Cardioverter-defibrillator reduces mortality risk in eligible ischemic and non-ischemic cardiomyopathy patients: Sub-analysis of the multi-center Improve SCA study.

BACKGROUND & OBJECTIVE: Despite the burden of sudden cardiac arrest (SCA) worldwide, implantable cardioverter-defibrillators (ICDs) are underutilized, particularly in Asia, Latin America, Eastern Europe, the Middle East, and Africa. The Improve SCA trial demonstrated that primary prevention (PP) patients in these regions benefit from an ICD or a cardiac resynchronization therapy defibrillator (CRT-D). We aimed to compare the rate of device therapy and mortality among ischemic and non-ischemic cardiomyopathy (ICM and NICM) PP patients who met guideline indications for ICD therapy and had an ICD/CRT-D implanted. METHODS: Improve SCA was a prospective, non-randomized, non-blinded multicenter trial that enrolled patients from the above-mentioned regions. All-cause mortality and device therapy were examined by cardiomyopathy (ICM vs NICM) and implantation status. Cox proportional hazards methods were used, adjusting for factors affecting mortality risk. RESULTS: Of 1848 PP NICM patients, 1007 (54.5%) received ICD/CRT-D, while 303 of 581 (52.1%) PP ICM patients received an ICD/CRT-D. The all-cause mortality rate at 3 years for NICM patients with and without an ICD/CRT-D was 13.1% and 18.3%, respectively (HR 0.51, 95% CI 0.38-0.68, p < 0.001). Similarly, all-cause mortality at 3 years in ICM patients was 13.8% in those with a device and 19.9% in those without an ICD/CRT-D (HR 0.54, 95% CI 0.33-.0.88, p = 0.011). The time to first device therapy, time to first shock, and time to first antitachycardia pacing (ATP) therapy were not significantly different between groups (p ≥ 0.263). CONCLUSIONS: In this large data set of patients with a guideline-based PP ICD indication, defibrillator device implantation conferred a significant mortality benefit in both NICM and ICM patients. The rate of appropriate device therapy was also similar in both groups. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov ID: NCT02099721.

New atrial arrhythmia occurrence in single chamber implantable cardioverter defibrillator patients: A real-world investigation.

INTRODUCTION: A current limitation of single chamber implantable cardioverter defibrillators (ICDs) is the lack of an atrial lead to reliably detect atrial fibrillation (AF) episodes. A novel ventricular based atrial fibrillation (VBAF) detection algorithm was created for single chamber ICDs to assess R-R variability for detection of AF. METHODS: Patients implanted with Visia AF™ ICDs were prospectively enrolled in the Medtronic Product Surveillance Registry from December 15, 2015 to January 23, 2019 and followed with at least 30 days of monitoring with the algorithm. Time to device-detected daily burden of AF ≥ 6 min, ≥6 h, and ≥23 h were reported. Clinical actions after device-detected AF were recorded. RESULTS: A total of 291 patients were enrolled with a mean follow-up of 22.5 ± 7.9 months. Of these, 212 (73%) had no prior history of AF at device implant. However, 38% of these individuals had AF detected with the VBAF algorithm with daily burden of ≥6 min within two years of implant. In these 80 patients with newly detected AF by their ICD, 23 (29%) had a confirmed clinical diagnosis of AF by their provider. Of patients with a clinical diagnosis of AF, nine (39%) were newly placed on anticoagulation, including five of five (100%) patients having a burden >23 h. CONCLUSIONS: Continuous AF monitoring with the new VBAF algorithm permits early identification and actionable treatment for patients with undiagnosed AF that may improve patient outcomes.

Risk factors for hematoma in patients undergoing cardiac device procedures: A WRAP-IT trial analysis.

Background: Implant site hematoma is a known complication of cardiac device procedures and can lead to major consequences. Objectives: To evaluate risk factors for hematoma and further understand the relationship between anticoagulant (AC), antiplatelet (AP) use, and hematoma development. Methods: We included 6800 patients from the WRAP-IT trial. To assess baseline and procedural characteristics associated with hematoma within the first 30 days postprocedure, a stepwise Cox regression model was implemented with minimal Akaike information criterion. Cox regressions were also used to evaluate AC/AP use and hematoma risk. Results: The overall rate of hematoma was 2.2%. The model identified 11 baseline and procedural characteristics associated with hematoma risk. AC use (hazard ratio [HR]: 2.44, P < .001), lower body mass index (HR: 1.06, P < .001), and history of valve surgery (HR: 2.11, P < .001) were associated with the highest risk. AP use, male sex, history of coronary artery disease, existing pocket, history of nonischemic cardiomyopathy, number of previous cardiac implantable electronic device (CIED) procedures, procedure time, and lead revision were associated with moderate risk. Antithrombotic use was high overall (86%) and AC+AP use was highly predictive of hematoma risk. Regardless of AC status, AP use was associated with an almost doubling of risk vs no AP (HR = 1.85, P = .0006) in the general cohort. Interruption of AC was associated with the lowest hematoma risk (HR = 2.35) while heparin bridging (HR = 4.98) and AP use vs no AP use (HR = 1.85) was associated with the highest hematoma risk. Conclusion: The results of this analysis highlight risk factors associated with the development of hematoma in patients undergoing CIED procedures and can inform antithrombotic management.

Performance evaluation of implantable cardioverter-defibrillators with SmartShock technology in patients with inherited arrhythmogenic diseases.

BACKGROUND: Patients with inherited arrhythmogenic diseases (IADs) are often prescribed preventative implantable cardioverter-defibrillators (ICDs) to manage their increased sudden cardiac arrest risk. However, it has been suggested that ICDs in IAD patients may come with additional risk. We aimed to leverage the PainFree SmartShock Technology dataset to compare inappropriate therapies, appropriate therapies, mortality, and complications in patients with and without IAD. METHODS: This retrospective analysis included extracted, physician-adjudicated, arrhythmic episodes from ICD devices. The incidence of arrhythmic events was estimated with the Kaplan-Meier method using the log-rank test. Cox proportional hazards regression was used to estimate hazard ratios (HRs) with their 95% confidence intervals (CIs). RESULTS: Of the 1699 ICD patients, 77 patients (4.5%) had IAD. Incidence of inappropriate shock was similar in both patients with (3.2% at 24 months) and without (3.8% at 24 months) IAD (HR: 0.80, CI: 0.19-3.30, p = 0.76). In a multivariable analysis IAD was not significantly associated with reduced mortality (HR: 0.64, CI: 0.08-4.80, p = 0.66). The rates of complications were numerically lower in patients with IAD vs without (8.8% vs 9.6% at 24 months respectively), but not statistically significant (HR: 0.83, CI: 0.20-3.38, p = 0.79). CONCLUSIONS: IAD patients showed a very low annual rate of inappropriate therapy. This suggests that newer algorithms, such as the SST algorithm, are equally good at identifying and treating life-threatening arrhythmias in patients regardless of whether they have IAD.

Trends in implantable cardioverter-defibrillator programming practices and its impact on therapies: Insights from a North American Remote Monitoring Registry 2007-2018.

BACKGROUND: Recent evidence has revealed the utility of prolonged arrhythmia detection duration and increased rate cutoff to reduce implantable cardioverter-defibrillator (ICD) therapies. Data on real-world trends in ICD programming and its impact on outcomes are limited. OBJECTIVE: The purpose of this study was to evaluate trends in ICD programming and its impact on ICD therapy using a large remote monitoring database. METHODS: A retrospective analysis of patients with ICD implanted from 2007 to 2018 was conducted using the de-identified Medtronic CareLink database. Data on ICD programming (number of intervals to detection [NID] and therapy rate cutoff) and delivered ICD therapies were collected. RESULTS: Among 210,810 patients, the proportion programmed to a rate cutoff of ≥188 beats/min increased from 41% to 49% and an NID of ≥30/40 increased from 17% to 67% before May 2013 vs after February 2016. Programming to a rate cutoff of ≥188 beats/min, a ventricular fibrillation (VF) NID of ≥30/40, or a combined rate cutoff of ≥188 beats/min and VF NID of ≥30/40 were associated with reductions in ICD therapy. The largest reductions in ICD therapy occurred when the combination of rate cutoff ≥ 188 beats/min and VF NID ≥ 30/40 was programmed (antitachycardia pacing: hazard ratio [HR] 0.35; 95% confidence interval [CI] 0.34-0.36; P < .001; shocks: HR 0.67; 95% CI 0.65-0.69; P < .001; and antitachycardia pacing/shocks: HR 0.43; 95% CI 0.42-0.44; P < .001). CONCLUSION: Despite evidence supporting the use of prolonged detection duration and high rate cutoff, implementation of shock reduction programming strategies in real-world clinical practice has been modest. The use of evidence-based ICD programming is associated with reduced ICD shocks over long-term follow-up.

Risk Factors for CIED Infection After Secondary Procedures: Insights From the WRAP-IT Trial.

OBJECTIVES: This study aimed to identify risk factors for infection after secondary cardiac implantable electronic device (CIED) procedures. BACKGROUND: Risk factors for CIED infection are not well defined and techniques to minimize infection lack supportive evidence. WRAP-IT (World-wide Randomized Antibiotic Envelope Infection Prevention trial), a large study that assessed the safety and efficacy of an antibacterial envelope for CIED infection reduction, offers insight into procedural details and infection prevention strategies. METHODS: This analysis included 2,803 control patients from the WRAP-IT trial who received standard preoperative antibiotics but not the envelope (44 patients with major infections through all follow-up). A multivariate least absolute shrinkage and selection operator machine learning model, controlling for patient characteristics and procedural variables, was used for risk factor selection and identification. Risk factors consistently retaining predictive value in the model (appeared >10 times) across 100 iterations of imputed data were deemed significant. RESULTS: Of the 81 variables screened, 17 were identified as risk factors with 6 being patient/device-related (nonmodifiable) and 11 begin procedure-related (potentially modifiable). Patient/device-related factors included higher number of previous CIED procedures, history of atrial arrhythmia, geography (outside North America and Europe), device type, and lower body mass index. Procedural factors associated with increased risk included longer procedure time, implant location (non-left pectoral subcutaneous), perioperative glycopeptide antibiotic versus nonglycopeptide, anticoagulant, and/or antiplatelet use, and capsulectomy. Factors associated with decreased risk of infection included chlorhexidine skin preparation and antibiotic pocket wash. CONCLUSIONS: In WRAP-IT patients, we observed that several procedural risk factors correlated with infection risk. These results can help guide infection prevention strategies to minimize infections associated with secondary CIED procedures.

Clinical performance of implantable cardioverter-defibrillator lead monitoring diagnostics.

BACKGROUND: Implantable cardioverter-defibrillator (ICD) lead monitoring diagnostic alerts facilitate the diagnosis of structural lead failure. OBJECTIVE: The purpose of this study was to prospectively study the performance of Medtronic ICD lead monitoring alerts. METHODS: A prespecified ancillary substudy, World-Wide Randomized Antibiotic Envelope Infection Prevention Trial, was conducted in patients with an ICD with all available alerts enabled. The investigators reported possible lead system events (LSEs), with or without an alert. An independent committee reviewed all data and classified events as lead failure, other LSE, or nonlead system events (NLEs). RESULTS: In 4942 patients who were followed for 19.4 ± 8.7 months, there were 124 alerts (65 LSEs, 59 NLEs) and 19 LSEs without an alert. Lead monitoring alerts had 100% sensitivity for the 48 adjudicated lead failures (95% confidence interval 92.6%-100%) and for 10 events adjudicated as either lead failure or connection issue. The positive predictive value of alerts for lead failure was 38.7% (48 of 124). For 34 pace-sense lead failures, an alert that incorporated oversensing was more sensitive than the pacing impedance threshold alert (33 patients [97.1%] vs 9 patients [26.5%]; P < .0001). However, the sensitivity was only 13.6% for lead dislodgments or perforations. Inappropriate shocks occurred in 2 patients with pace-sense lead failure (5.9%). No patient had unnecessary lead replacement for any of the NLEs. CONCLUSION: In this first real-world prospective study, lead monitoring alerts had 100% sensitivity for identifying lead failures. Although their positive predictive value was modest, no false-positive alerts resulted in an unnecessary lead replacement. For the diagnosis of pace-sense lead failure, an alert for oversensing was more sensitive than a pacing impedance threshold alert. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT02277990.

Infectious consequences of hematoma from cardiac implantable electronic device procedures and the role of the antibiotic envelope: A WRAP-IT trial analysis.

BACKGROUND: Hematoma is a complication of cardiac implantable electronic device (CIED) procedures and may lead to device infection. The TYRX antibacterial envelope reduced major CIED infection by 40% in the randomized WRAP-IT (World-wide Randomized Antibiotic Envelope Infection Prevention Trial) study, but its effectiveness in the presence of hematoma is not well understood. OBJECTIVE: The purpose of this study was to evaluate the incidence and infectious consequences of hematoma and the association between envelope use, hematomas, and major CIED infection among WRAP-IT patients. METHODS: All 6800 study patients were included in this analysis (control 3429; envelope 3371). Hematomas occurring within 30 days postprocedure (acute) were characterized and grouped by study treatment and evaluated for subsequent infection risk. Data were analyzed using Cox proportional hazard regression modeling. RESULTS: Acute hematoma incidence was 2.2% at 30 days, with no significant difference between treatment groups (envelope vs control hazard ratio [HR] 1.15; 95% confidence interval [CI] 0.84-1.58; P = .39). Through all follow-up, the risk of major infection was significantly higher among control patients with hematoma vs those without (13.1% vs 1.6%; HR 11.3; 95% CI 5.5-23.2; P <.001). The risk of major infection was significantly lower in the envelope vs control patients with hematoma (2.5% vs 13.1%; HR 0.18; 95% CI 0.04-0.85; P = .03). CONCLUSION: The risk of hematoma was 2.2% among WRAP-IT patients. Among control patients, hematoma carried a >11-fold risk of developing a major CIED infection. This risk was significantly mitigated with antibacterial envelope use, with an 82% reduction in major CIED infection among envelope patients who developed hematoma compared to control.

In vitro modeling accurately predicts cardiac lead fracture at 10 years.

BACKGROUND: Development of a cardiac lead fracture model has the potential to differentiate well-performing lead designs from poor performing ones and could aid in future lead development. OBJECTIVE: The purpose of this study was to demonstrate a predictive model for lead fracture and validate the results generated by the model by comparing them to observed 10-year implantable cardioverter-defibrillator lead fracture-free survival. METHODS: The model presented here uses a combination of in vivo patient data, in vitro conductor fatigue test data, and statistical simulation to predict the fracture-free survival of cardiac leads. The model was validated by comparing the results to human clinical performance data from the Medtronic Sprint Fidelis (Minneapolis, MN) models 6931 (single coil, active fixation) and 6949 (dual coil, active fixation), as well as the Quattro model 6947 (dual coil, active fixation). RESULTS: Median patient age in the single coil Fidelis 6931 population (64 years) was less than in the dual coil Fidelis 6949 and Quattro populations (68 years). Modeled and observed fracture-free survival for Quattro (>97%) was superior to that for Fidelis (<94%). The modeled survival agreed with the observed fracture-free survival data. The average model error was 0.3% (SD 1.2%). CONCLUSION: This model for cardiac lead fracture-free survival using in vivo lead bending measurements and in vitro bench testing can be used to predict lead performance as observed by alignment with field survival data.

Use of healthcare claims to validate the Prevention of Arrhythmia Device Infection Trial cardiac implantable electronic device infection risk score.

AIM: The Prevention of Arrhythmia Device Infection Trial (PADIT) infection risk score, developed based on a large prospectively collected data set, identified five independent predictors of cardiac implantable electronic device (CIED) infection. We performed an independent validation of the risk score in a data set extracted from U.S. healthcare claims. METHODS AND RESULTS: Retrospective identification of index CIED procedures among patients aged ≥18 years with at least one record of a CIED procedure between January 2011 and September 2014 in a U.S health claims database. PADIT risk factors and major CIED infections (with system removal, invasive procedure without system removal, or infection-attributable death) were identified through diagnosis and procedure codes. The data set was randomized by PADIT score into Data Set A (60%) and Data Set B (40%). A frailty model allowing multiple procedures per patient was fit using Data Set A, with PADIT score as the only predictor, excluding patients with prior CIED infection. A data set of 54 042 index procedures among 51 623 patients with 574 infections was extracted. Among patients with no history of prior CIED infection, a 1 unit increase in the PADIT score was associated with a relative 28% increase in infection risk. Prior CIED infection was associated with significant incremental predictive value (HR 5.66, P < 0.0001) after adjusting for PADIT score. A Harrell's C-statistic for the PADIT score and history of prior CIED infection was 0.76. CONCLUSION: The PADIT risk score predicts increased CIED infection risk, identifying higher risk patients that could potentially benefit from targeted interventions to reduce the risk of CIED infection. Prior CIED infection confers incremental predictive value to the PADIT score.

Low-temperature electrocautery reduces adverse effects from secondary cardiac implantable electronic device procedures: Insights from the WRAP-IT trial.

BACKGROUND: Cardiac device procedures require tissue dissection to free existing device lead(s). Common techniques include blunt dissection, standard electrocautery, and low-temperature electrocautery (PlasmaBlade, Medtronic); however, data on the type of electrosurgical tool used and the development of procedure- or lead-related adverse events are limited. OBJECTIVE: The purpose of this study was to determine whether standard or low-temperature electrocautery impacts the development of an adverse event. METHODS: We evaluated patients enrolled in WRAP-IT (Worldwide Randomized Antibiotic EnveloPe Infection PrevenTion Trial) undergoing cardiac implantable electronic device (CIED) revision, upgrade, or replacement. All adverse events were adjudicated by an independent physician committee. Data were analyzed using Cox proportional hazard regression modeling. RESULTS: In total, 5641 patients underwent device revision/upgrade/replacement. Electrocautery was used in 5205 patients (92.3%) (mean age 70.6 ± 12.7 years; 28.8% female), and low-temperature electrocautery was used in 1866 patients (35.9%). Compared to standard electrocautery, low-temperature electrocautery was associated with a 23% reduction in the incidence of a procedure- or lead-related adverse event through 3 years of follow up (hazard ratio [HR] 0.77; 95% confidence interval [CI] 0.65-0.91; P = .002). After controlling for the number of active leads, degree of capsulectomy, degree of lead dissection, and renal dysfunction, low-temperature electrocautery was associated with a 32% lower risk of lead-related adverse events (HR 0.68; 95% CI 0.52-0.89; P = .004). These effects were consistent across a spectrum of lead-related adverse event types. CONCLUSION: This study represents one of the largest assessments of electrocautery use in patients undergoing CIED revision, upgrade, or replacement procedures. Compared to standard electrocautery, low-temperature electrocautery significantly reduces adverse effects from these procedures.

Clinical Presentation, Timing, and Microbiology of CIED Infections: An Analysis of the WRAP-IT Trial.

OBJECTIVES: This study characterized the microbiology of major cardiac implantable electronic device (CIED) infections that occurred during the WRAP-IT (Worldwide Randomized Antibiotic Envelope Infection Prevention Trial) study. BACKGROUND: The WRAP-IT study offers a unique opportunity for further understanding of the pathogens involved in major CIED infections in a prospective dataset, with implications for clinical practice and infection management. METHODS: A total of 6,800 patients randomized 1:1 to receive an antibacterial envelope or not (control subjects) were included in this analysis. Patient characteristics, infection manifestation (pocket vs. systemic), and infection microbiology were evaluated through all follow-up (36 months). Data were analyzed using Cox proportional hazards regression. RESULTS: A total of 3,371 patients received an envelope, and 3,429 patients were control subjects. Major CIED infection occurred in 32 patients who received an envelope and 51 control subjects (36-month Kaplan-Meier estimated event rate, 1.3% and 1.9%, respectively; p = 0.046). A 61% reduction in major pocket infection was observed within 12 months of the procedure in the envelope group (hazard ratio: 0.39, 95% confidence interval: 0.21 to 0.73; p = 0.003). Among 76 patients with major infections who had a sample taken, causative pathogens were identified in 47 patients. Staphylococcus species were the predominate pathogen (n = 31) and envelope use resulted in a 76% reduction in Staphylococcus-related pocket infections (n = 4 vs. 17; p = 0.010). Envelope use was not associated with delayed onset of pocket infections and did not affect the presentation of infections. CONCLUSIONS: Antibacterial envelope use resulted in a significant reduction of major CIED pocket infections and was particularly effective against Staphylococcus species, the predominant cause of pocket infections. (Worldwide Randomized Antibiotic Envelope Infection Prevention Trial [WRAP-IT]; NCT02277990).

Cost-Effectiveness of an Antibacterial Envelope for Cardiac Implantable Electronic Device Infection Prevention in the US Healthcare System From the WRAP-IT Trial.

BACKGROUND: In the WRAP-IT trial (Worldwide Randomized Antibiotic Envelope Infection Prevention), adjunctive use of an absorbable antibacterial envelope resulted in a 40% reduction of major cardiac implantable electronic device infection without increased risk of complication in 6983 patients undergoing cardiac implantable electronic device revision, replacement, upgrade, or initial cardiac resynchronization therapy defibrillator implant. There is limited information on the cost-effectiveness of this strategy. As a prespecified objective, we evaluated antibacterial envelope cost-effectiveness compared with standard-of-care infection prevention strategies in the US healthcare system. METHODS: A decision tree model was used to compare costs and outcomes of antibacterial envelope (TYRX) use adjunctive to standard-of-care infection prevention versus standard-of-care alone over a lifelong time horizon. The analysis was performed from an integrated payer-provider network perspective. Infection rates, antibacterial envelope effectiveness, infection treatment costs and patterns, infection-related mortality, and utility estimates were obtained from the WRAP-IT trial. Life expectancy and long-term costs associated with device replacement, follow-up, and healthcare utilization were sourced from the literature. Costs and quality-adjusted life years were discounted at 3%. An upper willingness-to-pay threshold of $150 000 per quality-adjusted life year was used to determine cost-effectiveness, in alignment with the American College of Cardiology/American Heart Association practice guidelines and as supported by the World Health Organization and contemporary literature. RESULTS: The base case incremental cost-effectiveness ratio of the antibacterial envelope compared with standard-of-care was $112 603/quality-adjusted life year. The incremental cost-effectiveness ratio remained lower than the willingness-to-pay threshold in 74% of iterations in the probabilistic sensitivity analysis and was most sensitive to the following model inputs: infection-related mortality, life expectancy, and infection cost. CONCLUSIONS: The absorbable antibacterial envelope was associated with a cost-effectiveness ratio below contemporary benchmarks in the WRAP-IT patient population, suggesting that the envelope provides value for the US healthcare system by reducing the incidence of cardiac implantable electronic device infection. Registration: URL: https://www.clinicaltrials.gov. Unique identifier: NCT02277990.

Correction: Chronic Alcohol Ingestion Increases Mortality and Organ Injury in a Murine Model of Septic Peritonitis.

[This corrects the article DOI: 10.1371/journal.pone.0062792.].

Characteristics of ventricular tachyarrhythmias and their susceptibility to antitachycardia pacing termination in patients with ischemic and nonischemic cardiomyopathy: A patient-level meta-analysis of three large clinical trials.

BACKGROUND: Implantable cardioverter defibrillators (ICDs) reduce all-cause mortality among cardiomyopathy patients. Whether or not antitachycardia pacing (ATP) is equally effective in ischemic (ICM) and nonischemic (NICM) cardiomyopathy patients remains poorly understood. We describe the distribution of monomorphic (MVT) and non-monomorphic (polymorphic ventricular tachycardia/ventricular fibrillation [PVT/VF]) ventricular tachyarrhythmias among ICM and NICM primary prevention patients. METHODS: This patient-level meta-analysis included primary prevention patients from the Shock-Less (n = 3519), PainFree SST (n = 1917), and PREPARE (n = 690) studies. Distribution of MVT and PVT/VF events were compared with χ2 tests. ATP success was estimated using a generalized estimating equation model to correct for multiple episodes for a patient between cohorts for slow (≥320 ms) and fast (240-310 ms) MVTs. RESULTS: Among 6126 patients, 714 (29% NICM, age 66 ± 13 years, female 18%, EF = 29 ± 12%) had a total of 4444 treated ventricular tachyarrhythmia episodes. The rate of individuals treated for MVT or PVT/VF was comparable between ICM (11.9%) and NICM (11.2%) over 21 ± 10 months. In addition, the distribution of MVT (76% ICM vs. 71% NICM) and PVT/VF (15% ICM vs. 20% NICM) was not significantly different (p = .28). Among MVT episodes, the average tachycardia cycle lengths (332 ± 58 ms ICM vs. 313 ± 40 ms NICM; p = .27) were similar, as was the likelihood of ATP-associated termination (74.6% ICM vs. 76.4% NICM; p = .58). Overall, ATP success was higher for slow (≥320 ms) MVT versus faster (240-310 ms) episodes (84.1% vs. 69%; p < .001). CONCLUSION: In a large cohort of primary prevention ICD patients, ICM and NICM patients have similar rates and proportions of MVT and PVT/VF episodes. ATP-associated termination of MVT was comparable between the two groups.

Impact of Cardiac Implantable Electronic Device Infection: A Clinical and Economic Analysis of the WRAP-IT Trial.

BACKGROUND: Current understanding of the impact of cardiac implantable electronic device (CIED) infection is based on retrospective analyses from medical records or administrative claims data. The WRAP-IT (Worldwide Randomized Antibiotic Envelope Infection Prevention Trial) offers an opportunity to evaluate the clinical and economic impacts of CIED infection from the hospital, payer, and patient perspectives in the US healthcare system. METHODS: This was a prespecified, as-treated analysis evaluating outcomes related to major CIED infections: mortality, quality of life, disruption of CIED therapy, healthcare utilization, and costs. Payer costs were assigned using medicare fee for service national payments, while medicare advantage, hospital, and patient costs were derived from similar hospital admissions in administrative datasets. RESULTS: Major CIED infection was associated with increased all-cause mortality (12-month risk-adjusted hazard ratio, 3.41 [95% CI, 1.81-6.41]; P<0.001), an effect that sustained beyond 12 months (hazard ratio through all follow-up, 2.30 [95% CI, 1.29-4.07]; P=0.004). Quality of life was reduced (P=0.004) and did not normalize for 6 months. Disruptions in CIED therapy were experienced in 36% of infections for a median duration of 184 days. Mean costs were $55 547±$45 802 for the hospital, $26 867±$14 893, for medicare fee for service and $57 978±$29 431 for Medicare Advantage (mean hospital margin of -$30 828±$39 757 for medicare fee for service and -$6055±$45 033 for medicare advantage). Mean out-of-pocket costs for patients were $2156±$1999 for medicare fee for service, and $1658±$1250 for medicare advantage. CONCLUSIONS: This large, prospective analysis corroborates and extends understanding of the impact of CIED infections as seen in real-world datasets. CIED infections severely impact mortality, quality of life, healthcare utilization, and cost in the US healthcare system. Registration: URL: https://www.clinicaltrials.gov Unique Identifier: NCT02277990.

Utilization of implantable cardioverter-defibrillators for the prevention of sudden cardiac death in emerging countries: Improve SCA clinical trial.

BACKGROUND: Implantable cardioverter-defibrillators (ICDs) are underutilized in Asia, Latin America, Eastern Europe, the Middle East, and Africa. The Improve SCA Study is the largest prospective study to evaluate the benefit of ICD therapy in underrepresented geographies. This analysis reports the primary objective of the study. OBJECTIVES: The objectives of this study was to determine whether patients with primary prevention (PP) indications with specific risk factors (1.5PP: syncope, nonsustained ventricular tachycardia, premature ventricular contractions >10/h, and low ventricular ejection fraction <25%) are at a similar risk of life-threatening arrhythmias as patients with secondary prevention (SP) indications and to evaluate all-cause mortality rates in 1.5PP patients with and without devices. METHODS: A total of 3889 patients were included in the analysis to evaluate ventricular tachycardia or fibrillation therapy and mortality rates. Patients were stratified as SP (n = 1193) and patients with PP indications. The PP cohort was divided into 1.5PP patients (n = 1913) and those without any 1.5PP criteria (n = 783). The decision to undergo ICD implantation was left to the patient and/or physician. The Cox proportional hazards model was used to compute hazard ratios. RESULTS: Patients had predominantly nonischemic cardiomyopathy. The rate of ventricular tachycardia or fibrillation in 1.5PP patients was not equivalent (within 30%) to that in patients with SP indications (hazard ratio 0.47; 95% confidence interval 0.38-0.57) but was higher than that in PP patients without any 1.5PP criteria (hazard ratio 0.67; 95% confidence interval 0.46-0.97) (P = .03). There was a 49% relative risk reduction in all-cause mortality in ICD implanted 1.5PP patients. In addition, the number needed to treat to save 1 life over 3 years was 10.0 in the 1.5PP cohort vs 40.0 in PP patients without any 1.5PP criteria. CONCLUSION: These data corroborate the mortality benefit of ICD therapy and support extension to a selected PP population from underrepresented geographies.

Additional antitachycardia pacing programming strategies further reduce unnecessary implantable cardioverter-defibrillator shocks.

BACKGROUND: Antitachycardia pacing (ATP) is routinely used to terminate ventricular tachyarrhythmias (VTs). However, little guidance exists on the most effective programming of ATP. OBJECTIVE: This study evaluated whether additional ATP sequences are more effective in reducing implantable cardioverter-defibrillator shocks. METHODS: In patients from the Shock-Less study, the number of overall shocks were compared between patients programmed to ≤3 ATP sequences (VT zone) and ≤1 ATP sequence (fast ventricular tachycardia [FVT] zone) (nominal group) and patients programmed to receive additional ATP sequences in VT (>3) or FVT (>1) zones. RESULTS: Of the 4112 patients (15% receiving secondary prevention; 77% men; mean age 65.9 ± 12.6 years), 1532 patients (37%) were programmed with additional ATP sequences (1025 with >3 ATP sequences in the VT zone; 699 patients with >1 ATP sequence in the FVT zone). Over a mean follow-up period of 19.6 ± 10.7 months, 4359 VT/FVT episodes occurred in 591 patients. Compared with the nominal group, in patients with additional ATP programming, there was a 39% reduction in the number of shocked VT episodes (0.46 episodes per patient-year vs 0.28 episodes per patient-year; incidence rate ratio [IRR] 0.61; P < .001) and a 44% reduction in the number of shocked FVT episodes (0.83 episodes per patient-year vs 0.47 episodes per patient-year; IRR 0.56; P < .001). The reduction in shocked VT episodes was observed in both primary (IRR 0.68; 95% confidence interval 0.51-0.90; P = .007) and secondary (IRR 0.51; 95% confidence interval 0.35-0.72; P < .001) prevention patients. CONCLUSION: Programming more than the nominal number of ATP sequences in both the VT and FVT zones is associated with a lower occurrence of implantable cardioverter-defibrillator shocks in clinical practice.

SVT discrimination algorithms significantly reduce the rate of inappropriate therapy in the setting of modern-day delayed high-rate detection programming.

BACKGROUND: Contemporary implantable cardioverter-defibrillator (ICD) programming involving delayed high-rate detection and use of supraventricular tachycardia (SVT) discriminators has significantly reduced the rate of inappropriate shocks. The extent to which SVT algorithms alone reduce inappropriate therapies is poorly understood. METHODS AND RESULTS: PainFree SST enrolled 2770 patients with a single- or dual-chamber ICD or cardiac resynchronization defibrillator. Patients were followed for 22 ± 9 months with SVT discriminators on in 96% of patients. Sustained ventricular tachyarrhythmias and SVT episodes were adjudicated by an independent physician committee. For this analysis, all episodes were subjected to postprocessing computer simulation with SVT discriminators off with and without delayed high-rate detection criteria (ventricular fibrillation zone only, 30/40 at 320 ms). There were 3282 adjudicated SVT episodes of which 115 resulted in an ICD shock and 113 received only ATP (2-year inappropriate shock and therapy rates of 3.1% and 4.1%). Therapy was appropriately withheld for the remaining 3054 SVT episodes. With both SVT discriminators and delayed high-rate detection simulated off, the 2-year inappropriate therapy rate would have been 22.9% (hazard ratio [HR] = 6.24; 95% confidence interval [CI]: 5.20-7.49). With SVT discriminators simulated off and delayed high-rate detection simulated on in all patients, the 2-year rate would have been 6.4% (HR = 1.63; CI: 1.44-1.85). CONCLUSIONS: The use of SVT discriminators has a significant role in reducing the rate of inappropriate ICD therapy even in the setting of delayed high-rate detection settings. Deactivating SVT discriminators would have resulted in an overall increase in the inappropriate ICD therapy rate by 63% and 524% with and without delayed high-rate detection programming, respectively.

Antibacterial Envelope to Prevent Cardiac Implantable Device Infection.

BACKGROUND: Infections after placement of cardiac implantable electronic devices (CIEDs) are associated with substantial morbidity and mortality. There is limited evidence on prophylactic strategies, other than the use of preoperative antibiotics, to prevent such infections. METHODS: We conducted a randomized, controlled clinical trial to assess the safety and efficacy of an absorbable, antibiotic-eluting envelope in reducing the incidence of infection associated with CIED implantations. Patients who were undergoing a CIED pocket revision, generator replacement, or system upgrade or an initial implantation of a cardiac resynchronization therapy defibrillator were randomly assigned, in a 1:1 ratio, to receive the envelope or not. Standard-of-care strategies to prevent infection were used in all patients. The primary end point was infection resulting in system extraction or revision, long-term antibiotic therapy with infection recurrence, or death, within 12 months after the CIED implantation procedure. The secondary end point for safety was procedure-related or system-related complications within 12 months. RESULTS: A total of 6983 patients underwent randomization: 3495 to the envelope group and 3488 to the control group. The primary end point occurred in 25 patients in the envelope group and 42 patients in the control group (12-month Kaplan-Meier estimated event rate, 0.7% and 1.2%, respectively; hazard ratio, 0.60; 95% confidence interval [CI], 0.36 to 0.98; P = 0.04). The safety end point occurred in 201 patients in the envelope group and 236 patients in the control group (12-month Kaplan-Meier estimated event rate, 6.0% and 6.9%, respectively; hazard ratio, 0.87; 95% CI, 0.72 to 1.06; P<0.001 for noninferiority). The mean (±SD) duration of follow-up was 20.7±8.5 months. Major CIED-related infections through the entire follow-up period occurred in 32 patients in the envelope group and 51 patients in the control group (hazard ratio, 0.63; 95% CI, 0.40 to 0.98). CONCLUSIONS: Adjunctive use of an antibacterial envelope resulted in a significantly lower incidence of major CIED infections than standard-of-care infection-prevention strategies alone, without a higher incidence of complications. (Funded by Medtronic; WRAP-IT ClinicalTrials.gov number, NCT02277990.).