Renal denervation for the treatment of ventricular arrhythmias: A systematic review and meta-analysis.

INTRODUCTION: Ventricular arrhythmias (VAs) are a major cause of morbidity and mortality in patients with heart disease. Recent studies evaluated the effect of renal denervation (RDN) on the occurrence of VAs. We conducted a systematic review and meta-analysis to determine the efficacy and safety of this procedure. METHODS AND RESULTS: A systematic search of the literature was performed to identify studies that evaluated the use of RDN for the management of VAs. Primary outcomes were reduction in the number of VAs and implantable cardioverter-defibrillator (ICD) therapies. Secondary outcomes were changes in blood pressure and renal function. Ten studies (152 patients) were included in the meta-analysis. RDN was associated with a reduction in the number of VAs, antitachycardia pacing, ICD shocks, and overall ICD therapies of 3.53 events/patient/month (95% confidence interval [CI] = -5.48 to -1.57), 2.86 events/patient/month (95% CI = -4.09 to -1.63), 2.04 events/patient/month (95% CI = -2.12 to -1.97), and 2.68 events/patient/month (95% CI = -3.58 to -1.78), respectively. Periprocedural adverse events occurred in 1.23% of patients and no significant changes were seen in blood pressure or renal function. CONCLUSIONS: In patients with refractory VAs, RDN was associated with a reduction in the number of VAs and ICD therapies, and was shown to be a safe procedure.

Effect of age on efficacy and safety of vorapaxar in patients with non-ST-segment elevation acute coronary syndrome: Insights from the Thrombin Receptor Antagonist for Clinical Event Reduction in Acute Coronary Syndrome (TRACER) trial.

BACKGROUND: Antithrombotic therapy plays an important role in the treatment of non-ST-segment elevation acute coronary syndromes (NSTE ACS) but is associated with bleeding risk. Advanced age may modify the relationship between efficacy and safety. METHODS: Efficacy and safety of vorapaxar (a protease-activated receptor 1 antagonist) was analyzed across ages as a continuous and a categorical variable in the 12,944 patients with NSTE ACS enrolled in the TRACER trial. To evaluate the effect of age, Cox regression models were developed to estimate hazard ratios (HRs) with the adjustment of other baseline characteristics and randomized treatment for the primary efficacy composite of cardiovascular death, myocardial infarction (MI), stroke, recurrent ischemia with rehospitalization, or urgent coronary revascularization, and the primary safety composite of moderate or severe Global Use of Strategies to Open Occluded Coronary Arteries (GUSTO) bleeding. RESULTS: The median age of the population was 64years (25th, 75th percentiles = 58, 71). Also, 1,791 patients (13.8%) were ≤54years of age, 4,968 (38.4%) were between 55 and 64 years, 3,979 (30.7%) were between 65 and 74 years, and 2,206 (17.1%) were 75years or older. Older patients had higher rates of hypertension, renal insufficiency, and previous stroke and worse Killip class. The oldest age group (≥75years) had substantially higher 2-year rates of the composite ischemic end point and moderate or severe GUSTO bleeding compared with the youngest age group (≤54years). The relationships between treatment assignment (vorapaxar vs placebo) and efficacy outcomes did not vary by age. For the primary efficacy end point, the HRs (95% CIs) comparing vorapaxar and placebo in the 4 age groups were as follows: 1.12 (0.88-1.43), 0.88 (0.76-1.02), 0.89 (0.76-1.04), and 0.88 (0.74-1.06), respectively (P value for interaction = .435). Similar to what was observed for efficacy outcomes, we did not observe any interaction between vorapaxar and age on bleeding outcomes. For the composite of moderate or severe bleeding according to the GUSTO classification, the HRs (95% CIs) comparing vorapaxar and placebo in the 4 age groups were 1.73 (0.89-3.34), 1.39 (1.04-1.86), 1.10 (0.85-1.42), and 1.73 (1.29-2.33), respectively (P value for interaction = .574). CONCLUSION: Older patients had a greater risk for ischemic and bleeding events; however, the efficacy and safety of vorapaxar in NSTE ACS were not significantly influenced by age.

Are elderly patients at increased risk of complications following pacemaker implantation? A meta-analysis of randomized trials.

BACKGROUND: Patients over the age of 75 represent more than half the recipients of permanent pacemakers. It is not known if they have a different risk of complications than younger patients. METHODS: Patient-level data were pooled from the CTOPP, UKPACE, and Danish pacing trials. These three randomized trials of pacing mode systematically captured early and late complications following pacemaker insertion. Early postimplant complications included lead dislodgement or loss of capture, cardiac perforation, pneumothorax, hematoma, infection, and death. Lead fracture was considered a late complication. RESULTS: A total of 4,814 patients were included in this analysis, with an average follow-up of 5.1 years. The average age was 76 years and 43% were female. Any early complication occurred in 5.1% of patients ≥75 years of age compared to 3.4% of patients aged <75 years (P = 0.006). This was driven by an increased risk of pneumothorax (1.6% vs 0.8%, P = 0.07) and both atrial and ventricular lead dislodgement/loss of capture (2.0% vs 1.1%, P = 0.07). Early complications were higher in patients receiving atrial-based pacemakers in both age groups (<75 years: 4.6% vs 2.4%; ≥75 years: 6.6% vs 3.7%); however, the relative risk was not influenced by age group. Older patients had a lower risk of lead fracture (3.6% vs 2.7%, P = 0.08). CONCLUSION: Elderly patients (≥75 years of age) are at increased risk of early postimplant complications but are at lower risk for lead fracture.

Renal denervation for the treatment of ventricular arrhythmias: A systematic review and meta-analysis

INTRODUCTION: Ventricular arrhythmias (VAs) are a major cause of morbidity and mortality in patients with heart disease. Recent studies evaluated the effect of renal denervation (RDN) on the occurrence of VAs. We conducted a systematic review and meta-analysis to determine the efficacy and safety of this procedure. METHODS AND RESULTS: A systematic search of the literature was performed to identify studies that evaluated the use of RDN for the management of VAs. Primary outcomes were reduction in the number of VAs and implantable cardioverter-defibrillator (ICD) therapies. Secondary outcomes were changes in blood pressure and renal function. Ten studies (152 patients) were included in the meta-analysis. RDN was associated with a reduction in the number of VAs, antitachycardia pacing, ICD shocks, and overall ICD therapies of 3.53 events/patient/month (95% confidence interval [CI] = -5.48 to -1.57), 2.86 events/patient/month (95% CI = -4.09 to -1.63), 2.04 events/patient/month (95% CI = -2.12 to -1.97), and 2.68 events/patient/month (95% CI = -3.58 to -1.78), respectively. Periprocedural adverse events occurred in 1.23% of patients and no significant changes were seen in blood pressure or renal function. CONCLUSIONS: In patients with refractory VAs, RDN was associated with a reduction in the number of VAs and ICD therapies, and was shown to be a safe procedure.

6-Month Outcomes in Patients With Implantable Cardioverter-Defibrillators Undergoing Renal Sympathetic Denervation for the Treatment of Refractory Ventricular Arrhythmias.

OBJECTIVES: This study aimed to assess 6-month outcomes in patients with implantable cardioverter-defibrillators (ICDs) undergoing renal sympathetic denervation (RSD) for refractory ventricular arrhythmias (VAs). BACKGROUND: ICDs are generally indicated for patients at high risk of malignant VAs. Sympathetic hyperactivity plays a critical role in the development, maintenance, and aggravation of VAs. METHODS: A total of 10 patients with refractory VA underwent RSD. Underlying conditions were Chagas disease (n = 6), nonischemic dilated cardiomyopathy (n = 2), and ischemic cardiomyopathy (n = 2). Information on the number of ventricular tachycardia (VT)/ventricular fibrillation (VF) episodes and device therapies (antitachycardia pacing/shocks) in the previous 6 months as well as 1 and 6 months post-treatment was obtained from ICD interrogation. RESULTS: The median number of VT/VF episodes/antitachycardia pacing/shocks 6 months before RSD was 28.5 (range 1 to 106)/20.5 (range 0 to 52)/8 (range 0 to 88), respectively, and was reduced to 1 (range 0 to 17)/0 (range 0 to 7)/0 (range 0 to 3) at 1 month and 0 (range 0 to 9)/0 (range 0 to 7)/0 (range 0 to 3) at 6 months afterward, respectively. There were no major procedure-related complications. Two patients experienced sustained VT within the first week; in both cases, no further episodes occurred during follow-up. Two patients were nonresponders: 1 with persistent idioventricular rhythm and 1 with multiple renal arteries and incomplete ablation. Three patients died during follow-up. None of the deaths was attributed to VA. CONCLUSIONS: In patients with ICDs and refractory VAs, RSD was associated with reduced arrhythmic burden with no procedure-related complications. Randomized controlled trials investigating RSD for treatment of refractory VAs in patients with increased sympathetic activity are needed.

Treatment of neurally mediated reflex syncope.

Neurally mediated reflex syncope, more commonly known as vasovagal syncope (VVS), remains the most common cause of transient loss of consciousness and syncope in all age groups. Most evidence assessing treatment of VVS derived from randomized clinical trials is limited. Multiple modalities of both nonpharmacologic and pharmacologic strategies have been tested, with conflicting results. The treatment of VVS has been directed toward interventions that interrupt the reflex response at different levels, hypothetically preventing the onset of syncope. This article reviews the available evidence of the different nonpharmacologic and pharmacologic therapies available for the treatment of recurrent VVS.

Very long-term follow-up of strut apposition and tissue coverage with Biolimus A9 stents analyzed by optical coherence tomography.

First generation drug-eluting stents (DES) are associated with reduced in-stent restenosis but significant increased risk of very late stent thrombosis (VLST). The absence of polymer in DES systems may reduce the occurrence of VLST. Optic coherence tomography (OCT) has been used for stent analysis as a surrogate safety endpoint. This study aimed to assess the long-term follow up of strut apposition and tissue coverage of BioMatrix DES by OCT. 20 patients undergoing BioMatrix DES (n = 15) or S-Stent BMS (n = 5) implantation were followed for at least 5 years and evaluated by quantitative coronary angiography, intravascular ultrasound, and OCT. The difference between the stent types was evaluated by nonparametric Mann-Whitney U test while categorical variables were evaluated by Fisher exact test. Rates of in-stent late loss were similar between groups [0.40 (0.21;0.77) vs. 0.68 (0.66; 0.82) mm, p = 0.205, for BioMatrix and S-Stent, respectively]. The vessel, stent and lumen volumes did not differ between groups. Patients treated with BioMatrix had significantly less stent obstruction [5.6 (4.4;9.7) vs. 28.6 (24.7;29.0) %, p = 0.001]. OCT analysis of 12 stents (Biomatrix = 9 and S-Stent = 3) demonstrated 126 (8.7 %) uncovered struts in the BioMatrix group compared to 23 (4.0 %) in the S-Stent group (p = 0.297), being the majority of them well apposed (117/126 and 21/23, respectively, p = 0.292). Only 9 (0.6 %) struts in the DES and 2 (0.4 %) struts in the BMS groups were simultaneously uncovered and malapposed (p = 0.924). BioMatrix DES was associated with lower rates of in-stent obstruction, and similar percentage of neointimal coverage on struts and of complete strut apposition.

Atrial fibrillation catheter ablation in females: same hardware, different findings.

Atrial fibrillation catheter ablation has gained a significant role in the management of the frequent arrhythmia and has been shown to be safe and effective. As with many other interventional therapies, gender bias is present and females are referred for catheter ablation less frequently than their male counterparts. Women referred for catheter ablation tend to be older, more symptomatic, have failed more antiarrhythmic agents and may have poorer procedure success and increased vascular complication rates. Efforts to close this referral gap are clearly needed and it is likely that early referral will reduce gender differences in atrial fibrillation catheter ablation success rates.

Experiência inicial com novo amplatzer TM cardiac plug para oclusão percutânea do apêndice atrial esquerdo / Initial experience with the new amplatzer TM cardiac plug for percutaneous closure of the left atrial appendage

Introdução: A formação de trombos no apêndice atrial esquerdo (AAE) constitui a principal causa de fenômenos tromboembólicos em pacientes com fibrilação atrial (FA). A anticoagulação oral é considerada terapia de primeira linha na prevenção de tromboembolismo associado à FA. Apesar de comprovada eficácia, a terapia com anticoagulantes orais está associada a inúmeras limitações. A oclusão percutânea do AAE surgiu como uma nova estratégia para prevenção de acidentes vasculares cerebrais em pacientes com FA considerados de alto risco e não candidatos a tratamento com anticoagulantes. Métodos: Relatamos a experiência inicial da oclusão percutânea do AAE utilizando o novo dispositivo AmplatzerTM Cardiac Plug (ACP – AGA Medical Corp., Golden Valley, Estados Unidos) em pacientes com FA e escore CHADS2 > 2, não elegíveis à terapêutica com anticoagulantes. Os procedimentos foram realizados sob anestesia geral e monitoração por ecocardiografia transesofágica tridimensional em tempo real. Resultados: Três pacientes do sexo masculino, com média de idade de 79 anos e escores CHADS2 2, 3 e 5, foram submetidos a implante do dispositivo por via transeptal sem complicações, resultando em oclusão imediata do AAE e alta hospitalar após dois dias. No seguimento de 50 dias, todos os pacientes se apresentavam bem clinicamente e a ecocardiografia transtorácica confirmou oclusão total do AAE e ausência de complicações. Conclusões: A oclusão percutânea do AAE com ACP parece ser uma alternativa terapêutica atrativa na prevenção de eventos tromboembólicos em pacientes com FA e contraindicações ou limitações para anticoagulação oral.

Background: Thrombus formation in the left atrial appendage (LAA) is the main cause of thromboembolic events in patients with non-valvular atrial fibrillation (AF). Oral anticoagulantsare considered first-line therapy for stroke prevention in AF patients. Despite its proven efficacy, long-term oral anticoagulation is associated to innumerous limitations. PercutaneousLAA closure has emerged as a new strategy for stroke prevention in high risk AF patients who are not candidatesfor long term oral anticoagulation therapy. Methods: We report the initial experience with percutaneous occlusionof the LAA using the new AmplatzerTM Cardiac Plug (ACP – AGA Medical Corp., Golden Valley, USA) in patients withAF and CHADS2 score > 2 who were not eligible for anticoagulation therapy. Procedures were carried out undergeneral anesthesia and 3D transesophageal echocardiographymonitoring in real time. Results: Three male patients, mean age of 79 years and CHADS2 2, 3 and 5 scores had thedevice successfully implanted using a transeptal approach with no complications, resulting in immediate LAA occlusion and hospital discharge two days later. At the 50-day followup,all patients were clinically well with complete LAA occlusion and no complications at transthoracic echocardiography. Conclusions: Percutaneous LAA occlusion with thenew ACP seems to be an attractive alternative to prevent thromboembolic events in patients with AF and contraindications or limitations for anticoagulation therapy.

Effect of age on efficacy and safety of vorapaxar in patients with non–ST-segment elevation acute coronary syndrome: Insights from the Thrombin Receptor Antagonist for Clinical Event Reduction in Acute Coronary Syndrome (TRACER) trial

Methods: Efficacy and safety of vorapaxar (a protease-activated receptor 1 antagonist) was analyzed across ages as a continuous and a categorical variable in the 12,944 patients with NSTE ACS enrolled in the TRACER trial. To evaluate the effect of age, Cox regression models were developed to estimate hazard ratios (HRs) with the adjustment of other baseline characteristics and randomized treatment for the primary efficacy composite of cardiovascular death, myocardial infarction (MI), stroke, recurrent ischemia with rehospitalization, or urgent coronary revascularization, and the primary safety composite of moderate or severe Global Use of Strategies to Open Occluded Coronary Arteries (GUSTO) bleeding. ResultsThe median age of the population was 64 years (25th, 75th percentiles = 58, 71). Also, 1,791 patients (13.8%) were ≤54 years of age, 4,968 (38.4%) were between 55 and 64 years, 3,979 (30.7%) were between 65 and 74 years, and 2,206 (17.1%) were 75 years or older. Older patients had higher rates of hypertension, renal insufficiency, and previous stroke and worse Killip class. The oldest age group (≥75 years) had substantially higher 2-year rates of the composite ischemic end point and moderate or severe GUSTO bleeding compared with the youngest age group (≤54 years). The relationships between treatment assignment (vorapaxar vs placebo) and efficacy outcomes did not vary by age. For the primary efficacy end point, the HRs (95% CIs) comparing vorapaxar and placebo in the 4 age groups were as follows: 1.12 (0.88-1.43), 0.88 (0.76-1.02), 0.89 (0.76-1.04), and 0.88 (0.74-1.06), respectively (P value for interaction = .435)...

6 Month Outcomes in Patients WithImplantable Cardioverter-DefibrillatorsUndergoing Renal SympatheticDenervation for the Treatment ofRefractory Ventricular Arrhythmias

This study aimed to assess 6-month outcomes in patients with implantable cardioverter-defibrillators(ICDs) undergoing renal sympathetic denervation (RSD) for refractory ventricular arrhythmias (VAs).BACKGROUND ICDs are generally indicated for patients at high risk of malignant VAs. Sympathetic hyperactivityplays a critical role in the development, maintenance, and aggravation of VAs.METHODS A total of 10 patients with refractory VA underwent RSD. Underlying conditions were Chagas disease (n » 6),nonischemic dilated cardiomyopathy (n » 2), and ischemic cardiomyopathy (n » 2). Information on the number ofventricular tachycardia (VT)/ventricular fibrillation (VF) episodes and device therapies (antitachycardia pacing/shocks) inthe previous 6 months as well as 1 and 6 months post-treatment was obtained from ICD interrogation.RESULTS The median number of VT/VF episodes/antitachycardia pacing/shocks 6 months before RSD was 28.5 (range1 to 106)/20.5 (range 0 to 52)/8 (range 0 to 88), respectively, and was reduced to 1 (range 0 to 17)/0 (range 0 to 7)/0 (range 0 to 3) at 1 month and 0 (range 0 to 9)/0 (range 0 to 7)/0 (range 0 to 3) at 6 months afterward, respectively.There were no major procedure-related complications. Two patients experienced sustained VT within the first week; inboth cases, no further episodes occurred during follow-up. Two patients were nonresponders: 1 with persistent idioventricularrhythm and 1 with multiple renal arteries and incomplete ablation. Three patients died during follow-up. Noneof the deaths was attributed to VA.CONCLUSIONS In patients with ICDs and refractory VAs, RSD was associated with reduced arrhythmic burden withno procedure-related complications. Randomized controlled trials investigating RSD for treatment of refractory VAs inpatients with increased sympathetic activity are needed.

Very long-term follow-up of strut apposition and tissue coverage with Biolimus A9 stents analyzed by optical coherence tomography

associated with reduced in-stent restenosis but significant

increased risk of very late stent thrombosis (VLST).

The absence of polymer in DES systems may reduce the

occurrence of VLST. Optic coherence tomography (OCT)

has been used for stent analysis as a surrogate safety

endpoint. This study aimed to assess the long-term follow

up of strut apposition and tissue coverage of BioMatrixTM

DES by OCT. 20 patients undergoing BioMatrixTM DES

(n = 15) or S-StentTM BMS (n = 5) implantation were

followed for at least 5 years and evaluated by quantitative

coronary angiography, intravascular ultrasound, and OCT.

The difference between the stent types was evaluated by

variables were evaluated by Fisher exact test. Rates of

BioMatrixTM and S-StentTM, respectively]. The vessel,

stent and lumen volumes did not differ between groups.

Patients treated with BioMatrixTM had significantly less

p = 0.001]. OCT analysis of 12 stents (BiomatrixTM = 9

struts in the BioMatrixTM group compared to 23 (4.0 %)

in the S-StentTM group (p = 0.297), being the majority of

them well apposed (117/126 and 21/23, respectively,

p = 0.292). Only 9 (0.6 %) struts in the DES and 2 (0.4 %)

struts in the BMS groups were simultaneously uncovered

associated with lower rates of in-stent obstruction, and

similar percentage of neointimal coverage on struts and of