Competing risks of monomorphic vs. non-monomorphic ventricular arrhythmias in primary prevention implantable cardioverter-defibrillator recipients: Global Electrical Heterogeneity and Clinical Outcomes (GEHCO) study.

AIMS: Ablation of monomorphic ventricular tachycardia (MMVT) has been shown to reduce shock frequency and improve survival. We aimed to compare cause-specific risk factors for MMVT and polymorphic ventricular tachycardia (PVT)/ventricular fibrillation (VF) and to develop predictive models. METHODS AND RESULTS: The multicentre retrospective cohort study included 2668 patients (age 63.1 ± 13.0 years; 23% female; 78% white; 43% non-ischaemic cardiomyopathy; left ventricular ejection fraction 28.2 ± 11.1%). Cox models were adjusted for demographic characteristics, heart failure severity and treatment, device programming, and electrocardiogram metrics. Global electrical heterogeneity was measured by spatial QRS-T angle (QRSTa), spatial ventricular gradient elevation (SVGel), azimuth, magnitude (SVGmag), and sum absolute QRST integral (SAIQRST). We compared the out-of-sample performance of the lasso and elastic net for Cox proportional hazards and the Fine-Gray competing risk model. During a median follow-up of 4 years, 359 patients experienced their first sustained MMVT with appropriate implantable cardioverter-defibrillator (ICD) therapy, and 129 patients had their first PVT/VF with appropriate ICD shock. The risk of MMVT was associated with wider QRSTa [hazard ratio (HR) 1.16; 95% confidence interval (CI) 1.01-1.34], larger SVGel (HR 1.17; 95% CI 1.05-1.30), and smaller SVGmag (HR 0.74; 95% CI 0.63-0.86) and SAIQRST (HR 0.84; 95% CI 0.71-0.99). The best-performing 3-year competing risk Fine-Gray model for MMVT [time-dependent area under the receiver operating characteristic curve (ROC(t)AUC) 0.728; 95% CI 0.668-0.788] identified high-risk (> 50%) patients with 75% sensitivity and 65% specificity, and PVT/VF prediction model had ROC(t)AUC 0.915 (95% CI 0.868-0.962), both satisfactory calibration. CONCLUSION: We developed and validated models to predict the competing risks of MMVT or PVT/VF that could inform procedural planning and future randomized controlled trials of prophylactic ventricular tachycardia ablation. CLINICAL TRIAL REGISTRATION: URL:www.clinicaltrials.gov Unique identifier:NCT03210883.

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.

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.

Imaging-guided cardiac resynchronization therapy: A meta-analysis of randomized controlled trials.

BACKGROUND: Among patients with heart failure and left ventricular (LV) dysfunction despite guideline directed medical therapy, cardiac resynchronization (CRT) is an effective technology to reverse LV remodeling. Given that a large portion of patients are non-responders, alternatives to traditional LV-lead placement have been explored. A promising alternative is image targeted placement of an LV-lead to latest mechanically activated segment without scar. METHODS: Electronic database search for randomized controlled trials (RCTs) that evaluated the imaging-guided LV-lead placement on clinical, echocardiographic, and functional outcomes. The primary outcome was a composite of mortality and heart failure hospitalization. The secondary outcomes included CRT responders, New York Heart Association (NYHA), 6-minute walk test, Minnesota Living with Heart Failure Questionnaire (MLHFQ), and ejection fraction (EF) changes. RESULTS: Analysis included 4 RCTs of 691 patients with an average follow-up of 2 years (age 69.5 ± 10.3 years, 76% males, 54% ischemic cardiomyopathy, 81% with NYHA classes III/IV, and EF of 24.4% ± 8). The most common site for LV-lead paced segment was the anterolateral segment (45%) and at mid-LV (49%). Compared with the control, imaging-guided LV-lead placement was associated with a significant reduction of the primary outcome (hazard ratio [HR] = 0.60; 95% CI = 0.40-0.88; p = .01), higher CRT responders (odd ratio [OR] = 2.10; p < .01), more NYHA improvements by ≥1 (OR = 1.89; p = .01), increased 6MWT (mean difference [MD] = 25.78 feet; p < .01), and lower MLHFQ (MD = -4.04; p = .04), without significant differences in the LVEF (p = .08). CONCLUSIONS: In patients undergoing CRT, imaging-guided LV-lead placement was associated with improved clinical, echocardiographic, and functional status.

Competing risks in patients with primary prevention implantable cardioverter-defibrillators: Global Electrical Heterogeneity and Clinical Outcomes study.

BACKGROUND: Global electrical heterogeneity (GEH) is associated with sudden cardiac death in the general population. Its utility in patients with systolic heart failure who are candidates for primary prevention (PP) implantable cardioverter-defibrillators (ICDs) is unclear. OBJECTIVE: The purpose of this study was to investigate whether GEH is associated with sustained ventricular tachycardia/ventricular fibrillation leading to appropriate ICD therapies in patients with heart failure and PP ICDs. METHODS: We conducted a multicenter retrospective cohort study. GEH was measured by spatial ventricular gradient (SVG) direction (azimuth and elevation) and magnitude, QRS-T angle, and sum absolute QRST integral on preimplant 12-lead electrocardiograms. Survival analysis using cause-specific hazard functions compared the strength of associations with 2 competing outcomes: sustained ventricular tachycardia/ventricular fibrillation leading to appropriate ICD therapies and all-cause death without appropriate ICD therapies. RESULTS: We analyzed 2668 patients (mean age 63 ± 12 years; 624 (23%) female; 78% white; 43% nonischemic cardiomyopathy; left ventricular ejection fraction 28% ± 11% from 6 academic medical centers). After adjustment for demographic, clinical, device, and traditional electrocardiographic characteristics, SVG elevation (hazard ratio [HR] per 1SD 1.14; 95% confidence interval [CI] 1.04-1.25; P = .004), SVG azimuth (HR per 1SD 1.12; 95% CI 1.01-1.24; P = .039), SVG magnitude (HR per 1SD 0.75; 95% CI 0.66-0.85; P < .0001), and QRS-T angle (HR per 1SD 1.21; 95% CI 1.08-1.36; P = .001) were associated with appropriate ICD therapies. Sum absolute QRST integral had different associations in infarct-related cardiomyopathy (HR 1.29; 95% CI 1.04-1.60) and nonischemic cardiomyopathy (HR 0.78; 95% CI 0.62-0.96) (Pinteraction = .022). CONCLUSION: In patients with PP ICDs, GEH is independently associated with appropriate ICD therapies. The SVG vector points in distinctly different directions in patients with 2 competing outcomes.

Mechanisms of Arrhythmogenicity in Hypertrophic Cardiomyopathy: Insight From Non-invasive Electrocardiographic Imaging.

BACKGROUND: Mechanisms of arrhythmogenicity in hypertrophic cardiomyopathy (HCM) are not well understood. OBJECTIVE: To characterize an electrophysiological substrate of HCM in comparison to ischemic cardiomyopathy (ICM), or healthy individuals. METHODS: We conducted a prospective case-control study. The study enrolled HCM patients at high risk for ventricular tachyarrhythmia (VT) [n = 10; age 61 ± 9 years; left ventricular ejection fraction (LVEF) 60 ± 9%], and three comparison groups: healthy individuals (n = 10; age 28 ± 6 years; LVEF > 70%), ICM patients with LV hypertrophy (LVH) and known VT (n = 10; age 64 ± 9 years; LVEF 31 ± 15%), and ICM patients with LVH and no known VT (n = 10; age 70 ± 7 years; LVEF 46 ± 16%). All participants underwent 12-lead ECG, cardiac CT or MRI, and 128-electrode body surface mapping (BioSemi ActiveTwo, Netherlands). Non-invasive voltage and activation maps were reconstructed using the open-source SCIRun (University of Utah) inverse problem-solving environment. RESULTS: In the epicardial basal anterior segment, HCM patients had the greatest ventricular activation dispersion [16.4 ± 5.5 vs. 13.1 ± 2.7 (ICM with VT) vs. 13.8 ± 4.3 (ICM no VT) vs. 8.1 ± 2.4 ms (Healthy); P = 0.0007], the largest unipolar voltage [1094 ± 211 vs. 934 ± 189 (ICM with VT) vs. 898 ± 358 (ICM no VT) vs. 842 ± 90 µV (Healthy); P = 0.023], and the greatest voltage dispersion [median (interquartile range) 215 (161-281) vs. 189 (143-208) (ICM with VT) vs. 158 (109-236) (ICM no VT) vs. 110 (106-168) µV (Healthy); P = 0.041]. Differences were also observed in other endo-and epicardial basal and apical segments. CONCLUSION: HCM is characterized by a greater activation dispersion in basal segments, a larger voltage, and a larger voltage dispersion through LV. CLINICAL TRIAL REGISTRATION: www.clinicaltrials.gov Unique identifier: NCT02806479.

Meta-Analysis of Secondary Prevention of Cryptogenic Stroke.

BACKGROUND: Cryptogenic stroke and embolic stroke of undetermined source (ESUS) are a frequently encountered categories of ischemic stroke with an uncertain cause. METHODS: We analyzed all randomized clinical trials (RCTs) that evaluated antithrombotic therapy and patent foramen ovale (PFO) closure in cryptogenic stroke and/or ESUS. We calculated aggregate hazard ratios (HRs) using direct and network meta-analysis. The primary outcome was recurrent ischemic stroke. RESULTS: Ten RCTs with a total of 16,876 patients, randomizing 32,143 patient-years of follow-up (mean age 61.2 ±â€¯13.5 with 39.2% female) were identified. Anticoagulation therapy was associated with significantly reduced recurrent ischemic stroke compared with antiplatelet therapy (HR = 0.66; [95% confidence interval (CI) = 0.47-0.94]). Meta-regression analysis showed significantly reduced recurrent stroke with longer duration of therapy, and significantly increased events with advanced age. Significant interactions were observed based on the presence of PFO, stroke type, and anticoagulant used. There were no significant differences with regard to the composite ischemic outcome, transient ischemic attack, any death, major bleeding, or intracranial bleeding. In the network meta-analysis, compared to antiplatelet therapy, warfarin (HR = 0.31; [95% credible interval (CrI) = 0.12-0.68]) and PFO closure (HR = 0.14; 95% CrI = 0.05-0.31]) were associated with significantly reduced recurrent ischemic stroke. In rank order, PFO closure was associated with the best outcome, followed by warfarin. CONCLUSIONS: Among patients with cryptogenic stroke, anticoagulation therapy, as compared with antiplatelet therapy is associated with lower rate of recurrent stroke. The small sample size and high heterogeneity with regards to bleeding outcomes require further large trials. In patients with PFO, closure and warfarin are associated with the lowest rates of recurrent stroke.

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.

VV' Alternans Triplets on Near-Field ICD Intracardiac Electrogram is Associated with Mortality.

BACKGROUND: In heart failure patients with implantable cardioverter defibrillator (ICD) the risk of death from causes other than tachyarrhythmia is substantial. Benefit from ICD is determined by two competing risks: appropriate ICD shock or nonarrhythmic death. The goal of the study was to test predictors of competing outcomes. METHODS: Patients with structural heart disease (N = 234, mean age 58.5 ± 15.1; 71% men, 80% whites, 61% ischemic cardiomyopathy) and primary (75%) or secondary prevention ICD underwent a 5-minute baseline near-field electrogram (NF EGM) recording. VV' alternans triplets were quantified as a percentage of three sinus VV' cycles sequences of "short-long-short" or "long-short-long" order. Appropriate ICD shock for fast ventricular tachycardia (FVT, cycle length ≤240 ms)/ventricular fibrillation (VF) and composite nonarrhythmic death (pump failure death or heart transplant) served as competing outcomes. RESULTS: Over a median follow-up of 2.4 years, 26 patients (4.6% per person-year of follow-up) developed FVT/VF with ICD shock, and 35 (6.3% per person-year of follow-up) had nonarrhythmic death. In competing risk analysis, after adjustment for demographics, left ventricular ejection fraction, New York Heart Association class, cardiomyopathy type, use of class I antiarrhythmics, and diabetes, increased percentage of VV' alternans triplets (>69%) was associated with nonarrhythmic death (subhazard ratio [SHR] 2.09; 95% confidence interval [CI] 1.03-4.23; P = 0.041), rather than with FVT/VF (SHR 1.05; 95% CI 0.45-2.46; P = 0.901). Risk of nonarrhythmic death was especially high in diabetics with VV' alternans triplets in the highest quartile (SHR 3.46; 95% CI 1.41-8.50; P = 0.007). CONCLUSION: In ICD patients with structural heart disease sinus VV' alternans triplets on NF EGM is independently associated with nonarrhythmic death, rather than with FVT/VF.