg/g, n = 22) and found a significant reduction in UACR in all patients (p b 0.001) and in both subgroups (p b 0.001). They have implicated that, following RDN, the magnitude of albuminuria as well as the prevalence of microand macroalbuminuria decreased in patients with treatment-resistant hypertension and concluded that, since albuminuria is an independent renal and cardiovascular risk factor, a reduction of renal and cardiovascular risk could be achieved by RDN in these patients. The effect of catheter-based RDN on resistant hypertension in humans was assessed clinically in 2009, by the first proof-of-principle multicenter study from 45 patients with treatment-resistant hypertension [4]. The initial cohort was subsequently expanded from 45 to 153 patients, and the follow-up durationwas increased to a minimum of 2 years (Symplicity HTN-1) [5]. Both studies reported promising results favoring RDN. As it was an unblinded prospective cohort study without a control group, it was soon followed by the Symplicity HTN-2 trial to further assess RDN in a randomized fashion [6]. The Symplicity HTN-2 included 106 patients with severe resistant hypertensionwhowere randomized to RDN and conventional medical therapy versus conventional medical therapy alone. RDN was found to bemore effective thanmedical therapy alone in reducing blood pressure (BP), causing a reduction of 32 mmHg in systolic and 12 mm Hg in diastolic BP in the RDN group and no significant change in the control group. However, no changes in renal function or UACRwere identified in either group. The studywasdesigned such that patients from the control group were allowed to crossover to RDN therapy after six months, provided that the BP remained uncontrolled with a systolic BP greater than 160mmHg. Interestingly, the crossover group consisting of 35 patients experienced a significant drop in BP similar to that observed in the initial RDN group at 6 months' follow-up [7]. Recently published long-term results of the Symplicity HTN-1 study also imply that the efficacy gradually increases in 3 years' follow-up [7]. There is also evidence that patients with milder forms of hypertension may benefit from RDN [8]. Furthermore, there is emerging evidence that RDN may have a role in the treatment of heart failure, obstructive sleep apnea, insulin resistance, atrial fibrillation, hypertension associatedwith end-stage renal disease and, as shown recently, even in patients with ventricular storm where sympathetic nervous system seems to have a crucial role [9–13]. Thus, given the fact that resistant hypertension and other diseases associated with elevated sympathetic tone have significant morbidity and mortality rates, RDN therapy might be expected to have a crucial role on public health. However, the results of the Symplicity-3 trial overturned this optimistic mood about the RDN [14]. In the Symplicity HTN-3 study, RDN had no significant effect on office or 24-hour ambulatory systolic BP, findings that contradict most published studies on RDN. A recent trial even suggested inferiority of RDN as compared to adjusted drug treatment [15]. There is now growing evidence of lack of BP response following RDN in up to 50% of cases in some reports [16,17]. Clinical use of RDN had significantly increased after the encouraging results of Symplicity HTN-1 trial [5]. Afterwards, clinical studies with encouraging results appeared in the literature [18–20]. Parallel to these developments, medical device companies fancied RDN as the next big innovation and as a blockbuster therapy for millions of patients with resistant hypertension. But, what exactly happened that suddenly reversed this optimistic mood? Actually, it seems like there is no significant change; only the puzzle pieces are beginning to fall into place. Possibly because of the methodological problems involved in the initial studies, exaggerated interpretations led to heightened expectations from this exciting new treatment modality. There are three crucial points which need to be discussed.

Catheter-Based Renal Nerve Ablation and Centrally Generated Sympathetic Activity in Difficult-to-Control Hypertensive Patients: Prospective Case Series

The recently published article by Brinkmann et al1 attempted to investigate the effect of catheter-based renal denervation (RDN) on blood pressure (BP) and muscle sympathetic nerve activity. The article is of interest; however, some aspects require clarification. In disagreement with several other studies, the authors report no significant overall blood BP lowering effect after RDN in a small group of 12 patients, and not surprisingly did not observe any changes in muscle sympathetic nerve activity. As shown in larger series, procedural success is clearly observed in patients with high BP as a surrogate of increased sympathetic activity. In contrast to the Symplicity trials, the baseline BP herein was 157/85 mm …

Cost-Effectiveness and Clinical Effectiveness of Catheter-Based Renal Denervation for Resistant Hypertension

The purpose of this study was to assess cost-effectiveness and long-term clinical benefits of renal denervation in resistant hypertensive patients. Resistant hypertension affects 12% of hypertensive persons. In the Symplicity HTN-2 randomized controlled trial, catheter-based renal denervation (RDN) lowered systolic blood pressure by 32 ± 23 mm Hg from 178 ± 18 mm Hg at baseline. A state-transition model was used to predict the effect of RDN and standard of care on 10-year and lifetime probabilities of stroke, myocardial infarction, all coronary heart disease, heart failure, end-stage renal disease, and median survival. We adopted a societal perspective and estimated an incremental cost-effectiveness ratio in U.S. dollars per quality-adjusted life-year, both discounted at 3% per year. Robustness and uncertainty were evaluated using deterministic and probabilistic sensitivity analyses. Renal denervation substantially reduced event probabilities (10-year/lifetime relative risks: stroke 0.70/0.83; myocardial infarction 0.68/0.85; all coronary heart disease 0.78/0.90; heart failure 0.79/0.92; end-stage renal disease 0.72/0.81). Median survival was 18.4 years for RDN versus 17.1 years for standard of care. The discounted lifetime incremental cost-effectiveness ratio was $3,071 per quality-adjusted life-year. Findings were relatively insensitive to variations in input parameters except for systolic blood pressure reduction, baseline systolic blood pressure, and effect duration. The 95% credible interval for incremental cost-effectiveness ratio was cost-saving to $31,460 per quality-adjusted life-year. The model suggests that catheter-based renal denervation, over a wide range of assumptions, is a cost-effective strategy for resistant hypertension that might result in lower cardiovascular morbidity and mortality.