Catheter ablation of ventricular tachycardia in ischemic cardiomyopathy: Impact of concomitant amiodarone therapy on short- and long-term clinical outcomes.

BACKGROUND: Substrate catheter ablation of scar-related ventricular tachycardia (VT) is a widely accepted therapeutic option for patients with ischemic cardiomyopathy (ICM). OBJECTIVE: The purpose of this study was to investigate whether concomitant amiodarone therapy affects procedural outcomes. METHODS: A total of 134 consecutive patients (89% male; age 66 ± 10 years) with ICM undergoing catheter ablation of VT were included in the study. Patients were sorted by amiodarone therapy before ablation. In all patients, a substrate-based catheter ablation (endocardial ± epicardial) in sinus rhythm abolishing all "abnormal" electrograms within the scar was performed. The endpoint of the procedure was VT noninducibility. After the ablation procedure, all antiarrhythmic medications were discontinued. All patients had an implantable cardioverter-defibrillator, and recurrences were analyzed through the device. RESULTS: In 84 patients (63%), the ablation was performed on amiodarone; the remaining 50 patients (37%) were off amiodarone. Patients had comparable baseline characteristics. Mean scar size area was 143.6 ± 44.9 cm2 on amiodarone vs 139.2 ± 36.8 cm2 off amiodarone (P = .56). More radiofrequency time was necessary to achieve noninducibility in the off-amiodarone group compared to the on-amiodarone group (68.1 ± 20.1 minutes vs 51.5 ± 19.7 minutes; P <.001). In addition, due to persistent VT inducibility, more patients in the off-amiodarone group required epicardial ablation than in the on-amiodarone group (13/50 [26%] vs 5/84 [6%], respectively; P <.001). During mean follow-up of 23.9 ± 11.6 months, recurrence of any ventricular arrhythmias off antiarrhythmic drugs was 44% (37/84) in the on-amiodarone group vs 22% (11/50) in the off-amiodarone group (P = .013). CONCLUSION: Albeit, VT noninducibility after substrate catheter ablation for scar related VT was achieved faster, with less radiofrequency time and less need for epicardial ablation in patients taking amiodarone, these patients had significantly higher VT recurrence at long-term follow-up when this medication was discontinued.

MiR-375 silencing attenuates pro-inflammatory macrophage response and foam cell formation by targeting KLF4.

Macrophage mediated inflammation and foam cell formation play crucial roles in the development of atherosclerosis. MiR-375 is a small noncoding RNA that significantly implicated in multiple tumor regulation and has been emerged as a novel biomarker for type 2 diabetes. However, the exact role of miR-375 on macrophage activation remains unknown. In the present study, we observed that miR-375 expression showed an up-regulated expression in atherosclerotic aortas, as well as in bone marrow derived macrophages (BMDMs) and mouse peritoneal macrophages (MPMs) isolated from ApoE deficiency mice and was gradually increased followed the Ox-LDL treated time. Functionally, miR-375 inhibition significantly decreased foam cell formation accompanied by up-regulated genes expression involved in cholesterol efflux but reduced genes expression implicated in cholesterol influx. Moreover, miR-375 silencing increased resolving M2 macrophage but reduced pro-inflammatory M1 macrophage markers expression. Such above effects can be reversed by miR-375 overexpression. Mechanistically, we noticed that miR-375 knockdown promoted KLF4 expression which was required for the ameliorated effect of miR-375 silencing on macrophage activation. Importantly, the consistent results in mRNA expression of M1 and M2 markers were observed in vivo, and miR-375-/-ApoE-/- mice significant decreased atherosclerotic lesions in the whole aorta and aortic sinus. Taken together, these evidences suggested that miR-375 knockdown attenuated macrophage activation partially through activation of KLF4-dependent mechanism.

First-line ablation of ventricular tachycardia in ischemic cardiomyopathy: stratification of outcomes by left ventricular function.

PURPOSE: First-line catheter ablation of ventricular tachycardia/ventricular fibrillation (VT/VF) in patients with ischemic cardiomyopathy (ICM) has been associated with improved outcomes; however, most benefit seems to be in patients with moderately depressed left ventricular ejection fraction (LVEF). Herein, outcomes were stratified based on LVEF. METHODS: A meta-analysis of randomized controlled trials (RCTs) evaluating first-line ablation versus medical therapy in patients with VT and ICM was performed. Risk estimates and 95% confidence intervals (CI) were measured. RESULTS: Four RCTs with a total of 505 patients (mean age 66 ± 9 years, 89% male, 80% with previous revascularization) were included. Mean LVEF was 35 ± 8%. At a mean follow-up of 24 ± 9 months, a significant benefit in survival-free from appropriate implantable cardioverter-defibrillator (ICD) therapies was observed in all patients undergoing first-line catheter ablation compared with medical management (RR 0.70, 95% CI 0.56-0.86). In patients with moderately depressed LVEF (> 30-50%), first-line VT ablation was associated with a statistically significant reduction in the composite endpoint of survival free from VT/VF and appropriate ICD therapies (HR 0.52, 95% CI 0.36-0.76), whereas there was no difference in patients with severely depressed LVEF (≤30%) (HR 0.56, 95% CI 0.24-1.32). Funnel plots did not show asymmetry suggesting lack of bias. CONCLUSIONS: Patients with ICM and VT undergoing first-line ablation have a significantly lower rate of appropriate ICD therapies without a mortality difference compared with patients receiving an initial approach based on medical therapy. The beneficial effect of a first-line ablation approach was only observed in patients with moderately depressed LVEF (> 30-50%).

T-wave inversion as a manifestation of COVID-19 infection: a case series.

PURPOSE: Cardiac involvement with COVID-19 infection has become evident by elevated troponin, cardiac arrhythmias, ST segment elevation, myocarditis, fulminant heart failure, and sudden cardiac death. We aimed to describe the association of COVID-19 and T-wave inversion (TWI) in a large case series. METHODS: We conducted an observational, retrospective study of confirmed COVID-19 cases with at least one electrocardiogram (ECG) in a large hospital in New York City (March 23, 2020-April 23, 2020). Patients with new TWI or pseudonormalization were further analyzed. Mortality and the need for invasive mechanical ventilation were the main outcomes. RESULTS: A total of 3225 patients were screened; 195 (6%) were selected for further analysis: 181 with TWI and 14 with T-wave pseudonormalization. Mean age was 66 ± 7 years; 51% were male. TWI were more commonly noted in the lateral (71%), followed by anterior (64%), inferior (57%), and septal (26%) leads. A total of 44 patients (23%) had elevated troponin. A total of 50 patients died (26%). Mortality rates of 35%, and 52% were observed in patients with diffuse TWI, and elevated troponin, respectively. Mortality rate of 80% was observed in patients with both elevated troponin and diffuse TWI. Additionally, 30% of the entire cohort and 58% of patients with elevated troponin required invasive mechanical ventilation. CONCLUSION: Our study demonstrates that new TWI is a relatively common finding in COVID-19 patients. Importantly, our findings suggest that new TWI or T-wave pseudonormalization, particularly with elevated troponin, was associated with higher rates of mechanical ventilation and in-hospital mortality.

Long-Term Outcomes of Left Atrial Appendage Electrical Isolation in Patients With Nonparoxysmal Atrial Fibrillation: A Propensity Score-Matched Analysis.

BACKGROUND: Left atrial appendage electrical isolation (LAAEI) has been proposed for the treatment of nonparoxysmal atrial fibrillation (AF). The long-term clinical outcomes of this approach remain unclear. The objective of our study was to investigate the incremental benefit and safety of LAAEI in patients undergoing catheter ablation for nonparoxysmal AF. METHODS: Propensity score-matched analysis was performed using a prospective registry database from 2010 to 2014. All patients in the LAAEI group were matched based on baseline characteristics, echocardiographic parameters, and procedural ablation techniques. RESULTS: We identified 1842 patients who underwent catheter ablation for nonparoxysmal AF. Propensity score matching yielded 1092 patients, 546 patients with LAAEI, and 546 patients without LAAEI. At 5-year follow-up, overall freedom from all-atrial arrhythmia recurrence, off-antiarrhythmic drugs, in patients who underwent LAAEI was 68.9% versus 50.2% in those who underwent standard ablation alone (P<0.001). Acute complication rates were similar between groups (LAAEI 1.3% versus non-LAAEI 0.73%, P=0.36). At 5-year follow-up, 382 (70%) patients in the LAAEI group remained on oral anticoagulation versus 217 (39.7%) in the non-LAAEI group. At 5-year follow-up, thromboembolic events occurred in 15/546 (2.75%) in the LAAEI group and 4/546 (0.73%) in the non-LAAEI group (P=0.01). No thromboembolic events occurred in either group on-oral anticoagulation. In patients who were off-oral anticoagulation, at 5-year follow-up, thromboembolic events occurred in 15/164 (9.1%) in the LAAEI group and 4/329 (1.2%) in the non-LAAEI group (P<0.001). CONCLUSIONS: At 5-year follow-up, LAAEI was associated with significantly higher freedom from all-atrial arrhythmia recurrence in patients with persistent and long-standing persistent AF without increasing acute procedural complication rate. In patients off-oral anticoagulation, there appears to be a higher risk of thromboembolic events in the LAAEI group.

Is transesophageal echocardiography necessary in patients undergoing ablation of atrial fibrillation on an uninterrupted direct oral anticoagulant regimen? Results from a prospective multicenter registry.

BACKGROUND: Thromboembolic stroke is a rare but devastating consequence of atrial fibrillation (AF) ablation. Transesophageal echocardiography (TEE) is recommended to rule out left atrial appendage thrombus; however, its use is variable. OBJECTIVE: The purpose of this study was to assess whether TEE is mandatory in patients undergoing AF ablation on uninterrupted direct oral anticoagulants (DOACs). METHODS: Data from our prospective multicenter registry of patients with AF undergoing radiofrequency catheter ablation on uninterrupted DOACs were analyzed. All the included patients were on anticoagulation for at least 4 weeks before ablation. All AF ablation procedures were performed under intracardiac echocardiography guidance. Before transseptal puncture, heparin bolus was administered, followed by continuous infusion, with a target activated clotting time of >300 seconds. RESULTS: A total of 6186 patients (3180 on apixaban [51.4%], 2528 on rivaroxaban [40.9%], 404 on dabigatran [6.5%], and 74 on edoxaban [1.2%]) were analyzed. The mean age of the study population was 69.4 ± 10.3 years; 4194 patients (67.8%) were male, and 5120 patients (82.8%) had persistent and long-standing persistent AF. The mean CHA2DS2-VASc score was 2.86 ± 1.58; the mean CHADS2 score was 1.65 ± 1.14. Intracardiac echocardiography ruled out left atrial appendage and left atrial thrombi in all patients and revealed "smoke" in 1672 patients (27.03%). Transient ischemic attack was noted in 1 patient with long-standing persistent AF in the setting of a missed dose of rivaroxaban before ablation. CONCLUSION: Our study showed that performing AF ablation in patients on uninterrupted DOACs without TEE is safe and feasible in high stroke risk patients. Elimination of routine preablation TEE would have significant economic and clinical implications.

Endo-epicardial ablation vs endocardial ablation for the management of ventricular tachycardia in arrhythmogenic right ventricular cardiomyopathy: A systematic review and meta-analysis.

BACKGROUND: The pathologic process of ARVC (arrhythmogenic right ventricular cardiomyopathy) typically originates in the epicardium or subepicardial layers with progression toward endocardium. However, in the most recent ARVC international task force consensus statement, epicardial ventricular tachycardia (VT) ablation is recommended as a Class I indication only in patients with at least one failed endocardial VT ablation attempt. OBJECTIVE: The aim of this meta-analysis is to assess the outcomes of ARVC patients undergoing combined endo-epicardial VT ablation, as compared to endocardial ablation alone. METHODS: A systematic review of PubMed, Embase, and Cochrane was performed for studies reporting clinical outcomes of endo-epicardial VT ablation vs endocardial-only VT ablation in patients with ARVC. Fixed-Effect model was used if I2 < 25 and the Random-Effects Model was used if I2 ≥ 25%. RESULTS: Nine studies consisting of 452 patients were included (mean age 42.3 ± 5.7 years; 70% male). After a mean follow-up of 48.1 ± 21.5 months, endo-epicardial ablation was associated with 42% relative risk reduction in VA recurrence as opposed to endocardial ablation alone (risk ratio [RR], 0.58; 95% confidence interval [CI], 0.45-0.75; P < .0001). No significant differences were noted between endo-epicardial and endocardial VT ablation groups in terms of all-cause mortality (RR, 1.19; 95% CI, 0.03-47.08; P = .93) and acute procedural complications (RR, 5.39; 95% CI, 0.60-48.74; P = .13). CONCLUSIONS: Our findings suggest that in patients with ARVC, endo-epicardial VT ablation is associated with a significant reduction in VA recurrence as opposed to endocardial ablation alone, without a significant difference in all-cause mortality or acute procedural complications.