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Objective The efficacy of add-on use of spironolactone in patients with resistant hypertension has been investigated in several small studies. We performed this meta-analysis evaluating the efficacy of add-on use of spironolactone in these patients. Methods We searched Pubmed, Web of Science, and Cochrane Central for all published studies evaluating add-on use of spironolactone in patients with resistant hypertension. Only randomized controlled trials determining antihypertensive effects of spironolactone were considered. Results The antihypertensive effects were assessed in 869 patients included in 4 trials with a mean follow-up of 12 ± 3 weeks. The reduction of systolic blood pressure (SBP) and diastolic BP (DBP) in patients treated with spironolactone was greater than placebo (weighted mean differences (WMD) for SBP − 16.67 mm Hg (95% confidence interval (CI), − 27.54, − 5.80), p < 0.01; WMD for DBP − 6.11 mm Hg (95% CI, − 9.34, − 2.88), p < 0.001), respectively. The rates of serious adverse effects or patient withdrawals from the trials tended to be higher in patients treated with spironolactone than placebo (WMD for odds ratio 2.11 (95% CI, 0.98, 4.53), p = 0.05). Conclusions This meta-analysis provides the evidence that add-on use of spironolactone in patients with resistant hypertension is effective in lowering SBP and DBP, suggesting an add-on use of spironolactone as fourth line therapy in patients with resistant hypertension. [ABSTRACT FROM AUTHOR]

Introduction Increased central sympathetic activity has a central role in the pathophysiology of cardiac arrhythmias. Despite the recently published negative results regarding the impact of renal sympathetic denervation (RDN) on resistant hypertension treatment, the beneficial effects of this intervention on cardiac arrhythmias seems to be promising. The aim of this systematic review is to analyze the existing data regarding the impact of RDN on atrial and ventricular arrhythmias. Methods We systematically searched MEDLINE/PubMed database until January 2016 by using the algorithm “renal denervation AND (arrhythmias OR atrial OR ventricular)” without limitations. Additionally, the reference lists of the included studies and the relevant review studies were also manually searched. Results Of the 467 studies yielded from the initial search, 34 were finally included in the systematic review (15 human studies, 18 animal studies and 1 study with both experimental and clinical data). The critical analysis of data from both human and animal studies indicates that RDN can modulate atrial and ventricular electrophysiological properties and exerts favorable effects in the development and recurrence of atrial and ventricular arrhythmias. Conclusion In this systematic review we showed that RDN reduces the burden of atrial and ventricular arrhythmias in various experimental and clinical settings. Appropriately designed randomized sham controlled trials are needed in order to elucidate the exact impact of RDN on arrhythmia management. [ABSTRACT FROM AUTHOR]

Background Defining an adequate endpoint for renal denervation trials represents a major challenge. A high inter-individual and intra-individual variability of blood pressure levels as well as a partial or total non-adherence on antihypertensive drugs hamper treatment evaluations after renal denervation. Blood pressure measurements at a single point in time as used as primary endpoint in most clinical trials on renal denervation, might not be sufficient to discriminate between patients who do or do not respond to renal denervation. Methods We compared the traditional responder classification (defined as systolic 24-hour blood pressure reduction of − 5 mm Hg six months after renal denervation) with a novel definition of an ideal respondership (based on a 24 h blood pressure reduction at no point in time, one, or all follow-up timepoints). Results We were able to re-classify almost a quarter of patients. Blood pressure variability was substantial in patients traditionally defined as responders. On the other hand, our novel classification of an ideal respondership seems to be clinically superior in discriminating sustained from pseudo-response to renal denervation. Conclusion Based on our observations, we recommend that the traditional response classification should be reconsidered and possibly strengthened by using a composite endpoint of 24 h-BP reductions at different follow-up-visits. [ABSTRACT FROM AUTHOR]

Background Renal denervation (RDN) has been shown to reduce blood pressure (BP), muscle sympathetic nerve activity (MSNA) and target organ damage in patients with resistant hypertension (RH) and bilateral single renal arteries. The safety and efficacy of RDN in patients with multiple renal arteries remains unclear. Methods We measured office and 24-hour BP at baseline, 3 and 6 months following RDN in 91 patients with RH, including 65 patients with single renal arteries bilaterally (group 1), 16 patients with dual renal arteries on either one or both sides (group 2) and 10 patients with other anatomical constellations or structural abnormalities (group 3). Thirty nine out of 91 patients completed MSNA at baseline and follow-up. Results RDN significantly reduced office and daytime SBP in group 1 at both 3 and 6 months follow-up (P < 0.001) but not in groups 2 and 3. Similarly, a significant reduction in resting baseline MSNA was only observed in group 1 (P < 0.05). There was no deterioration in kidney function in any group. Conclusion While RDN can be performed safely irrespective of the underlying renal anatomy, the presence of single renal arteries with or without structural abnormalities is associated with a more pronounced BP and MSNA lowering effect than the presence of dual renal arteries in patients with RH. However, when patients with dual renal arteries received renal nerve ablation in all arteries there was trend towards a greater BP reduction. Insufficient renal sympathetic nerve ablation may account for these differences. [ABSTRACT FROM AUTHOR]

Background Renal denervation (RDN) is a promising treatment option in addition to medical antihypertensive treatment in patients suffering from resistant hypertension. Despite the growing interest in RDN, only few long-term results are published so far. Methods We systematically investigated the effects of RDN on ABPM in a consecutive series of patients with resistant hypertension out to 24 months. Office BP measurements and ABPM assessment were offered at 3, 6, 12 and 24 months. The patients with an average systolic BP reduction of more than 10 mm Hg in office BP 6 months after RDN were classified as responders. Additional to this classical responder concept, we categorized response to RDN by an individual-patient visit-by-visit evaluation of office BP and 24-hour-BP, separately. Results We included 32 patients. In 21 patients (65.6%) we found a mean systolic BP reduction > 10 mm Hg in office BP six months after RDN. These patients were classified as responders. In responders, mean office BP dropped from 175.3 ± 15.9/96 ± 14.2 mm Hg to 164.8 ± 24.4/93.2 ± 10.4 mm Hg (p = 0.040/p = 0.323) and mean 24-h BP in ABPM decreased from 146.8 ± 17.0/89.1 ± 11 mm Hg to 136.8 ± 15.0/83.2 ± 10.7 mm Hg after 24 months (p = 0.034/p = 0.014). Additionally, we performed a visit-by-visit evaluation of all patients and results were divided in larger-than-median and smaller-than-median response. By this evaluation, we found a high variation of office BP reductions and the 24-hour BP results demonstrated a significant BP reduction in patients with larger-than-median response, which sustained over the 24 months of follow-up. Conclusions In contrast to the observed variation of office BP measurements, ABPM demonstrated a reproducible and sustained significant BP reduction in patients with larger-than-median response to RDN. [ABSTRACT FROM AUTHOR]

Background Transluminal renal sympathetic denervation (RDN) has been shown to reduce blood pressure (BP) in patients with treatment-resistant hypertension. Methods We assessed the effect of multi-electrode RDN on short-term BP variability indexes in resistant hypertensives. Thirty-one patients with drug-resistant uncontrolled hypertension, participants in the EnligHTN I study, underwent ambulatory BP measurements at baseline and 6 months after RDN using the EnligHTN ablation catheter (St. Jude Medical). Twelve resistant hypertensives matched for office BP served as control group. Results At 6 months post-RDN, office BP and 24-hour BP were reduced by 25.6/10.3 mm Hg and by 10.2/6 mm Hg (p < 0.001 for all cases), respectively. No significant changes were observed 6 months post-RDN in standard short-term BP variability indexes including 24-hour systolic and diastolic average real variability. The rates of systolic and diastolic 24-hour BP variation were decreased 6 months after RDN, (from 0.40/0.30 to 0.34/0.24, p = 0.030/0.006, respectively), especially in the responders group (n = 23, 74.2%). No significant differences in BP and BP variability parameters in the control group were detected. ROC analysis revealed an area under the curve for prediction of response to RDN by systolic time rate of 66.8% (95% CI: 46.7% to 87%; p = 0.16) and by diastolic time rate of 76.1% (95% CI: 58.2% to 93.9%; p = 0.030). Conclusions Although standard BP variability indexes remained unchanged, the rate of systolic and diastolic BP variation was significantly decreased 6 months after RDN in patients with drug-resistant hypertension. These novel indexes might also be useful as predictors of response. [ABSTRACT FROM AUTHOR]

Background: An increase in sympathetic drive to the heart and the peripheral circulation characterizes mild and severe essential hypertension. However, it remains unsettled whether sympathetic cardiovascular influences are potentiated in true resistant hypertension (RHT). Methods: In 32 RHT patients treated with 4.6 ± 0.3 drugs (mean ± SEM) and aged 58.6 ± 2.1 years, 35 non-resistant treated hypertensives (HT) and 19 normotensive controls (NT), all age-matched with RHT, we measured clinic, 24-hour ambulatory and beat-to-beat blood pressures (BP), heart rate (HR, EKG), muscle sympathetic nerve traffic (MSNA, microneurography) and spontaneous baroreflex MSNA-sensitivity. Results: BP values were markedly greater in RHT patients than in NT and HT (172.2 ± 1.7/100.7 ± 1.2 vs 132.1 ± 1.3/82.1 ± 0.9 and 135.5 ± 1.2/83.6 ± 0.9 mm Hg, P < 0.01). This was paralleled by a significant and marked increase in MSNA (87.8 ± 2.0 vs 46.8 ± 2.6 and 59.3 ± 1.7 and bursts/100 heartbeats, P < 0.01). In multiple regression analysis the MSNA increase observed in RHT was significantly related to hemodynamic, hormonal and metabolic variables. It was also significantly related to plasma aldosterone values as well as spontaneous baroreflex MSNA-sensitivity, which were the variables that at the multivariate analysis were more closely related to the adrenergic activation of RHT after adjustment for confounders, including antihypertensive treatment (r²partial = 0.04405 and r²partial = 0.00878, P < 0.05 for both). Conclusions: These data represent the first evidence that RHT is a state of marked adrenergic overdrive, greater for magnitude than that detectable in HT. They also suggest that impaired baroreflex mechanisms, along with hemodynamic and neurohumoral factors, may be responsible for the phenomenon. [ABSTRACT FROM AUTHOR]

Objective The rationale of percutaneous renal denervation (RDN) is based on extensive studies suggesting that renal nerves contribute to hypertension and that they comprise a sensible treatment target. Muscle sympathetic nerve activity (MSNA) is considered to be one of the few reliable methods to quantify central sympathetic activity. The aim of this current study is to determine the effect of RDN on MSNA in a standardized fashion. Methods MSNA was determined in 13 patients before and 6 months after RDN. Anti-hypertensive medication was stopped before MSNA. If cessation of medication was considered unsafe, a patient was instructed to use the exact same medication on both occasions. Results Ten sets of MSNA recordings were of good quality for analysis. Mean age was 57 ± 3 years and mean eGFR was 85 ± 18 mL/min/1.73 m². MSNA was determined twice during a medication free interval in 5 patients; 1 patient used the exact same medication twice, and 4 patients used different drugs. Mean BP changed from 206 ± 7 over 116 ± 4 mm Hg, to 186 ± 6 over 106 ± 3 mm Hg, 6 months after RDN (p = 0.06 for systolic BP, p = 0.04 for diastolic BP). Mean resting heart rate did not change (p = 0.44). MSNA did not change after RDN: 37 ± 4 bursts/min and 43 ± 4 bursts/min (p = 0.11) at baseline and after RDN, respectively. In the 6 patients with standardized medication use during the MSNA sessions, results were comparable. Conclusions Treatment with RDN did not result in a change in MSNA. Changes in BP did not correlate with changes in MSNA. [ABSTRACT FROM AUTHOR]

Background: Renal sympathetic denervation (RDN) reduces sympathetic activity and blood pressure (BP) in patients with resistant hypertension. The present study aimed to investigate the effects of RDN on HR and other electrocardiographic parameters. Methods: 136 patients aged 62.2±0.8years (58% male, BP 177±2/93±1mmHg) with resistant hypertension underwent RDN. BP and a 12-lead electrocardiogram (ECG) were recorded before, 3months (n=127), and 6months (n=88) after RDN. Results: After 3months (3M) and 6months (6M), systolic BP was reduced by 25.5±2.4mmHg (p<0.0001) and 28.1±3mmHg (p<0.0001). HR at baseline was 66.1±1beats per minute (bpm) and was reduced by 2.6±0.8bpm after 3months (p=0.001) and 2.1±1.1bpm after 6months (p=0.046). Patients with HR at baseline between 60–71bpm and ≥71bpm had a reduction of 2.9±7.6bpm (p=0.008) and 9.0±8.6bpm (p<0.0001), respectively, whereas in patients with baseline HR<60bpm HR slightly increased after 3months (2.7±8.4bpm; p=0.035). Neither baseline HR nor change of HR correlated with the reduction of systolic BP. The PR interval was prolonged by 11.3±2.5ms (p<0.0001) and 10.3±2.5ms (p<0.0001) at 3 and 6months after RDN, respectively. Conclusions: Renal sympathetic denervation reduced heart rate and the PR interval as indicators of cardiac autonomic activity. [ABSTRACT FROM AUTHOR]

Abstract: Resistant hypertension, defined as the failure to achieve target blood pressure despite concurrent use of 3 antihypertensive agents of different classes, is estimated to affect 20–30% of hypertensive patients. These patients are vulnerable to cardiovascular, cerebrovascular and renal complications. There is ample evidence that sympathetic nervous system hyperactivity contributes to the initiation, maintenance and progression of hypertension. The renal sympathetic nervous system, in particular, has been identified as a major culprit for the development and progression of hypertension, heart failure and chronic kidney disease in both preclinical and human studies. Traditional surgical sympathectomy proposed in 1940s was halted due to unacceptable operative risk and the emergence of anti-hypertensive medications. Recently, catheter-based renal sympathetic denervation by radiofrequency ablation has shown encouraging intermediate-term results with minimal complications in patients with resistant hypertension. This review summarizes the patho-physiological role of the renal sympathetic nervous system and the potential application of renal denervation therapy for the treatment of resistant hypertension. [Copyright &y& Elsevier]

Abstract: Renal denervation is increasingly being adopted as a treatment option in patients with resistant hypertension. The long-term safety of this procedure is unknown. Though the procedure interrupts the sympathetic nerves at the renal level, it also has effects on other organ beds, notably the heart and vasculature. These effects have been purported to be clinically beneficial and thus formed a rationale for examining the role of renal denervation in other conditions, including heart failure, arrhythmia, obstructive sleep apnoea and the metabolic syndrome. There is a theoretical concern that attenuating the renal sympathetic nerves might cause orthostatic hypotension or syncope. From the limited data available from hypertension trials, the procedure has not been associated with excessive episodes of syncope and this is supported by mechanistic tilt table data in asymptomatic patients. Ultimately, the safety of this technique will only be established once we have larger phase III/IV studies. [Copyright &y& Elsevier]

Abstract: Microalbuminuria is a well-known marker for cardiovascular and renal complications. The purpose of our study was to identify factors associated with microalbuminuria in individuals with resistant hypertension. Urine albumin excretion (UAE) was evaluated in 187 patients with resistant hypertension. The association between UAE and clinical, laboratory, and 24-h ABPM variables was investigated through comparison of means, correlation analysis, and logistic regression. A high prevalence of microalbuminuria was found (29.4%–95% CI: 22.9–36.5). In logistic regression, 24-h, HDL-cholesterol, serum creatinine, and diabetes mellitus were independently associated with UAE. Blood pressure control appears to be fundamental for reducing microalbuminuria. Moreover, early identification of individuals with microalbuminuria is of the utmost importance due to its association with cardiovascular and renal damage. [Copyright &y& Elsevier]