Machine Learned Cellular Phenotypes in Cardiomyopathy Predict Sudden Death.

RATIONALE: Susceptibility to VT/VF (ventricular tachycardia/fibrillation) is difficult to predict in patients with ischemic cardiomyopathy either by clinical tools or by attempting to translate cellular mechanisms to the bedside. OBJECTIVE: To develop computational phenotypes of patients with ischemic cardiomyopathy, by training then interpreting machine learning of ventricular monophasic action potentials (MAPs) to reveal phenotypes that predict long-term outcomes. METHODS AND RESULTS: We recorded 5706 ventricular MAPs in 42 patients with coronary artery disease and left ventricular ejection fraction ≤40% during steady-state pacing. Patients were randomly allocated to independent training and testing cohorts in a 70:30 ratio, repeated K=10-fold. Support vector machines and convolutional neural networks were trained to 2 end points: (1) sustained VT/VF or (2) mortality at 3 years. Support vector machines provided superior classification. For patient-level predictions, we computed personalized MAP scores as the proportion of MAP beats predicting each end point. Patient-level predictions in independent test cohorts yielded c-statistics of 0.90 for sustained VT/VF (95% CI, 0.76-1.00) and 0.91 for mortality (95% CI, 0.83-1.00) and were the most significant multivariate predictors. Interpreting trained support vector machine revealed MAP morphologies that, using in silico modeling, revealed higher L-type calcium current or sodium-calcium exchanger as predominant phenotypes for VT/VF. CONCLUSIONS: Machine learning of action potential recordings in patients revealed novel phenotypes for long-term outcomes in ischemic cardiomyopathy. Such computational phenotypes provide an approach which may reveal cellular mechanisms for clinical outcomes and could be applied to other conditions.

Duration of Inducible Ventricular Tachycardia Early After ST-Segment-Elevation Myocardial Infarction and Its Impact on Mortality and Ventricular Tachycardia Recurrence.

Background The clinical significance of the duration of inducible ventricular tachycardia (VT) at electrophysiology study (EPS) in patients soon after ST-segment-elevation myocardial infarction and its predictive utility for VT recurrence are not known. Methods and Results Consecutive ST-segment-elevation myocardial infarction patients with day 3 to 5 left ventricular ejection fraction ≤40% underwent EPS. A positive EPS was defined as sustained monomorphic VT with cycle length ≥200 ms. The induced VT was terminated by overdrive pacing or direct current shock at 30 s or earlier if hemodynamic decompensation occurred. Patients with inducible VT duration 2 to 10 s were compared with patients with inducible VT >10 s. The primary end point was survival free of VT or cardiac mortality. From 384 consecutive ST-segment-elevation myocardial infarction patients who underwent EPS, 29% had inducible VT (n=112, 87% men). After mean follow-up of 5.9±3.9 years, primary end point occurred in 35% of patients with induced VT 2 to 10 s duration (n=68) and in 22% of patients with induced VT >10 s (n=41) (P=0.61). This was significantly different from the noninducible VT group, in which primary end point occurred in 3% of patients (n=272) (P=0.001). Conclusions This study is the first to show that in patients who undergo EPS early after myocardial infarction, inducible VT of short duration (2-10 s) has similar predictive utility for ventricular tachyarrhythmia as longer duration (>10 s) inducible VT, which was significantly different to those without inducible VT. It is possible that immediate cardioversion of rapid VT might have contributed to some of the short durations of inducible VT.

Ablation of Reentry-Vulnerable Zones Determined by Left Ventricular Activation From Multiple Directions: A Novel Approach for Ventricular Tachycardia Ablation: A Multicenter Study (PHYSIO-VT).

BACKGROUND: The optimal method to identify the arrhythmogenic substrate of scar-related ventricular tachycardia (VT) is unknown. Sites of activation slowing during sinus rhythm (SR) often colocalize with the VT circuit. However, the utility and limitations of such approach for guiding ablation are unknown. METHODS: We conducted a multicenter study in patients with infarct-related VT. The left ventricular (LV) was mapped during activation from 3 directions: SR (or atrial pacing), right ventricular, and LV pacing at 600 ms. Ablation was applied selectively to the cumulative area of slow activation, defined as the sum of all regions with activation times of ≥40 ms per 10 mm. Hemodynamically tolerated VTs were mapped with activation or entrainment. The primary outcome was a composite of appropriate implanted cardioverter-defibrillator therapies and cardiovascular death. RESULTS: In 85 patients, the LV was mapped during activation from 2.4±0.6 directions. The direction of LV activation influenced the location and magnitude of activation slowing. The spatial overlap of activation slowing between SR and right ventricular pacing was 84.2±7.1%, between SR and LV pacing was 61.4±8.8%, and between right ventricular and LV pacing was 71.3±9.6% (P<0.05 between all comparisons). Mapping during SR identified only 66.2±8.2% of the entire area of activation slowing and 58% critical isthmus sites. Activation from other directions by right ventricular and LV stimulation unmasked an additional 33% of slowly conducting zones and 25% critical isthmus sites. The area of maximal activation slowing often corresponded to the site where the wavefront first interacted with the infarct. During a follow-up period of 3.6 years, the primary end point occurred in 14 out of 85 (16.5%) patients. CONCLUSIONS: The spatial distribution of activation slowing is dependent on the direction of LV activation with the area of maximal slowing corresponding to the site where the wavefront first interacts with the infarct. This data may have implications for VT substrate mapping strategies.

Islets of heterogeneous myocardium within the scar in cardiac magnetic resonance predict ventricular tachycardia after myocardial infarction.

INTRODUCTION: We assessed findings in cardiac magnetic resonance (CMR) as predictors of ventricular tachycardia (VT) after myocardial infarction (MI), which could allow for more precise identification of patients at risk of sudden cardiac death. METHODS: Forty-eight patients after prior MI were enrolled and divided into two groups: with (n = 24) and without (n = 24) VT. VT was confirmed by electrophysiological study and exit site was estimated based on 12-lead electrocardiogram. All patients underwent CMR with late gadolinium enhancement. RESULTS: The examined groups did not differ significantly in clinical and demographical parameters (including LV ejection fraction). There was a significant difference in the infarct age between the VT and non-VT group (15.8 ± 8.4 vs 7.1 ± 6.7 years, respectively; P = .002), with the cut-off point at the level of 12 years. In the scar core, islets of heterogeneous myocardium were revealed. They were defined as areas of potentially viable myocardium within or adjacent to the core scar. The number of islets was the strongest independent predictor of VT (odds ratio [OR], 1.42; confidence interval [CI], 1.17-1.73), but total islet size and the largest islet area were also significantly higher in the VT group (OR, 1.04; CI, 1.02-1.07 and OR, 1.16; CI, 1.01-1.27, respectively). Myocardial segments with fibrosis forming 25%-75% of the ventricular wall were associated with a higher incidence of VT (7.5 ± 2.1 vs 5.7 ± 2.6; P = .014). Three-dimension CMR reconstruction confirmed good correlation of the location of the islets/channels with VT exit site during electroanatomical mapping in five cases. CONCLUSIONS: The identification and quantification of islets of heterogeneous myocardium within the scar might be useful for predicting VT in patients after MI.

Cardiopulmonary support in patients undergoing catheter ablation of poorly tolerated ventricular arrhythmias and electrical storm.

INTRODUCTION: Catheter ablation is an important treatment option for sustained ventricular arrhythmias (VA) that are refractory to pharmacological treatment; however, patients with fast VA or electrical storm (ES) are at risk for cardiogenic shock. We report our experience using cardiopulmonary support with extracorporeal membrane oxygenation (ECMO) during catheter ablation of VA. METHODS: Nineteen patients (mean age, 62 ± 10 years; 84% male) were referred to our center for CA of ES between January 2017 and April 2018. ES was defined as the occurrence of ≥3 ventricular tachycardia or ventricular fibrillation episodes requiring electrical cardioversion or defibrillation in a 24-hour period. ECMO support was implemented for all patients. RESULTS: CA of ES was completed in all patients. Activation mapping was performed for all VTs and substrate modification was performed by targeting sites identified by late/fragmented abnormal potentials. VTs were not inducible after ablation in 16 of 19 patients (84%). With regard to procedural complications, two patients underwent percutaneous angioplasty with stenting for a femoral artery dissection and one patient was treated for a dislodged ECMO arterial cannula and subsequent hemorrhagic shock. After a median follow-up of 10 months, three patients died from refractory heart failure and one patient died as a result of ES. Overall, the procedural success rate was 68% and the Kaplan-Meier mortality rate was 21%. CONCLUSIONS: ECMO support may be used for ablation procedures in patients with ES.

Failure to detect life-threatening arrhythmias in ICDs using single-chamber detection criteria.

BACKGROUND: There are anecdotal reports of sudden death despite a functional implantable cardioverter defibrillator (ICD). We sought to describe scenarios leading to fatal or near-fatal outcome due to inappropriately inhibited ICD therapy in devices programmed with single-chamber detection criteria. METHODS: Programmed settings, episode lists, and intracardiac electrograms from 24 patients with a life-threatening event (n = 12) or fatal outcome (n = 12) related to failed ventricular arrhythmia detection were used to clarify the underlying scenario. RESULTS: Fifty episodes of failed ventricular arrhythmia detection were identified and categorized into six scenarios: (1) spontaneous ventricular tachycardia (VT) or ventricular fibrillation (VF) with a rate below the detection limits, (2) misclassification of polymorphic VT (PVT) or VF as supraventricular tachycardia (SVT), (3) misclassification of VT/VF as cluster of nonsustained VT episodes, (4) misclassification of monomorphic VT (MVT) as SVT, (5) inappropriate shock abortion, and (6) false termination detection. These scenarios occurred respectively 6, 9, 3, 9, 8, and 15 times. In 9/9 (100%) patients with PVT/VF classified as SVT, rate stability was active for rates ranging from 222 to 250 beats/min. MVT detected as SVT was due to the sudden onset criterion in 7/9 (78%) patients and twice a consequence of the rate stability criterion active for rates ranging from 200 to 250 beats/min. CONCLUSION: We describe six scenarios leading to failure of ventricular arrhythmia detection in a single-chamber detection setting withholding life-saving therapy. These scenarios are more likely to occur with high-rate programming and long detection times, especially if combined with rate stability and sudden onset.

Early and long-term outcomes after manual and remote magnetic navigation-guided catheter ablation for ventricular tachycardia.

Aims: Remote magnetic navigation (RMN) is a safe and effective means of performing ventricular tachycardia (VT) ablation. It may have advantages over manual catheter ablation due to ease of manoeuvrability and catheter stability. We sought to compare the safety and efficacy of RMN vs. manual VT ablation. Methods and results: Retrospective study of procedural outcomes of 139 consecutive VT ablation procedures (69 RMN, 70 manual ablation) in 113 patients between 2009 and 2015 was performed. Remote magnetic navigation was associated with overall higher acute procedural success (80% vs. 60%, P = 0.01), with a trend to fewer major complications (3% vs. 9% P = 0.09). Seventy-nine patients were followed up for a median of 17.0 [interquartile range (IQR) 3.0-41.0] months for the RMN group and 15.5 (IQR 6.5-30.0) months for manual ablation group. In the ischaemic cardiomyopathy subgroup, RMN was associated with longer survival from the composite endpoint of VT recurrence leading to defibrillator shock, re-hospitalization or repeat catheter ablation and all-cause mortality; single-procedure adjusted hazard ratio (HR) 0.240 (95% CI 0.070-0.821) P = 0.023, multi-procedure HR 0.170 (95% CI 0.046-0.632) P = 0.002. In patients with implanted defibrillators, multi-procedure VT-free survival was superior with RMN, HR 0.199 (95% CI 0.060-0.657) P = 0.003. Conclusion: Remote magnetic navigation may improve clinical outcomes after catheter ablation of VT in patients with ischaemic cardiomyopathy. Further prospective clinical studies are required to confirm these findings.

Long-term outcome of surgical cryoablation for refractory ventricular tachycardia in patients with non-ischemic cardiomyopathy.

Aims: Limited data exist on the long-term outcome of patients (pts) with non-ischemic cardiomyopathy (NICM) and ventricular tachycardia (VT) refractory to conventional therapies undergoing surgical ablation (SA). We aimed to investigate the long-term survival and VT recurrence in NICM pts with VT refractory to radiofrequency catheter ablation (RFCA) who underwent SA. Methods and results: Consecutive pts with NICM and VT refractory to RFCA who underwent SA were included. VT substrate was characterized in the electrophysiology lab and targeted by RFCA. During SA, previous RFCA lesions/scars were identified and targeted with cryoablation (CA; 3 min/lesion; target -150 °C). Follow-up comprised office visits, ICD interrogations and the social security death index. Twenty consecutive patients with NICM who underwent SA (age 53 ± 16 years, 18 males, LVEF 41 ± 20%; dilated CM = 9, arrhythmogenic right ventricular CM = 3, hypertrophic CM = 2, valvular CM = 4, and mixed CM = 2) were studied. Percutaneous mapping/ablation in the electrophysiology lab was performed in 18 and 2 pts had primary SA. During surgery, 4.9 ± 4.0 CA lesions/pt were delivered to the endocardium (2) and epicardium (11) or both (7). VT-free survival was 72.5% at 1 year and over 43 ± 31 months (mos) (range 1-83mos), there was only one arrhythmia-related death. There was a significant reduction in ICD shocks in the 3-mos preceding SA vs. the entire follow-up period (6.6 ± 4.9 vs. 2.3 ± 4.3 shocks/pt, P = 0.001). Conclusion: In select pts with NICM and VT refractory to RFCA, SA guided by pre-operative electrophysiological mapping and ablation may be a therapeutic option.

Ventricular tachycardia ablation in arrhythmogenic right ventricular cardiomyopathy patients with TMEM43 gene mutations.

INTRODUCTION: Catheter ablation of VT in patients with arrhythmogenic right ventricular cardiomyopathy (ARVC) is often challenging, frequently requiring multiple or epicardial ablation procedures; TMEM43 gene mutations typically cause aggressive disease. We sought to compare VT ablation outcomes for ARVC patients with and without TMEM43 mutations. METHODS: Patients with prior ablation for ARVC-related VT were reviewed. Demographic, procedural, and follow-up data were reviewed retrospectively. Patients with confirmed TMEM43 gene mutations were compared to those with other known mutations or who had no known mutations. RESULTS: Thirteen patients (10 male, mean age 49 ± 14 years) underwent 29 ablation procedures (median 2 procedures/patient, range 1-6) with a median of 4 targeted VTs/patient (range 1-9). They were followed for a mean duration of 7.3 ± 4.2 years. Gene mutations included TMEM43 (n = 5), PKP2 (n = 2), DSG2 (n = 2), unidentifiable (n = 4). TMEM patients showed more biventricular involvement compared to non-TMEM patients (80% vs. 12.5%, P = 0.032), more inducible VTs during their ablation procedures (mean VTs/patient: 5.8 ± 3 vs. 2.6 ± 1, P = 0.021). Acute and long-term procedural outcomes did not show a significant difference between the two groups, however TMEM patients had worse composite endpoint of death or transplantation (60% vs. 0, P = 0.035; log-rank P = 0.013). CONCLUSIONS: TMEM43 mutation patients were more likely to have biventricular arrhythmogenic substrate and more inducible VTs at EP study. Despite comparable acute VT ablation outcomes, long-term prognosis is unfavorable.

Systematic Review for the 2017 AHA/ACC/HRS Guideline for Management of Patients With Ventricular Arrhythmias and the Prevention of Sudden Cardiac Death: A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines and the Heart Rhythm Society.

BACKGROUND: Although large randomized clinical trials have found that primary prevention use of an implantable cardioverter-defibrillator (ICD) improves survival in patients with cardiomyopathy and heart failure symptoms, patients who receive ICDs in practice are often older and have more comorbidities than patients who were enrolled in the clinical trials. In addition, there is a debate among clinicians on the usefulness of electrophysiological study for risk stratification of asymptomatic patients with Brugada syndrome. AIM: Our analysis has 2 objectives. First, to evaluate whether ventricular arrhythmias (VAs) induced with programmed electrostimulation in asymptomatic patients with Brugada syndrome identify a higher risk group that may require additional testing or therapies. Second, to evaluate whether implantation of an ICD is associated with a clinical benefit in older patients and patients with comorbidities who would otherwise benefit on the basis of left ventricular ejection fraction and heart failure symptoms. METHODS: Traditional statistical approaches were used to address 1) whether programmed ventricular stimulation identifies a higher-risk group in asymptomatic patients with Brugada syndrome and 2) whether ICD implantation for primary prevention is associated with improved outcomes in older patients (>75 years of age) and patients with significant comorbidities who would otherwise meet criteria for ICD implantation on the basis of symptoms or left ventricular function. RESULTS: Evidence from 6 studies of 1138 asymptomatic patients were identified. Brugada syndrome with inducible VA on electrophysiological study was identified in 390 (34.3%) patients. To minimize patient overlap, the primary analysis used 5 of the 6 studies and found an odds ratio of 2.3 (95% CI: 0.63-8.66; P=0.2) for major arrhythmic events (sustained VAs, sudden cardiac death, or appropriate ICD therapy) in asymptomatic patients with Brugada syndrome and inducible VA on electrophysiological study versus those without inducible VA. Ten studies were reviewed that evaluated ICD use in older patients and 4 studies that evaluated unique patient populations were identified. In our analysis, ICD implantation was associated with improved survival (overall hazard ratio: 0.75; 95% confidence interval: 0.67-0.83; P<0.001). Ten studies were identified that evaluated ICD use in patients with various comorbidities including renal disease, chronic obstructive pulmonary disease, atrial fibrillation, heart disease, and others. A random effects model demonstrated that ICD use was associated with reduced all-cause mortality (overall hazard ratio: 0.72; 95% confidence interval: 0.65-0.79; P<0.0001), and a second "minimal overlap" analysis also found that ICD use was associated with reduced all-cause mortality (overall hazard ratio: 0.71; 95% confidence interval: 0.61-0.82; P<0.0001). In 5 studies that included data on renal dysfunction, ICD implantation was associated with reduced all-cause mortality (overall hazard ratio: 0.71; 95% confidence interval: 0.60-0.85; P<0.001).

Prediction and prognosis of ventricular tachycardia recurrence after catheter ablation with remote magnetic navigation for electrical storm in patients with ischemic cardiomyopathy.

BACKGROUND: Ventricular tachycardia (VT) recurrence after catheter ablation for electrical storm is commonly seen in patients with ischemic cardiomyopathy (ICM). HYPOTHESIS: We hypothesized that VT recurrence can be predicted and be related to the all-cause death after VT storm ablation guided by remote magnetic navigation (RMN) in patients with ICM. METHODS: A total of 54 ICM patients (87% male; mean age, 65 ± 7.1 years) presenting with VT storm undergoing acute ablation using RMN were enrolled. Acute complete ablation success was defined as noninducibility of any sustained monomorphic VT at the end of the procedure. Early VT recurrence was defined as the occurrence of sustained VT within 1 month after the first ablation. RESULTS: After a mean follow-up of 17.1 months, 27 patients (50%) had freedom from VT recurrence. Sustained VT recurred in 12 patients (22%) within 1 month following the first ablation. In univariate analysis, VT recurrence was associated with incomplete procedural success (hazard ratio [HR]: 6.25, 95% confidence interval [CI]: 1.20-32.47, P = 0.029), lack of amiodarone usage before ablation (HR: 4.71, 95% CI: 1.12-19.7, P = 0.034), and a longer procedural time (HR: 1.023, 95% CI: 1.00-1.05, P = 0.05). The mortality of patients with early VT recurrence was higher than that of patients without recurrence (P < 0.01). CONCLUSIONS: Inducibility of any VT at the end of procedure for VT storm guided by RMN is the strongest predictor of VT recurrence. ICM patients who have early recurrences after VT storm ablation are at high risk of all-cause death.

Increased risk of ventricular tachycardia and cardiovascular death in patients with myocarditis during the long-term follow-up: A national representative cohort from the National Health Insurance Research Database.

The incidence of acute myocarditis complicated with ventricular tachycardia (VT) is unknown. This study aimed to investigate the association between myocarditis and the incidence of VT and mortality. We also aimed to determine the independent predictors that increased the VT risk in those patients. From 2000 to 2004, 13,250 patients with a history of myocarditis were identified from the Taiwan National Health Insurance Research Database. The same number of individuals without heart disease with a matched sex and underlying diseases were selected as the control group. The long-term risks of life-threatening ventricular arrhythmias and mortality in patients with a history of myocarditis were investigated by an adjusted Cox proportional hazards regression. After a mean follow-up of 10.4 ±â€Š2.94 years (interquartile range: 12, 10.19-12), the myocarditis patients showed a higher incidence of new onset VT events compared with healthy controls (5.4% [519 per 100,000 person-year] in the myocarditis group vs, 0.47% [43 per 100,000 person-year] in the healthy controls; adjusted hazard ratio [HR]: 16.1, 95% confidence interval [CI]: 12.4-20.9; P < .001). A higher incidence of cardiovascular death was noted in the myocarditis group than healthy controls (6.52% vs 3.18%; HR: 2.42, 95% CI: 2.14-2.73; P < .001) after adjusting for the multivariate confounders including sex, age, underlying comorbidities, and medications. The results of this study suggested that there was higher incidence of life-threatening VT and mortality during the very long-term follow-up in patients with a history of myocarditis. Future work should focus on an in-depth risk stratification of VT in myocarditis patients.

Ten-year outcomes of monomorphic ventricular tachycardia catheter ablation in repaired tetralogy of Fallot.

BACKGROUND: Monomorphic ventricular tachycardia (MVT) is common in adults with repaired tetralogy of Fallot (TOF), and is associated with sudden cardiac death. Management of MVT is not defined, and results of catheter ablation (CA) are limited. AIMS: To evaluate long-term outcomes of MVT CA in repaired TOF. METHODS: Thirty-four patients (mean age 32±10.3 years; 59% male) with repaired TOF underwent CA for symptomatic MVT between 1990 and 2012 in our centre; direct-current ablation (DCA) was used in 6%, radiofrequency followed by DCA in 29% and radiofrequency alone in 65%. RESULTS: Right ventricular (RV) dysfunction was present in 35% and left ventricular (LV) dysfunction in 21%. Mean numbers of clinical and induced MVTs were 1 and 2, respectively. Mean VT rate was 225±95bpm. Ablation targeted a single site (range 1-2), which was RV outflow tract in 85%. Primary success, defined as ventricular tachycardia (VT) termination during CA and final non-inducibility, was obtained in 82%. Seven patients (21%) required redo ablation in the first 3 months (before 2004; DCA). No death related to CA occurred. Mean follow-up time was 9.5±5.2 years. Antiarrhythmic therapy was discontinued in 71%. There were two cases of sudden cardiac death and four VT recurrences. Freedom from death and arrhythmia recurrence was 94% at 5 years, 81% at 10 years and 70% at 20 years. Global survival was 91% at 20 years. Baseline LV ejection fraction<60% was significantly associated with ventricular arrhythmia recurrence (hazard ratio 16.4, 95% confidence interval 1.8-147; P=0.01). CONCLUSIONS: CA can safely address macroreentrant MVT in repaired TOF patients with an acceptable long-term rate of recurrence in this high-risk population. Anatomical classification of isthmuses with electroanatomical mapping provides reproducible endpoints for CA. Attention should be given to LV systolic function in risk assessment and selection of candidates for implantable cardioverter-defibrillator.

Characterization of Ventricular Tachycardia After Left Ventricular Assist Device Implantation as Destination Therapy: A Single-Center Ablation Experience.

OBJECTIVES: This study sought to report mechanisms of ventricular tachycardia (VT) and outcomes of VT ablation in patients with a left ventricular assist device (LVAD) as destination therapy. BACKGROUND: Continuous flow LVAD implantation plays a growing role in the management of end-stage heart failure, and VT is common. There are limited reports of VT ablation in patients with a destination LVAD. METHODS: Patients with a continuous-flow LVAD referred for VT ablation from 2010 to 2016 were analyzed retrospectively. Baseline patient characteristics, procedural data, and clinical follow-up were evaluated. Arrhythmia-free survival was assessed. RESULTS: Twenty-one patients (90% male, 62 ± 10 years) underwent catheter ablation of VT at a median of 191 days (interquartile range: 55 to 403 days) after LVAD implantation (15 HeartMate II, 6 HeartWare HVAD). Five patients (24%) had termination (n = 4) or slowing (n = 1) of VT with ablation near the apical inflow cannula, and 3 (14%) had bundle-branch re-entry. Freedom from recurrent VT among surviving patients was 64% at 1 year, with overall survival 67% at 1 year for patients without arrhythmia recurrence and 29% for patients with recurrence (p = 0.049). One patient had suspected pump thrombosis within 30 days of the ablation procedure, with no other major acute complications. CONCLUSIONS: In this relatively large, single-center experience of VT ablation in destination LVAD, freedom from recurrent VT and implantable cardioverter-defibrillator shocks was associated with improved 1-year survival. Bundle branch re-entry was more prevalent than anticipated, and cannula-adjacent VT was less common. This challenging population remains at risk for late pump thrombosis and mortality.

Sex Differences in Inappropriate ICD Device Therapies: MADIT-II and MADIT-CRT.

INTRODUCTION: Approximately 10-20% of ICD recipients receive inappropriate device therapies. The purpose of this study was to compare the frequency of inappropriate therapies (IT) between men and women enrolled in MADIT II and MADIT-CRT, and assess for potential adverse outcomes. METHODS: The electrograms for each ICD or CRT-D therapy, defined as either ATP or shock, were reviewed by adjudication committees for both studies. ICD therapy was considered inappropriate if it was delivered for reasons other than VT/VF. The rhythm triggering IT was categorized as atrial fibrillation/flutter, SVT, or inappropriate sensing when possible. RESULTS: One thousand nine hundred and fifty-four men and 556 women received ICD or CRT-D devices. The risk of IT was significantly lower in women than men (9.2% vs. 13.5%, P = 0.006). The most common cause of IT in men was atrial fibrillation (38%) and SVT in women (43%). Inappropriate shock was not associated with increased mortality in either women (HR 0.82 [95% CI 0.11-6.08]; P = NS) or men (HR 1.37 [95% CI 0.75-2.48]; P = NS) by multivariate analysis. Conversely, appropriate shock therapy strongly correlated with increased risk of death during subsequent post-shock follow-up in women (HR 5.99 [95% CI 2.75-13.02]; P < 0.0001) and men (HR 2.61 [95% CI 1.82-3.74]; P < 0.0001). CONCLUSIONS: Women experience significantly less IT than men, partially explained by the increased frequency of atrial fibrillation in men. IT was not associated with increased mortality in either sex. Appropriate shock therapy was a strong predictor of death in both, with women showing a 2-fold higher risk than men during post-shock long-term follow-up.

Clinical Significance of Nonsustained Ventricular Tachycardia on Stored Electrograms in Permanent Pacemaker Patients.

BACKGROUND: Permanent pacemaker electrograms record a variety of arrhythmias, including nonsustained ventricular tachycardia (NSVT). Little has been reported regarding incidence and clinical significance of NSVT in pacemaker patients after long-term monitoring. METHODS: Records from all patients implanted with Medtronic pacemakers (Medtronic, Minneapolis, MN, USA) at a single institution from January 1, 2009 to February 27, 2012 were reviewed. Demographic characteristics, imaging studies, pacemaker interrogations, and the Social Security Death Index were examined in patients older than 18 years of age who had ≥ 2 follow-up device interrogations. RESULTS: A total of 262 patients with an ejection fraction (EF) >40% were included in the final analysis with a mean follow-up of 29.2 months. Of these patients, 83.2% (n = 218) had hypertension (HTN) and 45.4% (n = 119) had NSVT. Among patients with an EF ≥ 55%, hypertensive patients had a NSVT burden 2.46 times greater than normotensive patients (incidence rate ratio: 2.46, 95% confidence interval: 1.10-5.50; P < 0.028). NSVT was not associated with increased mortality (P < 0.1229). CONCLUSION: In this cohort of patients, there was a high prevalence of HTN and while hypertensive subjects had a significantly higher NSVT burden, NSVT was not associated with an increased mortality.

Substrate-Based Ablation Versus Ablation Guided by Activation and Entrainment Mapping for Ventricular Tachycardia: A Systematic Review and Meta-Analysis.

INTRODUCTION: Substrate-based ablation for scar-related ventricular tachycardia (VT) has gained prominence: however, there is limited data comparing it to ablation guided predominantly by activation and entrainment mapping of inducible and hemodynamically tolerated VTs. We compared the acute procedural efficacy and outcomes of predominantly substrate-based ablation versus ablation guided predominantly by activation and entrainment mapping. METHODS AND RESULTS: Database searches through April 2016 identified 6 eligible studies (enrolling 403 patients, with 1 randomized study) comparing the 2 strategies. The relative risk of VT recurrence at follow-up was assessed as the primary outcome using a random-effects meta-analysis. Secondary endpoints of acute success (based on noninducibility of VT), procedural complications, and mortality were assessed using weighted mean difference with the random effects model. At a median follow-up of 18 months, the relative risk (RR) of VT recurrence was not significantly different with substrate-based versus activation/entrainment guided VT ablation (0.72, 95% confidence interval [CI] 0.44-1.18), P = 0.2). Acute success (RR 1.02, 95% CI 0.95-1.1, P = 0.6), procedural complications (RR 0.8, 95% CI 0.35-1.82, P = 0.5) cardiovascular mortality and total mortality did not differ significantly (RR 0.83, 95% CI 0.38-1.79, P = 0.6 and RR 0.76, 95% CI 0.36-1.59, P = 0.5, respectively). CONCLUSIONS: This meta-analysis demonstrates similar acute procedural efficacy, and complications, VT recurrence and mortality rates when comparing a predominantly substrate-based ablation strategy to a strategy guided predominantly by activation and entrainment mapping of inducible and hemodynamically tolerated VTs.

High atrioventricular phase index on near-field intracardiac electrogram is associated with risk of ventricular arrhythmia.

The purposes of this study were to characterize and quantify concordance between consecutive atrial and ventricular activation time points through analysis of phases and to explore its association with outcomes in patients with implantable cardioverter-defibrillator (ICD). Patients with structural heart disease and dual-chamber ICDs underwent 5min baseline right ventricular (V) near-field and atrial (A) electrogram (EGM) recording. The cross-dependencies of phase dynamics of the changes in consecutive A (AA') and V (VV') were quantified and the AV phase dependency index was determined. In Cox regression analysis, a high AV phase index (in the highest quartile, >0.259) was significantly associated with higher risk of ventricular tachyarrhythmias (HR 2.84; 95% CI 1.05-7.67; P=0.04). In conclusion, in ICD patients with structural heart disease, high sinus AV phase dependency index on EGM is associated with the risk of ventricular arrhythmia.

Characteristics of ventricular tachycardia ablation in patients with continuous flow left ventricular assist devices.

BACKGROUND: Left ventricular assist devices (LVADs) are increasingly used as a bridge to cardiac transplantation or as destination therapy. Patients with LVADs are at high risk for ventricular arrhythmias. This study describes ventricular arrhythmia characteristics and ablation in patients implanted with a Heart Mate II device. METHODS AND RESULTS: All patients with a Heart Mate II device who underwent ventricular arrhythmia catheter ablation at 9 tertiary centers were included. Thirty-four patients (30 male, age 58±10 years) underwent 39 ablation procedures. The underlying cardiomyopathy pathogenesis was ischemic in 21 and nonischemic in 13 patients with a mean left ventricular ejection fraction of 17%±5% before LVAD implantation. One hundred and ten ventricular tachycardias (VTs; cycle lengths, 230-740 ms, arrhythmic storm n=28) and 2 ventricular fibrillation triggers were targeted (25 transseptal, 14 retrograde aortic approaches). Nine patients required VT ablation <1 month after LVAD implantation because of intractable VT. Only 10/110 (9%) of the targeted VTs were related to the Heart Mate II cannula. During follow-up, 7 patients were transplanted and 10 died. Of the remaining 17 patients, 13 were arrhythmia-free at 25±15 months. In 1 patient with VT recurrence, change of turbine speed from 9400 to 9000 rpm extinguished VT. CONCLUSIONS: Catheter ablation of VT among LVAD recipients is feasible and reasonably safe even soon after LVAD implantation. Intrinsic myocardial scar, rather than the apical cannula, seems to be the dominant substrate.