Direct Oral Anticoagulants Versus Warfarin Across the Spectrum of Kidney Function: Patient-Level Network Meta-Analyses From COMBINE AF.

BACKGROUND: There is uncertainty surrounding the use of direct oral anticoagulants (DOACs) in patients with kidney dysfunction. METHODS: Using the COMBINE AF (A Collaboration Between Multiple Institutions to Better Investigate Non-Vitamin K Antagonist Oral Anticoagulant Use in Atrial Fibrillation) database (data from RE-LY [Randomized Evaluation of Long-term Anticoagulation Therapy], ROCKET AF [Rivaroxaban Once Daily Oral Direct Factor Xa Inhibition Compared With Vitamin K Antagonism for Prevention of Stroke and Embolism Trial in Atrial Fibrillation], ARISTOTLE [Apixaban for Reduction in Stroke and Other Thromboembolic Events in Atrial Fibrillation], and ENGAGE AF-TIMI 48 [Effective Anticoagulation With Factor Xa Next Generation in Atrial Fibrillation-Thrombolysis in Myocardial Infarction 48]), we performed an individual patient-level network meta-analysis to evaluate the safety and efficacy of DOACs versus warfarin across continuous creatinine clearance (CrCl). A multivariable Cox model including treatment-by-CrCl interaction with random effects was fitted to estimate hazard ratios for paired treatment strategies (standard-dose DOAC, lower-dose DOAC, and warfarin). Outcomes included stroke and systemic embolism (S/SE), major bleeding, intracranial hemorrhage (ICH), and death. RESULTS: Among 71 683 patients (mean age, 70.6±9.4 years; 37.3% female; median follow-up, 23.1 months), the mean CrCl was 75.5±30.5 mL/min. The incidence of S/SE, major bleeding, ICH, and death increased significantly with worsening kidney function. Across continuous CrCl values down to 25 mL/min, the hazard of major bleeding did not change for patients randomized to standard-dose DOACs compared with those randomized to warfarin (Pinteraction=0.61). Compared with warfarin, standard-dose DOAC use resulted in a significantly lower hazard of ICH at CrCl values <122 mL/min, with a trend for increased safety with DOAC as CrCl decreased (6.2% decrease in hazard ratio per 10-mL/min decrease in CrCl; Pinteraction=0.08). Compared with warfarin, standard-dose DOAC use resulted in a significantly lower hazard of S/SE with CrCl <87 mL/min, with a significant treatment-by-CrCl effect (4.8% decrease in hazard ratio per 10-mL/min decrease in CrCl; Pinteraction=0.01). The hazard of death was significantly lower with standard-dose DOACs for patients with CrCl <77 mL/min, with a trend toward increasing benefit with lower CrCl (2.1% decrease in hazard ratio per 10-mL/min decrease in CrCl; Pinteraction=0.08). Use of lower-dose rather than standard-dose DOACs was not associated with a significant difference in incident bleeding or ICH in patients with reduced kidney function but was associated with a higher incidence4 of death and S/SE. CONCLUSIONS: Standard-dose DOACs are safer and more effective than warfarin down to a CrCl of at least 25 mL/min. Lower-dose DOACs do not significantly lower the incidence of bleeding or ICH compared with standard-dose DOACs but are associated with a higher incidence of S/SE and death. These findings support the use of standard-dose DOACs over warfarin in patients with kidney dysfunction.

Self-administered intranasal etripamil using a symptom-prompted, repeat-dose regimen for atrioventricular-nodal-dependent supraventricular tachycardia (RAPID): a multicentre, randomised trial.

BACKGROUND: Etripamil is a fast-acting, intranasally administered calcium-channel blocker in development for on-demand therapy outside a health-care setting for paroxysmal supraventricular tachycardia. We aimed to evaluate the efficacy and safety of etripamil 70 mg nasal spray using a symptom-prompted, repeat-dose regimen for acute conversion of atrioventricular-nodal-dependent paroxysmal supraventricular tachycardia to sinus rhythm within 30 min. METHODS: RAPID was a multicentre, randomised, placebo-controlled, event-driven trial, conducted at 160 sites in North America and Europe as part 2 of the NODE-301 study. Eligible patients were aged at least 18 years and had a history of paroxysmal supraventricular tachycardia with sustained, symptomatic episodes (≥20 min) as documented by electrocardiogram. Patients were administered two test doses of intranasal etripamil (each 70 mg, 10 min apart) during sinus rhythm; those who tolerated the test doses were randomly assigned (1:1) using an interactive response technology system to receive either etripamil or placebo. Prompted by symptoms of paroxysmal supraventricular tachycardia, patients self-administered a first dose of intranasal 70 mg etripamil or placebo and, if symptoms persisted beyond 10 min, a repeat dose. Continuously recorded electrocardiographic data were adjudicated, by individuals masked to patient assignment, for the primary endpoint of time to conversion of paroxysmal supraventricular tachycardia to sinus rhythm for at least 30 s within 30 min after the first dose, which was measured in all patients who administered blinded study drug for a confirmed atrioventricular-nodal-dependent event. Safety outcomes were assessed in all patients who self-administered blinded study drug for an episode of perceived paroxysmal supraventricular tachycardia. This trial is registered at ClinicalTrials.gov, NCT03464019, and is complete. FINDINGS: Between Oct 13, 2020, and July 20, 2022, among 692 patients randomly assigned, 184 (99 from the etripamil group and 85 from the placebo group) self-administered study drug for atrioventricular-nodal-dependent paroxysmal supraventricular tachycardia, with diagnosis and timing confirmed. Kaplan-Meier estimates of conversion rates by 30 min were 64% (63/99) with etripamil and 31% (26/85) with placebo (hazard ratio 2·62; 95% CI 1·66-4·15; p<0·0001). Median time to conversion was 17·2 min (95% CI 13·4-26·5) with the etripamil regimen versus 53·5 min (38·7-87·3) with placebo. Prespecified sensitivity analyses of the primary assessment were conducted to test robustness, yielding supporting results. Treatment-emergent adverse events occurred in 68 (50%) of 99 patients treated with etripamil and 12 (11%) of 85 patients in the placebo group, most of which were located at the administration site and were mild or moderate, and all of which were transient and resolved without intervention. Adverse events occurring in at least 5% of patients treated with etripamil were nasal discomfort (23%), nasal congestion (13%), and rhinorrhea (9%). No serious etripamil-related adverse events or deaths were reported. INTERPRETATION: Using a symptom-prompted, self-administered, initial and optional-repeat-dosing regimen, intranasal etripamil was well tolerated, safe, and superior to placebo for the rapid conversion of atrioventricular-nodal-dependent paroxysmal supraventricular tachycardia to sinus rhythm. This approach could empower patients to treat paroxysmal supraventricular tachycardia themselves outside of a health-care setting, and has the potential to reduce the need for additional medical interventions, such as intravenous medications given in an acute-care setting. FUNDING: Milestone Pharmaceuticals.

Apixaban for Patients With Atrial Fibrillation on Hemodialysis: A Multicenter Randomized Controlled Trial.

BACKGROUND: There are no randomized data evaluating the safety or efficacy of apixaban for stroke prevention in patients with end-stage kidney disease on hemodialysis and with atrial fibrillation (AF). METHODS: The RENAL-AF trial (Renal Hemodialysis Patients Allocated Apixaban Versus Warfarin in Atrial Fibrillation) was a prospective, randomized, open-label, blinded-outcome evaluation (PROBE) of apixaban versus warfarin in patients receiving hemodialysis with AF and a CHA2DS2-VASc score ≥2. Patients were randomly assigned 1:1 to 5 mg of apixaban twice daily (2.5 mg twice daily for patients ≥80 years of age, weight ≤60 kg, or both) or dose-adjusted warfarin. The primary outcome was time to major or clinically relevant nonmajor bleeding. Secondary outcomes included stroke, mortality, and apixaban pharmacokinetics. Pharmacokinetic sampling was day 1, day 3, and month 1. RESULTS: From January 2017 through January 2019, 154 patients were randomly assigned to apixaban (n=82) or warfarin (n=72). The trial stopped prematurely because of enrollment challenges. Time in therapeutic range (international normalized ratio, 2.0-3.0) for warfarin-treated patients was 44% (interquartile range, 23%-59%). The 1-year rates for major or clinically relevant nonmajor bleeding were 32% and 26% in apixaban and warfarin groups, respectively (hazard ratio, 1.20 [95% CI, 0.63-2.30]), whereas 1-year rates for stroke or systemic embolism were 3.0% and 3.3% in apixaban and warfarin groups, respectively. Death was the most common major event in the apixaban (21 patients [26%]) and warfarin (13 patients [18%]) arms. The pharmacokinetic substudy enrolled the target 50 patients. Median steady-state 12-hour area under the curve was 2475 ng/mL×h (10th to 90th percentiles, 1342-3285) for 5 mg of apixaban twice daily and 1269 ng/mL×h (10th to 90th percentiles, 615-1946) for 2.5 mg of apixaban twice daily. There was substantial overlap between minimum apixaban blood concentration, 12-hour area under the curve, and maximum apixaban blood concentration for patients with and without a major or clinically relevant nonmajor bleeding event. CONCLUSIONS: There was inadequate power to draw any conclusion regarding rates of major or clinically relevant nonmajor bleeding comparing apixaban and warfarin in patients with AF and end-stage kidney disease on hemodialysis. Clinically relevant bleeding events were ≈10-fold more frequent than stroke or systemic embolism among this population on anticoagulation, highlighting the need for future randomized studies evaluating the risks versus benefits of anticoagulation among patients with AF and end-stage kidney disease on hemodialysis. REGISTRATION: URL: https://www. CLINICALTRIALS: gov; Unique identifier: NCT02942407.

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.

Left Atrial Appendage Occlusion Versus Oral Anticoagulation in Atrial Fibrillation : A Decision Analysis.

BACKGROUND: Left atrial appendage occlusion (LAAO) is a potential alternative to oral anticoagulants in selected patients with atrial fibrillation (AF). Compared with anticoagulants, LAAO decreases major bleeding risk, but there is uncertainty regarding the risk for ischemic stroke compared with anticoagulation. OBJECTIVE: To determine the optimal strategy for stroke prevention conditional on a patient's individual risks for ischemic stroke and bleeding. DESIGN: Decision analysis with a Markov model. DATA SOURCES: Evidence from the published literature informed model inputs. TARGET POPULATION: Women and men with nonvalvular AF and without prior stroke. TIME HORIZON: Lifetime. PERSPECTIVE: Clinical. INTERVENTION: LAAO versus warfarin or direct oral anticoagulants (DOACs). OUTCOME MEASURES: The primary end point was clinical benefit measured in quality-adjusted life-years. RESULTS OF BASE-CASE ANALYSIS: The baseline risks for stroke and bleeding determined whether LAAO was preferred over anticoagulants in patients with AF. The combined risks favored LAAO for higher bleeding risk, but that benefit became less certain at higher stroke risks. For example, at a HAS-BLED score of 5, LAAO was favored in more than 80% of model simulations for CHA2DS2-VASc scores between 2 and 5. The probability of LAAO benefit in QALYs (>80%) at lower bleeding risks (HAS-BLED score of 0 to 1) was limited to patients with lower stroke risks (CHA2DS2-VASc score of 2). Because DOACs carry lower bleeding risks than warfarin, the net benefit of LAAO is less certain than that of DOACs. RESULTS OF SENSITIVITY ANALYSIS: Results were consistent using the ORBIT bleeding score instead of the HAS-BLED score, as well as alternative sources for LAAO clinical effectiveness data. LIMITATION: Clinical effectiveness data were drawn primarily from studies on the Watchman device. CONCLUSION: Although LAAO could be an alternative to anticoagulants for stroke prevention in patients with AF and high bleeding risk, the overall benefit from LAAO depends on the combination of stroke and bleeding risks in individual patients. These results suggest the need for a sufficiently low stroke risk for LAAO to be beneficial. The authors believe that these results could improve shared decision making when selecting patients for LAAO. PRIMARY FUNDING SOURCE: None.

Leadless pacemaker implantation after lead extraction for cardiac implanted electronic device infection.

BACKGROUND: Cardiac implanted electronic device (CIED) pocket and systemic infection remain common complications with traditional CIEDs and are associated with high morbidity and mortality. Leadless pacemakers may be an attractive pacing alternative for many patients following complete hardware removal for a CIED infection by eliminating surgical pocket-related complications as well as lower risk of recurrent complications. OBJECTIVE: To describe use and outcomes associated with leadless pacemaker implantation following extraction of a CIED system due to infection. METHODS: Patient characteristics and postprocedural outcomes were described in patients who underwent leadless pacemaker implantation at Duke University Hospital between November 11, 2014 and November 18, 2019, following CIED infection and device extraction. Outcomes of interest included procedural complications, pacemaker syndrome, need for system revision, and recurrent infection. RESULTS: Among 39 patients, the mean age was 71 ± 17 years, 31% were women, and the most frequent primary pacing indication was complete heart block (64.1%) with 9 (23.1%) patients being pacemaker dependent at the time of Micra implantation. The primary organism implicated in the CIED infection was Staphylococcus aureus (43.6%). Nine of the 39 patients had a leadless pacemaker implanted before or on the same day as their extraction procedure, and the remaining 30 patients had a leadless pacemaker implanted after their extraction procedure. During follow-up (mean 24.8 ± 14.7 months) after leadless pacemaker implantation, there were a total of 3 major complications: 1 groin hematoma, 1 femoral arteriovenous fistula, and 1 case of pacemaker syndrome. No patients had evidence of recurrent CIED infection after leadless pacemaker implantation. CONCLUSIONS: Despite a prior CIED infection and an elevated risk of recurrent infection, there was no evidence of CIED infection with a mean follow up of over 2 years following leadless pacemaker implantation at or after CIED system removal. Larger studies with longer follow-up are required to determine if there is a long-term advantage to implanting a leadless pacemaker versus a traditional pacemaker following temporary pacing when needed during the periextraction period in patients with a prior CIED infection.

Apixaban Versus Warfarin in Patients With Atrial Fibrillation and Advanced Chronic Kidney Disease.

BACKGROUND: Compared with the general population, patients with advanced chronic kidney disease have a >10-fold higher burden of atrial fibrillation. Limited data are available guiding the use of nonvitamin K antagonist oral anticoagulants in this population. METHODS: We compared the safety of apixaban with warfarin in 269 patients with atrial fibrillation and advanced chronic kidney disease (defined as creatinine clearance [CrCl] 25 to 30 mL/min) enrolled in the ARISTOTLE trial (Apixaban for Reduction in Stroke and Other Thromboembolic Events in Atrial Fibrillation). Cox proportional models were used to estimate hazard ratios for major bleeding and major or clinically relevant nonmajor bleeding. We characterized the pharmacokinetic profile of apixaban by assessing differences in exposure using nonlinear mixed effects models. RESULTS: Among patients with CrCl 25 to 30 mL/min, apixaban caused less major bleeding (hazard ratio, 0.34 [95% CI, 0.14-0.80]) and major or clinically relevant nonmajor bleeding (hazard ratio, 0.35 [95% CI, 0.17-0.72]) compared with warfarin. Patients with CrCl 25 to 30 mL/min randomized to apixaban demonstrated a trend toward lower rates of major bleeding when compared with those with CrCl >30 mL/min (P interaction=0.08) and major or clinically relevant nonmajor bleeding (P interaction=0.05). Median daily steady-state areas under the curve for apixaban 5 mg twice daily were 5512 ng/(mL·h) and 3406 ng/(mL·h) for patients with CrCl 25 to 30 mL/min or >30 mL/min, respectively. For apixaban 2.5 mg twice daily, the median exposure was 2780 ng/(mL·h) for patients with CrCl 25 to 30 mL/min. The area under the curve values for patients with CrCl 25 to 30 mL/min fell within the ranges demonstrated for patients with CrCl >30 mL/min. CONCLUSIONS: Among patients with atrial fibrillation and CrCl 25 to 30 mL/min, apixaban caused less bleeding than warfarin, with even greater reductions in bleeding than in patients with CrCl >30 mL/min. We observed substantial overlap in the range of exposure to apixaban 5 mg twice daily for patients with or without advanced chronic kidney disease, supporting conventional dosing in patients with CrCl 25 to 30 mL/min. Randomized, controlled studies evaluating the safety and efficacy of apixaban are urgently needed in patients with advanced chronic kidney disease, including those receiving dialysis. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT00412984.

Trends in health care resource use and expenditures in patients with newly diagnosed paroxysmal supraventricular tachycardia in the United States.

BACKGROUND: Few data are available on the temporal patterns of health resource utilization (HRU) and expenditures around paroxysmal supraventricular tachycardia (PSVT) diagnosis. This study assessed the longitudinal trends in HRU and expenditures in the 3 years preceding and subsequent to PSVT diagnosis. METHODS: Adult patients (age 18-65 years) with newly diagnosed PSVT were identified using administrative claims from the IBM MarketScan Research Database between January 1, 2008 and December 31, 2016 and propensity-score matched (1:1) with non-PSVT controls. RESULTS: Among the 12,305 PSVT patients compared with matched controls, PSVT was associated with statistically significant higher annual rates of emergency department visits, physician office visits, inpatient hospitalizations, and diagnostic testing. HRU increased in the years preceding PSVT diagnosis, reaching its peak in the year following PSVT diagnosis. Over the 6-year follow-up period, PSVT was associated with higher mean annual per patient expenditures ($12,665) compared to matched controls ($6,004; P < .001). Upon diagnosis of PSVT, the mean expenditures per PSVT patient doubled from $11,714 in the year immediately preceding index diagnosis to $23,335 in the first postdiagnosis year. Inpatient services, diagnostic testing, and ablation procedures were the principle drivers of higher mean expenditures in the first year post-PSVT diagnosis versus the year prior to PSVT diagnosis. CONCLUSIONS: PSVT presents a substantial economic burden to health care systems. The annual expenditure per PSVT patient is within the range previously reported for atrial fibrillation. The increased HRU and expenditures in the year following diagnosis, which do not return to baseline, suggest a potential gap in non-interventional, long-term PSVT management.

Prevalence and incidence of patients with paroxysmal supraventricular tachycardia in the United States.

BACKGROUND: Paroxysmal supraventricular tachycardia (PSVT) encompasses a range of heart rhythm disorders leading to rapid heart rates. By virtue of its episodic nature, diagnosing PSVT is difficult and estimating incidence and prevalence on a population level is challenging. The objective of this study was to estimate the incidence and prevalence of PSVT in the United States (US) in contemporary practice. METHODS AND RESULTS: An observational retrospective longitudinal study using claims, enrollment, and demographic data from the IBM MarketScan® Commercial Research database (age < 65) and the Medicare Limited Data Set (age ≥ 65) from 2008 to 2016. Patients with a PSVT diagnosis code (ICD-9: 427.0; ICD-10: I47.1) on ≥2 outpatient, ≥1 emergency room, or ≥1 inpatient visit were considered as having PSVT. Patients with atrial fibrillation/atrial flutter (AF/AFL) were excluded from the initial analysis given the potential for misclassification. Incidence was estimated by assessing diagnoses made during year 5 of continuous enrollment. Finally, a sensitivity analysis was performed by including patients with both PSVT and AF/AFL diagnoses. Period prevalence and incidence rate were estimated to be 332.9 (323.2-342.9) and 57.8 (52.8-63.3) per 100 000 individuals, respectively, when excluding patients with AF/AFL. Projected to the 2018 US Census, prevalence and incidence are 1.26 million (1.21-1.30 million) and 188,981 (172,891-206,943), respectively. Including patients with AF/AFL, the prevalence may increase to 479.7 (467.9-491.8) with an incidence of 93.4 (86.9-100.5) per 100 000 individuals or a prevalence of 2.06 million (2.01-2.12 million). CONCLUSIONS: Approximately 1 in 300 people in the US had PSVT with the highest rates in older and female patients.

Comparative outcomes of Riata and Fidelis lead management strategies: Results from the NCDR-ICD Registry.

BACKGROUND: The Medtronic Sprint Fidelis® and Abbott Riata®/Riata ST® leads are at risk of failure and are subject to FDA recall. Comparative risks of various lead management strategies during elective generator change in a multi-center population are unknown. We aim to describe patients with functional, recalled ICD leads undergoing elective generator replacement and report outcomes according to lead management strategies. METHODS: Using data from the NCDR ICD Registry, patients with a functioning Riata® or Fidelis® lead undergoing generator replacement are described according to lead management: reuse, abandon/replace, and extract/replace. Adjusted rates of death and pre-discharge complications are reported. RESULTS: There were 13,144 generator replacement procedures involving a functioning, non-infected Riata® or Fidelis® lead (extraction n = 414, abandonment n = 427). Extraction patients were younger (mean 58 vs. 67 years) with fewer comorbidities than the reuse group. Maximum lead dwell time was similar between groups with average 94, 90, and 99 months in the extraction, abandonment, and reuse groups, respectively. In-hospital complications or mortality were more common in the extraction group (10.14%, 4.35%) compared with abandonment (1.64%, 0.47%) and reuse (0.22%, 0.07%). Compared with reuse, the adjusted odds of death or pre-discharge complication were significantly higher in the extraction group (OR 7.77 95% CI 2.42-24.95, p < .001) but not the abandonment group (OR 1.70 95% CI 0.52-5.61, p = .38). CONCLUSIONS: In this real-world population, extraction of functional recalled ICD leads was associated with significant risk of in-hospital mortality and complications. Additional work is needed to clarify whether longer term outcomes balance these peri-procedural risks.

Subclinical and Device-Detected Atrial Fibrillation: Pondering the Knowledge Gap: A Scientific Statement From the American Heart Association.

The widespread use of cardiac implantable electronic devices and wearable monitors has led to the detection of subclinical atrial fibrillation in a substantial proportion of patients. There is evidence that these asymptomatic arrhythmias are associated with increased risk of stroke. Thus, detection of subclinical atrial fibrillation may offer an opportunity to reduce stroke risk by initiating anticoagulation. However, it is unknown whether long-term anticoagulation is warranted and in what populations. This scientific statement explores the existing data on the prevalence, clinical significance, and management of subclinical atrial fibrillation and identifies current gaps in knowledge and areas of controversy and consensus.

Outcomes following cardioversion for patients with cardiac amyloidosis and atrial fibrillation or atrial flutter.

Atrial arrhythmias commonly occur in patients with cardiac amyloidosis (CA), but there is limited data on safety or efficacy of cardioversion (DCCV) for management of these rhythms in CA. We identified 25 patients with CA (20 with transthyretin (TTR) and 5 with light-chain (AL) amyloidosis) at Duke University who underwent DCCV for atrial arrhythmias and documented procedural success, complications, and long-term morbidity and mortality. While DCCV successfully restored sinus rhythm in 96% of patients, 36% of patients experienced immediate procedural complications (primarily bradycardia and hypotension), 80% had recurrence of atrial arrhythmias at 1 year, and 52% died at 3 years, highlighting short-term safety concerns, long-term inefficacy, and poor prognosis associated with symptomatic atrial arrhythmias requiring DCCV in CA.

Underuse of oral anticoagulants in privately insured patients with atrial fibrillation: A population being targeted by the IMplementation of a randomized controlled trial to imProve treatment with oral AntiCoagulanTs in patients with Atrial Fibrillation (IMPACT-AFib).

BACKGROUND: Many studies showing underuse of oral anticoagulants (OACs) in patients with atrial fibrillation (AF) predated the advent of the non-vitamin K antagonist OACs. We retrospectively examined use of OACs in a large commercially insured population. METHODS: Administrative claims data from 4 research partners participating in FDA-Catalyst, a program of the Sentinel Initiative, were queried in September 2017. Patients were included if they were ≥30 years old with ≥365 days of medical/pharmacy coverage, and had ≥2 diagnosis codes for AF, a CHA2DS2-VASc score ≥2, absence of contraindications to OAC use, and no evidence of OAC use in the 365 days before the index AF diagnosis. The main outcome measures of the current analysis were rates of OAC use in the prior 12 months of cohort identification and factors associated with non-use. RESULTS: A total of 197,806 AF patients met the eligibility criteria prior to assessment of OAC treatment. Of these, 179,580 (91%) patients were ≥65 years old and 73,286 (37%) patients were ≥80 years old. Half of the patients (98,903) were randomized to the early intervention arm in the IMPACT-AFib trial and constitute the cohort for this analysis. Of these, 32,295 (33%) had no evidence of OAC use in the prior 12 months. Compared with patients with evidence of OAC use in the prior 12 months, patients without OAC use were more likely to be ≥80 years old, women, and have a history of anemia (51% vs 47%) and less likely to have diabetes (41% vs 44%), history of stroke or TIA (15% vs 19%), and history of heart failure (39% vs 48%). CONCLUSIONS: Despite a high risk of stroke, one-third of privately insured patients with AF and no obvious contraindications to an OAC were not treated with an OAC. There is an unmet need for evidence-based interventions that could lead to greater use of OACs in patients with AF at risk for stroke.

Risk of major cardiovascular and neurologic events with obstructive sleep apnea among patients with atrial fibrillation.

BACKGROUND: Obstructive sleep apnea (OSA) is a known risk factor for atrial fibrillation (AF). However, it remains unclear whether OSA is independently associated with worse cardiovascular and neurological outcomes in patients with AF. METHODS: We used the ORBIT-AF I and ORBIT-AF II to conduct a retrospective cohort study of 22,760 patients with AF with and without OSA. Adjusted multivariable Cox proportional hazards models was used to determine whether OSA was associated with increased risk for major adverse cardiac and neurologic events (MACNEs) (cardiovascular death, myocardial infarction, stroke/transient ischemic attack/non-central nervous system embolism (stroke/SE), and new-onset heart failure], combined and individually. RESULTS: A total of 4,045 (17.8%) patients had OSA at baseline. Median follow-up time was 1.5 (interquartile range: 1-2.2) years, and 1,895 patients experienced a MACNE. OSA patients were younger (median [interquartile range] 68 [61-75] years vs 74 [66-81] years), were more likely male (70.7% vs 55.3%), and had increased body mass index (median 34.6 kg/m2 [29.8-40.2] vs 28.7 kg/m2 [25.2-33.0]). Those with OSA had a higher prevalence of concomitant comorbidities such as diabetes, chronic obstructive pulmonary disease, and heart failure. OSA patients had higher use of antithrombotic therapy. After adjustment, the presence of OSA was significantly associated with MACNE (hazard ratio: 1.16 [95% CI: 1.03-1.31], P = .011). OSA was also an independent risk factor for stroke/SE beyond the CHA2DS2-VASc risk factors (HR: 1.38 [95% CI 1.12-1.70], P = .003) but not cardiovascular death, myocardial infarction, new-onset heart failure, or major bleeding. CONCLUSIONS: Among patients with AF, OSA is an independent risk factor for MACNE and, more specifically, stroke/SE.

Patterns of amiodarone use and outcomes in clinical practice for atrial fibrillation.

BACKGROUND: Amiodarone is the most effective antiarrhythmic drug (AAD) for atrial fibrillation (AF), but it has a high incidence of adverse effects. METHODS: Using the ORBIT AF registry, patients with AF on amiodarone at enrollment, prescribed amiodarone during follow-up, or never on amiodarone were analyzed for the proportion treated with a guideline-based indication for amiodarone, the variability in amiodarone use across sites, and the outcomes (mortality, hospitalization, and stroke) among patients treated with amiodarone. Hierarchical logistic regression modeling with site-specific random intercepts compared rates of amiodarone use across 170 sites. A logistic regression model for propensity to receive amiodarone created a propensity-matched cohort. Cox proportional hazards modeling, stratified by matched pairs evaluated the association between amiodarone and outcomes. RESULTS: Among 6,987 AF patients, 867 (12%) were on amiodarone at baseline and 451 (6%) started on incident amiodarone during the 3-year follow-up. Use of amiodarone varied among sites from 3% in the lowest tertile to 21% in the highest (p<0.0001). Among those treated, 32% had documented contraindications to other AADs or had failed another AAD in the past. Mortality, cardiovascular hospitalization, and stroke were similar among matched patients on and not on amiodarone at baseline, while incident amiodarone use in matched patients was associated with higher all-cause mortality (adjusted HR 2.06, 95% CI 1.35-3.16). CONCLUSIONS: Use of amiodarone among AF patients in community practice is highly variable. More than 2 out of 3 patients treated with amiodarone appeared to be eligible for a different AAD.

Hands on: How to approach patients undergoing lead extraction.

Due to the growing number of patients treated with cardiac implantable electronic devices (CIEDs) there is an increased need for lead management, evaluation, and extraction. While CIED lead extraction has many indications, a consistent approach to preprocedural planning should be applied in all cases, including a thorough consultation with careful review of the patient's medical and device history, as well as a discussion of informed consent and shared decision-making with the patient and their loved ones. The use of chest X-ray, echocardiography, and computed tomography (CT) scan can further help with risk stratification and procedural planning. Intraprocedural echocardiography (transesophageal or intracardiac) is recommended and allows early recognition of cardiothoracic injury. Establishing an extraction team with cardiology/electrophysiology, anesthesiology, and CT surgery is is crucial to a successful and safe CIED extraction practice, including immediately available surgical backup. This hands-on review will address how to approach patients who are undergoing lead extraction, as well as several innovations in preprocedure and intraprocedural risk assessment.

Collaborative care for the wearable cardioverter defibrillator patient: Getting the patient and medical team "vested and active".

Patients with a reduced ejection fraction of 35% or less and a history of myocardial infarction (MI) are at increased risk of sudden cardiac death (SCD). These patients have a class I indication for an implantable cardioverter-defibrillator after allowing time for medical therapy optimization and potential cardiac recovery. The rates of SCD are highest in this "gap" period early after a cardiac event, and the wearable cardioverter-defibrillator (WCD) is an intervention that can be used to protect against SCD during this time period. There has been a clinical trial that randomized patients with a reduced ejection fraction at the time of MI to a WCD versus control. Results of the trial showed no statistically significant difference in the primary endpoint of SCD. There are many intricacies to the interpretation of the trial, including the importance of patient adherence to WCD therapy, which is affected by the patient experience and psychological factors. Patients with a new cardiomyopathy are affected by a mix of psychological factors, including the feeling of safety and protection from a WCD contrasted by the WCD providing a reminder of awareness and fear of ventricular arrhythmias and SCD. Beyond the capabilities of a WCD to defibrillate a life-threatening ventricular arrhythmia, the device can also provide activity and heart failure diagnostics monitoring. Patients need to be engaged in shared decision-making conversations about a WCD, so that patients can make a decision based on their own values construct, ultimately increasing adherence among the patients that want a WCD.

Preprocedural computed tomography before cardiac implanted electronic device lead extraction: Indication, technique, and approach to interpretation.

Cardiac implantable electronic devices (CIEDs) frequently need to be extracted due to infection, hardware failure, and other causes. The extraction of the CIED is typically performed using percutaneous methods. While these procedures are mostly performed without incident there is a small risk of significant complications. Dedicated imaging pre-CEID removal to include the central veins and heart with multidetector computed tomography (MDCT) can be utilized to evaluate the lead course and termination, the integrity of the central veins and cardiac chambers, and identify potential complications that may alter the lead extraction procedure as well as reimplantation of subsequent leads. Indications for preprocedural imaging, the technique of dedicated preprocedural lead extraction MDCT, and the approach to the interpretation of the images is discussed in this review.

Implantable cardioverter-defibrillator lead revision following left ventricular assist device implantation.

INTRODUCTION: Lead dysfunction can lead to serious consequences including failure to treat ventricular tachycardia or fibrillation (VT/VF). The incidence and mechanisms of lead dysfunction following left ventricular assist device (LVAD) implantation are not well-described. We sought to determine the incidence, mechanisms, timing, and complications of right ventricular lead dysfunction requiring revision following LVAD implantation. METHODS: Retrospective observational chart review of all LVAD recipients with pre-existing implantable cardioverter-defibrillator (ICD) from 2009 to 2018 was performed including device interrogation reports, laboratory and imaging data, procedural reports, and clinical outcomes. RESULTS: Among 583 patients with an ICD in situ undergoing LVAD implant, the median (interquartile range) age was 62.5 (15.7) years, 21% were female, and the types of LVADs included HeartWare HVAD (26%), HeartMate II (52%), and HeartMate III (22%). Right ventricular lead revision was performed in 38 patients (6.5%) at a median (25th, 75th) of 16.4 (3.6, 29.2) months following LVAD. Mechanisms of lead dysfunction included macrodislodgement (n = 4), surgical lead injury (n = 4), recall (n = 3), insulation failure (n = 8) or conductor fracture (n = 7), and alterations in the lead-myocardial interface (n = 12). Undersensing requiring revision occurred in 22 (58%) cases. Clinical sequelae of undersensing included failure to detect VT/VF (n = 4) and pacing-induced torsade de pointes (n = 1). Oversensing occurred in 12 (32%) and sequelae included inappropriate antitachycardia pacing ([ATP], n = 8), inappropriate ICD shock (n = 6), and ATP-induced VT (n = 1). CONCLUSION: The incidence of right ventricular lead dysfunction following LVAD implantation is significant and has important clinical sequelae. Physicians should remain vigilant for lead dysfunction after LVAD surgery and test lead function before discharge.

VVI pacing with normal QRS duration and ventricular function: MOST trial findings relevant to leadless pacemakers.

BACKGROUND: Leadless pacemakers (LPs) provide ventricular pacing without the risks associated with transvenous leads and device pockets. LPs are appealing for patients who need pacing, but do not need defibrillator or cardiac resynchronization therapy. Most implanted LPs provide right ventricular pacing without atrioventricular synchrony (VVIR mode). The Mode Selection Trial in Sinus Node Dysfunction (MOST) showed similar outcomes in patients randomized to dual-chamber (DDDR) versus ventricular pacing (VVIR). We compared outcomes by pacing mode in LP-eligible patients from MOST. METHODS: Patients enrolled in the MOST study with an left ventricular ejection fraction (LVEF) >35%, QRS duration (QRSd) <120 ms and no history of ventricular arrhythmias or prior implantable cardioverter defibrillators were included (LP-eligible population). Cox proportional hazards models were used to test the association between pacing mode and death, stroke or heart failure (HF) hospitalization and atrial fibrillation (AF). RESULTS: Of the 2010 patients enrolled in MOST, 1284 patients (64%) met inclusion criteria. Baseline characteristics were well balanced across included patients randomized to DDDR (N = 630) and VVIR (N = 654). Over 4 years of follow-up, there was no association between pacing mode and death, stroke or HF hospitalization (VVIR HR 1.28 [0.92-1.75]). VVIR pacing was associated with higher risk of AF (HR 1.32 [1.08-1.61], P = .007), particularly in patients with no history of AF (HR 2.38 [1.52-3.85], P < .001). CONCLUSION: In patients without reduced LVEF or prolonged QRSd who would be eligible for LP, DDDR, and VVIR pacing demonstrated similar rates of death, stroke or HF hospitalization; however, VVIR pacing significantly increased the risk of AF development.