Apixaban for Stroke Prevention in Subclinical Atrial Fibrillation.

BACKGROUND: Subclinical atrial fibrillation is short-lasting and asymptomatic and can usually be detected only by long-term continuous monitoring with pacemakers or defibrillators. Subclinical atrial fibrillation is associated with an increased risk of stroke by a factor of 2.5; however, treatment with oral anticoagulation is of uncertain benefit. METHODS: We conducted a trial involving patients with subclinical atrial fibrillation lasting 6 minutes to 24 hours. Patients were randomly assigned in a double-blind, double-dummy design to receive apixaban at a dose of 5 mg twice daily (2.5 mg twice daily when indicated) or aspirin at a dose of 81 mg daily. The trial medication was discontinued and anticoagulation started if subclinical atrial fibrillation lasting more than 24 hours or clinical atrial fibrillation developed. The primary efficacy outcome, stroke or systemic embolism, was assessed in the intention-to-treat population (all the patients who had undergone randomization); the primary safety outcome, major bleeding, was assessed in the on-treatment population (all the patients who had undergone randomization and received at least one dose of the assigned trial drug, with follow-up censored 5 days after permanent discontinuation of trial medication for any reason). RESULTS: We included 4012 patients with a mean (±SD) age of 76.8±7.6 years and a mean CHA2DS2-VASc score of 3.9±1.1 (scores range from 0 to 9, with higher scores indicating a higher risk of stroke); 36.1% of the patients were women. After a mean follow-up of 3.5±1.8 years, stroke or systemic embolism occurred in 55 patients in the apixaban group (0.78% per patient-year) and in 86 patients in the aspirin group (1.24% per patient-year) (hazard ratio, 0.63; 95% confidence interval [CI], 0.45 to 0.88; P = 0.007). In the on-treatment population, the rate of major bleeding was 1.71% per patient-year in the apixaban group and 0.94% per patient-year in the aspirin group (hazard ratio, 1.80; 95% CI, 1.26 to 2.57; P = 0.001). Fatal bleeding occurred in 5 patients in the apixaban group and 8 patients in the aspirin group. CONCLUSIONS: Among patients with subclinical atrial fibrillation, apixaban resulted in a lower risk of stroke or systemic embolism than aspirin but a higher risk of major bleeding. (Funded by the Canadian Institutes of Health Research and others; ARTESIA ClinicalTrials.gov number, NCT01938248.).

An Unexpected Pacemaker Response to Catheter Ablation: Failure of Pacing Pulse Delivery During Asynchronous Pacing Mode.

Radiofrequency (RF) ablation can be a source of electromagnetic interference (EMI) for cardiovascular implantable electronic devices (CIEDs). The response of CIEDs to this type of EMI can be variable and unpredictable. We report a case with an uncommon response where there was a failure to deliver pacing pulses to both atrial and ventricular pacing leads during RF ablation close to the atrial lead even when the pacemaker was set to pace asynchronously. We also explain the mechanism behind this unusual pacemaker response.

Junctional AV ablation in patients with atrial fibrillation undergoing cardiac resynchronization therapy (JAVA-CRT): results of a multicenter randomized clinical trial pilot program.

INTRODUCTION: Cardiac resynchronization therapy (CRT) improves outcomes in sinus rhythm, but the data in atrial fibrillation (AF) is limited. Atrio-ventricular junctional ablation (AVJA) has been proposed as a remedy. The objective was to test if AVJA results in LV end-systolic volume (ESV) reduction ≥ 15% from baseline to 6 months. METHODS: The trial was a prospective multicenter randomized trial in 26 patients with permanent AF who were randomized 1:1 to CRT-D with or without AVJA. RESULTS: LVESV improved similarly by at least 15% in 5/10 (50%) in the CRT-D-only arm and in 6/12 (50%) in the AVJA + CRT-D arm (OR = 1.00 [0.14, 7.21], p = 1.00). In the CRT-D-only arm, the median 6-month improvement in LVEF was 9.2%, not different from the AVJA + CRT-D arm, 8.2%. When both groups were combined, a significant increase in LVEF was observed (25.4% at baseline vs 36.2% at 6 months, p = 0.002). NYHA class from baseline to 6 months for all patients combined improved 1 class in 15 of 24 (62.5%), whereas 9 remained in the same class and 0 degraded to a worse class. CONCLUSION: In patients with permanent AF, reduced LVEF, and broad QRS who were eligible for CRT, there was insufficient evidence that AVJA improved echocardiographic or clinical outcomes; the results should be interpreted in light of a smaller than planned sample size. CRT, however, seemed to be effective in the combined study cohort overall, suggesting that CRT can be reasonably deployed in patients with AF. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02946853.

Health-Related Quality of Life in the Spironolactone to Reduce ICD Therapy (SPIRIT) Trial.

To describe health related quality of life (HRQOL) and symptoms in the SPIRIT trial and determine effects of implantable cardioverter defibrillator (ICD) shocks on HRQOL over 24 months. Ninety participants aged 66 ± 10 years, 96% men, 75% with NYHA class II, with an ICD were randomized to spironolactone 25 mg (N = 44) or placebo (N = 46). HRQOL was measured every 6 months for 24 months using: Patient Concerns Assessment (PCA), Short Form Health Survey-Veterans Version (SF-36V), and Kansas City Cardiomyopathy Questionnaire (KCCQ). Linear mixed modeling compared changes in HRQOL over-time and ANCOVA compared HRQOL between those getting an ICD shock or not. Over 24-months, there were no differences in HRQOL between the spironolactone versus placebo groups. Those with at least one ICD shock reported significantly lower HRQOL and more symptoms at 6- and 24-months. Patients receiving one or more ICD shocks reported significant reductions in HRQOL and higher symptoms.

Adaptive Cardiac Resynchronization Therapy Effect on Electrical Dyssynchrony (aCRT-ELSYNC): A randomized controlled trial.

BACKGROUND: Adaptive cardiac resynchronization therapy (aCRT) is known to have clinical benefits over conventional CRT, but the mechanisms are unclear. OBJECTIVE: Compare effects of aCRT and conventional CRT on electrical dyssynchrony. METHODS: A prospective, double-blind, 1:1 parallel-group assignment randomized controlled trial in patients receiving CRT for routine clinical indications. Participants underwent cardiac computed tomography and 128-electrode body surface mapping. The primary outcome was change in electrical dyssynchrony measured on the epicardial surface using noninvasive electrocardiographic imaging before and 6 months post-CRT. Ventricular electrical uncoupling (VEU) was calculated as the difference between the mean left ventricular (LV) and right ventricular (RV) activation times. An electrical dyssynchrony index (EDI) was computed as the standard deviation of local epicardial activation times. RESULTS: We randomized 27 participants (aged 64 ± 12 years; 34% female; 53% ischemic cardiomyopathy; LV ejection fraction 28% ± 8%; QRS duration 155 ± 21 ms; typical left bundle branch block [LBBB] in 13%) to conventional CRT (n = 15) vs aCRT (n = 12). In atypical LBBB (n = 11; 41%) with S waves in V5-V6, conduction block occurred in the anterior RV, as opposed to the interventricular groove in strict LBBB. As compared to baseline, VEU reduced post-CRT in the aCRT (median reduction 18.9 [interquartile range 4.3-29.2 ms; P = .034]), but not in the conventional CRT (21.4 [-30.0 to 49.9 ms; P = .525]) group. There were no differences in the degree of change in VEU and EDI indices between treatment groups. CONCLUSION: The effect of aCRT and conventional CRT on electrical dyssynchrony is largely similar, but only aCRT harmoniously reduced interventricular dyssynchrony by reducing RV uncoupling.

Dexmedetomidine Sedation for Paroxysmal Supraventricular Tachycardia Ablation Is Not Associated With Alteration of Arrhythmia Inducibility.

BACKGROUND: Dexmedetomidine (Dex) is an attractive agent for procedural sedation due to its unique pharmacodynamic profile, specifically affording predictable sedation without concurrent respiratory depression. However, Dex has previously been reported to prevent or terminate arrhythmias. The purpose of this study was to investigate paroxysmal supraventricular tachycardia (PSVT) inducibility and homeostatic stability during electrophysiology studies (EPSs) and ablation when a standardized Dex protocol was used as the primary sedation agent. METHODS: We performed a retrospective review of 163 consecutive procedures for PSVT ablation that received Dex as the primary sedative with adjunct fentanyl and midazolam boluses (DEX-FENT-MIDAZ). This cohort was compared to 163 consecutive control procedures wherein strictly fentanyl and midazolam were used for sedation. The primary outcome reviewed was PSVT inducibility assessed before ablation. Reviewed secondary outcomes included level of sedation and intraprocedure hemodynamics and oxygenation. RESULTS: The arrhythmia profiles of the DEX-FENT-MIDAZ and control cohorts were very similar. The overall incidence of a "negative" EPSs in which arrhythmia was not induced was 24% in the DEX-FENT-MIDAZ group and 26% in the control group (P = .7). Unintended deep sedation was significantly less with DEX-FENT-MIDAZ (4.3% vs 27%; P ≤ .0001). However, DEX-FENT-MIDAZ use was associated with a higher incidence of intraprocedure hypotension. CONCLUSIONS: Dex sedation during EPSs is not associated with a reduction in PSVT inducibility. The therapeutic utility of Dex during EPS arises from the predictable sedation Dex affords but is associated with an increased incidence of intraprocedure hypotension.

Effectiveness of dual external direct current cardioversion for initial cardioversion in atrial fibrillation.

INTRODUCTION: Dual external direct current cardioversion (dual-DCCV) is a rhythm control strategy for persistent atrial fibrillation (AF), involving simultaneous delivery of two shocks from two defibrillators. The long-term effectiveness of this approach has not been studied in the biphasic cardioversion era. METHODS: Seventy-seven consecutive patients at a single center were identified to receive dual-DCCV at the time of their initial cardioversion for AF, when maximum output standard external direct current cardioversion failed in two vectors. Logistic regression was used to analyze risk factors for dual-DCCV in a historical control group of 77 patients undergoing standard cardioversion and Cox proportional hazard models were used to compare time to AF recurrence. RESULTS: The dual-DCCV group had a significantly larger body mass index (BMI), but similar AF duration and left atrial size as controls. Multivariable logistic regression revealed that BMI and absence of prior paroxysmal AF were risk factors for dual-DCCV (P < 0.05). There was no difference observed between dual-DCCV and control groups (adjusted hazard ratio = 0.57; P = .12) after adjusting for number of shocks and age. Transient hypoxia was the only acute complication in either group (P > .999). CONCLUSION: Dual-DCCV appears to be a safe and effective cardioversion strategy for patients with AF. The need for dual-DCCV in the treatment of AF appears to be influenced more by body habitus than atrial substrate.

Outcomes of Telemedicine Video-Conferencing Clinic Versus In-Person Clinic Follow-Up for Implantable Cardioverter-Defibrillator Recipients.

BACKGROUND: Implantable cardioverter-defibrillator (ICD) recipients require close follow-up that can be difficult for patients who have to travel long distances for clinic follow-up. We aimed to compare clinical outcomes between ICD patients followed-up in a telemedicine video-conferencing clinic (TMVC) and a conventional in-person clinic (CIC). We hypothesized that outcomes of patients followed in the TMVC are noninferior to the CIC. METHODS AND RESULTS: This retrospective study compares time to first appropriate ICD therapy, time to first inappropriate ICD therapy, time to first shock, and overall survival in patients followed in TMVC compared with CIC between 2001 and 2016. Two hundred and eighty-seven patients were followed in the TMVC group and 236 patients in the CIC. The average age of the TMVC and CIC groups was 64.13±9.38 and 65.23±8.57 years, respectively (P=0.164). There was no difference in the modified Seattle heart failure model score between the 2 groups (-0.12±1.0 versus -0.21±0.99; P=0.287). The Charlson comorbidity index score was higher in the CIC group compared with the TMVC group (7.0 versus 6.0; P=0.01). Mean duration of follow-up was 4.8 years. Adjusted and unadjusted tests of noninferiority found TMVC was not inferior to in-person follow-up for the prespecified outcomes. CONCLUSIONS: Video-conferencing ICD follow-up for patients in areas where electrophysiology subspecialty care is not available leads to outcomes that are noninferior to CIC follow-up.

Successful Ablation of Epicardial Premature Ventricular Complexes Near the Great Cardiac Vein from the Left Ventricular Endocardium Despite Predictors of Failure.

Mapping and ablating premature ventricular complexes (PVCs) that originate near the great cardiac vein (GCV) and anterior interventricular vein (AIV) can pose several challenges related to the advancement and positioning of catheters within these veins, the delivery of effective lesions, and the risk of collateral injury to the left coronary arteries and left phrenic nerve. When ablation of these PVCs from inside the GCV/AIV is not possible, a systematic assessment of nearby vantage points, such as the left coronary cusp (LCC) and left ventricular (LV) endocardial breakout site, should be considered, in addition to the performance of a more invasive epicardial ablation procedure via a percutaneous pericardial puncture or thoracotomy. Several electrocardiographic, anatomic, and electrogram timing features have been shown to predict the likelihood of successful ablation from a non-epicardial site, such as the LCC or LV endocardium, but none of these spots is considered to be a perfect location. The case described here in this report is a demonstration of a safe and successful ablation of GCV PVCs from the LV endocardial breakout site using adequate power and lesion duration, even when the site was 17 mm away from the putative origin, and some previously described electrocardiographic and electrogram-based predictors of success suggested the outcome would not be positive.

Oral anticoagulation in elderly adults with atrial fibrillation: integrating new options with old concepts.

Atrial fibrillation (AF) is the most common sustained cardiac arrhythmia and the second most common cardiovascular condition in adults in the United States. It is prevalent in the elderly population and is an important risk factor for stroke. Oral anticoagulation offers significant protection against AF-related thromboembolic events, but several complex issues that contribute to its underuse in elderly adults surround it. To aid clinicians in their approach to these problems, a comprehensive PubMed-based search of the literature published in English from 1990 through July 2012 was conducted using the following terms or combination of terms: atrial fibrillation, elderly, antiplatelet, anticoagulation, stroke, bleeding, hemorrhage, and falls. Additional references were identified in a manual search of bibliographies in retrieved articles. The data were then synthesized to address the most relevant questions regarding anticoagulation in elderly adults, including fall risk, responsiveness to warfarin, physician perception of risks, and other barriers to the prescription of anticoagulants. Recently proposed risk-stratification schemes for stroke and hemorrhage that could refine the selection of antithrombotic therapy for AF are highlighted. Finally, available data on the use of antiplatelet therapy, warfarin, and new oral anticoagulants (direct thrombin inhibitor and factor Xa inhibitors) in AF are summarized.

The effect of spironolactone on ventricular tachyarrhythmias in patients with implantable cardioverter-defibrillators.

BACKGROUND: Previous studies have suggested that aldosterone blockade can reduce the incidence of ventricular tachycardia (VT) or ventricular fibrillation (VF) in patients with heart failure. The SPIronolactone to Reduce ICD Therapy (SPIRIT) trial was designed to test the hypothesis that spironolactone reduces the incidence of VT/VF in patients with implantable cardioverter-defibrillators (ICDs) who are at moderately high risk for recurrent VT/VF. METHODS AND RESULTS: Ninety patients who had ICDs who were at moderately high risk for recurrent VT/VF and who were not candidates for spironolactone by current heart failure guidelines were randomized to receive spironolactone 25 mg daily or placebo in a double-blind fashion. All patients had previously received ICD therapy (shock or antitachycardia pacing) for VT/VF within 2 years of randomization or an ICD for secondary prevention of VT/VF within 6 months of randomization. The primary end point was time to first recurrence of VT/VF requiring ICD therapy. After a median follow-up of 35 months, the Kaplan-Meier probability estimates for VT/VF requiring ICD therapy were 68.7% in the placebo group and 84.7% in the spironolactone group. Compared with placebo, spironolactone was associated with a similar risk of VT/VF (hazard ratio, 1.01; 95% CI, 0.64-1.83; P=0.71). There was no significant difference between the median times to first VT/VF recurrence requiring ICD therapy in the 2 groups. CONCLUSIONS: In patients with ICDs who were at moderately high risk for recurrent VT/VF on account of a recent VT/VF event that was either sustained or treated by the ICD and who were not candidates for spironolactone by current heart failure guidelines, spironolactone did not delay the first recurrence of VT/VF or reduce the risk of recurrent VT/VF.

Nonsense-mediated mRNA decay caused by a frameshift mutation in a large kindred of type 2 long QT syndrome.

BACKGROUND: Nonsense and frameshift mutations are common in congenital long QT syndrome type 2 (LQT2). We previously demonstrated that hERG nonsense mutations cause degradation of mutant mRNA by nonsense-mediated mRNA decay (NMD) and are associated with mild clinical phenotypes. The impact of NMD on the expression of hERG frameshift mutations and their phenotypic severity is not clear. OBJECTIVE: The purpose of this study was to examine the role of NMD in the pathogenesis of a hERG frameshift mutation, P926AfsX14, identified in a large LQT2 kindred and characterize genotype-phenotype correlations. METHODS: Genetic screening was performed among family members. Phenotyping was performed by assessment of ECGs and LQTS-related cardiac events. The functional effect of P926AfsX14 was studied using hERG cDNA and minigene constructs expressed in HEK293 cells. RESULTS: Significant cardiac events occurred in carriers of the P926AfsX14 mutation. When expressed from cDNA, the P926AfsX14 mutant channel was only mildly defective. However, when expressed from a minigene, the P926AfsX14 mutation caused a significant reduction in mutant mRNA, protein, and hERG current. Inhibition of NMD by RNA interference knockdown of up-frameshift protein 1 partially restored expression of mutant mRNA and protein and led to a significant increase in hERG current in the mutant cells. These results suggest that NMD is involved in the pathogenic mechanism of the P926AfsX14 mutation. CONCLUSION: Our findings suggest that the hERG frameshift mutation P926AfsX14 primarily results in degradation of mutant mRNA by the NMD pathway rather than production of truncated proteins. When combined with environmental triggers and genetic modifiers, LQT2 frameshift mutations associated with NMD can manifest with a severe clinical phenotype.

Simplified demonstration of cavotricuspid isthmus block after catheter ablation in patients after Mustard's operation.

BACKGROUND: The Mustard operation is a complex atrial rerouting performed in patients with transposition of the great arteries (TGA). Cavotricuspid isthmus (CTI)-dependent atrial flutter (AFL) is an important problem in these patients. While catheter ablation (CA) is successful, three-dimensional (3D) mapping is necessary to prove block at the CTI. 3D mapping, however, requires baffle puncture. We tested a simplified concept to prove isthmus block after CA for AFL in Mustard patients. METHODS: During electrophysiology study, catheters were placed in the high and low systemic venous atrium (HSVA and LSVA) and in the low pulmonary venous atrium (LPVA). LPVA and then LSVA were paced while recording in the HSVA and the alternate site. While pacing from one low site, the time taken to activate the other low site and the HSVA was compared before and after successful ablation. RESULTS: Three patients with Mustard operation and AFL underwent successful CA. Involvement of the CTI in AFL was proved by entrainment mapping. AFL was terminated during ablation and no longer inducible after ablation in all. LSVA pacing showed LPVA activation preceded HSVA activation preablation and activation pattern reversal after ablation. Likewise, LPVA pacing showed LSVA activation preceding HSVA preablation with reversal after ablation. CONCLUSION: This study provides a simple method to demonstrate bidirectional block at the CTI in patients with CTI-based AFL after Mustard operation for TGA.

Syncope, seizure, or both? An unusual case of complete heart block.

Syncope and epileptic seizures have common presenting features that make it difficult to determine if a patient's collapse is primarily cardiac or neurologic. The distinction is blurred further if epileptic neural activity provokes cardiac arrhythmias known to cause syncope. We present a case of convulsive movements, progressive atrioventricular block, and syncope in a patient known to have epilepsy. The history, serial electrocardiographic tracings, and other diagnostic tests strongly suggest the ictal bradycardia syndrome. The case illustrates interesting aspects of central autonomic function and the diagnostic and therapeutic dilemmas of evaluating and treating patients who present with this problem.

Coxibs and heart disease: what we have learned and what else we need to know.

Since their approval in 1998, the popularity of selective cyclooxygenase-2 (COX2) inhibitors has swung from a domination of drug sales to serious disputes about their cardiovascular safety. Despite the numerous studies on COX2 inhibitors that have emerged, drawing conclusions about their cardiovascular safety has been complicated by conflicting results, underpowered clinical trials, and the lack of a placebo group and use of post hoc analyses in many trials. Nonetheless, certain conclusions can be made with reasonable accuracy. This review addresses the controversy in 3 segments. It begins with a discussion of the several mechanisms proposed to explain how selective COX2 inhibition impacts the cardiovascular system. This is followed by a recount of the several clinical studies that delved into the cardiovascular outcomes associated with COX2 inhibitors. Finally, answers to key questions are provided to assist the clinician in devising a systematic approach to the risk-benefit analysis of COX2 inhibitors in actual practice.