Pulmonary Vein Isolation With or Without Left Atrial Appendage Ligation in Atrial Fibrillation: The aMAZE Randomized Clinical Trial.

Importance: Left atrial appendage elimination may improve catheter ablation outcomes for atrial fibrillation. Objective: To assess the safety and effectiveness of percutaneous left atrial appendage ligation adjunctive to catheter pulmonary vein isolation for nonparoxysmal atrial fibrillation. Design, Setting, and Participants: This multicenter, prospective, open-label, randomized clinical trial evaluated the safety and effectiveness of percutaneous left atrial appendage ligation adjunctive to planned pulmonary vein isolation for nonparoxysmal atrial fibrillation present for less than 3 years. Eligible patients were randomized in a 2:1 ratio to undergo left atrial appendage ligation and pulmonary vein isolation or pulmonary vein isolation alone. Use of a 2:1 randomization ratio was intended to provide more device experience and safety data. Patients were enrolled from October 2015 to December 2019 at 53 US sites, with the final follow-up visit on April 21, 2021. Interventions: Left atrial appendage ligation plus pulmonary vein isolation compared with pulmonary vein isolation alone. Main Outcomes and Measures: A bayesian adaptive analysis was used for primary end points. Primary effectiveness was freedom from documented atrial arrythmias of greater than 30 seconds duration 12 months after undergoing pulmonary vein isolation. Rhythm was assessed by Holter monitoring at 6 and 12 months after pulmonary vein isolation, symptomatic event monitoring, or any electrocardiographic tracing obtained through 12 months after pulmonary vein isolation. Primary safety was a composite of predefined serious adverse events compared with a prespecified 10% performance goal 30 days after the procedure. Left atrial appendage closure was evaluated through 12 months after pulmonary vein isolation. Results: Overall, 404 patients were randomized to undergo left atrial appendage ligation plus pulmonary vein isolation and 206 were randomized to undergo pulmonary vein isolation alone. Primary effectiveness was 64.3% with left atrial appendage ligation and pulmonary vein isolation and 59.9% with pulmonary vein isolation only (difference, 4.3% [bayesian 95% credible interval, -4.2% to 13.2%]; posterior superiority probability, 0.835), which did not meet the statistical criterion to establish superiority (0.977). Primary safety was met, with a 30-day serious adverse event rate of 3.4% (bayesian 95% credible interval, 2.0% to 5.0%; posterior probability, 1.0) which was less than the prespecified threshold of 10%. At 12 months after pulmonary vein isolation, complete left atrial appendage closure (0 mm residual communication) was observed in 84% of patients and less than or equal to 5 mm residual communication was observed in 99% of patients. Conclusions and Relevance: Percutaneous left atrial appendage ligation adjunctive to pulmonary vein isolation did not meet prespecified efficacy criteria for freedom from atrial arrhythmias at 12 months compared with pulmonary vein isolation alone for patients with nonparoxysmal atrial fibrillation, but met prespecified safety criteria and demonstrated high rates of closure at 12 months. Trial Registration: ClinicalTrials.gov Identifier: NCT02513797.

Identification of 2 Distinct Boundaries Distinguishes Critical From Noncritical Isthmuses in Ablating Atypical Atrial Flutter.

BACKGROUND: Atypical atrial flutters often involve complex circuits. Classic methods of identifying ablation targets, including detailed electroanatomical mapping and entrainment within a well-defined isthmus, may not always be sufficient to allow the critical isthmus to be delineated and ablated, with flutter termination and prevention of reinduction. OBJECTIVES: This study sought a systematic method to classify conduction barriers and isthmuses as critical or noncritical that would improve understanding and ablation success. We also sought a construct unifying single- and dual-loop re-entry. Re-entrant circuits are bounded on 2 sides, although these are not consistently identified. We hypothesized 2 distinct critical boundaries, and a critical isthmus could be consistently defined without requiring entrainment, and ablation connecting these 2 boundaries would terminate tachycardia. METHODS: Activation maps were created electroanatomically. Conduction barriers were classified as noncritical barriers or critical boundaries. Critical boundaries showed sequential activation around the barrier, spanning ≥90% of the cycle length. Noncritical barriers showed nonsequential, parallel, or colliding activation or <90% of the cycle length. Only tissue separating the 2 critical boundaries defined a critical isthmus (CI); all others were considered noncritical. The effect of ablation across a CI was assessed. RESULTS: Complete maps were obtained in 128 cases in 121 patients (28 atypical right atrial, 100 left atrial). In all cases, 2 distinct critical boundaries were identified. Ablation across a CI connecting these critical boundaries terminated tachycardia in 123 of 128 cases (96.1%). Failures were due to inability to achieve block across the isthmus. CONCLUSIONS: Activation mapping of atypical atrial flutter allows consistent identification of 2 critical boundaries. Successful ablation connecting the 2 critical boundaries reliably results in termination of atypical atrial flutter.

Long-Term Outcomes of Cardiac Sarcoid: Prognostic Implications of Isolated Cardiac Involvement and Impact of Diagnostic Delays.

Background Isolated cardiac sarcoid (iCS) is reported to have more severe clinical presentation and greater risk of adverse events compared with cardiac sarcoid (CS) with extracardiac involvement (nonisolated CS). Delays in diagnosing specific organ involvement may play a role in these described differences. Methods and Results A retrospective observational study of patients with CS over a 20-year period was conducted. Objective evidence of organ involvement and time of onset based on consensus criteria were identified. CS was confirmed by histology in all patients from myocardium only (iCS) or extracardiac tissue (nonisolated CS). The primary end point was a composite of mortality, orthotopic heart transplant, and durable left ventricular assist device implantation. CS was isolated in 9 of 50 patients (18%). Among baseline characteristics, iCS and nonisolated CS differed significantly only in the frequency of sustained ventricular tachycardia at presentation (78% versus 37%; P=0.03) and delay in CS diagnosis >6 months (67% versus 5%; P<0.01). A nonsignificant trend toward lower left ventricular ejection fraction and more frequent heart failure in iCS was observed. Over a median follow-up of 9.7 years (95% CI, 6.8-10.8), 18 patients reached the primary end point (13 deaths, 2 orthotopic heart transplants, and 3 durable left ventricular assist device implantations). The 1-, 5-, and 10-year event-free survival rates were 96% (95% CI, 85%-99%), 79% (95% CI, 64%-88%), and 58% (95% CI, 40%-73%), respectively, without differences between groups. There were no significant predictors of the primary end point, including delayed CS diagnosis. Conclusions Long-term outcomes were similar between iCS and nonisolated CS in patients with histologically documented sarcoid. Diagnostic delays may contribute to differences in the dominant clinical presentation, despite similar outcomes.

Randomized evaluation of redo ablation procedures of atrial fibrillation with focal impulse and rotor modulation-guided procedures: the REDO-FIRM study.

AIMS: REDO-FIRM evaluated safety and effectiveness of conventional vs. focal impulse and rotor modulation (FIRM)-guided ablation of recurrent persistent or paroxysmal atrial fibrillation (AF) after an initial AF ablation procedure. METHODS AND RESULTS: This prospective, multicentre, randomized study included patients with a single prior AF ablation, but with recurrent AF and reconnected pulmonary veins (PVs). Conventional ablation generally included PV re-isolation; however, additional ablation was permitted per physician discretion. In the FIRM arm, beyond PV re-isolation, basket catheter-based FIRM mapping created dynamic animations of putative rotors, which were targeted for ablation. Between May 2016 and July 2019, 269 subjects were randomized, with 243 subjects completing 12-month follow-up. Ablation beyond re-pulmonary vein isolation, the FIRM vs. Conventional arms did not differ significantly: cavo-tricuspid isthmus -9.0% vs. 15.3%, caval vein isolation -1.5% vs. 0.8%, non-PV trigger -2.2% vs. 3.8%, other -11.9% vs. 13.0%. Single procedure 12-month freedom from AF/atrial tachycardia/atrial flutter-recurrence was 63.3% (76/120) vs. 59.0% (72/122) in the FIRM and Conventional arms (P = 0.3503). Efficacy was similar in the paroxysmal and persistent AF subgroups (P = 0.22 and P = 0.48). The 10-day and 12-month safety endpoints were achieved in 93.3% vs. 93.8% (P = 0.89) and 88.4% vs. 93.4% (P = 0.22) in the FIRM and Conventional arms, respectively. CONCLUSIONS: In REDO-FIRM, as compared to standard ablation, FIRM-guided ablation did not provide additional efficacy in redo ablation procedures, but FIRM-guided ablation was equally safe. Additional studies are necessary to identify any potential population able to benefit from FIRM-guided ablation.

Impact of late gadolinium enhancement extent, location, and pattern on ventricular tachycardia and major adverse cardiac events in patients with ischemic vs. non-ischemic cardiomyopathy.

Background: Left ventricular late gadolinium enhancement (LGE) by cardiac magnetic resonance (CMR) has been associated with increased risk for life-threatening ventricular tachyarrhythmias. The differences in association between LGE characteristics and prognosis in patients with ischemic (ICM) vs. non-ischemic (NICM) cardiomyopathy is incompletely understood. Methods: A total of 168 consecutive patients who underwent CMR imaging with either ICM or NICM were included in our study. LGE extent, location and pattern were examined for association to the primary endpoint of ventricular tachycardia (VT) and secondary endpoint of major adverse cardiac events (MACE). Results: Of 68 (41%) patients with ICM and 97 (59%) patients with NICM, median LGE mass was 15% (IQR 9-28) for the ICM group and 10% (IQR 6-15) for the NICM group. On multivariate analysis for both groups, LGE characteristics were prognostic while LVEF was not. In patients with ICM, septal and apical segment LGE, and involvement of multiple walls predicted both endpoints on multivariate analysis. LGE extent (≥median) and inferior wall LGE independently predicted the primary endpoint. In patients with NICM, anterior, inferior and apical segment LGE, and involvement of multiple walls predicted both endpoints on multivariate analysis. LGE extent (≥median, number of LGE segments, LGE stratified per 5% increase) and midwall LGE were independent predictors of the primary endpoint. Conclusions: Although LGE was an independent predictor of prognosis in both groups, LGE extent, location, and pattern characteristics were more powerful correlates to worse outcomes in patients with NICM than ICM.

Ablation of Refractory Ventricular Tachycardia Using Intramyocardial Needle Delivered Heated Saline-Enhanced Radiofrequency Energy: A First-in-Man Feasibility Trial.

BACKGROUND: Ablation of ventricular tachycardia (VT) is limited by the inability to create penetrating lesions to reach intramyocardial origins. Intramural needle ablation using in-catheter, heated saline-enhanced radio frequency (SERF) energy uses convective heating to increase heat transfer and produce deeper, controllable lesions at intramural targets. This first-in-human trial was designed to evaluate the safety and efficacy of SERF needle ablation in patients with refractory VT. METHODS: Thirty-two subjects from 6 centers underwent needle electrode ablation. Each had recurrent drug-refractory monomorphic VT after implantable cardioverter defibrillator implantation and prior standard ablation. During the SERF study procedure, one or more VTs were induced and mapped. The SERF needle catheter was used to create intramural lesions at targeted VT site(s). Acute procedural success was defined as noninducibility of the clinical VT after the procedure. Patients underwent follow-up at 30 days, and 3 and 6 months, with implantable cardioverter defibrillator interrogation at follow-up to determine VT recurrence. RESULTS: These refractory VT patients (91% male, 66±10 years, ejection fraction 35±11%; 56% ischemic, and 44% nonischemic) had a median of 45 device therapies (shock/antitachycardia pacing) for VT in the 3 to 6 months pre-SERF ablation. The study catheter was used to deliver an average of 10±5 lesions per case, with an average of 430±295 seconds of radiofrequency time, 122±65 minute of catheter use time, and a procedural duration of 4.3±1.3 hours. Acute procedural success was 97% for eliminating the clinical VT. At average follow-up of 5 months (n=32), device therapies were reduced by 89%. Complications included 2 periprocedural deaths: an embolic mesenteric infarct and cardiogenic shock, 2 mild strokes, and a pericardial effusion treated with pericardiocentesis (n=1). CONCLUSIONS: Intramural heated saline needle ablation showed complete acute and satisfactory mid-term control of difficult VTs failing 1 to 5 prior ablations and drug therapy. Further study is warranted to define safety and longer-term efficacy. REGISTRATION: URL: https://www. CLINICALTRIALS: gov; Unique Identifier: NCT03628534 and NCT02994446.

Effect of Catheter Ablation vs Antiarrhythmic Drug Therapy on Mortality, Stroke, Bleeding, and Cardiac Arrest Among Patients With Atrial Fibrillation: The CABANA Randomized Clinical Trial.

Importance: Catheter ablation is effective in restoring sinus rhythm in atrial fibrillation (AF), but its effects on long-term mortality and stroke risk are uncertain. Objective: To determine whether catheter ablation is more effective than conventional medical therapy for improving outcomes in AF. Design, Setting, and Participants: The Catheter Ablation vs Antiarrhythmic Drug Therapy for Atrial Fibrillation trial is an investigator-initiated, open-label, multicenter, randomized trial involving 126 centers in 10 countries. A total of 2204 symptomatic patients with AF aged 65 years and older or younger than 65 years with 1 or more risk factors for stroke were enrolled from November 2009 to April 2016, with follow-up through December 31, 2017. Interventions: The catheter ablation group (n = 1108) underwent pulmonary vein isolation, with additional ablative procedures at the discretion of site investigators. The drug therapy group (n = 1096) received standard rhythm and/or rate control drugs guided by contemporaneous guidelines. Main Outcomes and Measures: The primary end point was a composite of death, disabling stroke, serious bleeding, or cardiac arrest. Among 13 prespecified secondary end points, 3 are included in this report: all-cause mortality; total mortality or cardiovascular hospitalization; and AF recurrence. Results: Of the 2204 patients randomized (median age, 68 years; 37.2% female; 42.9% had paroxysmal AF and 57.1% had persistent AF), 89.3% completed the trial. Of the patients assigned to catheter ablation, 1006 (90.8%) underwent the procedure. Of the patients assigned to drug therapy, 301 (27.5%) ultimately received catheter ablation. In the intention-to-treat analysis, over a median follow-up of 48.5 months, the primary end point occurred in 8.0% (n = 89) of patients in the ablation group vs 9.2% (n = 101) of patients in the drug therapy group (hazard ratio [HR], 0.86 [95% CI, 0.65-1.15]; P = .30). Among the secondary end points, outcomes in the ablation group vs the drug therapy group, respectively, were 5.2% vs 6.1% for all-cause mortality (HR, 0.85 [95% CI, 0.60-1.21]; P = .38), 51.7% vs 58.1% for death or cardiovascular hospitalization (HR, 0.83 [95% CI, 0.74-0.93]; P = .001), and 49.9% vs 69.5% for AF recurrence (HR, 0.52 [95% CI, 0.45-0.60]; P < .001). Conclusions and Relevance: Among patients with AF, the strategy of catheter ablation, compared with medical therapy, did not significantly reduce the primary composite end point of death, disabling stroke, serious bleeding, or cardiac arrest. However, the estimated treatment effect of catheter ablation was affected by lower-than-expected event rates and treatment crossovers, which should be considered in interpreting the results of the trial. Trial Registration: ClinicalTrials.gov Identifier: NCT00911508.

Lessons Learned From the First Human Low-Field MRI Guided Radiation Therapy of the Heart in the Presence of an Implantable Cardiac Defibrillator.

Magnetic resonance imaging (MRI) guided radiation therapy is reported for the first time in a patient with an implantable cardioverter defibrillator (ICD) and cardiac fibroma in the left ventricle. Stereotactic body radiation therapy was delivered in 5 fractions at a dose of 700 cGy/fraction using a 0.35 T MRI-linear accelerator with real-time tumor tracking and beam gating. The average treatment time per fraction was 12.13 minutes, including gating dead time and gantry rotation, and the average duty cycle was 56.8%. Lessons learned included the need for MRI safety workflows that address the ICD and are tailored to the radiation oncology environment, selection of a suitable tracking target to ensure satisfactory duty cycle, and the presence of null band artifacts within the tracking target caused by ferrous components in the ICD.

Interactions Among Vitamin D, Atrial Fibrillation, and the Renin-Angiotensin-Aldosterone System.

Blockade of the renin-angiotensin-aldosterone system (RAAS) with angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARB) has been shown to decrease incident atrial fibrillation (AF). Vitamin D deficiency has been implicated but associations between vitamin D and AF are inconsistent. However, vitamin D deficiency results in renin and angiotensin upregulation. This study seeks to determine the relation between vitamin D deficiency and incident AF and characterize this relation in the setting of RAAS inhibition. A total of 47,062 patients with 25-hydroxyvitamin D [25(OH)D] laboratory testing were retrospectively identified. Clinical information was extracted from the medical record. The primary outcome was incidence of AF. Given significant patient variation, propensity score matching was used to select comparable groups of those who initiated ACEI/ARB ("AI") versus those who did not ("NAI"). Odds ratios (ORs) for incident AF associated with ACEI/ARB initiation and 25(OH)D level were estimated using generalized linear mixed models. AI patients had less incident AF than NAI patients (OR 0.36, 95% confidence interval [CI] 0.32 to 0.39) consistent with previous studies, but 25(OH)D deficiency was not associated with incident AF (OR 1.08, 95% CI 0.95 to 1.22). When stratified by 25(OH)D, there was a statistically significant decreased rate of AF in AI patients. Interestingly, this benefit was attenuated in 25(OH)D deficiency (deficient: OR 0.48, 95% CI 0.38 to 0.60 vs normal: OR 0.34, 95% CI 0.30 to 0.37). In conclusion, 25(OH)D deficiency was not associated with incident AF, and the benefit of ACE/ARB use was attenuated in 25(OH)D deficiency; this suggests that 25(OH)D may act as a cofactor in the mitigation of AF by RAAS inhibition.

Impact of ventricular tachycardia ablation on health care utilization.

BACKGROUND: Catheter ablation of ventricular tachycardia (VT) has been shown to reduce the number of recurrent shocks in patients with an implantable cardioverter-defibrillator (ICD). However, how VT ablation affects postprocedural medical and pharmaceutical usage remains unclear. OBJECTIVE: The purpose of this study was to investigate changes in health care resource utilization (HCRU) after VT ablation. METHODS: This large-scale, real-world, retrospective study used the MarketScan databases to identify patients in the United States with an ICD or cardiac resynchronization therapy-defibrillator (CRT-D) undergoing VT ablation. We calculated cumulative medical and pharmaceutical expenditures, office visits, hospitalizations, and emergency room (ER) visits in the 1-year periods before and after ablation. RESULTS: A total of 523 patients met the study inclusion criteria. After VT ablation, median annual cardiac rhythm-related medical expenditures decreased by $5,408. Moreover, the percentage of patients with at least 1 cardiac rhythm-related hospitalization and ER visit decreased from 53% and 41% before ablation to 28% and 26% after ablation, respectively. Similar changes were observed in the number of all-cause hospitalizations and ER visits, but there were no significant changes in all-cause medical expenditures. During the year before VT ablation, there was an increasing rate of health care resource utilization, followed by drastic slowing after ablation. CONCLUSION: This retrospective study demonstrated that catheter ablation seems to reduce hospitalization and overall health care utilization in VT patients with an ICD or CRT-D in place.

Spatial Relationships of Complex Fractionated Atrial Electrograms and Continuous Electrical Activity to Focal Electrical Sources: Implications for Substrate Ablation in Human Atrial Fibrillation.

OBJECTIVES: This study sought to evaluate the spatial relationships of focal electrical sources (FSs) to complex fractionated atrial electrograms (CFAE) and continuous electrical activity (CEA). BACKGROUND: Fractionated atrial electrograms have been associated with atrial fibrillation (AF) drivers in computational studies and represent ablation targets in the management of persistent AF. METHODS: We included a subset of 66 patients (age: 63 [56, 67] years, 69% persistent AF) with electroanatomic data from the SELECT AF (Selective complex fractionated atrial electrograms targeting for atrial fibrillation) randomized control trial that compared the efficacy of CFAE with CEA ablation in AF patients undergoing pulmonary vein antral ablation. Focal sources were identified based on bipolar electrogram periodicity and QS unipolar electrogram morphology. RESULTS: A total of 77 FSs (median: 1 [1st quartile, 3rd quartile: 1, 2] per patient) were identified most commonly in the pulmonary vein antrum and left atrial appendage. The proportions of FSs inside CFAE and CEA regions were similar (13% vs. 1.3%, respectively; p = 0.13). Focal sources were more likely to be on the border zone of CFAEs than in CEAs (49% vs. 7.8%, respectively; p = 0.012). Following ablation, 53% of patients had ≥1 unablated extrapulmonary vein FS. The median number of unablated FS was higher in patients with AF recurrence post ablation than in patients without (median: 1 [0, 1] vs. 0 [0, 1], respectively; p = 0.026). CONCLUSIONS: One-half of the FSs detected during AF localized to the border of CFAE areas, whereas most of the FSs were found outside CEA areas. CFAE or CEA ablation leaves a number of FS unablated, which is associated with AF recurrence. These findings suggest that many CFAEs may arise from passive wave propagation, remote from FS, which may limit their therapeutic efficacy in AF substrate modification.