Colchicine for the Prevention of Recurrent Arrhythmia After Catheter Ablation of Atrial Fibrillation: Results of a Single-Center, Retrospective Study.

BACKGROUND: There is evidence to suggest that colchicine reduces the risk of recurrent atrial fibrillation (AF) after catheter ablation; however, the tolerability and safety of colchicine in routine practice is unknown. METHODS: Patients undergoing catheter ablation for AF who received colchicine after ablation were matched 1:1 to patients who did not by age, sex, and renal function. Recurrent AF was compared between groups categorically at 12 months and via propensity weighted Cox proportional hazards models with and without a 3-month blanking period. RESULTS: Overall, 180 patients (n = 90 colchicine and n = 90 matched controls) were followed for a median (Q1, Q3) of 10.3 (7.0, 12.0) months. Mean age was 65.3 ± 9.1 years, 33.9% were women, mean CHA2DS2-VASc score was 2.9 ± 1.5, and 51.1% had persistent AF. Most patients (70%) received colchicine 0.6 mg daily for a median of 30 days. In the colchicine group, 55 patients (61.1%) were receiving at least one known interacting medication with colchicine. After ablation, one patient required colchicine dose reduction and four patients required discontinuation. After adjusting for covariate imbalance using propensity weighting, no significant association between colchicine use and AF recurrence was identified (adjusted hazard ratio 0.94, 95% confidence interval [CI] 0.48-1.85; p = 0.853). No significant association was found between colchicine use and all-cause hospitalizations (adjusted odds ratio 0.74, 95% CI 0.28-1.96; p = 0.548). CONCLUSION: Despite the frequent presence of drug-drug interactions, a 30-day course of colchicine is well-tolerated after AF ablation; however, we did not observe any association between colchicine and lower rates of AF recurrence or hospitalization.

Use of Ripple mapping to enhance localization and ablation of outflow tract premature ventricular contractions.

INTRODUCTION: Accurate localization of septal outflow tract premature ventricular contractions (PVCs) is often difficult due to frequent mid-myocardial or protected origin. Compared with traditional activation mapping, CARTO Ripple mapping provides visualization of all captured electrogram data without assignment of a specific local activation time and thus may enhance PVC localization. METHODS: Electroanatomic maps for consecutive catheter ablation procedures for septal outflow tract PVCs (July 2018-December 2020) were analyzed. For each PVC, we identified the earliest local activation point (EA), defined by the point of maximal -dV/dt in a simultaneously recorded unipolar electrogram, and the earliest Ripple signal (ERS), defined as the earliest point at which three grouped simultaneous Ripple bars appeared in late diastole. Immediate success was defined as full suppression of the clinical PVC. RESULTS: Fifty-seven unique PVCs in 55 procedures were included. When ERS and EA were in the same chamber (RV, LV, or CS), the odds ratio for the successful procedure was 13.1 (95% confidence interval [CI] 2.2-79.9, p = .005). Discordance between sites was associated with a higher likelihood of needing multi-site ablation (odds ratio [OR] 7.9 [1.4-4.6; p = .020]). Median EA-ERS distance in successful versus unsuccessful cases was 4.6 mm (interquartile range 2.9-8.5) versus 12.5 mm (7.8-18.5); (p = .020). CONCLUSION: Greater EA-ERS concordance was associated with higher odds of single-site PVC suppression and successful septal outflow tract PVC ablation. Visualization of complex signals via automated Ripple mapping may offer rapid localization information complementary to local activation mapping for PVCs of mid-myocardial origin.

Subcutaneous implantable cardioverter-defibrillator troubleshooting in patients with a left ventricular assist device: A case series and systematic review.

BACKGROUND: There are limited data on the performance of the subcutaneous implantable cardioverter-defibrillator (S-ICD) in patients with a left ventricular assist device (LVAD). OBJECTIVE: The purpose of this study was to describe the clinical course and outcomes of patients with both an S-ICD and an LVAD at our institution and via a systematic review of published studies. METHODS: We performed a retrospective cohort study of all patients who underwent LVAD implantation from 2009 to 2019 at Duke University Hospital. We also performed a systematic review of studies involving patients with an S-ICD and LVAD using the PubMed/Embase databases. RESULTS: Of 588 patients undergoing LVAD implantation with a preexisting implantable cardioverter-defibrillator, 4 had an S-ICD in situ after LVAD implantation. All 4 patients developed electromagnetic interference (EMI) in the primary/secondary vectors after LVAD implantation, resulting in inappropriate implantable cardioverter-defibrillator shocks in 2 patients. Sensing in the alternate vector was adequate immediately postoperatively in 1 patient. Postoperative undersensing was present in the alternate vector in 3 patients but improved at first outpatient follow-up in 2 patients, allowing tachy therapies to be reenabled. Eight studies involving 27 patients were identified in the systematic review. EMI was common and frequently absent in the alternate vector (6 of 7 patients). CONCLUSION: Undersensing and EMI are common after LVAD implantation in patients with an S-ICD in situ, particularly in the primary and secondary sensing vectors. Undersensing in the alternate vector may improve during follow-up, obviating the need for device revision or extraction.

Focal impulse and rotor modulation of atrial rotors during atrial fibrillation leads to organization of left atrial activation as reflected by waveform morphology recurrence quantification analysis and organizational index.

BACKGROUND: Focal impulse and rotor modulation (FIRM) can cause slowing, organization, and occasionally termination of atrial fibrillation (AF), although results have been mixed. To further characterize changes in AF during rotor ablation, we quantified morphologic and temporal activation changes following FIRM. METHODS: In patients undergoing FIRM ablation for AF, we retrospectively analyzed coronary sinus bipolar EGMs before and after rotor ablation, including EGM activation frequency and regularity, dominant frequency (DF), and organizational index (OI). Changes in EGM waveform morphology were determined with recurrence quantification analysis (RQA) consisting of recurrence rate (RR), determinism (DET), laminarity (LAM), average diagonal line length (L), and trapping time (TT) using Wilcoxon signed-rank testing. RESULTS: Overall, 36 rotors from 21 patients undergoing FIRM ablation were analyzed. All morphology RQA parameters demonstrated significant organization of atrial activation after rotor ablation (RR P = .03, DET P = .005, LAM P = .03, L P = .005, TT P = .009). The organizational index also showed a significant increase after rotor ablation (P = .01), and the change in OI correlated with changes in all morphology parameters. Of the rotors, 14/36 (39%) rotors showed organizational changes in all morphology parameters and OI, and an additional 5 rotors (19/36, 53%) showed organizational changes in 4 of 5 morphology parameters and OI. CONCLUSIONS: Coronary sinus EGM waveform morphologies and activation patterns are significantly altered after FIRM ablation even when there is no fibrillatory slowing. RQA morphology analysis and organizational index may impart important information regarding underlying AF organization and may be useful in quantifying the acute response to ablation.

Catheter ablation of atrial fibrillation in patients with diabetes mellitus.

BACKGROUND: Diabetes mellitus (DM) is an independent risk factor for atrial fibrillation (AF). Few studies have compared clinical outcomes after catheter ablation between patients with and those without DM. OBJECTIVE: The purpose of this study was to compare AF ablation outcomes in patients with and those without DM. METHODS: We performed a retrospective analysis of 351 consecutive patients who underwent first-time AF ablation. Clinical outcomes included freedom from recurrent atrial arrhythmia, symptom burden (Mayo AF Symptom Inventory score), cardiovascular and all-cause hospitalizations, and periprocedural complications. RESULTS: Patients with DM (n = 65) were older, had a higher body mass index, more persistent AF, more hypertension, and larger left atrial diameter (P <.05 for all). Median (Q1, Q3) total radiofrequency duration [64.0 (43.6, 81.4) minutes vs 54.3 (39.2, 76.4) minutes; P = .132] and periprocedural complications (P = .868) did not differ between patients with and those without DM. After a median follow-up of 29.5 months, arrhythmia recurrence was significantly higher in the DM group compared to the no-DM group after adjustment for baseline differences (adjusted hazard ratio [HR] 2.24; 95% confidence [CI] 1.42-3.55; P = .001). There was a nonsignificant trend toward higher AF recurrence with worse glycemic levels (HR 1.29; 95% CI 0.99-1.69; P = .064). CONCLUSION: Although safety outcomes associated with AF ablation were similar between patients with and those without DM, arrhythmia-free survival was significantly lower among patients with DM. Poor glycemic control seems to an important risk factor for AF recurrence.

Predicting atrial fibrillation recurrence after ablation in patients with heart failure: Validity of the APPLE and CAAP-AF risk scoring systems.

BACKGROUND: Compared with medical therapy, catheter ablation of atrial fibrillation (AF) in patients with heart failure (HF) improves cardiovascular outcomes. Risk scores (CAAP-AF and APPLE) have been developed to predict the likelihood of AF recurrence after ablation, have not been validated specifically in patients with AF and HF. METHODS: We analyzed baseline characteristics, risk scores, and rates of AF recurrence 12 months postablation in a cohort of 230 consecutive patients with AF and HF undergoing PVI in the Duke Center for Atrial Fibrillation registry from 2009-2013. RESULTS: During a follow-up period of 12 months, 76 of 230 (33%) patients with HF experienced recurrent AF after ablation. The median APPLE and CAAP-AF scores were 1.5 ([Q1, Q3]: [1.0, 2.0]) and 4.0 ([Q1, Q3]: [3.0, 5.0]), respectively and were not different from those patients with and without recurrent AF. Freedom from AF was not different according to APPLE and CAAP-AF scores. Discrimination for recurrent AF with the CAAP-AF score was modest with a C-statistic of 0.60 (95% CI 0.52-0.67). Discrimination with the APPLE score was similarly modest, with a C-statistic of 0.54 (95% CI: 0.47-0.62). CONCLUSIONS: Validated predictive risk scores for recurrent AF after catheter ablation exhibit limited predictive ability in cohorts of AF and HF. Additional tools are needed to facilitate risk stratification and patient selection for AF ablation in patients with concomitant HF.

Net clinical benefit of rivaroxaban compared with warfarin in atrial fibrillation: Results from ROCKET AF.

AIMS: The aim of this study was to determine the net clinical benefit (NCB) of rivaroxaban compared with warfarin in patients with atrial fibrillation. METHODS: This was a retrospective analysis of 14,236 patients included in ROCKET AF who received at least one dose of study drug. We analyzed NCB using four different methods: (1) composite of death, stroke, systemic embolism, myocardial infarction, and major bleeding; (2) method 1 with fatal or critical organ bleeding substituted for major bleeding; (3) difference between the rate of ischemic stroke or systemic embolism minus 1.5 times the difference between the rate of intracranial hemorrhage; and (4) weighted sum of differences between rates of death, ischemic stroke or systemic embolism, intracranial hemorrhage, and major bleeding. RESULTS: Rivaroxaban was associated with a lower risk of the composite outcome of death, myocardial infarction, stroke, or systemic embolism (rate difference per 10,000 patient-years [RD]=-86.8 [95% CI -143.6 to -30.0]) and fatal or critical organ bleeding (-41.3 [-68 to -14.7]). However, rivaroxaban was associated with a higher risk of major bleeding other than fatal or critical organ bleeding (55.9 [14.7 to 97.2]). Method 1 showed no difference between treatments (-35.5 [-108.4 to 37.3]). Methods 2-4 favored treatment with rivaroxaban (2: -96.8 [-157.0 to -36.8]; 3: -65.2 [-112.3 to -17.8]; 4: -54.8 [-96.0 to -10.2]). CONCLUSIONS: Rivaroxaban was associated with favorable NCB compared with warfarin. The NCB was attributable to lower rates of ischemic events and fatal or critical organ bleeding.

Left Atrial Appendage Electrical Isolation for Treatment of Recurrent Atrial Fibrillation: A Meta-Analysis.

OBJECTIVES: In this study, the authors sought to perform a meta-analysis of controlled studies assessing the relationship between left atrial appendage (LAA) electrical isolation (EI) and recurrent atrial fibrillation (AF). BACKGROUND: LAA triggers could play an important role in AF and can be treated with complete EI of the LAA via surgical or percutaneous approaches. METHODS: We conducted a meta-analysis of all controlled studies published as of November 21, 2016, assessing the relationship between left atrial appendage electrical isolation (LAAEI) and recurrent AF. The primary endpoint was atrial tachycardia (AT) or AF recurrence after the post-procedure blanking period. The association between LAAEI and AT/AF was estimated using random-effects modeling. Odds ratios (ORs) with 95% confidence intervals (CIs) were calculated using the DerSimonian and Laird method. RESULTS: We identified 7 studies including 1,037 patients; LAAEI was performed in 566 patients (55%). LAAEI was associated with a significantly lower rate of AT/AF recurrence in the primary analysis (OR: 0.38; 95% CI: 0.16 to 0.90; p = 0.02). The association between LAAEI and recurrent AT/AF was strongest in a sensitivity analysis restricted to studies of percutaneous LAAEI (OR: 0.22; 95% CI: 0.11 to 0.46; p < 0.001; 5 studies, n = 623). LAAEI was not associated with thromboembolism (OR: 0.50; 95% CI: 0.18 to 1.39; p = 0.18; 5 studies, n = 767), although these studies either incorporated LAA occlusion (3 studies, n = 552 patients) or follow-up echocardiography to assess LAA function (2 studies, n = 215 patients) to inform antithrombotic strategies. CONCLUSIONS: LAAEI is associated with a significant reduction in recurrent AT/AF. Randomized trials are required to confirm the efficacy and long-term safety of LAAEI and to determine the optimal concomitant antithrombotic strategy.

Obstructive sleep apnea is associated with increased rotor burden in patients undergoing focal impulse and rotor modification guided atrial fibrillation ablation.

Aims: To assess whether obstructive sleep apnea (OSA) was associated with increased rotor burden among atrial fibrillation (AF) patients. Methods and results: We studied 33 consecutive patients who were scheduled for focal impulse and rotor modulation (FIRM) ablation at our institution to describe the mapping, ablation, and outcomes, among patients with and without OSA. Patients underwent biatrial FIRM mapping in AF with ablation of stable rotors in addition to conventional ablation lesion sets. Differences between groups were tested with student's t-tests and Fisher's exact tests, as appropriate. Survival analyses were performed using the Kaplan-Meier method. Twelve of the 33 (36%) patients had OSA and 8 (66%) used continuous positive airway pressure ventilation (CPAP). Obstructive sleep apnea patients had a higher body mass index (BMI) (33.6 vs. 28.8 kg/m2, P = 0.01) and were more commonly on beta blockers (67% vs. 29%, P = 0.03) but were otherwise similar regarding baseline characteristics, medication use, and prior AF treatments, including antiarrhythmic drugs and prior ablation. Focal impulse and rotor modulation mapping demonstrated increased rotor burden in the OSA patients (2.6 ± 0.9 vs. 2.0 ± 1.0, P =0.03). The increased rotor burden was more evident in the right atrium (RA) (1.0 ± 0.7 vs. 0.5 ± 0.7, P =0.04 compared with left atrium (1.7 ± 0.8 vs. 1.4 ± 0.7, P = 0.15). There was no correlation between BMI and total number of rotors (r = 0.0961, P = 0.59). Among the population of patients with OSA, CPAP therapy was associated with a lower number of RA rotors (0.8 ± 0.7 vs. 1.5 ± 0.6, P = 0.05) but no significant difference in overall rotors (P = 0.33). Conclusion: Obstructive sleep apnea patients demonstrate increased rotor prevalence, driven predominantly by an increase in RA rotors. CPAP therapy was associated with fewer RA rotors.

Catheter ablation of atrial fibrillation in patients with heart failure and preserved ejection fraction.

BACKGROUND: Few studies have examined outcomes of catheter ablation for atrial fibrillation (AF) in patients with heart failure (HF) with preserved ejection fraction (HFpEF). OBJECTIVE: The purpose of this study was to compare outcomes of AF ablation in patients with HFpEF vs HF with reduced ejection fraction (HFrEF). METHODS: We performed a retrospective study of 230 patients with HF who underwent AF ablation, including 97 (42.2%) with HFrEF and 133 (57.8%) with HFpEF. Outcomes included adverse events, symptoms (Mayo AF Symptom Inventory [MAFSI]), New York Heart Association (NYHA) functional class, and freedom from recurrent atrial arrhythmia at 12 months. RESULTS: Overall, 150 of 230 patients had nonparoxysmal AF (62.8% HFpEF vs 63.0% HFrEF). Patients with HFpEF had a smaller mean left atrial diameter (4.4 ± 0.8 cm vs 4.7 ± 0.7 cm; P = .013) and were less likely to be taking a beta-blocker at baseline (72.9% vs 85.6%; P = .022). Median (Q1, Q3) procedure times (233 minutes [192, 290] vs 233.5 minutes [193.0, 297.5]; P = .780) and adverse events such as acute HF (3.8% vs 6.2%; P = .395) were similar between HFpEF and HFrEF patients. Freedom from recurrent atrial arrhythmia was not significantly different in HFpEF vs HFrEF patients (33.9% vs 32.6%; adjusted hazard ratio 1.47; 95% confidence interval 0.72-3.01), with similar improvements in NYHA functional class (-0.32 vs -0.19; P = .135) and MAFSI symptom severity (-0.23 vs -0.09; P = .116) after ablation. CONCLUSION: Catheter ablation of AF seems to have similar effectiveness in patients with HF, regardless of presence of systolic dysfunction. There were no significant differences in procedural characteristics, arrhythmia-free recurrence, or functional improvements between patients with HFpEF and those with HFrEF.

Increased Ca2+ signaling through CaV1.2 promotes bone formation and prevents estrogen deficiency-induced bone loss.

While the prevalence of osteoporosis is growing rapidly with population aging, therapeutic options remain limited. Here, we identify potentially novel roles for CaV1.2 L-type voltage-gated Ca2+ channels in osteogenesis and exploit a transgenic gain-of-function mutant CaV1.2 to stem bone loss in ovariectomized female mice. We show that endogenous CaV1.2 is expressed in developing bone within proliferating chondrocytes and osteoblasts. Using primary BM stromal cell (BMSC) cultures, we found that Ca2+ influx through CaV1.2 activates osteogenic transcriptional programs and promotes mineralization. We used Prx1-, Col2a1-, or Col1a1-Cre drivers to express an inactivation-deficient CaV1.2 mutant in chondrogenic and/or osteogenic precursors in vivo and found that the resulting increased Ca2+ influx markedly thickened bone not only by promoting osteogenesis, but also by inhibiting osteoclast activity through increased osteoprotegerin secretion from osteoblasts. Activating the CaV1.2 mutant in osteoblasts at the time of ovariectomy stemmed bone loss. Together, these data highlight roles for CaV1.2 in bone and demonstrate the potential dual anabolic and anticatabolic therapeutic actions of tissue-specific CaV1.2 activation in osteoblasts.

Treatment of Atrial Fibrillation and Concordance With the American Heart Association/American College of Cardiology/Heart Rhythm Society Guidelines: Findings From ORBIT-AF (Outcomes Registry for Better Informed Treatment of Atrial Fibrillation).

BACKGROUND: It is unclear how frequently patients with atrial fibrillation receive guideline-concordant (GC) care and whether guideline concordance is associated with improved outcomes. METHODS AND RESULTS: Using data from ORBIT-AF (Outcomes Registry for Better Informed Treatment of Atrial Fibrillation), we determined how frequently patients received care that was concordant with 11 recommendations from the 2014 American Heart Association/American College of Cardiology/Heart Rhythm Society atrial fibrillation guidelines pertaining to antithrombotic therapy, rate control, and antiarrhythmic medications. We also analyzed the association between GC care and clinical outcomes at both the patient level and center level. A total of 9570 patients were included. The median age was 75 years (interquartile range, 67-82), and the median CHA2DS2-VASc score was 4 (interquartile range, 3-5). A total of 5977 patients (62.5%) received care that was concordant with all guideline recommendations for which they were eligible. Rates of GC care were higher in patients treated by providers with greater specialization in arrhythmias (60.0%, 62.4%, and 67.0% for primary care physicians, cardiologists, and electrophysiologists, respectively; P<0.001). During a median of 30 months of follow-up, patients treated with GC care had a higher risk of bleeding hospitalization (hazard ratio=1.21; P=0.021) but a similar risk of death, stroke, major bleeding, and all-cause hospitalization. CONCLUSIONS: Over a third of patients with atrial fibrillation in this large outpatient registry received care that differed in some respect from guideline recommendations. There was no apparent association between GC care and improved risk-adjusted outcomes.

Risk of atrioesophageal fistula formation with contact force-sensing catheters.

BACKGROUND: Atrioesophageal fistula formation is a rare but life-threatening complication of atrial fibrillation ablation. Contact force (CF)-sensing catheters improve procedural effectiveness. However, the impact of the implementation of CF-sensing technology on the risk of atrioesophageal fistula formation has not been explored. OBJECTIVE: The purpose of this study was to determine the association between the use of CF-sensing catheters and atrioesophageal fistula development. METHODS: We searched the Manufacturer and User Facility Device Experience database for adverse event reports involving Food and Drug Administration-approved ablation catheters. RESULTS: Among 2689 device reports, we identified 78 atrioesophageal fistula cases, 65 of which involved CF-sensing catheters and 13 non-CF-sensing catheters. The percentage of total reports involving atrioeosphageal fistula was 5.4% for CF-sensing catheters (65 of 1202) and 0.9% for non-CF-sensing catheters (13 of 1487) (P < .0001). Procedural details (CF and power settings) were not consistently reported. Esophageal temperature increases were detected in only 2.5% of cases (2 of 78). The mean time to presentation was 16 ± 9 days. Overall mortality was at least 56%, with patients who underwent surgical repair more likely to survive than those treated with stenting or no intervention. CONCLUSION: Atrioesophageal fistula formation accounted for a much higher proportion of reported adverse events with CF-sensing catheters compared with non-CF-sensing catheters. Improved understanding of the relationship between power/force delivery and esophageal damage is needed to minimize the risk of atrioesophageal fistula formation.

Crizotinib Inhibits Hyperpolarization-activated Cyclic Nucleotide-Gated Channel 4 Activity.

BACKGROUND: Sinus bradycardia is frequently observed in patients treated with crizotinib, a receptor tyrosine kinase inhibitor used for the treatment of anaplastic lymphoma kinase (ALK)-rearranged non-small cell lung cancer (NSCLC). We investigated whether crizotinib could influence heart rate (HR) through direct cardiac effects. METHODS: The direct effect of crizotinib on HR was studied using ECG analysis of Langendorff-perfused mouse hearts. The whole-cell patch clamp technique was used to measure the effects of crizotinib on the hyperpolarization-activated funny current, If, in mouse sinoatrial node cells (SANCs) and hyperpolarization-activated cyclic nucleotide-gated channel 4 (HCN4) activity in HEK-293 cells stably expressing human HCN4. RESULTS: Crizotinib resulted in a dose-dependent reduction in HR in isolated intact mouse hearts with a half maximal inhibitory concentration (IC50) of 1.7 ± 0.4 µmol/L. Because ECG analysis revealed that crizotinib (0-5 µmol/L) resulted in significant reductions in HR in isolated mouse hearts without changes in PR, QRS, or QT intervals, we performed whole-cell patch clamp recordings of SANCs which showed that crizotinib inhibited If which regulates cardiac pacemaker activity. Crizotinib resulted in diminished current density of HCN4, the major molecular determinant of If, with an IC50 of 1.4 ± 0.3 µmol/L. Crizotinib also slowed HCN4 activation and shifted the activation curve to the left towards more hyperpolarized potentials. CONCLUSIONS: Our results suggest that crizotinib's effects on HCN4 channels play a significant role in mediating its observed effects on HR.