Poole, Jeanne E.

Abstract Background Cardiovascular implantable electronic device (CIED) infections are associated with significant morbidity, mortality, and cost. There is limited evidence on antibiotic prophylactic strategies to prevent CIED infection. Recently, the TYRX Envelope, which elutes a combination of rifampin and minocycline for a minimum of 7 days, was shown to significantly reduce major CIED infections in the WRAP-IT trial. We sought to characterize the pathogens among patients who experienced an infection in the current era. Methods All patients undergoing CIED replacement, upgrade, revision, or de novo cardiac resynchronization therapy (CRT-D) received standard of care antibiotic prophylaxis and were randomized 1:1 to receive TYRX or not. The primary endpoint was major CIED infection within 12 months of the procedure. Major infection was defined as an infection resulting in (1) system extraction or revision, (2) long-term suppressive antibiotic therapy, or (3) death. Data were analyzed using the Cox proportional hazards regression model. Results A total of 6,983 patients were randomized worldwide with 3,495 randomized to receive an envelope and 3,488 randomized to the control. At 12 months, 25 major infections (0.7%) were observed in the envelope group and 42 major infections (1.2%) in the control group, resulting in a 40% reduction of major infections (HR: 0.60, 95% CI: 0.36–0.98, P = 0.04). Of 63 infections assayed, causative pathogens were identified in 36 infections whereas cultures were negative in 27 cases. Staphylococcus species (n = 22) were the predominate pathogens and a 53% reduction was observed with the use of TYRX (Figure 1). Moreover, there was only 1 CIED pocket infection with Staphylococcus species in the envelope group compared with 14 pocket infections in the control group. A comparison of timing of infection in the envelope group showed the presence of 11 endocarditis/bacteremia infections at 103 ± 84 days compared with 14 pocket infections presenting at 70 ± 78 days from the procedure. Conclusion In this large randomized trial, the use of the TYRX Envelope containing rifampin and minocycline resulted in a significant reduction of major CIED infections and was effective against staphylococcal species, which are the predominant cause of pocket infections. Disclosures All Authors: No reported Disclosures.

Abstract Background Sex-specific outcomes may differ amongst patients receiving catheter ablation for atrial fibrillation (AF). Purpose Assess sex-specific outcomes in the patients randomized to catheter ablation or drug therapy in CABANA. Methods CABANA randomized 2204 pts with AF to catheter ablation or drug therapy (rate/rhythm-control). The outcomes of combined death, disabling stroke, severe bleeding, or cardiac arrest (intention to treat-ITT) or all-cause death were not different. But, ablation significantly improved combined death or CV hospitalization. This analysis compares clinical characteristics by sex and determines sex-specific hazard ratios based on a comparison of ablation vs drug therapy. Results Females were 37.3% of ablation and 37.0% of drug therapy patients. Females were older, more often white race, had less CAD, or sleep apnea, but had higher NYHA Class, higher CHA2DS2VASc, and more often had paroxysmal (v. persistent) AF, and prior AF hospitalization. (Table) HTN, CVA and diabetes were the same (Table). For the CABANA primary endpoint, an ITT comparison of ablation vs. drug therapy, showed a female hazard ratio (HR) of 1.14 (95% confidence interval (CI) 0.70–1.86), and a male HR of 0.74, (95% CI 0.52–1.06). For all-cause mortality, the female HR was 0.75 (95% CI 0.41–1.40) and male HR was 0.91 (95% CI 0.59–1.40) and for all-cause mortality or CV hospitalization, the female HR was 0.90 (95% CI 0.75–1.09) and male HR was 0.79 (95% CI 0.69–0.92). All interaction p values were non-significant. Recurrent AF (post 90-day blanking) was significantly reduced for both females and males: female HR 0.64 (95% CI 0.51–0.82), male HR 0.46 95% CI 0.39–0.56), p=0.035 Clinical Characteristics and Outcomes Baseline Characteristics Female (N=818) Male (N=1385) p-value Age: Median (Q1, Q3) 69 (65, 74) 66 (60, 71) <0.001 White 766 (93.9%) 1259 (91.0%) 0.015 CAD 92 (11.2%) 332 (24.0%) <0.001 NYHA ≥II 345 (42.4%) 433 (31.5%) <0.001 Sleep apnea 136 (16.6%) 372 (26.9%) <0.001 CHA2DS2-VASc: Median (Q1, Q3) 3 (3, 4) 2 (1, 3) <0.001 Paroxysmal AF 406 (49.6%) 540 (39.0%) <0.001 Persistent AF 412 (50.4%) 845 (61.0%) AF Hospitalization 353 (43.2%) 521 (37.7%) 0.011 Conclusion Significant sex-specific outcomes differences were not observed. Sex should not be used as a determining factor in selecting patients for AF therapy. Acknowledgement/Funding NIH, St Jude Medical Foundation and Corporation, Biosense Webster Inc., Medtronic Corporation, and Boston Scientific Corporation

Abstract Background Prior studies suggest that catheter ablation (ABL) for atrial fibrillation (AF) is a treatment option for patients (pts) with paroxysmal AF (PAF). Pts with persistent (Per) or long-standing persistent (LSP) were routinely excluded from most ABL based clinical trials. The effectiveness of ABL compared to drug therapy (MED) in relation to underlying AF type has not been evaluated in a large randomized clinical trial. Objective To assess the impact of AF type on clinical outcomes of ABL vs. MED in pts with AF. Methods The CABANA trial randomized 2204 pts with AF at 126 sites worldwide to ABL vs. MED with rate or rhythm control drugs. The primary endpoint was a composite of death, disabling stroke, severe bleeding, or cardiac arrest. Key secondary endpoints included mortality and recurrence of AF. Outcomes of ABL vs. MED were compared within subgroups defined by AF type using Intention-to-Treat (ITT) analyses. Results Of the 2204 pts, 946 had PAF, 1042 had Per and 215 presented with LSP. There were baseline differences among AF types in age, gender, HTN, LVH, CHF and NYHA Class. For the primary endpoint, there were no significant differences between ABL and MED in pts with PAF (hazard ratio (HR) 0.82; 95% confidence interval (CI) 0.51, 1.31), Per (HR 0.87; 95% CI 0.59, 1.28), or LSP (HR 1.01, 95% CI 0.39, 2.61). Likewise, there were no significant treatment differences in mortality; PAF (HR 0.84; 95% CI 0.46, 1.52), Per (HR 0.90; 95% CI 0.56, 1.46) and LSP (HR 0.67, 95% CI 0.23, 1.94). Post-blanking AF (time to first recurrence) was significantly reduced by ABL compared to MED across all AF types (PAF by 51%), (Per by 47%) and (LSP by 36%). Clinical Characteristics and Outcomes Clinical Outcomes Comparing ABL vs. MED (HR and 95% CI) Interaction p-value Primary Endpoint 0.82 (0.51, 1.31) 0.87 (0.59, 1.28) 1.01 (0.39, 2.61) 0.925 Mortality 0.84 (0.46, 1.52) 0.90 (0.56, 1.46) 0.67 (0.23, 1.94) 0.881 Recurrent AF 0.49 (0.38, 0.62) 0.53 (0.43, 0.65) 0.64 (0.41, 1.01) 0.564 Conclusion Pts with LSP have a lower proportion of women, and a higher proportion with manifestations of heart failure despite lower CHA2DS2VASc scores. By ITT analysis, there is no significant effect of ABL compared to MED in the primary endpoint or mortality in any AF group. However, ABL is more effective than MED for reducing recurrences of AF regardless of AF type, but with a greater effect in PAF vs Per vs LSP. Acknowledgement/Funding NIH, St Jude Medical Foundation and Corporation, Biosense Webster Inc., Medtronic Corporation, and Boston Scientific Corporation

Background— The Sudden Cardiac Death in Heart Failure Trial (SCD-HeFT) demonstrated that implantable cardioverter-defibrillator (ICD) therapy reduces all-cause mortality in patients with New York Heart Association class II/III heart failure and a left ventricular ejection fraction ≤35% on optimal medical therapy. Whether ICD therapy reduced sudden death caused by ventricular tachyarrhythmias without affecting heart failure deaths in this population is unknown. Methods and Results— SCD-HeFT randomized 2521 subjects to placebo, amiodarone, or shock-only, single-lead ICD therapy. Over a median follow-up of 45.5 months, a total of 666 deaths occurred, which were reviewed by an Events Committee and initially categorized as cardiac or noncardiac. Cardiac deaths were further adjudicated as resulting from sudden death presumed to be ventricular tachyarrhythmic, bradyarrhythmia, heart failure, or other cardiac causes. ICD therapy significantly reduced cardiac mortality compared with placebo (adjusted hazard ratio, 0.76; 95% confidence interval, 0.60 to 0.95) and tachyarrhythmia mortality (adjusted hazard ratio, 0.40; 95% confidence interval, 0.27 to 0.59) and had no impact on mortality resulting from heart failure or noncardiac causes. The cardiac and tachyarrhythmia mortality reductions were evident in subjects with New York Heart Association class II but not in subjects with class III heart failure. The reduction in tachyarrhythmia mortality with ICD therapy was similar in subjects with ischemic and nonischemic disease. Compared with placebo, amiodarone had no significant effect on any mode of death. Conclusions— ICD therapy reduced cardiac mortality and sudden death presumed to be ventricular tachyarrhythmic in SCD-HeFT and had no effect on heart failure mortality. Amiodarone had no effect on all-cause mortality or its cause-specific components, except an increase in non-cardiac mortality in class III patients. Clinical Trial Registration Information— URL: http://www.clinicaltrials.gov. Unique identifier: NCT00000609.