Pulsed Field Ablation for the Treatment of Atrial Fibrillation: PULSED AF Pivotal Trial.

BACKGROUND: Pulsed field ablation uses electrical pulses to cause nonthermal irreversible electroporation and induce cardiac cell death. Pulsed field ablation may have effectiveness comparable to traditional catheter ablation while preventing thermally mediated complications. METHODS: The PULSED AF pivotal study (Pulsed Field Ablation to Irreversibly Electroporate Tissue and Treat AF) was a prospective, global, multicenter, nonrandomized, paired single-arm study in which patients with paroxysmal (n=150) or persistent (n=150) symptomatic atrial fibrillation (AF) refractory to class I or III antiarrhythmic drugs were treated with pulsed field ablation. All patients were monitored for 1 year using weekly and symptomatic transtelephonic monitoring; 3-, 6-, and 12-month ECGs; and 6- and 12-month 24-hour Holter monitoring. The primary effectiveness end point was freedom from a composite of acute procedural failure, arrhythmia recurrence, or antiarrhythmic escalation through 12 months, excluding a 3-month blanking period to allow recovery from the procedure. The primary safety end point was freedom from a composite of serious procedure- and device-related adverse events. Kaplan-Meier methods were used to evaluate the primary end points. RESULTS: Pulsed field ablation was shown to be effective at 1 year in 66.2% (95% CI, 57.9 to 73.2) of patients with paroxysmal AF and 55.1% (95% CI, 46.7 to 62.7) of patients with persistent AF. The primary safety end point occurred in 1 patient (0.7%; 95% CI, 0.1 to 4.6) in both the paroxysmal and persistent AF cohorts. CONCLUSIONS: PULSED AF demonstrated a low rate of primary safety adverse events (0.7%) and provided effectiveness consistent with established ablation technologies using a novel irreversible electroporation energy to treat patients with AF. REGISTRATION: URL: https://www. CLINICALTRIALS: gov; Unique identifier: NCT04198701.

Cryoballoon Ablation as Initial Therapy for Atrial Fibrillation.

BACKGROUND: In patients with symptomatic paroxysmal atrial fibrillation that has not responded to medication, catheter ablation is more effective than antiarrhythmic drug therapy for maintaining sinus rhythm. However, the safety and efficacy of cryoballoon ablation as initial first-line therapy have not been established. METHODS: We performed a multicenter trial in which patients 18 to 80 years of age who had paroxysmal atrial fibrillation for which they had not previously received rhythm-control therapy were randomly assigned (1:1) to receive treatment with antiarrhythmic drugs (class I or III agents) or pulmonary vein isolation with a cryoballoon. Arrhythmia monitoring included 12-lead electrocardiography conducted at baseline and at 1, 3, 6, and 12 months; patient-activated telephone monitoring conducted weekly and when symptoms were present during months 3 through 12; and 24-hour ambulatory monitoring conducted at 6 and 12 months. The primary efficacy end point was treatment success (defined as freedom from initial failure of the procedure or atrial arrhythmia recurrence after a 90-day blanking period to allow recovery from the procedure or drug dose adjustment, evaluated in a Kaplan-Meier analysis). The primary safety end point was assessed in the ablation group only and was a composite of several procedure-related and cryoballoon system-related serious adverse events. RESULTS: Of the 203 participants who underwent randomization and received treatment, 104 underwent ablation, and 99 initially received drug therapy. In the ablation group, initial success of the procedure was achieved in 97% of patients. The Kaplan-Meier estimate of the percentage of patients with treatment success at 12 months was 74.6% (95% confidence interval [CI], 65.0 to 82.0) in the ablation group and 45.0% (95% CI, 34.6 to 54.7) in the drug-therapy group (P<0.001 by log-rank test). Two primary safety end-point events occurred in the ablation group (Kaplan-Meier estimate of the percentage of patients with an event within 12 months, 1.9%; 95% CI, 0.5 to 7.5). CONCLUSIONS: Cryoballoon ablation as initial therapy was superior to drug therapy for the prevention of atrial arrhythmia recurrence in patients with paroxysmal atrial fibrillation. Serious procedure-related adverse events were uncommon. (Supported by Medtronic; STOP AF First ClinicalTrials.gov number, NCT03118518.).

Procedural and Intermediate-term Results of the Electroanatomical-guided Cardioneuroablation for the Treatment of Supra-Hisian Second- or Advanced-degree Atrioventricular Block: the PIRECNA multicentre registry.

AIMS: Prior case series showed promising results for cardioneuroablation in patients with vagally induced atrioventricular blocks (VAVBs). We aimed to examine the acute procedural characteristics and intermediate-term outcomes of electroanatomical-guided cardioneuroablation (EACNA) in patients with VAVB. METHODS AND RESULTS: This international multicentre retrospective registry included data collected from 20 centres. Patients presenting with symptomatic paroxysmal or persistent VAVB were included in the study. All patients underwent EACNA. Procedural success was defined by the acute reversal of atrioventricular blocks (AVBs) and complete abolition of atropine response. The primary outcome was occurrence of syncope and daytime second- or advanced-degree AVB on serial prolonged electrocardiogram monitoring during follow-up. A total of 130 patients underwent EACNA. Acute procedural success was achieved in 96.2% of the cases. During a median follow-up of 300 days (150, 496), the primary outcome occurred in 17/125 (14%) cases with acute procedural success (recurrence of AVB in 9 and new syncope in 8 cases). Operator experience and use of extracardiac vagal stimulation were similar for patients with and without primary outcomes. A history of atrial fibrillation, hypertension, and coronary artery disease was associated with a higher primary outcome occurrence. Only four patients with primary outcome required pacemaker placement during follow-up. CONCLUSION: This is the largest multicentre study demonstrating the feasibility of EACNA with encouraging intermediate-term outcomes in selected patients with VAVB. Studies investigating the effect on burden of daytime symptoms caused by the AVB are required to confirm these findings.

Thromboembolism, bleeding and vascular death in nonvalvular atrial fibrillation patients with type 2 diabetes receiving rivaroxaban or warfarin.

BACKGROUND: Diabetes increases a patient's risk of developing atrial fibrillation by 49%. Patients with nonvalvular atrial fibrillation are at a fivefold increased risk of stroke and die more frequently from vascular causes. We sought to evaluate the effectiveness and safety of rivaroxaban versus warfarin in nonvalvular atrial fibrillation patients with type 2 diabetes. METHODS: This was an analysis of Optum® De-Identified electronic health record data from 11/2010 to 12/2019. We included adults with nonvalvular atrial fibrillation and type 2 diabetes, newly started on rivaroxaban or warfarin and with ≥ 12-months of prior electronic health record activity. Patients who were pregnant, had alternative indications for oral anticoagulation or valvular heart disease were excluded. We evaluated the incidence rate (%/year) of developing the composite outcome of stroke/systemic embolism or vascular death and major or clinically relevant nonmajor bleeding as well as each endpoint individually. Hazard ratios with 95% confidence intervals were calculated using propensity score-overlap weighted proportional hazards regression. RESULTS: We included 32,078 rivaroxaban (31% initiated on 15 mg dose) and 83,971warfarin users (time-in-therapeutic range = 47 ± 28%). Rivaroxaban was associated with a reduced risk of stroke/systemic embolism or vascular death (3.79 vs. 4.19; hazard ratio = 0.91, 95% confdience interval = 0.88-0.95), driven mostly by reductions in vascular death (2.81 vs 3.18, hazard ratio = 0.90, 95% confidence interval = 0.86-0.95) and systemic embolism (0.13 vs. 0.16; hazard ratio = 0.82, 95% confidence interval = 0.66-1.02). Major/clinically relevant nonmajor bleeding was less frequent with rivaroxaban versus warfarin (2.17 vs. 2.31; hazard ratio = 0.94, 95% confidence interval = 0.89-0.99) due to decreased critical organ bleeding (including intracranial hemorrhage) (0.35 vs. 0.54; hazard ratio = 0.63, 95% confidence interval = 0.55-0.72). CONCLUSIONS: In nonvalvular atrial fibrillation patients with type 2 diabetes, rivaroxaban was associated with an ~ 10% relative reduction in vascular mortality and fewer bleeding-related hospitalizations versus warfarin.

Rivaroxaban versus apixaban in non-valvular atrial fibrillation patients with end-stage renal disease or receiving dialysis.

OBJECTIVES: We sought to evaluate the effectiveness and safety of rivaroxaban vs apixaban in non-valvular atrial fibrillation (NVAF) patients with end-stage renal disease (ESRD) and/or receiving dialysis in routine practice. METHODS: Using US MarketScan claims data from January 1, 2014, to December 31, 2017, we identified new-users of rivaroxaban or apixaban during 2015 with at least 12 months of insurance coverage prior to oral anticoagulant (OAC) initiation. Differences in baseline covariates between cohorts were adjusted using inverse probability-of-treatment weighting based on propensity scores. Patients were followed for stroke or systemic embolism (SSE) or major bleeding hospitalizations. Cox proportion hazards regression was used to compare rivaroxaban and apixaban. Analyses stratified by age, sex, CHA2DS2-VASc score, prior stroke, prior bleed, diabetes, and reduced OAC dose were performed. RESULTS: We identified 787 rivaroxaban and 1836 apixaban users. Median (25, 75% range) age = 70 (61, 79), CHA2DS2-VASc score = 3 (2, 4), and follow-up = 0.87 (0.38, 1.56) years. No differences in the risks of SSE (HR = 1.18, 95% CI = 0.53-2.63), ischemic stroke (HR = 1.12, 95%CI = 0.45-2.76), or major bleeding (HR = 1.00, 95% CI = 0.63-1.58) were observed. No significant interactions were observed upon subgroup analysis. CONCLUSION: In NVAF patients with ESRD and/or receiving dialysis, rivaroxaban and apixaban were associated with similar risks of SSE and major bleeding.

Effectiveness and safety of rivaroxaban and warfarin for prevention of major adverse cardiovascular or limb events in patients with non-valvular atrial fibrillation and type 2 diabetes.

AIMS: To assess the effectiveness and safety of rivaroxaban versus warfarin for the prevention of major adverse cardiovascular events (MACE) and major adverse limb events (MALE) in patients with type 2 diabetes (T2D) and non-valvular atrial fibrillation (NVAF). MATERIALS AND METHODS: Using MarketScan data from January 2012 to December 2017, we identified oral anticoagulant-naïve patients with NVAF and comorbid T2D and ≥12 months of insurance coverage prior to rivaroxaban or warfarin initiation. Differences in baseline covariates between cohorts were adjusted for using inverse probability of treatment weights based on propensity scores (absolute standardized differences <0.1 achieved for all covariates after adjustment). Patients were followed until a MACE, MALE or major bleeding event, oral anticoagulant discontinuation/switch, insurance disenrolment or end of data availability. Hazard ratios (HRs) and 95% confidence intervals (CIs) comparing the cohorts were calculated using Cox regression. RESULTS: We identified 10 700 rivaroxaban users (24.1% received a reduced dose) and 13 946 warfarin users. The median (25%, 75% range) age was 70 (62, 79) years, CHA2DS2-VASc score was 4 (3, 5) and duration of available follow-up was 1.4 (0.6, 2.7) years. Eleven percent of patients had peripheral artery disease, 5.1% had coronary artery disease, and 5.1% had a prior MALE, at baseline. Rivaroxaban was associated with a 25% (95% CI 4-41) reduced risk of MACE and a 63% (95% CI 35-79) reduced risk of MALE compared to warfarin. Major bleeding risk did not significantly differ between cohorts (HR 0.95). CONCLUSIONS: Among patients with NVAF and T2D treated in routine practice, rivaroxaban was associated with lower risks of both MACE and MALE versus warfarin, with no significant difference in major bleeding.

Association between myocardial substrate, implantable cardioverter defibrillator shocks and mortality in MADIT-CRT.

OBJECTIVE: The aim of the present study was to assess a possible association between myocardial substrate, implantable cardioverter defibrillator (ICD) shocks, and subsequent mortality. METHODS: Within the multicentre automatic defibrillator implantation trial-cardiac resynchronization therapy (MADIT-CRT) population (n = 1790), we investigated the association between myocardial substrate, ICD shocks and subsequent mortality using multivariate Cox regression analyses and landmark analyses at 1-year follow-up. RESULTS: The 4-year cumulative probability of ICD shocks was 13% for appropriate shock and 6% for inappropriate shock. Compared with patients who never received ICD therapy, patients who received appropriate shock had an increased risk of mortality [HR = 2.3 (1.47-3.54), P < 0.001], which remained increased after adjusting for echocardiographic remodelling at 1 year (HR = 2.8, P = 0.001). Appropriate anti-tachycardia pacing (ATP) only was not associated with increased mortality (P = 0.42). We were not able to show an association between inappropriate shocks (P = 0.53), or inappropriate ATP (P = 0.10) and increased mortality. Advanced myocardial structural disease, i.e. higher baseline echocardiographic volumes and lack of remodelling at 1 year, was present in patients who received appropriate shocks but not in patients who received inappropriate shocks or no shocks. CONCLUSION: In the MADIT-CRT study, receiving appropriate ICD shocks was associated with an increased risk of subsequent mortality. This association was not evident for appropriate ATP only. These findings, along with advanced cardiac structural disease in the patients who received appropriate shocks, suggest that the compromised myocardium is a contributing factor to the increased mortality associated with appropriate ICD shock therapy. Clinical trials.gov identifier: NCT00180271.

Relationship between quantitative cardiac neuronal imaging with ¹²³I-meta-iodobenzylguanidine and hospitalization in patients with heart failure.

PURPOSE: Hospitalization in patients with systolic heart failure is associated with morbidity, mortality, and cost. Myocardial sympathetic innervation, imaged by (123)I-meta-iodobenzylguanidine ((123)I-mIBG), has been associated with cardiac events in a recent multicenter study. The present analysis explored the relationship between (123)I-mIBG imaging findings and hospitalization. METHODS: Source documents from the ADMIRE-HF trial were reviewed to identify hospitalization events in patients with systolic heart failure following cardiac neuronal imaging using (123)I-mIBG. Time to hospitalization was analyzed with the Kaplan-Meier method and compared to the mIBG heart-to-mediastinum (H/M) ratio using multiple-failure Cox regression. RESULTS: During 1.4 years of median follow-up, 362 end-point hospitalizations occurred in 207 of 961 subjects, 79 % of whom had H/M ratio <1.6. Among subjects hospitalized for any cause, 88 % had H/M ratio <1.6 and subjects with H/M ratio <1.6 experienced hospitalization earlier than subjects with higher H/M ratios (log-rank p = 0.003). After adjusting for elevated brain natriuretic peptide (BNP) and time since heart failure diagnosis, a low mIBG H/M ratio was associated with cardiac-related hospitalization (HR 1.48, 95 % CI 1.05 - 2.0; p = 0.02). CONCLUSION: The mIBG H/M ratio may risk-stratify patients with heart failure for cardiac-related hospitalization, especially when used in conjunction with BNP. Further studies are warranted to examine these relationships.

Prevalence, Timing, and Impact of Early Recurrence of Atrial Tachyarrhythmias after Pulsed Field Ablation: A Secondary Analysis of the PULSED AF Trial.

BACKGROUND: Early recurrence of atrial tachyarrhythmias (ERATs) within three months following thermal ablation for atrial fibrillation (AF) is common and often considered transient. Pulsed field ablation (PFA) is a non-thermal energy source in which ERAT is not well described. OBJECTIVE: To analyze ERAT in AF patients undergoing PFA in the PULSED AF trial. METHODS: This analysis included 294 patients (154 paroxysmal, 140 persistent AF) that had ≥10 rhythm assessments during the 90-day blanking period. ERAT was defined as any instance of ≥30s of AF, atrial flutter, or atrial tachycardia on trans-telephonic monitoring (weekly and symptomatic) or ≥10s on ECG (at 3 months), both within 90 days. Late recurrence of atrial tachyarrhythmias (LRATs) was defined as observed atrial tachyarrhythmias between 90 days and 12 months. RESULTS: The overall prevalence of ERAT was 27.1% in paroxysmal and 31.6% in persistent AF patients. In patients with ERAT, 73% had ERAT onset within the first month post-procedure. Presence of ERAT was associated with LRAT in paroxysmal (HR 6.4 (95% c.i. 3.6-11.3)) and persistent (HR 3.8 (95% c.i. 2.2-6.6)) AF patients. Yet, in 29.4% of paroxysmal and 34.3% of persistent AF patients with ERAT, LRAT was not observed. LRAT was positively correlated with the number of ERAT observations. CONCLUSION: ERAT post PFA predicted LRAT in paroxysmal and persistent AF patients. However, the concept of a blanking period post PFA is still valid as approximately 1/3 of patients with ERAT did not continue on to LRAT during follow-up and may not need re-ablation.

Cardioneuroablation for the management of patients with recurrent vasovagal syncope and symptomatic bradyarrhythmias: the CNA-FWRD Registry.

BACKGROUND: Cardioneuroablation has been emerging as a potential treatment alternative in appropriately selected patients with cardioinhibitory vasovagal syncope (VVS) and functional AV block (AVB). However the majority of available evidence has been derived from retrospective cohort studies performed by experienced operators. METHODS: The Cardioneuroablation for the Management of Patients with Recurrent Vasovagal Syncope and Symptomatic Bradyarrhythmias (CNA-FWRD) Registry is a multicenter prospective registry with cross-over design evaluating acute and long-term outcomes of VVS and AVB patients treated by conservative therapy and CNA. RESULTS: The study is a prospective observational registry with cross-over design for analysis of outcomes between a control group (i.e., behavioral and medical therapy only) and intervention group (Cardioneuroablation). Primary and secondary outcomes will only be assessed after enrollment in the registry. The follow-up period will be 3 years after enrollment. CONCLUSIONS: There remains a lack of prospective multicentered data for long-term outcomes comparing conservative therapy to radiofrequency CNA procedures particularly for key outcomes including recurrence of syncope, AV block, durable impact of disruption of the autonomic nervous system, and long-term complications after CNA. The CNA-FWRD registry has the potential to help fill this information gap.

Frequency of inappropriate therapy in patients implanted with dual- versus single-chamber ICD devices in the ICD arm of MADIT-CRT.

BACKGROUND: The majority of implantable cardioverter defibrillators (ICDs) are dual-chamber devices, but studies on the frequency of inappropriate therapy in dual- versus single-chamber devices have shown conflicting results. The aim of this study is to determine whether implantation of dual-chamber ICD devices decrease the incidence of inappropriate therapy without an unacceptable increase in complications. METHODS: In the ICD arm of the MADIT-CRT study (N = 704), comparisons of single- versus dual-chamber ICD devices were investigated on the endpoints of inappropriate therapy (antitachycardia pacing [ATP] and shocks) and device- and procedure-related complications by use of multivariate Cox proportional hazard regression analysis (hazard ratio dual:single chamber) adjusting for relevant covariates. RESULTS: The frequency of inappropriate therapies in single- and dual-chamber recipients was 41/294 (14%) and 50/410 (12%), respectively. There was no significant difference in overall inappropriate therapy (hazard ratio [HR] = 0.95 [CI: 0.63-1.45], P = 0.95) or inappropriate ATP (HR = 0.98 [CI: 0.61-1.58], P = 0.94), between single- and dual-chamber devices, using single-chamber as a reference (Dual:Single). However, there was a trend toward a decrease in inappropriate shocks (HR = 0.60 [CI: 0.34-1.08], P = 0.09) in the dual-chamber group. The same was evident when only analyzing inappropriate therapy for atrial tachyarrhythmias (HR = 0.88 [CI: 0.56-1.38], P = 0.58). There was no significant difference between the groups in device- or procedure-related complications (HR = 1.54 [CI: 0.82-2.90], P = 0.18). CONCLUSION: No significant difference was found in inappropriate therapy or complications in patients treated with single- versus dual-chamber ICD devices.

Resting perfusion MPI-SPECT combined with cardiac 123I-mIBG sympathetic innervation imaging improves prediction of arrhythmic events in non-ischemic cardiomyopathy patients: sub-study from the ADMIRE-HF trial.

BACKGROUND: Delayed Iodine-123 meta-iodobenzylguanidine heart/mediastinum (H/M) uptake ratio predicted arrhythmic events in patients with heart failure (HF) and significant left ventricular dysfunction in ADMIRE-HF. We tested the hypothesis that resting perfusion defects on MPI-SPECT, representing scar, would further risk stratify patients beyond H/M ratio in the prediction of ventricular arrhythmic events in both ischemic (ICM) and non-ischemic cardiomyopathy (NICM) patients. METHODS: Patients from the ADMIRE-HF database were classified as ICM and NICM and were stratified by delayed H/M ratio (<1.6/≥1.6) and by summed rest score (SRS) (≤8/>8) on MPI-SPECT. The entire cohort was also classified as high risk (H/M <1.6, SRS >8) and low risk (H/M ≥1.6, SRS ≤8). Scores were from visual interpretation of individual and derived consensus (average) reads per ASNC guidelines. RESULTS: There were 612 (66%) ICM and 317 (34%) NICM patients. ICM patients had higher mean SRS than NICM patients (25 ± 13 vs 12 ± 10). Sixty-three arrhythmic events occurred over a median follow-up of 17 months. SRS had incremental predictive value among NICM patients with low H/M ratio (<1.6). There was no risk stratification in patients with ICM. Multivariable analysis for NICM with H/M ratio <1.6 demonstrated SRS score >8 as the only independent predictor of arrhythmic events (hazard ratio 3.3, 95% CI 1.1-9.8, P = .03). Patients classified in high-risk subgroup had statistically significant increased risk of arrhythmic events (hazard ratio 2.080, 95% CI 1.112-3.894, P = .022). There was only one event in low-risk subgroup with a trend towards lower risk of arrhythmic events (P = .07). CONCLUSION: Resting perfusion defects provide independent risk stratification in addition to Iodine-123 meta-iodobenzylguanidine sympathetic innervation imaging in predicting arrhythmic events in patients with NICM and HF. High and potentially low-risk groups for arrhythmic events can be identified based on the severity of resting perfusion defect score and H/M ratio.

Predictors of pacemaker dependence and pacemaker dependence as a predictor of mortality in patients with implantable cardioverter defibrillator.

BACKGROUND: The prevalence, predictors, and survival for the development of pacemaker dependence (PD) in patients implanted with an implantable cardioverter defibrillator (ICD) are unknown. METHODS: This was a retrospective analysis of 1,550 consecutive patients with ICD implantation at a single center from 1996 to 2008 with a mean of 4.2 ± 3.4 years. Patients with implant intrinsic heart rates less than 40 beats/min (n = 48) and cardiac resynchronization therapy (n = 444) were excluded leaving 1,058 patients in this study. PD was defined as an intrinsic rhythm <40 beats/min after inhibiting the pacemaker, <50 beats/min with transient symptoms of dizziness relieved by resumption of pacing and right ventricle pacing despite algorithms to promote intrinsic conduction at the 3 monthly follow-up ICD clinic visits. Multivariate regression and Cox proportional hazard models were used for analysis. RESULTS: The mean age was 64 ± 13 years; 79% were male with a primary indication for the ICD in 57%. PD occurred in 142 (13.4%) of patients, with a mean time to PD of 2.6 ± 1.9 years. PD was associated with a 48% increased odds for mortality versus non-PD ICD patients during the mean follow-up time of 4.2 ± 3.4 years (adjusted odds ratio = 1.48 [95% confidence interval 1.080-2.042]; P = 0.015). Older age, a history of atrial fibrillation, amiodarone use, and secondary prevention were the strongest predictors for the development of PD. CONCLUSIONS: In this single-center ICD cohort, the development of PD was not uncommon and was associated with decreased survival.

The role of ablation of the atrioventricular junction in patients with heart failure and atrial fibrillation.

Ablation of the atrioventricular junction (AVJ) is a technically easy procedure that is safe and has a high success rate as an intervention for effective ventricular rate control in patients in symptomatic atrial fibrillation. AVJ ablation has been reported to improve quality of life, left ventricular ejection fraction, and exercise duration in these patients and minimize the incidence of inappropriate shocks. Because right ventricular pacing after AVJ ablation may result in decrease in left ventricular function and worsening of heart failure symptoms, there is increasing evidence to support the effectiveness of cardiac resynchronization therapy in atrial fibrillation populations.

Effectiveness and Safety of Rivaroxaban Versus Warfarin among Nonvalvular Atrial Fibrillation Patients with Concomitant Obstructive Sleep Apnea.

Background Obstructive sleep apnea (OSA) is associated with an increased incidence of atrial fibrillation (AF), hypertension, diabetes, heart failure, coronary heart disease, stroke, and death. We sought to evaluate the effectiveness and safety of rivaroxaban versus warfarin in nonvalvular AF (NVAF) patients with concomitant OSA. Methods This was an analysis of electronic health record (EHR) data from November 2010 to December 2021. We included adults with NVAF and OSA at baseline, newly initiated on rivaroxaban or warfarin, and with ≥12 months of prior EHR activity. Patients with valvular disease, alternative indications for oral anticoagulation, or who were pregnant were excluded. The incidence rates of developing stroke or systemic embolism (SSE) and bleeding-related hospitalization were evaluated. Hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated using propensity score-overlap weighted proportional hazards regression. Multiple sensitivity and subgroup analyses were performed. Results We included 21,940 rivaroxaban (20.1% at the 15 mg dose) and 38,213 warfarin (time-in-therapeutic range = 47.3 ± 28.3%) patients. Rivaroxaban was found to have similar hazard of SSE compared to warfarin (HR = 0.92, 95% CI = 0.82-1.03). Rivaroxaban was associated with a reduced rate of bleeding-related hospitalizations (HR = 0.85, 95% CI = 0.78-0.92) versus warfarin, as well as reductions in intracranial (HR = 0.76, 95% CI = 0.62-0.94) and extracranial (HR = 0.89, 95%CI = 0.81-0.97) bleeding. Upon sensitivity analysis restricting the population to men with a CHA 2 DS 2 VASc score ≥2 or women with a score ≥3, rivaroxaban was associated with a significant 33% risk reduction in SSE and 43% reduction in the risk of bleeding-related hospitalization. No significant interaction for the SSE or bleeding-related hospitalization outcomes was observed upon subgroup analyses. Conclusion Among patients with NVAF and OSA, rivaroxaban had similar SSE risk versus warfarin but was associated with reductions in any intracranial and extracranial bleeding-related hospitalizations. Rivaroxaban was associated with significant reductions in SSE and bleeding-related hospitalizations when the study population was restricted to patients with a moderate-to-high risk of SSE. These data should provide prescribers with additional confidence in selecting rivaroxaban in NVAF patients who have OSA at the time of anticoagulation initiation.

Influence of monitoring and atrial arrhythmia burden on quality of life and health care utilization in patients undergoing pulsed field ablation: A secondary analysis of the PULSED AF trial.

BACKGROUND: Freedom from atrial arrhythmia (AA) recurrence ≥30 seconds after pulsed field ablation (PFA) in patients with atrial fibrillation (AF) was reported in PULSED AF (Pulsed Field Ablation to Irreversibly Electroporate Tissue and Treat AF; ClinialTrials.gov Identifier: NCT04198701). AA burden may be a more clinically meaningful endpoint. OBJECTIVE: The purpose of this study was to determine the influence of monitoring strategies on AA detection and AA burden association with quality of life (QoL) and health care utilization (HCU) after PFA. METHODS: Patients underwent 24-hour Holter monitoring at 6 and 12 months and weekly, and symptomatic transtelephonic monitoring (TTM). AA burden post-blanking was calculated as the greater of (1) percentage of AA on total Holter time; or (2) percentage of weeks with ≥1 TTM with AA out of all weeks with ≥1 TTM. RESULTS: Freedom from all AAs varied by >20% when differing monitoring strategies were used. PFA resulted in zero burden in 69.4% of paroxysmal atrial fibrillation (PAF) and 62.2% of persistent atrial fibrillation (PsAF) patients. Median burden was low (<9%). Most PAF and PsAF patients had ≤1 week of AA detection on TTM (82.6% and 75.4%) and <30 minutes of AA per day of Holter monitoring (96.5% and 89.6%), respectively. Only PAF patients with <10% AA burden averaged a clinically meaningful (>19 point) QoL improvement. PsAF patients experienced clinically meaningful QoL improvements irrespective of burden. Repeat ablations and cardioversions significantly increased with higher AA burden (P <.01). CONCLUSION: The ≥30-second AA endpoint is dependent on the monitoring protocol used. PFA resulted in low AA burden for most patients, which was associated with clinically relevant improvement in QoL and reduced AA-related HCU.

Risk stratification of CAD with SPECT-MPI in women with known estrogen status.

OBJECTIVE: To compare exercise tolerance testing (ETT) with gated single photon emission computed tomography-myocardial perfusion imaging (SPECT-MPI) risk stratification in women with an intermediate to high CAD pretest risk and known estrogen status (ES). BACKGROUND: SPECT-MPI is an effective test for risk stratifying patients with stable angina. However in women, the current guidelines recommend the exercise tolerance testing (ETT) as first line test. Further, the relationship of stress imaging to ES, an independent risk indicator for CAD, is unknown. METHODS: 2,194 women with an intermediate to high CAD pre-test risk were referred for a clinically indicated ETT with gated SPECT-MPI. Duke treadmill scores (DTS) and summed stress score (SSS) were calculated. SSS were classified as normal (SSS < 3), mildly abnormal (SSS 4-8), or moderate-severely abnormal (SSS > 8). The ES was assessed as premenopausal, postmenopausal on hormone replacement therapy (HRT) as ES+ while postmenopausal not on HRT were ES-. An annualized cardiac event rate of a composite of cardiac death, unstable angina (UA) leading to hospitalization, non-fatal myocardial infarction, or late coronary revascularization was calculated for all the groups. RESULTS: The annualized cardiac event rate was 1.3% PPY, 2.1% PPY, and 3.2% PPY for low, intermediate, and high risk DTS (P = .2). Patients with intermediate DTS and mildly abnormal or moderate-severely abnormal gated SPECT-MPI had a significantly higher cardiac event rates (5.3% PPY and 10.8% PPY, respectively) than those with a normal gated SPECT-MPI (1.2%, PPY, P = .01). This was also demonstrated on further Cox-regression analysis. Risk stratification of SPECT-MPI over DTS was independent of ES. CONCLUSION: Gated SPECT-MPI provides risk stratification beyond standard exercise stress testing for women with suspected coronary artery disease, especially in patients with intermediate DTS and is independent of ES.

A RIVA-DM Subanalysis Investigating Patients With Nonvalvular Atrial Fibrillation and Type 2 Diabetes Aged Under Versus Over 80 Years.

BACKGROUND: Advanced age and type 2 diabetes (T2D) are common in patients with nonvalvular atrial fibrillation (NVAF). We evaluated the impact of age on the effectiveness and safety of rivaroxaban versus warfarin in this population. METHODS: We analyzed electronic health record data from November 2010, to December 2019 including adults with NVAF and T2D, newly started on rivaroxaban or warfarin. Propensity score-overlap weighted hazard ratios (HRs) for stroke/systemic embolism (SSE), hospitalization for major or clinically relevant nonmajor bleeding (CRNMB), vascular death, major adverse limb events (MALE), major bleeding, and intracranial hemorrhage (ICH) were calculated for older (≥80 years) and younger (<80 years) cohorts. RESULTS: We included 32 078 rivaroxaban and 83 971 warfarin users (6606 rivaroxaban and 25,335 warfarin patients were aged ≥80 years). No significant interaction for rivaroxaban versus warfarin by age was observed for any outcome, including SSE (HR = 1.05 vs 0.95), hospitalization for major or CRNMB (HR = 1.06 vs 0.90), vascular death (HR = 0.92 vs 0.90), MALE (HR = 0.80 vs 0.76), major bleeding or ICH. CONCLUSIONS: The effectiveness and safety of rivaroxaban versus warfarin remained consistent across patient age subgroups.

Quality of life after the initial treatment of atrial fibrillation with cryoablation versus drug therapy.

BACKGROUND: The STOP AF First trial recently demonstrated that initial treatment with cryoballoon ablation (CBA) is safe and superior to antiarrhythmic drug (AAD) therapy for preventing atrial arrhythmia recurrence in patients with symptomatic atrial fibrillation (AF). OBJECTIVE: The purpose of this study was to evaluate the change in quality of life (QoL) and symptoms after first-line CBA vs AAD therapy. METHODS: Patients with symptomatic AF not previously receiving rhythm control therapy were randomized to AAD (class I or III) or CBA (Arctic Front Advance, Medtronic, Mounds View, MN). QoL was evaluated at baseline and at 6 and 12 months by using the Atrial Fibrillation Effect on QualiTy-of-Life (AFEQT) and the European Quality of Life-5 Dimensions questionnaires. A review of AF-associated symptoms was conducted at baseline and at 1, 3, 6, and 12 months. RESULTS: In total, 203 subjects received either CBA (n = 104 [51.2%]) or AAD therapy (n = 99 [48.8%]). Improvements in the AFEQT summary and subscale scores were significantly larger with CBA than with AAD therapy at 6 and 12 months (P < .02 for all). Clinically meaningful improvement (>5 points) in the AFEQT summary score from baseline to 12 months was observed in 96.0% (100) of patients in the CBA arm vs 72.2% (71) of patients in the AAD arm (P < .001). No significant between-group differences were observed in the change in the European Quality of Life-5 Dimensions index or visual analog scale scores. Overall, 54.4% (57) of the CBA group vs 29.7% (29) of the AAD group reported no AF-specific symptom recurrence after a 90-day blanking period (P = .0005). CONCLUSION: First-line CBA vs AAD therapy is associated with larger improvements in AF-specific QoL and a higher rate of symptom resolution.