Comparative arrhythmia patterns among patients on tyrosine kinase inhibitors.

BACKGROUND: Tyrosine kinase inhibitors (TKIs) are widely used in the treatment of hematologic malignancies. Limited studies have shown an association between treatment-limiting arrhythmias and TKI, particularly ibrutinib, a Bruton's tyrosine kinase (BTK) inhibitor. We sought to comprehensively assess the arrhythmia burden in patients receiving ibrutinib vs non-BTK TKI vs non-TKI therapies. METHODS: We performed a retrospective analysis of consecutive patients who received long-term cardiac event monitors while on ibrutinib, non-BTK TKIs, or non-TKI therapy for a hematologic malignancy between 2014 and 2022. RESULTS: One hundred ninety-three patients with hematologic malignancies were included (ibrutinib = 72, non-BTK TKI = 46, non-TKI therapy = 75). The average duration of TKI therapy was 32 months in the ibrutinib group vs 64 months in the non-BTK TKI group (p = 0.003). The ibrutinib group had a higher prevalence of atrial fibrillation (n = 32 [44%]) compared to the non-BTK TKI (n = 7 [15%], p = 0.001) and non-TKI (n = 15 [20%], p = 0.002) groups. Similarly, the prevalence of non-sustained ventricular tachycardia was higher in the ibrutinib group (n = 31, 43%) than the non-BTK TKI (n = 8 [17%], p = 0.004) and non-TKI groups (n = 20 [27%], p = 0.04). TKI therapy was held in 25% (n = 18) of patients on ibrutinib vs 4% (n = 2) on non-BTK TKIs (p = 0.005) secondary to arrhythmias. CONCLUSIONS: In this large retrospective analysis of patients with hematologic malignancies, patients receiving ibrutinib had a higher prevalence of atrial and ventricular arrhythmias compared to those receiving other TKI, with a higher rate of treatment interruption due to arrhythmias.

Tyrosine kinase inhibitor-associated ventricular arrhythmias: a case series and review of literature.

BACKGROUND: Tyrosine kinase inhibitors (TKIs) have been increasingly used as first-line therapy in hematologic and solid-organ malignancies. Multiple TKIs have been linked with the development of cardiovascular complications, especially atrial arrhythmias, but data on ventricular arrhythmias (VAs) is scarce. METHODS: Herein we describe five detailed cases of VAs related to TKI use in patients with varied baseline cardiovascular risk factors between 2019 and 2022 at three centers. Individual chart review was conducted retrospectively. RESULTS: Patient ages ranged from 43 to 83 years. Three patients were on Bruton's TKI (2 ibrutinib and 1 zanubrutinib) at the time of VAs; other TKIs involved were afatinib and dasatinib. Three patients had a high burden of non-sustained ventricular tachycardia (NSVT) requiring interventions, whereas two patients had sustained VAs. While all patients in our case series had significant improvement in VA burden after TKI cessation, two patients required new long-term antiarrhythmic drug therapy, and one had an implantable defibrillator cardioverter (ICD) placed due to persistent VAs after cessation of TKI therapy. One patient reinitiated TKI therapy after control of arrhythmia was achieved with antiarrhythmic drug therapy. CONCLUSIONS: Given the expanding long-term use of TKIs among a growing population of cancer patients, it is critical to acknowledge the association of TKIs with cardiovascular complications such as VAs, to characterize those at risk, and deploy preventive and therapeutic measures to avoid such complications and interference with oncologic therapy. Further efforts are warranted to develop monitoring protocols and optimal treatment strategies for TKI-induced VAs.

Hybrid Ablation for Atrial Fibrillation: Safety & Efficacy of Unilateral Epicardial Access.

Hybrid ablation combines thoracoscopic epicardial ablation with percutaneous catheter based endocardial ablation for the treatment of AF. The purpose of this study was to evaluate the safety and efficacy of hybrid ablation surgery for the treatment of atrial fibrillation (AF), and to compare outcomes of unilateral vs bilateral thoracoscopic epicardial ablation. Patients with documented AF who underwent hybrid ablation were followed post-operatively for major events. Major events were classified into 2 categories consisting of (1) safety, comprising all-cause mortality and major morbidities, and (2) efficacy, which included recurrence of atrial arrhythmia, cessation of antiarrhythmic drugs (AAD), and completeness of lesion set. A total of 84 consecutive patients were consented for hybrid ablation. Patients presented with an average AF duration of 85.9 months before hybrid ablation. 80 patients underwent successful thoracoscopic epicardial ablation. At 1-year, 87% (60/69) of patients were free from AF and 73% (50/69) were free from AF and off AAD. 63 patients completed both epicardial and endocardial hybrid ablation with posterior wall isolation achieved in 89% (56/63) of patients. Unilateral epicardial ablation was associated with significantly shorter hospital length of stay compared to bilateral surgical approached (3.9 vs 6.7 days, p = 0.002) with no difference in freedom from AF between groups at 1 year. Hybrid ablation for atrial fibrillation is effective for patients at high risk for recurrence after catheter ablation. The unilateral surgical approach may be associated with shorter hospital stay with no appreciable effect on procedure success rates.

Advances in Cardiac Electrophysiology.

Despite the global COVID-19 pandemic, during the past 2 years, there have been numerous advances in our understanding of arrhythmia mechanisms and diagnosis and in new therapies. We increased our understanding of risk factors and mechanisms of atrial arrhythmias, the prediction of atrial arrhythmias, response to treatment, and outcomes using machine learning and artificial intelligence. There have been new technologies and techniques for atrial fibrillation ablation, including pulsed field ablation. There have been new randomized trials in atrial fibrillation ablation, giving insight about rhythm control, and long-term outcomes. There have been advances in our understanding of treatment of inherited disorders such as catecholaminergic polymorphic ventricular tachycardia. We have gained new insights into the recurrence of ventricular arrhythmias in the setting of various conditions such as myocarditis and inherited cardiomyopathic disorders. Novel computational approaches may help predict occurrence of ventricular arrhythmias and localize arrhythmias to guide ablation. There are further advances in our understanding of noninvasive radiotherapy. We have increased our understanding of the role of His bundle pacing and left bundle branch area pacing to maintain synchronous ventricular activation. There have also been significant advances in the defibrillators, cardiac resynchronization therapy, remote monitoring, and infection prevention. There have been advances in our understanding of the pathways and mechanisms involved in atrial and ventricular arrhythmogenesis.

Mapping Atrial Fibrillation After Surgical Therapy to Guide Endocardial Ablation.

BACKGROUND: Surgical ablation for atrial fibrillation (AF) can be effective, yet has mixed results. It is unclear which endocardial lesions delivered as part of hybrid therapy' will best augment surgical lesion sets in individual patients. We addressed this question by systematically mapping AF endocardially after surgical ablation and relating findings to early recurrence, then performing tailored endocardial ablation as part of hybrid therapy. METHODS: We studied 81 consecutive patients undergoing epicardial surgical ablation (stage 1 hybrid), of whom 64 proceeded to endocardial catheter mapping and ablation (stage 2). Stage 2 comprised high-density mapping of pulmonary vein (PV) or posterior wall (PW) reconnections, low-voltage zones (LVZs), and potential localized AF drivers. We related findings to postsurgical recurrence of AF. RESULTS: Mapping at stage 2 revealed PW isolation reconnection in 59.4%, PV isolation reconnection in 28.1%, and LVZ in 42.2% of patients. Postsurgical recurrence of AF occurred in 36 patients (56.3%), particularly those with long-standing persistent AF (P=0.017), but had no relationship to reconnection of PVs (P=0.53) or PW isolation (P=0.75) when compared with those without postsurgical recurrence of AF. LVZs were more common in patients with postsurgical recurrence of AF (P=0.002), long-standing persistent AF (P=0.002), advanced age (P=0.03), and elevated CHA2DS2-VASc (P=0.046). AF mapping revealed 4.4±2.7 localized focal/rotational sites near and also remote from PV or PW reconnection. After ablation at patient-specific targets, arrhythmia freedom at 1 year was 81.0% including and 73.0% excluding previously ineffective antiarrhythmic medications. CONCLUSIONS: After surgical ablation, AF may recur by several modes particularly related to localized mechanisms near low voltage zones, recovery of posterior wall or pulmonary vein isolation, or other sustaining mechanisms. LVZs are more common in patients at high clinical risk for recurrence. Patient-specific targeting of these mechanisms yields excellent long-term outcomes from hybrid ablation.

Research Priorities in the Secondary Prevention of Atrial Fibrillation: A National Heart, Lung, and Blood Institute Virtual Workshop Report.

There has been sustained focus on the secondary prevention of coronary heart disease and heart failure; yet, apart from stroke prevention, the evidence base for the secondary prevention of atrial fibrillation (AF) recurrence, AF progression, and AF-related complications is modest. Although there are multiple observational studies, there are few large, robust, randomized trials providing definitive effective approaches for the secondary prevention of AF. Given the increasing incidence and prevalence of AF nationally and internationally, the AF field needs transformative research and a commitment to evidenced-based secondary prevention strategies. We report on a National Heart, Lung, and Blood Institute virtual workshop directed at identifying knowledge gaps and research opportunities in the secondary prevention of AF. Once AF has been detected, lifestyle changes and novel models of care delivery may contribute to the prevention of AF recurrence, AF progression, and AF-related complications. Although benefits seen in small subgroups, cohort studies, and selected randomized trials are impressive, the widespread effectiveness of AF secondary prevention strategies remains unknown, calling for development of scalable interventions suitable for diverse populations and for identification of subpopulations who may particularly benefit from intensive management. We identified critical research questions for 6 topics relevant to the secondary prevention of AF: (1) weight loss; (2) alcohol intake, smoking cessation, and diet; (3) cardiac rehabilitation; (4) approaches to sleep disorders; (5) integrated, team-based care; and (6) nonanticoagulant pharmacotherapy. Our goal is to stimulate innovative research that will accelerate the generation of the evidence to effectively pursue the secondary prevention of AF.

Guidance for Rebooting Electrophysiology Through the COVID-19 Pandemic From the Heart Rhythm Society and the American Heart Association Electrocardiography and Arrhythmias Committee of the Council on Clinical Cardiology: Endorsed by the American College of Cardiology.

Coronavirus disease 2019 (COVID-19) has presented substantial challenges to patient care and impacted health care delivery, including cardiac electrophysiology practice throughout the globe. Based upon the undetermined course and regional variability of the pandemic, there is uncertainty as to how and when to resume and deliver electrophysiology services for arrhythmia patients. This joint document from representatives of the Heart Rhythm Society, American Heart Association, and American College of Cardiology seeks to provide guidance for clinicians and institutions reestablishing safe electrophysiological care. To achieve this aim, we address regional and local COVID-19 disease status, the role of viral screening and serologic testing, return-to-work considerations for exposed or infected health care workers, risk stratification and management strategies based on COVID-19 disease burden, institutional preparedness for resumption of elective procedures, patient preparation and communication, prioritization of procedures, and development of outpatient and periprocedural care pathways.

Year in Review in Cardiac Electrophysiology.

In the past year, there have been numerous advances in our understanding of arrhythmia mechanisms, diagnosis, and new therapies. We have seen advances in basic cardiac electrophysiology with data suggesting that secretoneurin may be a biomarker for patients at risk of ventricular arrhythmias, and we have learned of the potential role of an NPR-C (natriuretic peptide receptor-C) in atrial fibrosis and the role of an atrial specific 2-pore potassium channel TASK-1 as a therapeutic target for atrial fibrillation. We have seen studies demonstrating the role of sensory neurons in sleep apnea-related atrial fibrillation and the association between bariatric surgery and atrial fibrillation ablation outcomes. Artificial intelligence applied to electrocardiography has yielded estimates of age, sex, and overall health. We have seen new tools for collection of patient-centered outcomes following catheter ablation. There have been significant advances in the ability to identify ventricular tachycardia termination sites through high-density mapping of deceleration zones. We have learned that right ventricular dysfunction may be a predictor of survival benefit after implantable cardioverter-defibrillator implantation in patients with nonischemic cardiomyopathy. We have seen further insights into the role of His bundle pacing on improving outcomes. As our understanding of cardiac laminopathies advances, we may have new tools to predict arrhythmic event rates in gene carriers. Finally, we have seen numerous advances in the treatment of arrhythmias in patients with congenital heart disease.

Novel three-dimensional imaging approach for cryoballoon navigation and confirmation of pulmonary vein occlusion.

BACKGROUND: Cryoballoon apposition is crucial for durable pulmonary vein isolation (PVI) in atrial fibrillation, yet the balloon is difficult to visualize by conventional mapping systems, and pulmonary venography may miss small or out-of-plane leaks. We report a novel imaging system that offers real-time 3D navigation of the cryoballoon within atrial anatomy that may circumvent these issues. METHODS AND RESULTS: A novel overlay guidance system (OGS) registers already-acquired segmented atrial cardiac tomography (CT) with fluoroscopy, enabling real-time visualization of the cryoballoon within tomographic left atrial imaging during PVI. Phantom experiments in a patient-specific 3D printed left atrium showed feasibility for confirming PV apposition and leaks. We applied OGS prospectively to 68 PVs during PVI in 17 patients. The cryoballoon was successfully reconstructed in all cases, and its apposition was compared to concurrent PV venography. The OGS uncovered leaks undetected by venography in nine veins (eight cases), which enabled repositioning, confirming apposition in remaining 68 veins. Concordance of OGS to venography was 83.8% (χ2 , P < .01) CONCLUSIONS: We report a new system for real-time imaging of cryoballoon catheters to ensure PV apposition within the tomography of the left atrium. While providing high concordance with other imaging modalities for confirming balloon apposition or leak, the system also identified leaks missed by venography. Future studies should determine if this tool can provide a new reference for cryoballoon positioning.

Cryoballoon Ablation for Atrial Fibrillation: a Comprehensive Review and Practice Guide.

The cryoballoon was invented to achieve circumferential pulmonary vein isolation more efficiently to compliment the shortcomings of point-by-point ablation by radiofrequency ablation (RFA). Its efficacy and safety were shown to be comparable to those of RFA, and the clinical outcomes have improved with the second-generation cryoballoon. The basic biophysics, implemental techniques, procedural recommendations, clinical outcomes, and complications of the cryoballoon are presented in this practical and systematic review.

Recurrent Post-Ablation Paroxysmal Atrial Fibrillation Shares Substrates With Persistent Atrial Fibrillation : An 11-Center Study.

INTRODUCTION: The role of atrial fibrillation (AF) substrates is unclear in patients with paroxysmal AF (PAF) that recurs after pulmonary vein isolation (PVI). We hypothesized that patients with recurrent post-ablation (redo) PAF despite PVI have electrical substrates marked by rotors and focal sources, and structural substrates that resemble persistent AF more than patients with (de novo) PAF at first ablation. METHODS: In 175 patients at 11 centers, we compared AF substrates in both atria using 64 pole-basket catheters and phase mapping, and indices of anatomical remodeling between patients with de novo or redo PAF and first ablation for persistent AF. RESULTS: Sources were seen in all patients. More patients with de novo PAF (78.0%) had sources near PVs than patients with redo PAF (47.4%, p=0.005) or persistent AF (46.9%, p=0.001). The total number of sources per patient (p=0.444), and number of non-PV sources (p=0.701) were similar between groups, indicating that redo PAF patients had residual non-PV sources after elimination of PV sources by prior PVI. Structurally, left atrial size did not separate de novo from redo PAF (49.5±9.5 vs. 49.0±7.1mm, p=0.956) but was larger in patients with persistent AF (55.2±8.4mm, p=0.001). CONCLUSIONS: Patients with paroxysmal AF despite prior PVI show electrical substrates that resemble persistent AF more closely than patients with paroxysmal AF at first ablation. Notably, these subgroups of paroxysmal AF are indistinguishable by structural indices. These data motivate studies of trigger versus substrate mechanisms for patients with recurrent paroxysmal AF after PVI.

Multicentre safety of adding Focal Impulse and Rotor Modulation (FIRM) to conventional ablation for atrial fibrillation.

AIMS: Focal Impulse and Rotor Modulation (FIRM) uses 64-electrode basket catheters to identify atrial fibrillation (AF)-sustaining sites for ablation, with promising results in many studies. Accordingly, new basket designs are being tested by several groups. We set out to determine the procedural safety of adding basket mapping and map-guided ablation to conventional pulmonary vein isolation (PVI). METHODS AND RESULTS: We collected 30 day procedural safety data in five US centres for consecutive patients undergoing FIRM plus PVI (FIRM-PVI) compared with contemporaneous controls undergoing PVI without FIRM. A total of 625 cases were included in this analysis: 325 FIRM-PVI and 300 PVI-controls. FIRM-PVI patients were more likely than PVI-controls to be male (83% vs. 66%, P < 0.001) and have long-standing persistent AF (26% vs. 13%, P < 0.001) reflecting patients referred for FIRM. Total ablation time was greater for FIRM-PVI (62 ± 22 min) vs. PVI-controls (52 ± 18 min, P = 0.03). The complication rate for FIRM-PVI procedures (4.3%) was similar to controls (4.0%, P = 1) for both major and minor complications; no deaths were reported. The rate of complications potentially attributable to the basket catheter was small and did not differ between basket types (Constellation 2.8% vs. FIRMap 1.8%, P = 0.7) or between cases in which basket catheters were and were not used (P = 0.5). Complication rates did not differ between centres (P = 0.6). CONCLUSIONS: Procedural complications from the use of the basket catheters for AF mapping are low, and thus procedural safety appears similar between FIRM-PVI and PVI-controls in a large multicentre cohort. Future studies are required to determine the optimal approach to maximize the efficacy of FIRM-guided ablation.

Effect of cardiac resynchronization therapy on the risk of ventricular tachyarrhythmias in patients with chronic kidney disease.

BACKGROUND: The effect of chronic kidney disease (CKD) on benefit from cardiac resynchronization therapy with defibrillator (CRT-D) in reducing ventricular tachyarrhythmia (VTA) risk among mild heart failure (HF) patients is not well understood. METHODS: We evaluated the impact of baseline renal function on VTAs in 1274 left bundle branch block (LBBB) patients enrolled in MADIT-CRT. Two prespecified subgroups were created based on estimated glomerular filtration rate (GFR): GFR <60 (n = 413) and GFR ≥60 ml/min/1.73 m2 (n = 861). Primary end point was ventricular tachycardia/ventricular fibrillation/death (VT/VF/death). Secondary end points were any VT/VF and ventricular tachycardia ≥ 200 bpm or VF (fast VT/VF). RESULTS: There were 413 (32%) LBBB patients presenting with CKD, primarily of moderate severity (GFR mean 48.1 ± 8.3). For patients with and without CKD, CRT-D was associated with lower risk of the primary end point (GFR<60: HR = 0.61, 95% CI: 0.41-0.89, p = .010; GFR≥60: HR = 0.58, 95% CI: 0.52-0.89, p = .005), relative to ICD-only treatment. For patients in both renal function categories, CRT-D in comparison to ICD alone was associated with lower risk of VT/VF (GFR<60: HR = 0.68, 95% CI: 0.42-1.10, p = .113; GFR≥60: HR = 0.65, 95% CI: 0.48-0.88, p = .005) and fast VT/VF (GFR<60: HR = 0.49, 95% CI: 0.25-0.96, p = .038; GFR≥60: HR = 0.55, 95% CI: 0.39-0.80, p = .001), when accounting for competing mortality risk. This effect was independent of CRT-induced reverse remodeling. CONCLUSION: Among mild HF patients with LBBB, those with and without CKD both derived benefit from CRT-D in risk reduction in VTAs, independent of cardiac reverse remodeling.

Novel usage of the cryoballoon catheter to achieve large area atrial substrate modification in persistent and long-standing persistent atrial fibrillation.

BACKGROUND: The cryoballoon catheter has proven to be both safe and effective when used for pulmonary vein (PV) isolation in patients with paroxysmal atrial fibrillation (AF). More recently, the cryoballoon catheter has demonstrated the ability to create durable, transmural, and large areas of PV ablation. However, persistent and long-standing persistent AF can require additional cardiac substrate modification(s) before a patient is returned to normal sinus rhythm. Yet, no study has reported the techniques necessary to achieve extra-PV lesion sets using the cryoballoon catheter. METHODS: Cryoballoon ablation was completed in 225 patients with varying degrees of AF disease. In several cases, the balloon was used for more than PV isolation. This study examines the 11 anatomical cardiac locations where extra-PV lesion sets were utilized. RESULTS: This study demonstrates that these extra-PV ablations can be done safely with the balloon catheter (3.6 % total complication rate). The 12-month efficacy (freedom from all atrial arrhythmia) using these techniques was 88 % in 88 patients with paroxysmal AF, 71 % in 75 patients with persistent AF, and 55 % in 62 patients with long-standing persistent AF. While using this protocol, mean procedure time was 2.2 ± 0.6 h, and average fluoroscopy time was 4.2 ± 2.2 min. CONCLUSIONS: The cryoballoon catheter can be used to make effective and safe extra-PV lesions. However, these techniques will need to be validated in more multi-center studies with review of complication rates and long-term freedom from AF.

Reduction of Iatrogenic Atrial Septal Defects with an Anterior and Inferior Transseptal Puncture Site when Operating the Cryoballoon Ablation Catheter.

The cryoballoon catheter ablates atrial fibrillation (AF) triggers in the left atrium (LA) and pulmonary veins (PVs) via transseptal access. The typical transseptal puncture site is the fossa ovalis (FO) - the atrial septum's thinnest section. A potentially beneficial transseptal site, for the cryoballoon, is near the inferior limbus (IL). This study examines an alternative transseptal site near the IL, which may decrease the frequency of acute iatrogenic atrial septal defect (IASD). Also, the study evaluates the acute pulmonary vein isolation (PVI) success rate utilizing the IL location. 200 patients were evaluated by retrospective chart review for acute PVI success rate with an IL transseptal site. An additional 128 IL transseptal patients were compared to 45 FO transseptal patients by performing Doppler intracardiac echocardiography (ICE) post-ablation to assess transseptal flow after removal of the transseptal sheath. After sheath removal and by Doppler ICE imaging, 42 of 128 (33%) IL transseptal patients demonstrated acute transseptal flow, while 45 of 45 (100%) FO transseptal puncture patients had acute transseptal flow. The difference in acute transseptal flow detection between FO and IL sites was statistically significant (P <0.0001). Furthermore, 186 of 200 patients (with an IL transseptal puncture) did not need additional ablation(s) and had achieved an acute PVI by a "cryoballoon only" technique. An IL transseptal puncture site for cryoballoon AF ablations is an effective location to mediate PVI at all four PVs. Additionally, an IL transseptal location can lower the incidence of acute transseptal flow by Doppler ICE when compared to the FO. Potentially, the IL transseptal site may reduce later IASD complications post-cryoballoon procedures.

Feasibility of extended ambulatory electrocardiogram monitoring to identify silent atrial fibrillation in high-risk patients: the Screening Study for Undiagnosed Atrial Fibrillation (STUDY-AF).

BACKGROUND: Identification of silent atrial fibrillation (AF) could prevent stroke and other sequelae. HYPOTHESIS: Screening for AF using continuous ambulatory electrocardiographic (ECG) monitoring can detect silent AF in asymptomatic in patients with known risk factors. METHODS: We performed a single-center prospective screening study using a wearable patch-based device that provides up to 2 weeks of continuous ambulatory ECG monitoring (iRhythm Technologies, Inc.). Inclusion criteria were age ≥55 years and ≥2 of the following risk factors: coronary disease, heart failure, hypertension, diabetes, sleep apnea. We excluded patients with prior AF, stroke, transient ischemic attack, implantable pacemaker or defibrillator, or with palpitations or syncope in the prior year. RESULTS: Out of 75 subjects (all male, age 69 ± 8.0 years; ejection fraction 57% ± 8.7%), AF was detected in 4 subjects (5.3%; AF burden 28% ± 48%). Atrial tachycardia (AT) was present in 67% (≥4 beats), 44% (≥8 beats), and 6.7% (≥60 seconds) of subjects. The combined diagnostic yield of sustained AT/AF was 11%. In subjects without sustained AT/AF, 11 (16%) had ≥30 supraventricular ectopic complexes per hour. CONCLUSIONS: Outpatient extended ECG screening for asymptomatic AF is feasible, with AF identified in 1 in 20 subjects and sustained AT/AF identified in 1 in 9 subjects, respectively. We also found a high prevalence of asymptomatic AT and frequent supraventricular ectopic complexes, which may be relevant to development of AF or stroke. If confirmed in a larger study, primary screening for AF could have a significant impact on public health.

Effects of postmenopausal hormone therapy on incident atrial fibrillation: the Women's Health Initiative randomized controlled trials.

BACKGROUND: Atrial fibrillation (AF) is less prevalent in women versus men, but associated with higher risks of stroke and death in women. The role hormone therapy plays in AF is not well understood. METHODS AND RESULTS: The Women's Health Initiative randomized postmenopausal women to placebo or conjugated equine estrogens (0.625 mg/d) plus medroxyprogesterone acetate (2.5 mg/d) if they had a uterus (N=16 608) or to conjugated equine estrogens only if they had prior hysterectomy (N=10 739). Incident AF was identified by ECG and diagnosis codes from Medicare claims or hospitalization records. Hazard ratios for incident AF were estimated using Cox proportional hazards regression. After excluding participants with baseline AF, there were 611 incident AF cases over a mean of 5.6 years among 16 128 estrogen plus progestin participants, and 683 cases over a mean of 7.1 years among 10 251 conjugated equine estrogens alone participants. Incident AF was more frequent in the active groups of both trials, reaching statistical significance in the trial of conjugated equine estrogens alone in women with prior hysterectomy (hazard ratio, 1.17; CI, 1.00-1.36; P=0.045) and in the pooled analysis (hazard ratio, 1.12; CI, 1.00-1.24; P=0.05), but not in the estrogen plus progestin trial (hazard ratio, 1.07; CI, 0.91-1.25; P=0.44). These results were only minimally affected by adjustment for incident stroke, coronary heart disease, and heart failure. CONCLUSIONS: Incident AF was modestly elevated in hysterectomized women randomized to postmenopausal E-alone, and in the pooled group randomized to E-alone or estrogen plus progestin. The trend in women with intact uterus receiving estrogen plus progestin, considered separately, was not statistically significant. CLINICAL TRIAL REGISTRATION INFORMATION: ClinicalTrials.gov; Identifier: NCT00000611.

Procedural complications, rehospitalizations, and repeat procedures after catheter ablation for atrial fibrillation.

OBJECTIVES: The purpose of this study was to estimate rates and identify predictors of inpatient complications and 30-day readmissions, as well as repeat hospitalization rates for arrhythmia recurrence following atrial fibrillation (AF) ablation. BACKGROUND: AF is the most common clinically significant arrhythmia and is associated with increased morbidity and mortality. Radiofrequency or cryotherapy ablation of AF is a relatively new treatment option, and data on post-procedural outcomes in large general populations are limited. METHODS: Using data from the California State Inpatient Database, we identified all adult patients who underwent their first AF ablation from 2005 to 2008. We used multivariable logistic regression to identify predictors of complications and/or 30-day readmissions and Kaplan-Meier analyses to estimate rates of all-cause and arrhythmia readmissions. RESULTS: Among 4,156 patients who underwent an initial AF ablation, 5% had periprocedural complications, most commonly vascular, and 9% were readmitted within 30 days. Older age, female, prior AF hospitalizations, and less hospital experience with AF ablation were associated with higher adjusted risk of complications and/or 30-day readmissions. The rate of all-cause hospitalization was 38.5% by 1 year. The rate of readmission for recurrent AF, atrial flutter, and/or repeat ablation was 21.7% by 1 year and 29.6% by 2 years. CONCLUSIONS: Periprocedural complications occurred in 1 of 20 patients undergoing AF ablation, and all-cause and arrhythmia-related rehospitalizations were common. Older age, female sex, prior AF hospitalizations, and recent hospital procedure experience were associated with a higher risk of complications and/or 30-day readmission after AF ablation.