Mortality Benefit Among Primary Prevention Implantable Cardioverter-Defibrillator Recipients on Contemporary Heart Failure Treatment.

BACKGROUND: Past clinical trials have shown the benefit of implantable cardioverter-defibrillators (ICDs) for reducing sudden cardiac death in at-risk patients. However, heart failure management and ICD technology have changed since these trials were first published. An updated assessment of ICD mortality benefit is needed. OBJECTIVES: The purpose of this study was to compare mortality rates between patients with a primary prevention (PP) indication for an ICD who did or did not receive an ICD using a contemporary, real-world data set. METHODS: Data was obtained from a large electronic health record data set covering patients in the United States from 2012 through 2020 who had a PP indication for an ICD and survived at least 1-year postindication. RESULTS: A total of 25,296 patients were identified as having a PP indication for ICD implantation, of which 2,118 (8.4%) were treated with an ICD within a year. Treated patients were younger than nontreated patients (age 63.4 years vs 66.1 years) with a smaller proportion of women (25.0% vs 36.7%). After 4-to-1 propensity matching, treated patients had similar clinical characteristics to nontreated patients. A Cox proportional hazard model estimated a 24.3% lower risk of all-cause mortality in patients when treated vs not treated with an ICD (HR: 0.757; 95% CI: 0.678-0.835; P <0.001). There was no detectable difference in ICD benefit between patients with ischemic and nonischemic heart disease (P = 0.50). CONCLUSIONS: ICD treatment of patients with a PP indication is associated with improved mortality even in the context of evolving adjunctive HF treatment, consistent with earlier landmark trials.

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.

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.

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.

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.).

Cryoballoon-to-Pulmonary Vein Occlusion Assessment via Capnography Technique: Where Does Occlusion Testing by End-Tidal CO2 Measurement "Fit" as a Predictor of Long-Term Efficacy?

INTRODUCTION: Parameters used to gauge the effectiveness of a cryoballoon lesion have been described that monitor the ablation at the time of balloon-to-pulmonary vein (PV) occlusion, during the cryoablation freeze, and at the thaw phase of the cryoablation. This study examines the balloon-to-PV occlusion step and monitors the completeness of occlusion using capnography to measure end-tidal CO2 (ETCO2). Specifically, the main objective was to determine if ETCO2 measurements can be used to quantify the amount of balloon-to-PV occlusion and to determine if acute ETCO2 parameters could predict long-term freedom from atrial fibrillation (AF). METHODS AND RESULTS: In a prospective study, 30 subjects were cryoballoon ablated for drug refractory symptomatic paroxysmal AF by pulmonary vein isolation method. During the balloon-to-PV occlusion and throughout the cryoablation, ETCO2 measurements were recorded. The subjects were followed for a 12-month period to monitor their freedom from AF. Five subjects had a recurrence of AF outside of a 90-day blanking period but before the 12-month endpoint. Between the 25 subjects that maintained normal sinus rhythm (NSR) and the 5 subjects that had recurrent AF (rAF), there were no statistical differences in procedural parameters, including: the number of cryoablations per PV, duration of each cryoablation, balloon nadir temperature, or balloon thaw time. Additionally, there were no statistical differences in baseline ETCO2 and in nadir ETCO2 between the two cohorts; however, when examining Δ ETCO2, the subjects in the NSR cohort had a significantly larger change compared to the rAF cohort (P<0.001). The largest change in ETCO2 during balloon-to-PV occlusion was observed during the cryoballoon ablation of the superior PVs; however, Δ ETCO2 did not solely predict long-term freedom from AF for the individual subject. CONCLUSION: Δ ETCO2 did tend to be larger in the NSR cohort compared to the rAF cohort; however, ETCO2 monitoring was more responsive in the superior PVs and less useful in the inferior PVs. Moreover, ETCO2 monitoring could not be used as a sole indicator of long-term efficacy. Suggesting that monitoring balloon-to-PV occlusion is a necessary first in cryoballoon ablation, but other parameters must be incorporated and observed as surrogates of a circumferential and transmural lesion formation with long-term durability.

Azithromycin Causes a Novel Proarrhythmic Syndrome.

BACKGROUND: The widely used macrolide antibiotic azithromycin increases risk of cardiovascular and sudden cardiac death, although the underlying mechanisms are unclear. Case reports, including the one we document here, demonstrate that azithromycin can cause rapid, polymorphic ventricular tachycardia in the absence of QT prolongation, indicating a novel proarrhythmic syndrome. We investigated the electrophysiological effects of azithromycin in vivo and in vitro using mice, cardiomyocytes, and human ion channels heterologously expressed in human embryonic kidney (HEK 293) and Chinese hamster ovary (CHO) cells. METHODS AND RESULTS: In conscious telemetered mice, acute intraperitoneal and oral administration of azithromycin caused effects consistent with multi-ion channel block, with significant sinus slowing and increased PR, QRS, QT, and QTc intervals, as seen with azithromycin overdose. Similarly, in HL-1 cardiomyocytes, the drug slowed sinus automaticity, reduced phase 0 upstroke slope, and prolonged action potential duration. Acute exposure to azithromycin reduced peak SCN5A currents in HEK cells (IC50=110±3 µmol/L) and Na+ current in mouse ventricular myocytes. However, with chronic (24 hour) exposure, azithromycin caused a ≈2-fold increase in both peak and late SCN5A currents, with findings confirmed for INa in cardiomyocytes. Mild block occurred for K+ currents representing IKr (CHO cells expressing hERG; IC50=219±21 µmol/L) and IKs (CHO cells expressing KCNQ1+KCNE1; IC50=184±12 µmol/L), whereas azithromycin suppressed L-type Ca++ currents (rabbit ventricular myocytes, IC50=66.5±4 µmol/L) and IK1 (HEK cells expressing Kir2.1, IC50=44±3 µmol/L). CONCLUSIONS: Chronic exposure to azithromycin increases cardiac Na+ current to promote intracellular Na+ loading, providing a potential mechanistic basis for the novel form of proarrhythmia seen with this macrolide antibiotic.

Feedback to providers improves evidence-based implantable cardioverter-defibrillator programming and reduces shocks.

BACKGROUND: Implantable cardioverter-defibrillator (ICD) shocks are associated with increased anxiety, health care utilization, and potentially mortality. OBJECTIVE: The purpose of the Shock-Less Study was to determine if providing feedback reports to physicians on their adherence to evidence-based shock reduction programming could improve their programming behavior and reduce shocks. METHODS: Shock-Less enrolled primary prevention (PP) and secondary prevention (SP) ICD patients between 2009 and 2012 at 118 study centers worldwide and followed patients longitudinally after their ICD implant. Center-specific therapy programming reports (TPRs) were delivered to each center 9 to 12 months after their first enrollment. The reports detailed adherence to evidence-based programming targets: number of intervals to detect ventricular fibrillation (VF NID), longest treatment interval (LTI), supraventricular tachycardia (SVT) discriminators (Wavelet, PR Logic), SVT limit, Lead Integrity Alert (LIA), and antitachycardia pacing (ATP). Clinicians programmed ICDs at their discretion. The primary outcome measure was the change in utilization of evidence-based shock reduction programming before (phase I, n = 2694 patients) and after initiation of the TPR (phase II, n = 1438 patients). RESULTS: Patients implanted after feedback reports (phase II) were up to 20% more likely to have their ICDs programmed in line with evidence-based shock reduction programming (eg, VF NID in PP patients 30/40 in 33.5% vs 18.6%, P < .0001). Patients implanted in phase II had a lower risk of all-cause shock (adjusted hazard ratio 0.72, 95% confidence interval 0.58-0.90, P = .003). CONCLUSION: Providing programming feedback reports improves adherence to evidence-based shock reduction programming and is associated with lower risk of ICD shocks.

R-wave sensing in an implantable cardiac monitor without ECG-based preimplant mapping: results from a multicenter clinical trial.

INTRODUCTION: Reducing the form factor of an implantable cardiac monitor (ICM) may simplify device implant. This study evaluated R-wave sensing at a range of electrode distances and a preferred device implant location without mapping. METHODS: Patients scheduled for a Medtronic Reveal® ICM implant (Medtronic Inc., Minneapolis, MN, USA) underwent a preimplant pocket recording using a diagnostic recording catheter. The ICM implant location was left to the discretion of the implanting physician, but a "recommended" position spanned the V2 -V3 electrocardiogram electrode location in an oblique 45° angle. R-wave amplitudes were analyzed from ICM follow-up. RESULTS: Seventeen of 41 subjects (15 male, age 57 ± 16 years) had the maximum surface-filtered R-wave at the recommended location. Fourteen patients underwent diagnostic recording across the range of electrode spacing. There was a strong correlation between the R-wave amplitude and electrode distance (r(2) = 0.97, P < 0.001) with an increase of 29 µV per 2.5 mm. Comparing normalized R-wave distributions between the recommended ICM implant group (Group 1, n = 19) and the remaining patients (Group 2, n = 7), the proportion of ICM R-wave counts of amplitude 0.25-1.2 mV was higher (79% vs 46%, P < 0.05). Of 17 patients in Group 1 who had ≥ 1-month ICM follow-up (79 ± 45 days), no sensing-related false arrhythmia detection was found in 16 (93%) patients. CONCLUSIONS: The subcutaneous R-wave amplitude correlates with electrode spacing in the implant zone of ICM patients. Implant locations at the V2 -V3 position at a 45° angle offer an adequate R wave for sensing. Preimplant mapping to achieve acceptable R-wave amplitude may not be necessary.