Successful treatment of hypertension is difficult despite the availability of several classes of antihypertensive drug, and the value of strategies to combat the effect of adverse lifestyle ...behaviours on blood pressure. In this paper, we discuss two promising therapeutic alternatives for patients with resistant hypertension: novel drugs, including new pharmacological classes (such as vasopeptidase inhibitors and aldosterone synthase inhibitors) and new molecules from present pharmacological classes with additional properties in blood-pressure or metabolism pathways; and new procedures and devices, including stimulation of arterial baroreceptors and catheter-based renal denervation. Although several pharmacological targets have been discovered with promising preclinical results, the clinical development of novel antihypertensive drugs has been more difficult and less productive than expected. The effectiveness and safety of new devices and procedures should be carefully assessed in patients with resistant hypertension, thus leading to a new era of outcome trials and evidence-based guidelines.
Renal denervation in moderate to severe CKD Hering, Dagmara; Mahfoud, Felix; Walton, Antony S ...
Journal of the American Society of Nephrology
23, Številka:
7
Journal Article
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Sympathetic activation contributes to the progression of CKD and is associated with adverse cardiovascular outcomes. Ablation of renal sympathetic nerves reduces sympathetic nerve activity and BP in ...patients with resistant hypertension and preserved renal function, but whether this approach is safe and effective in patients with an estimated GFR (eGFR) < 45 ml/min per 1.73 m(2) is unknown. We performed bilateral renal denervation in 15 patients with resistant hypertension and stage 3-4 CKD (mean eGFR, 31 ml/min per 1.73 m(2)). We used CO(2) angiography in six patients to minimize exposure to contrast agents. Estimated GFR remained unchanged after the procedure, irrespective of the use of CO(2) angiography. Mean baseline BP ± SD was 174 ± 22/91 ± 16 mmHg despite the use of 5.6 ± 1.3 antihypertensive drugs. Mean changes in office systolic and diastolic BP at 1, 3, 6, and 12 months were -34/-14, -25/-11, -32/-15, and -33/-19 mmHg, respectively. Night-time ambulatory BP significantly decreased (P<0.05), restoring a more physiologic dipping pattern. In conclusion, this study suggests a favorable short-term safety profile and beneficial BP effects of catheter-based renal nerve ablation in patients with stage 3-4 CKD and resistant hypertension.
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±29.1/-11.1±12.9 mm Hg (P<0.001 for both systolic BP and diastolic BP) with RDN at 3-, 6-, and 12-month follow-up, respectively. MSNA was reduced by -8±12, -6±12, and -6±11 bursts/min (P<0.01) at 3-, 6-, and 12-month follow-up. The reduction in MSNA was maintained, despite a progressive fall in BP over time. No such changes were observed in 7 control subjects at 6-month follow-up. These findings confirm previous reports on the favorable effects of RDN on elevated BP and demonstrate sustained reduction of central sympathetic outflow ≤1-year follow-up in patients with resistant hypertension and high baseline MSNA. These observations are compatible with the hypothesis of a substantial contribution of afferent renal nerve signaling to increased BP in resistant hypertension and argue against a relevant reinnervation at 1 year after procedure.
Sympathetic nervous system hyperactivity is observed in patients with renal injury, renovascular hypertension, chronic kidney disease (CKD) and end-stage renal disease (ESRD). Elevated sympathetic ...activity is of prognostic relevance in that plasma norepinephrine concentrations predict survival and the incidence of cardiovascular events in patients with ESRD, as well as future renal injury in normotensive healthy subjects with renal function in the normal range. Renal injury, CKD and ESRD are often associated with obesity, and its common sequelae hypertension and diabetes. In fact, hypertension and diabetes mellitus are the main causes of ESRD in western societies and together account for approximately more than 50% of ESRD incidence in the United States and Japan. Obesity also leads to increases in the incidence of cardiovascular diseases. Several clinical and epidemiological studies have clearly documented that heightened sympathetic nervous activity has an important role in the onset and maintenance of obesity and hypertension. Elevated sympathetic nervous activity may actually represent an important mechanism contributing to the onset and maintenance of renal injury at least in part through its concomitant adverse effects on obesity and hypertension. Understanding the contribution of sympathetic nervous hyperactivity to the onset and maintenance of renal injury might aid in the prevention and treatment of renal injury, CKD and ESRD. Very recently, renal sympathetic denervation was shown to be a potentially novel therapeutic strategy in resistant hypertension. In addition, renin-angiotensin system inhibitors are recommended as the initial therapy because of their renal protective effect, especially in hypertensive patients with type 2 diabetes or with proteinuria. The purpose of this review is to provide an overview of our current knowledge on the relationships between sympathetic nerve activity and renal function to further our understanding of the precise roles of sympathetic nerve activity in renal injury, particularly in the context of obesity and hypertension. These insights may be useful to improve prevention and treatment of renal injury in these patients.
Recent sham-controlled randomized clinical trials have confirmed the safety and efficacy of catheter-based renal denervation (RDN). Long-term safety and efficacy data beyond 3 years are scarce. Here, ...we report on outcomes after RDN in a cohort of patients with resistant hypertension with an average of ≈9-year follow-up (FU).
We recruited patients with resistant hypertension who were previously enrolled in various RDN trials applying radiofrequency energy for blood pressure (BP) lowering. All participants had baseline assessments before RDN and repeat assessment at long-term FU including medical history, automated office and ambulatory BP measurement, and routine blood and urine tests. We analyzed changes between baseline and long-term FU.
A total of 66 participants (mean±SD, 70.0±10.3 years; 76.3% men) completed long-term FU investigations with a mean of 8.8±1.2 years post-procedure. Compared with baseline, ambulatory systolic BP was reduced by -12.1±21.6 (from 145.2 to 133.1) mm Hg (
<0.0001) and diastolic BP by -8.8±12.8 (from 81.2 to 72.7) mm Hg (
<0.0001). Mean heart rate remained unchanged. At long-term FU, participants were on one less antihypertensive medication compared with baseline (
=0.0052). Renal function assessed by estimated glomerular filtration rate fell within the expected age-associated rate of decline from 71.1 to 61.2 mL/min per 1.73 m
. Time above target was reduced significantly from 75.0±25.9% at baseline to 47.3±30.3% at long-term FU (
<0.0001).
RDN results in a significant and robust reduction in both office and ambulatory systolic and diastolic BP at ≈9-year FU after catheter-based RDN on less medication and without evidence of adverse consequences on renal function.
The autonomic nervous system regulates all aspects of normal cardiac function, and is recognized to play a critical role in the pathophysiology of many cardiovascular diseases. As such, the value of ...neuroscience‐based cardiovascular therapeutics is increasingly evident. This White Paper reviews the current state of understanding of human cardiac neuroanatomy, neurophysiology, pathophysiology in specific disease conditions, autonomic testing, risk stratification, and neuromodulatory strategies to mitigate the progression of cardiovascular diseases.
Summary Background Activation of renal sympathetic nerves is key to pathogenesis of essential hypertension. We aimed to assess effectiveness and safety of catheter-based renal denervation for ...reduction of blood pressure in patients with treatment-resistant hypertension. Methods In this multicentre, prospective, randomised trial, patients who had a baseline systolic blood pressure of 160 mm Hg or more (≥150 mm Hg for patients with type 2 diabetes), despite taking three or more antihypertensive drugs, were randomly allocated in a one-to-one ratio to undergo renal denervation with previous treatment or to maintain previous treatment alone (control group) at 24 participating centres. Randomisation was done with sealed envelopes. Data analysers were not masked to treatment assignment. The primary effectiveness endpoint was change in seated office-based measurement of systolic blood pressure at 6 months. Primary analysis included all patients remaining in follow-up at 6 months. This trial is registered with ClinicalTrials.gov , number NCT00888433. Findings 106 (56%) of 190 patients screened for eligibility were randomly allocated to renal denervation (n=52) or control (n=54) groups between June 9, 2009, and Jan 15, 2010. 49 (94%) of 52 patients who underwent renal denervation and 51 (94%) of 54 controls were assessed for the primary endpoint at 6 months. Office-based blood pressure measurements in the renal denervation group reduced by 32/12 mm Hg (SD 23/11, baseline of 178/96 mm Hg, p<0·0001), whereas they did not differ from baseline in the control group (change of 1/0 mm Hg 21/10, baseline of 178/97 mm Hg, p=0·77 systolic and p=0·83 diastolic). Between-group differences in blood pressure at 6 months were 33/11 mm Hg (p<0·0001). At 6 months, 41 (84%) of 49 patients who underwent renal denervation had a reduction in systolic blood pressure of 10 mm Hg or more, compared with 18 (35%) of 51 controls (p<0·0001). We noted no serious procedure-related or device-related complications and occurrence of adverse events did not differ between groups; one patient who had renal denervation had possible progression of an underlying atherosclerotic lesion, but required no treatment. Interpretation Catheter-based renal denervation can safely be used to substantially reduce blood pressure in treatment-resistant hypertensive patients. Funding Ardian.
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