Changes in Plasma Renin Activity After Renal Artery Sympathetic Denervation

BackgroundThe renin-angiotensin-aldosterone system plays a key role in blood pressure (BP) regulation and is the target of several antihypertensive medications. Renal denervation (RDN) is thought to interrupt the sympathetic-mediated neurohormonal pathway as part of its mechanism of action to reduce BP.ObjectivesThe purpose of this study was to evaluate plasma renin activity (PRA) and aldosterone before and after RDN and to assess whether these baseline neuroendocrine markers predict response to RDN.MethodsAnalyses were conducted in patients with confirmed absence of antihypertensive medication. Aldosterone and PRA levels were compared at baseline and 3 months post-procedure for RDN and sham control groups. Patients in the SPYRAL HTN-OFF MED Pivotal trial were separated into 2 groups, those with baseline PRA ≥0.65 ng/ml/h (n = 110) versus <0.65 ng/ml/h (n = 116). Follow-up treatment differences between RDN and sham control groups were adjusted for baseline values using multivariable linear regression models.ResultsBaseline PRA was similar between RDN and control groups (1.0 ± 1.1 ng/ml/h vs. 1.1 ± 1.1 ng/ml/h; p = 0.37). Change in PRA at 3 months from baseline was significantly greater for RDN compared with control subjects (?0.2 ± 1.0 ng/ml/h; p = 0.019 vs. 0.1 ± 0.9 ng/ml/h; p = 0.14), p = 0.001 for RDN versus control subjects, and similar differences were seen for aldosterone: RDN compared with control subjects (?1.2 ± 6.4 ng/dl; p = 0.04 vs. 0.4 ± 5.4 ng/dl; p = 0.40), p = 0.011. Treatment differences at 3 months in 24-h and office systolic blood pressure (SBP) for RDN versus control patients were significantly greater for patients with baseline PRA ≥0.65 ng/ml/h versus <0.65 ng/ml/h, despite similar baseline BP. Differences in office SBP changes according to baseline PRA were also observed earlier at 2 weeks post-RDN.ConclusionsPlasma renin activity and aldosterone levels for RDN patients were significantly reduced at 3 months when compared with baseline as well as when compared with sham control. Higher baseline PRA levels were associated with a significantly greater reduction in office and 24-h SBP. (SPYRAL PIVOTAL - SPYRAL HTN-OFF MED Study; NCT02439749)     

12-Month Results From the Unblinded Phase of the RADIANCE-HTN SOLO Trial of Ultrasound Renal Denervation

ObjectivesThis study reports the 12-month results of the RADIANCE-HTN (A Study of the ReCor Medical Paradise System in Clinical Hypertension) SOLO trial following unblinding of patients at 6 months.BackgroundThe blood pressure (BP)–lowering efficacy and safety of endovascular ultrasound renal denervation (RDN) in the absence (2 months) and presence (6 months) of antihypertensive medications were previously reported.MethodsPatients with daytime ambulatory BP ≥135/85 mm Hg after 4 weeks off medication were randomized to RDN (n = 74) or sham (n = 72) and maintained off medication for 2 months. A standardized medication escalation protocol was instituted between 2 and 5 months (blinded phase). Between 6 and 12 months (unblinded phase), patients received antihypertensive medications at physicians’ discretion. Outcomes at 12 months included medication burden, change in daytime ambulatory systolic BP (dASBP) and office or home systolic BP (SBP), visit-to-visit variability in SBP, and safety.ResultsSixty-five of 74 RDN patients and 67 of 72 sham patients had 12-month dASBP measurements. The proportion of patients on ≥2 medications (27.7% vs. 44.8%; p = 0.041), the number of medications (1.0 vs. 1.4; p = 0.015), and defined daily dose (1.4 vs. 2.2; p = 0.007) were less with RDN versus sham. The decrease in dASBP from baseline in the RDN group (−16.5 ± 12.9 mm Hg) remained stable at 12 months. The RDN versus sham adjusted difference at 12 months was −2.3 mm Hg (95% confidence interval [CI]: −5.9 to 1.3 mm Hg; p = 0.201) for dASBP, −6.3 mm Hg (95% CI: −11.1 to −1.5 mm Hg; p = 0.010) for office SBP, and −3.4 mm Hg (95% CI: −6.9 to 0.1 mm Hg; p = 0.062) for home SBP. Visit-to-visit variability in SBP was smaller in the RDN group. No renal artery injury was detected on computed tomographic or magnetic resonance angiography.ConclusionsDespite unblinding, the BP-lowering effect of RDN was maintained at 12 months with fewer prescribed medications compared with sham.     

The REDUCE HTN: REINFORCE: Randomized,Sham-Controlled Trial of Bipolar Radiofrequency Renal Denervation for the Treatment of Hypertension

ObjectivesThe aim of this study was to investigate bipolar radiofrequency renal denervation in patients with hypertension not receiving medications at baseline.BackgroundA blood pressure–reducing effect of renal denervation has been difficult to isolate in clinical investigations.MethodsREDUCE HTN: REINFORCE (Renal Denervation Using the Vessix Renal Denervation System for the Treatment of Hypertension) was a randomized, sham-controlled multicenter trial. Patients with office systolic blood pressure (SBP) of 150 to 180 mm Hg and average 24-h ambulatory SBP of 135 to 170 mm Hg after medication washout underwent bipolar radiofrequency renal denervation or a sham procedure. The planned outcome was 8-week change in 24-h ambulatory SBP. Enrollment was terminated for apparent futility before a sufficient sample for powered efficacy comparisons was enrolled. Safety assessments included all-cause death, renal failure, severe hypotension or syncope, hypertensive crisis, and renal artery stenosis.ResultsBaseline 24-h blood pressure was 148.3 ± 10.9/85.7 ± 9.1 mm Hg for the denervation group (n = 34, mean age 58.5 ± 10.1 years, 47% women) and 149.1 ± 7.2/86.4 ± 9.8 mm Hg for the control group (n = 17, mean age 58.2 ± 9.8 years, 24% women). At 8 weeks, mean 24-h SBP reductions for the renal denervation and control groups were −5.3 mm Hg (95% confidence interval [CI]: −8.8 to −1.8 mm Hg) and −8.5 mm Hg (95% CI: −13.3 to −3.8 mm Hg), respectively (difference 3.3 mm Hg; 95% CI: −2.8 to 9.3 mm Hg; p = 0.30). Antihypertensive medications could then be added. By 6 months, decreases in SBP were greater for the denervation group, yielding between-group differences of −7.2 mm Hg (95% CI: −15.2 to 0.8 mm Hg; p = 0.08), −9.7 mm Hg (95% CI: −17.7 to −1.7 mm Hg; p = 0.02), and −11.4 mm Hg (95% CI: −19.2 to −3.7 mm Hg; p < 0.01) for 24-h, daytime ambulatory, and office measurements, respectively. Through 12 months, 1 patient (renal denervation group) had a hypertensive urgency requiring immediate management, and 1 experienced progression of renal artery stenosis.ConclusionsFuture studies of radiofrequency renal denervation must anticipate delayed treatment effects. (Renal Denervation Using the Vessix Renal Denervation System for the Treatment of Hypertension [REDUCE HTN: REINFORCE]; NCT02392351)     

Renal Denervation in High-Risk Patients With Hypertension

BackgroundRenal denervation (RDN) is under investigation for treatment of uncontrolled hypertension and might represent an attractive treatment for patients with high cardiovascular (CV) risk. It is important to determine whether baseline CV risk affects the efficacy of RDN.ObjectivesThe purpose of this study was to assess blood pressure (BP) reduction and event rates after RDN in patients with various comorbidities, testing the hypothesis that RDN is effective and durable in these high-risk populations.MethodsBP reduction and adverse events over 3 years were evaluated for several high-risk subgroups in the GSR (Global proSpective registrY for syMPathetic renaL denervatIon in seleCted IndicatIons Through 3 Years Registry), an international registry of RDN in patients with uncontrolled hypertension (n = 2,652). Comparisons were made for patients age ≥65 years versus age <65 years, with versus without isolated systolic hypertension, with versus without atrial fibrillation, and with versus without diabetes mellitus. Baseline cardiovascular risk was estimated using the American Heart Association (AHA)/American College of Cardiology (ACC) atherosclerosis cardiovascular disease (ASCVD) risk score.ResultsReduction in 24-h systolic BP at 3 years was −8.9 ± 20.1 mm Hg for the overall cohort, and for high-risk subgroups, BP reduction was −10.4 ± 21.0 mm Hg for resistant hypertension, −8.7 ± 17.4 mm Hg in patients age ≥65 years, −10.2 ± 17.9 mm Hg in patients with diabetes, −8.6 ± 18.7 mm Hg in isolated systolic hypertension, −10.1 ± 20.3 mm Hg in chronic kidney disease, and −10.0 ± 19.1 mm Hg in atrial fibrillation (p < 0.0001 compared with baseline for all). BP reduction in patients with measurements at 6, 12, 24, and 36 months showed similar reductions in office and 24-h BP for patients with varying baseline ASCVD risk scores, which was sustained to 3 years. Adverse event rates at 3 years were higher for patients with higher baseline CV risk.ConclusionsBP reduction after RDN was similar for patients with varying high-risk comorbidities and across the range of ASCVD risk scores. The impact of baseline risk on clinical event reduction by RDN-induced BP changes could be evaluated in further studies. (Global proSpective registrY for syMPathetic renaL denervatIon in seleCted IndicatIons Through 3 Years Registry; NCT01534299)     

Renal Denervation for Hypertension: A Systematic Review and Meta-Analysis of Randomized, Blinded,Placebo-Controlled Trials

ObjectivesThe authors performed an updated meta-analysis of randomized placebo-controlled trials of renal denervation and specifically compared the effect of renal denervation in patients taking medications and in those not taking medications.BackgroundRenal denervation has now undergone several blinded placebo-controlled trials, covering the spectrum from patients with drug-resistant hypertension to those not yet taking antihypertensive medications.MethodsAll blinded placebo-controlled randomized trials of catheter-based renal sympathetic denervation for hypertension were systematically identified, and a random-effects meta-analysis was performed. The primary efficacy outcome was the change in ambulatory systolic blood pressure beyond the effect of the placebo procedure. Analysis was stratified by whether there was background antihypertensive medication use.ResultsThere were 7 eligible trials, totaling 1,368 patients. Denervation significantly reduced ambulatory systolic (mean difference −3.61 mm Hg; 95% CI: −4.89 to –2.33 mm Hg; P < 0.0001), ambulatory diastolic (−1.85 mm Hg; 95% CI: −2.78 to −0.92 mm Hg; P < 0.0001), office systolic (−5.86 mm Hg; 95% CI: −7.77 to −3.94 mm Hg; P < 0.0001), and office diastolic (−3.63 mm Hg; 95% CI: −4.77 to −2.50; P < 0.0001) blood pressure. There was no evidence that the use of concomitant antihypertensive medication had a significant impact on the effect of denervation on any of these endpoints (P_interaction = NS for each comparison).ConclusionsThe randomized placebo-controlled trials show consistently that renal denervation provides significant reduction in ambulatory and office blood pressure. Although the magnitude of benefit, about 4/2 mm Hg, is modest, it is similar between patients on background antihypertensive medications and those who are not. Denervation could therefore be a useful strategy at various points for patients who are not willing to add antihypertensive agents. Whether the effect changes with time is currently unknown.     

Combined Minimally Invasive Surgical and Percutaneous Catheter Ablation of Atrial Fibrillation: JACC Review Topic of the Week

Hybrid ablation is a novel therapy in the invasive management of patients with atrial fibrillation (AF) which combines minimally invasive surgical and percutaneous catheter-based techniques. The evidence is mainly based on observational studies from experienced centers, with success rates of approximately 70% and risks that are 2.0-fold to 3.6-fold higher than catheter-based ablation. Hybrid ablation is offered typically to patients with persistent or longstanding persistent AF which, by design, requires 2 procedures (epicardial surgical and endocardial catheter-based ablation). One randomized trial demonstrated that hybrid ablation was more effective than catheter-based ablation, but with higher complication rates. The incidence of the most serious complications has decreased in contemporary studies of hybrid ablation. At present, hybrid ablation should be performed by experienced centers on selected patients with persistent or longstanding persistent AF. Additional randomized trials are needed to define the risks, benefits, and cost effectiveness of hybrid ablation to identify its most appropriate application in clinical practice.     

Alcohol-Mediated Renal Denervation Using the Peregrine System Infusion Catheter for Treatment of Hypertension

ObjectivesThe aim of this multicenter, open-label trial was to evaluate the safety and efficacy of alcohol-mediated renal denervation using a novel catheter system (the Peregrine System Infusion Catheter) for the infusion of dehydrated alcohol as a neurolytic agent into the renal periarterial space.BackgroundThe number of hypertensive patients with uncontrolled blood pressure (BP) remains unacceptably high. The renal sympathetic nervous system has been identified as an attractive therapeutic target.MethodsForty-five patients with uncontrolled hypertension on ≥3 antihypertensive medications underwent bilateral renal denervation using the Peregrine Catheter with 0.6 ml alcohol infused per renal artery.ResultsAll patients were treated as intended. Mean 24-h ambulatory BP reduction at 6 months versus baseline was −11 mm Hg (95% confidence interval [CI]: −15 to −7 mm Hg) for systolic BP and −7 mm Hg (95% CI: −9 to −4 mm Hg) for diastolic BP (p < 0.001 for both). Office systolic BP was reduced by −18/−10 mm Hg (95% CI: −25 to −12/−13 to −6 mm Hg) at 6 months. Antihypertensive medications were reduced in 23% and increased in 5% of patients at 6 months. Adherence to the antihypertensive regimen remained stable over time. The primary safety endpoint, defined as the absence of periprocedural major vascular complications, major bleeding, acute kidney injury, or death within 1 month, was met in 96% of patients (95% CI: 85% to 99%). Two patients had major adverse events of periprocedural access-site pseudoaneurysms, with major bleeding in one. There were no deaths or instances of myocardial infarction, stroke, transient ischemic attack, or renal artery stenosis. Transient microleaks were noted in 42% and 49% of the left and right main renal arteries, respectively. There were 2 cases of minor vessel dissection that resolved without treatment.ConclusionsPrimary results from this trial suggest that alcohol-mediated renal denervation using the Peregrine Catheter safely reduces blood pressure and as such may represent a novel approach for the treatment of hypertension.     

Renal Denervation Update From the International Sympathetic Nervous System Summit: JACC State-of-the-Art Review

Three recent renal denervation studies in both drug-naïve and drug-treated hypertensive patients demonstrated a significant reduction of ambulatory blood pressure compared with respective sham control groups. Improved trial design, selection of relevant patient cohorts, and optimized interventional procedures have likely contributed to these positive findings. However, substantial variability in the blood pressure response to renal denervation can still be observed and remains a challenging and important problem. The International Sympathetic Nervous System Summit was convened to bring together experts in both experimental and clinical medicine to discuss the current evidence base, novel developments in our understanding of neural interplay, procedural aspects, monitoring of technical success, and others. Identification of relevant trends in the field and initiation of tailored and combined experimental and clinical research efforts will help to address remaining questions and provide much-needed evidence to guide clinical use of renal denervation for hypertension treatment and other potential indications.     

Treatment of Resistant Hypertension With Endovascular Baroreflex Amplification: 3-Year Results From the CALM-FIM Study

ObjectivesThe aim of this study was to evaluate the long-term (3-year) safety and effectiveness of endovascular baroreflex amplification (EVBA) from both the European and American CALM-FIM cohorts.BackgroundThe CALM-FIM study demonstrated that EVBA in patients with resistant hypertension significantly lowered blood pressure (BP) with an acceptable safety profile during 6-month follow-up.MethodsThe CALM-FIM studies were prospective, nonrandomized, first-in-human studies that enrolled patients with resistant hypertension (office systolic BP ≥160 mm Hg and mean 24-hour ambulatory BP ≥130/80 mm Hg despite a stable regimen of ≥3 antihypertensive medications, including a diuretic agent). The incidence of (serious) adverse events and changes in BP, heart rate, and prescribed antihypertensive medication up to 3 years after implantation were determined.ResultsThe Mobius device was implanted in 47 patients (30 in Europe, 17 in the United States; mean age 54 years, 23 women). Five serious adverse events (hypotension, n = 2; hypertension, n = 1; vascular access complications, n = 2) and 2 transient ischemic attacks occurred within 30 days postprocedure. Two strokes and 1 transient ischemic attack occurred more than 2 years postimplantation. Mean office BP at baseline was 181 ± 17/107 ± 16 mm Hg and decreased by 25/12 mm Hg (95% CI: 17-33/8-17 mm Hg) at 6 months and 30/12 mm Hg (95% CI: 21-38/8-17 mm Hg) at 3 years. Mean 24-hour ambulatory BP at baseline was 166 ± 16/98 ± 15 mm Hg and decreased by 20/11 mm Hg (95% CI: 14-25/8-15 mm Hg) at 6 months.ConclusionsEVBA with the MobiusHD was effective in reducing BP at 3-year follow-up and appears to have an acceptable safety profile in patients with uncomplicated implantation, although data from randomized sham-controlled trials are needed to further evaluate the risk-benefit profile. (Controlling and Lowering Blood Pressure With the MobiusHD? [CALM-FIM_EUR], NCT01911897; Controlling and Lowering Blood Pressure With the MobiusHD? [CALM-FIM_US], NCT01831895)     

Catheter-based renal denervation in Chinese patients with chronic kidney disease and uncontrolled hypertension

Sympathetic activation contributes to the progression of hypertension and chronic kidney disease (CKD). Ablation of renal sympathetic nerves lowers blood pressure (BP) and preserves renal function in patients with CKD and uncontrolled hypertension by reducing sympathetic nerve activity. But whether this approach is safe and effective in Chinese patients with CKD is unknown. We performed an observational study of eight patients with CKD stages from 1 to 5, office BP ≥150/90 mmHg, while on at least three antihypertensive drug classes including a diuretic, and diagnosis confirmed by 24 h ambulatory systolic BP measurement ≥135 mmHg. All patients underwent catheter-based renal denervation (RDN) using a newly designed RDN System (Golden Leaf Medtech, Shanghai, China). For up to 6 months after RDN, BP was monitored and renal function was assessed. Mean baseline office BP was 165.0 ± 13.9/97.8 ± 5.5 mmHg, despite treatment with three antihypertensive drugs. Six months after RDN, office BP was reduced by 22.1 ± 12.0 (P = .002)/11.0 ± 8.8 mmHg (P = .012) and average 24 h ambulatory BP by 18 ± 13.7 (P = .01)/9.3 ± 7.7 mmHg (P = .016). After RDN, heart rate and estimated glomerular filtration rate (GFR) had no significant change compared with before RDN. In Chinese patients with CKD, our observational pilot study found that treating hypertension with RDN lowers BP while not affecting renal function. Brief Abstract: We performed RDN in eight Chinese patients with hypertension and CKD. The results showed that RDN lowered blood pressure of these patients significantly and eGFR was stable. No obvious adverse event was observed.     

Pulmonary Artery Denervation for Pulmonary Arterial Hypertension: A Sham-Controlled Randomized PADN-CFDA Trial

BackgroundWorld Health Organization (WHO) group 1 pulmonary arterial hypertension (PAH) is a progressive, debilitating disease. Previous observational studies have demonstrated that pulmonary artery denervation (PADN) reduces pulmonary artery pressures in PAH. However, the safety and effectiveness of PADN have not been established in a randomized trial.ObjectivesThe aim of this study was to determine the treatment effects of PADN in patients with group 1 PAH.MethodsPatients with WHO group 1 PAH not taking PAH-specific drugs for at least 30 days were enrolled in a multicenter, sham-controlled, single-blind, randomized trial. Patients were assigned to receive PADN plus a phosphodiesterase-5 inhibitor or a sham procedure plus a phosphodiesterase-5 inhibitor. The primary endpoint was the between-group difference in the change in 6-minute walk distance from baseline to 6 months.ResultsAmong 128 randomized patients, those treated with PADN compared with sham had a greater improvement in 6-minute walk distance from baseline to 6 months (mean adjusted between-group difference 33.8 m; 95% CI: 16.7-50.9 m; P < 0.001). From baseline to 6 months, pulmonary vascular resistance was reduced by ?3.0 ± 0.3 WU after PADN and ?1.9 ± 0.3 WU after sham (adjusted difference ?1.4; 95% CI: ?2.6 to ?0.2). PADN also improved right ventricular function, reduced tricuspid regurgitation, and decreased N-terminal pro–brain natriuretic peptide. Clinical worsening was less (1.6% vs 13.8%; OR: 0.11; 95% CI: 0.01-0.87), and a satisfactory clinical response was greater (57.1% vs 32.3%; OR: 2.79; 95% CI: 1.37-5.82) with PADN treatment during 6-month follow-up.ConclusionsIn patients with WHO group 1 PAH, PADN improved exercise capacity, hemodynamic status, and clinical outcomes during 6-month follow-up. (Safety and Efficacy of Pulmonary Artery Denervation in Patients With Pulmonary Arterial Hypertension [PADN-CFDA]; NCT03282266)     

Resistant Hypertension and Renal Nerve Denervation

Patients with resistant hypertension are a subgroup of the hypertensive population that are at even greater risk of cardiovascular outcomes. Therapeutic options for these patients are limited to antihypertensive medications. However, renal denervation (RDN) is a novel nonpharmacologic intervention that involves a catheter-based ablation of the sympathetic nerves within the renal artery wall. The procedure initially showed promise with remarkable blood pressure reductions until the pivotal SYMPLICITY HTN-3 trial failed to demonstrate superiority of RDN over control. This trial was notable for a substantial placebo effect and an attenuated response to RDN. These findings, which contradicted those of prior studies, have raised numerous questions, including whether adequate RDN occurred in those patients. Further research is planned to resolve some of these questions and to clarify the role of RDN in treating patients with resistant hypertension.     

Chronobiology of Natriuretic Peptides and Blood Pressure in Lean and Obese Individuals

BackgroundDiurnal variation of natriuretic peptide (NP) levels and its relationship with 24-h blood pressure (BP) rhythm has not been established. Obese individuals have a relative NP deficiency and disturbed BP rhythmicity.ObjectivesThis clinical trial evaluated the diurnal rhythmicity of NPs (B-type natriuretic peptide [BNP], mid-regional pro-atrial natriuretic peptide [MR-proANP], N-terminal pro–B-type natriuretic peptide [NT-proBNP]) and the relationship of NP rhythm with 24-h BP rhythm in healthy lean and obese individuals.MethodsOn the background of a standardized diet, healthy, normotensive, lean (body mass index 18.5 to 25 kg/m²) and obese (body mass index 30 to 45 kg/m²) individuals, age 18 to 40 years, underwent 24-h inpatient protocol involving ambulatory BP monitoring starting 24 h prior to the visit, controlled light intensity, and repeated blood draws for assessment of analytes. Cosinor analysis of normalized NP levels (normalized to 24-h mean value) was conducted to assess the diurnal NP rhythm and its relationship with systolic BP.ResultsAmong 52 participants screened, 40 participants (18 lean, 22 obese; 50% women; 65% Black) completed the study. The median range spread (percentage difference between the minimum and maximum values) over 24 h for MR-proANP, BNP, and NT-proBNP levels was 72.0% (interquartile range [IQR]: 50.9% to 119.6%), 75.5% (IQR: 50.7% to 106.8%), and 135.0% (IQR: 66.3% to 270.4%), respectively. A cosine wave-shaped 24-h oscillation of normalized NP levels (BNP, MR-proANP, and NT-proBNP) was noted both in lean and obese individuals (p_rhythmicity <0.05 for all). A larger phase difference between MR-proANP BP rhythm (?4.9 h vs. ?0.7 h) and BNP BP rhythm (?3.3 h vs. ?0.9 h) was seen in obese compared with lean individuals.ConclusionsThis human physiological trial elucidates evidence of diurnal NP rhythmicity and the presence of an NP-BP rhythm axis. There exists a misalignment of the NP-BP diurnal rhythm in the obese, which may contribute to the disturbed diurnal BP pattern observed among obese individuals. (The Diurnal Rhythm in Natriuretic Peptide Levels; NCT03834168)     

Clinical significance of heart rate variability for the monitoring of cardiac autonomic neuropathy in end-stage renal disease patients

Background and aimsThe aim of this study is to determine whether the measurement of continuous heart rate variability (HRV) is useful in the evaluation of cardiac autonomic neuropathy (CAN) in end-stage renal disease (ESRD) patients.Methods and resultsThis cross-sectional study was performed at Seoul St. Mary's hospital between June 2017 and February 2018. Seventy-seven ESRD patients, and 29 healthy controls (HCs) were asked to wear a continuous ambulatory HRV monitor for 24 h. General cardiac function was evaluated using transthoracic echocardiogram (TTE), pulse wave velocity (PWV), coronary calcium scoring (CCS), and 24-h ambulatory blood pressure monitoring (ABPM). HRV parameters of ESRD patients and HCs, and the correlation of HRV parameters with cardiovascular screening methods were observed. All HRV parameters were significantly decreased in ESRD patients compared to HCs (P < 0.001). In the correlation analysis between TTE results and HRV parameters, 24-h standard deviation of all N–N intervals (24SDNN), 24-h standard deviation of sequential 5-min N–N interval means (24DANN) and Low Frequency Power/High Frequency Power (LF/HF) ratio showed negative correlations with E/e’, LAVI and TR velocity which are representative indices for the diastolic function of the heart (P < 0.05). HRV parameters showed negative correlations with baPWV, CCS, and 24-h ABPM results as well (P < 0.05). Hemoglobin and serum albumin showed positive correlations with HRV parameters, and glucose, BUN, creatinine, and iPTH levels showed negative correlations (P < 0.05).ConclusionContinuous HRV monitoring may be a useful tool for the evaluation of CAN in ESRD.     

Association between difference in blood pressure reduction and risk of cardiovascular events in a type 2 diabetes population: A meta-regression analysis

AimRecent US recommendations indicate a target blood pressure (BP) of 130/80 mmHg for patients with type 2 diabetes (T2D). Our aim was to characterize the association between risk of cardiovascular events and differences in BP decreases in randomized trials of a T2D population.MethodsA systematic search was made for randomized clinical trials assessing the effects of antihypertensive treatments in T2D patients on mortality, and fatal and non-fatal cardiovascular events, using a meta-regression technique to explore the influence of BP decreases on treatment effects.ResultsA total of 88,503 patients from 44 randomized trials were included. There was no significant association between BP decreases and risk of all-cause or cardiovascular mortality, cardiovascular events or myocardial infarction. However, stroke risk was influenced by BP decreases: compared with no reduction, a 10-mmHg reduction in systolic BP was associated with a relative odds ratio (OR) decrease of 33% (OR: 0.67, 95% CI: 0.54–0.82), and a 5-mmHg diastolic BP reduction was associated with a relative OR decrease of 38% (OR: 0.62, 95% CI: 0.50–0.76). Restricting the analysis to double-blind studies did not change the results for diastolic BP.ConclusionA reduction in BP lowers the risk of stroke, but does not appear to affect the risk of other cardiovascular events in a T2D population.     

Ultrathin Bioresorbable-Polymer Sirolimus-Eluting Stents Versus Thin Durable-Polymer Everolimus-Eluting Stents for Coronary Revascularization: 3-Year Outcomes From the Randomized BIOFLOW V Trial

ObjectivesThe aim of this study was to compare late-term clinical outcomes among patients treated with ultrathin-strut (60-μm) bioresorbable-polymer sirolimus-eluting stents (BP SES) and thin-strut (81μm) durable-polymer everolimus-eluting stents (DP EES).BackgroundEmerging evidence from comparative studies of drug-eluting stents demonstrates improved safety and efficacy with ultrathin-strut drug-eluting stents, but limited insight exists regarding late-term outcomes.MethodsBIOFLOW V (Biotronik Prospective Randomized Multicenter Study to Assess the Safety and Effectiveness of the Orsiro Sirolimus Eluting Coronary Stent System in the Treatment of Subjects With Up to Three De Novo or Restenotic Coronary Artery Lesions V) is an international randomized trial comparing coronary revascularization with BP SES and DP EES regarding the primary endpoint of 12-month target lesion failure. Analysis of pre-specified 3-year clinical outcomes was performed.ResultsAmong 1,334 patients randomized to treatment with BP SES (n = 884) or DP EES (n = 450), the 3-year rate of target lesion failure was 8.2% for BP SES and 13.6% for DP EES (p = 0.002), driven by differences in both target vessel myocardial infarction (MI) (5.0% vs. 9.2%; p = 0.003) and clinically driven target lesion revascularization (3.2% vs. 6.7%; p = 0.006). In landmark analysis, significant differences in target vessel MI and target lesion revascularization were observed favoring treatment with BP SES. Definite or probable late or very late stent thrombosis was significantly lower with BP SES (0.1% vs. 1.2%; p = 0.018). Cardiac death or MI rates were 7.7% and 11.7% (p = 0.017) for BP SES and DP EES, respectively.ConclusionsIn a large randomized trial, both target lesion failure and the outcomes of target vessel MI, clinically driven target lesion revascularization, and late or very late stent thrombosis at 3 years were significantly lower among patients treated with BP SES versus DP EES. The results endorse the continued superiority of ultrathin-strut BP SES compared with DP EES. (Safety and Effectiveness of the Orsiro Sirolimus Eluting Coronary Stent System in Subjects With Coronary Artery Lesions [BIOFLOW-V]; NCT02389946)     

Recurrence of Atrial Fibrillation After Catheter Ablation or Antiarrhythmic Drug Therapy in the CABANA Trial

BackgroundThe CABANA (Catheter Ablation Versus Antiarrhythmic Drug Therapy for Atrial Fibrillation) trial randomized 2,204 patients with atrial fibrillation (AF) to catheter ablation or drug therapy. Analysis by intention-to-treat showed a nonsignificant 14% relative reduction in the primary outcome of death, disabling stroke, serious bleeding, or cardiac arrest.ObjectivesThe purpose of this study was to assess recurrence of AF in the CABANA trial.MethodsThe authors prospectively studied CABANA patients using a proprietary electrocardiogram recording monitor for symptom-activated and 24-h AF auto detection. The AF recurrence endpoint was any post–90-day blanking atrial tachyarrhythmias lasting 30 s or longer. Biannual 96-h Holter monitoring was used to assess AF burden. Patients who used the CABANA monitors and provided 90-day post-blanking recordings qualified for this analysis (n = 1,240; 56% of CABANA population). Treatment comparisons were performed using a modified intention-to-treat approach.ResultsMedian age of the 1,240 patients was 68 years, 34.4% were women, and AF was paroxysmal in 43.0%. Over 60 months of follow-up, first recurrence of any symptomatic or asymptomatic AF (hazard ratio: 0.52; 95% confidence interval: 0.45 to 0.60; p < 0.001) or first symptomatic-only AF (hazard ratio: 0.49; 95% confidence interval: 0.39 to 0.61; p < 0.001) were both significantly reduced in the catheter ablation group. Baseline Holter AF burden in both treatment groups was 48%. At 12 months, AF burden in ablation patients averaged 6.3%, and in drug-therapy patients, 14.4%. AF burden was significantly less in catheter ablation compared with drug-therapy patients across the 5-year follow-up (p < 0.001). These findings were not sensitive to the baseline pattern of AF.ConclusionsCatheter ablation was effective in reducing recurrence of any AF by 48% and symptomatic AF by 51% compared with drug therapy over 5 years of follow-up. Furthermore, AF burden was also significantly reduced in catheter ablation patients, regardless of their baseline AF type. (Catheter Ablation vs Anti-arrhythmic Drug Therapy for Atrial Fibrillation Trial [CABANA]; NCT00911508)     

Sham-Controlled Randomized Trials of Catheter-Based Renal Denervation in Patients With Hypertension

Background

There are conflicting data regarding the relative effectiveness of renal sympathetic denervation (RSD) in patients with hypertension.

Magnetic Resonance Mapping of Catheter Ablation Lesions After Post-Infarction Ventricular Tachycardia Ablation

ObjectivesThis study sought to describe cardiac magnetic resonance (CMR) characteristics of ablation lesions within post-infarction scar.BackgroundChronic ablation lesions created during radiofrequency ablation of ventricular tachycardia (VT) in the setting of prior myocardial infarction have not been described in humans.MethodsSeventeen patients (15 men, ejection fraction 25 ± 8%, 66 ± 6 years of age) with CMR imaging prior to repeat ablation procedures for VT were studied. Electroanatomic maps from first-time procedures and subsequent CMR images were merged and retrospectively compared with electroanatomic maps from repeat procedures.ResultsThe delay between the index ablation procedure and the CMR study was 30 ± 29 months. Late gadolinium–enhanced CMR revealed a confluent nonenhancing subendocardial dark core within the infarct-related scar tissue in all patients. Intracardiac thrombi were ruled out by transthoracic and intracardiac echocardiography. These core lesions matched the distribution of prior ablation lesions, and corresponded to unexcitable areas at repeat procedures.ConclusionsAblation lesions can be detected by CMR after VT ablation in post-infarction patients and have a different appearance than scar tissue. These lesions can be observed many months after an initial ablation.     

The effect of renal denervation on resistant hypertension: Meta-analysis of randomized controlled clinical trials

Background: This meta-analysis was conducted to evaluate the efficiency of renal denervation (RDN) on resistant hypertension. Methods: PubMed, EMBASE, and the Cochrane Central database were searched for eligible randomized controlled clinical trials (RCTs). Changes from the baseline of the office blood pressure and the 24-h ambulatory blood pressure were extracted. Results: Nine RCTs were included. RDN reduced the mean systolic blood pressure (SBP) and diastolic blood pressure (DBP) by ?8.23 mm Hg (95%CI: ?16.86, 0.39) and ?3.77 mm Hg (95%CI: ?7.21, ?0.32), respectively, compared with the control. In the population with a baseline SBP more than 170 mm Hg, the RDN reduced SBP by ?17.77 mm Hg (95%CI: ?33.73, ?1.82) and DBP by ?7.51 mm Hg (95%CI: ?12.58, ?2.44). In the subgroup with no medication adjustment, the RDN reduced SBP by ?15.56 mm Hg (95%CI: ?26.33, ?4.80) and DBP by ?6.89 mm Hg (95%CI: ?9.99, ?3.79). The proportion of patients with SBP decrease of 10 mm Hg or more and the controlled office BP were not different between two groups. RDN reduced 24-h mean SBP and DBP by ?3.34 mm Hg (95%CI: ?5.30, ?1.38) and ?1.56 mm Hg (95%CI: ?2.71, ?0.41), respectively. The SBPs in the subgroups with higher baseline SBP and with no medication adjustment were significantly decreased after the HTN-3 was omitted. Conclusion: Radiofrequency RDN in a randomized manner did not have superiority compared with medical treatment at 6-month follow-up in general population. Current evidence provides insufficient evidence to support the use of such RDN strategy in the treatment of resistant hypertension. The result could not be used to extrapolate other strategies’ effect.