Long-Term Outcomes of Resynchronization-Defibrillation for Heart Failure.

BACKGROUND: The Resynchronization-Defibrillation for Ambulatory Heart Failure Trial (RAFT) showed a greater benefit with respect to mortality at 5 years among patients who received cardiac-resynchronization therapy (CRT) than among those who received implantable cardioverter-defibrillators (ICDs). However, the effect of CRT on long-term survival is not known. METHODS: We randomly assigned patients with New York Heart Association (NYHA) class II or III heart failure, a left ventricular ejection fraction of 30% or less, and an intrinsic QRS duration of 120 msec or more (or a paced QRS duration of 200 msec or more) to receive either an ICD alone or a CRT defibrillator (CRT-D). We assessed long-term outcomes among patients at the eight highest-enrolling participating sites. The primary outcome was death from any cause; the secondary outcome was a composite of death from any cause, heart transplantation, or implantation of a ventricular assist device. RESULTS: The trial enrolled 1798 patients, of whom 1050 were included in the long-term survival trial; the median duration of follow-up for the 1050 patients was 7.7 years (interquartile range, 3.9 to 12.8), and the median duration of follow-up for those who survived was 13.9 years (interquartile range, 12.8 to 15.7). Death occurred in 405 of 530 patients (76.4%) assigned to the ICD group and in 370 of 520 patients (71.2%) assigned to the CRT-D group. The time until death appeared to be longer for those assigned to receive a CRT-D than for those assigned to receive an ICD (acceleration factor, 0.80; 95% confidence interval, 0.69 to 0.92; P = 0.002). A secondary-outcome event occurred in 412 patients (77.7%) in the ICD group and in 392 (75.4%) in the CRT-D group. CONCLUSIONS: Among patients with a reduced ejection fraction, a widened QRS complex, and NYHA class II or III heart failure, the survival benefit associated with receipt of a CRT-D as compared with ICD appeared to be sustained during a median of nearly 14 years of follow-up. (RAFT ClinicalTrials.gov number, NCT00251251.).

Heart size disparity drives sex-specific response to cardiac resynchronization therapy: a post-hoc analysis of the MORE-MPP CRT trial.

Background: Studies have reported that female sex predicts superior cardiac resynchronization therapy (CRT) response. One theory is that this association is related to smaller female heart size, thus increased "relative dyssynchrony" at given QRS durations (QRSd). Objective: To investigate the mechanisms of sex-specific CRT response relating to heart size, relative dyssynchrony, cardiomyopathy type, QRS morphology, and other patient characteristics. Methods: A post-hoc analysis of the MORE-CRT MPP trial (n=3739, 28% female), with a sub-group analysis of patients with non-ischaemic cardiomyopathy (NICM) and left bundle branch block (LBBB) (n=1308, 41% female) to control for confounding characteristics. A multivariable analysis examined predictors of response to 6 months of conventional CRT, including sex and relative dyssynchrony, measured by QRSd/LVEDV (left ventricular end-diastolic volume). Results: Females had a higher CRT response rate than males (70.1% vs. 56.8%, p<0.0001). Subgroup analysis: Regression analysis of the NICM LBBB subgroup identified QRSd/LVEDV, but not sex, as a modifier of CRT response (p<0.0039). QRSd/LVEDV was significantly higher in females (0.919) versus males (0.708, p<0.001). CRT response was 78% for female patients with QRSd/LVEDV>median value, compared to 68% < median value (p=0.012). Association between CRT response and QRSd/LVEDV was strongest at QRSd<150ms. Conclusions: In the NICM LBBB population, increased relative dyssynchrony in females, who have smaller heart sizes than their male counterparts, is a driver of sex-specific CRT response, particularly at QRSd <150ms. Females may benefit from CRT at a QRSd <130ms, opening the debate on whether sex-specific QRSd cut-offs or QRS/LVEDV measurement should be incorporated into clinical guidelines.

Cardiac resynchronization therapy non-responder to responder conversion rate in the MORE-CRT MPP trial.

AIMS: To assess the impact of MultiPoint™ Pacing (MPP) in cardiac resynchronization therapy (CRT) non-responders after 6 months of standard biventricular pacing (BiVP). METHODS AND RESULTS: The trial enrolled 5850 patients who planned to receive a CRT device. The echocardiography core laboratory assessed CRT response before implant and after 6 months of BiVP; non-response to BiVP was defined as <15% relative reduction in left ventricular end-systolic volume (LVESV). Echocardiographic non-responders were randomized in a 1:1 ratio to receive MPP (541 patients) or continued BiVP (570 patients) for an additional 6 months and evaluated the conversion rate to the echocardiographic response. The characteristics of both groups at randomization were comparable. The percentage of non-responder patients who became responders to CRT therapy was 29.4% in the MPP arm and 30.4% in the BIVP arm (P = 0.743). In patients with ≥30 mm spacing between the two left ventricular pacing sites (MPP-AS), identified during the first phase as a potential beneficial subgroup, no significant difference in the conversion rate was observed. CONCLUSION: Our trial shows that ∼30% of patients, who do not respond to CRT in the first 6 months, experience significant reverse remodelling in the following 6 months. This finding suggests that CRT benefit may be delayed or slowly incremental in a relevant proportion of patients and that the percentage of CRT responders may be higher than what has been described in short-/middle-term studies. MultiPoint™ Pacing does not improve CRT response in non-responders to BiVP, even with MPP-AS.

Rationale and Design of the Randomized Bayesian Multicenter COME-TAVI Trial in Patients With a New Onset Left Bundle Branch Block.

Patients with new-onset left bundle branch block (LBBB) after transcatheter aortic valve implantation (TAVI) are at risk of developing delayed high-degree atrioventricular block. Management of new-onset LBBB post-TAVI remains controversial. In the Comparison of a Clinical Monitoring Strategy Versus Electrophysiology-Guided Algorithmic Approach in Patients With a New LBBB After TAVI (COME-TAVI) trial, consenting patients with new-onset LBBB that persists on day 2 after TAVI, meeting exclusion/inclusion criteria, are randomized to an electrophysiological study (EPS)-guided approach or 30-day electrocardiographic monitoring. In the EPS-guided approach, patients with a His to ventricle (HV) interval ≥ 65 ms undergo permanent pacemaker implantation. Patients randomized to noninvasive monitoring receive a wearable continuous electrocardiographic recording and transmitting device for 30 days. Follow-up will be performed at 3, 6, and 12 months. The primary endpoint is a composite outcome designed to capture net clinical benefit. The endpoint incorporates major consequences of both strategies in patients with new-onset LBBB after TAVI, as follows: (i) sudden cardiac death; (ii) syncope; (iii) atrioventricular conduction disorder requiring a pacemaker (for a class I or IIa indication); and (iv) complications related to the pacemaker or EPS. The trial incorporates a Bayesian design with a noninformative prior, outcome-adaptive randomization (initially 1:1), and 2 prespecified interim analyses once 25% and 50% of the anticipated number of primary endpoints are reached. The trial is event-driven, with an anticipated upper limit of 452 patients required to reach 77 primary outcome events over 12 months of follow-up. In summary, the aim of this Bayesian multicentre randomized trial is to compare 2 management strategies in patients with new-onset LBBB post-TAVI-an EPS-guided approach vs noninvasive 30-day monitoring. Trial registration number: NCT03303612.

Les patients chez qui un bloc de branche gauche (BBG) est récemment apparu à la suite de l'implantation valvulaire aortique par cathéter (IVAC) présentent un risque de bloc auriculoventriculaire de haut degré tardif. La prise en charge d'un BBG récemment apparu après une IVAC demeure controversée. Dans le cadre de l'essai COME-TAVI (Comparison of a ClinicalMonitoring Strategy VersusElectrophysiology-Guided Algorithmic Approach in Patients With a New LBBB AfterTAVI, ou comparaison d'une stratégie de surveillance clinique, par rapport à une approche guidée par étude électrophysiologique et fondée sur un algorithme, chez des patients présentant un BBG d'apparition récente à la suite d'une IVAC), des patients qui présentent un BBG d'apparition récente persistant le 2e jour après une IVAC, qui répondent aux critères d'admissibilité et qui ont donné leur consentement sont répartis aléatoirement pour être suivis à l'aide d'une approche guidée par une étude électrophysiologique (EEP) ou faire l'objet d'une surveillance électrocardiographique d'une durée de 30 jours. Un stimulateur cardiaque est implanté chez les patients du groupe de l'EEP dont l'intervalle HV (temps de conduction dans le tronc du faisceau de His jusqu'aux ventricules) est ≥ 65 ms. Les patients du groupe de surveillance non invasive reçoivent un dispositif portable d'enregistrement et de transmission continue de données électrocardiographiques pour une période de 30 jours. Le suivi sera réalisé aux 3e, 6e et 12e mois. Le critère d'évaluation principal est un paramètre composite conçu afin de saisir le bienfait clinique net. Il comprend les conséquences majeures des deux stratégies chez les patients présentant un BBG d'apparition récente après une IVAC, comme suit : (i) mort subite d'origine cardiaque; (ii) syncope; (iii) trouble de la conduction auriculoventriculaire nécessitant la pose d'un stimulateur cardiaque (pour une indication de classe I ou IIa); et (iv) complications relatives au stimulateur cardiaque ou à l'EEP. L'essai intègre une conception bayésienne avec une répartition aléatoire (dans un rapport initial de 1:1) antérieure non informative adaptée aux résultats et deux analyses intermédiaires définies au préalable lorsque 25 % et 50 % du nombre anticipé des critères d'évaluation principaux seront atteints. L'essai est axé sur les événements, et la limite supérieure anticipée pour atteindre 77 événements relatifs aux critères d'évaluation principaux sur 12 mois de suivi est de 452 patients. En résumé, l'objectif de cet essai bayésien multicentrique à répartition aléatoire est de comparer deux stratégies de prise en charge de patients présentant un BBG d'apparition récente après une IVAC, soit une approche guidée par une EEP, par rapport à une surveillance non invasive de 30 jours. Trial registration number: NCT03303612.

Association of the Timing and Extent of Cardiac Implantable Electronic Device Infections With Mortality.

Importance: Cardiac implantable electronic device (CIED) infection is a potentially devastating complication with an estimated 12-month mortality of 15% to 30%. The association of the extent (localized or systemic) and timing of infection with all-cause mortality has not been established. Objective: To evaluate the association of the extent and timing of CIED infection with all-cause mortality. Design, Setting, and Participants: This prospective observational cohort study was conducted between December 1, 2012, and September 30, 2016, in 28 centers across Canada and the Netherlands. The study included 19 559 patients undergoing CIED procedures, 177 of whom developed an infection. Data were analyzed from April 5, 2021, to January 14, 2023. Exposures: Prospectively identified CIED infections. Main Outcomes and Measures: Time-dependent analysis of the timing (early [≤3 months] or delayed [3-12 months]) and extent (localized or systemic) of infection was performed to determine the risk of all-cause mortality associated with CIED infections. Results: Of 19 559 patients undergoing CIED procedures, 177 developed a CIED infection. The mean (SD) age was 68.7 (12.7) years, and 132 patients were male (74.6%). The cumulative incidence of infection was 0.6%, 0.7%, and 0.9% within 3, 6, and 12 months, respectively. Infection rates were highest in the first 3 months (0.21% per month), reducing significantly thereafter. Compared with patients who did not develop CIED infection, those with early localized infections were not at higher risk for all-cause mortality (no deaths at 30 days [0 of 74 patients]: adjusted hazard ratio [aHR], 0.64 [95% CI, 0.20-1.98]; P = .43). However, patients with early systemic and delayed localized infections had an approximately 3-fold increase in mortality (8.9% 30-day mortality [4 of 45 patients]: aHR, 2.88 [95% CI, 1.48-5.61]; P = .002; 8.8% 30-day mortality [3 of 34 patients]: aHR, 3.57 [95% CI, 1.33-9.57]; P = .01), increasing to a 9.3-fold risk of death for those with delayed systemic infections (21.7% 30-day mortality [5 of 23 patients]: aHR, 9.30 [95% CI, 3.82-22.65]; P < .001). Conclusions and Relevance: Findings suggest that CIED infections are most common within 3 months after the procedure. Early systemic infections and delayed localized infections are associated with increased mortality, with the highest risk for patients with delayed systemic infections. Early detection and treatment of CIED infections may be important in reducing mortality associated with this complication.

Integration of 3D nuclear imaging in 3D mapping system for ventricular tachycardia ablation in patients with implanted devices: Perfusion/voltage retrospective assessment of scar location.

Background: The identification of low-voltage proarrhythmic areas for catheter ablation of scar-mediated ventricular tachycardia (VT) remains challenging. Integration of myocardial perfusion imaging (single-photon emission computed tomography/computed tomography; SPECT/CT) and electroanatomical mapping (EAM) may improve delineation of the arrhythmogenic substrate. Objective: To assess the feasibility of SPECT/CT image integration with voltage maps using the EnSite Precision system (Abbott) in patients undergoing scar-mediated VT ablation. Methods: Patients underwent SPECT/CT imaging prior to left ventricular (LV) EAM with the EnSite Precision mapping system. The SPECT/CT, EAM data, and ablation lesions were retrospectively co-registered in the EnSite Precision system and exported for analysis. Segmental tissue viability scores were calculated based on SPECT/CT perfusion and electrogram bipolar voltage amplitude. Concordance, specificity, and sensitivity between the 2 modalities as well as the impact of SPECT/CT spatial resolution were evaluated. Results: Twenty subjects (95% male, 67 ± 7 years old, left ventricular ejection fraction 36% ± 11%) underwent EAM and SPECT/CT integration. A concordance of 70% was found between EAM and SPECT/CT for identification of cardiac segments as scar vs viable, with EAM showing a 68.5% sensitivity and 76.4% specificity when using SPECT/CT as a gold standard. Projection on low-resolution 3D geometries led to an average decrease of 38% ± 22% of the voltage points used. Conclusion: The study demonstrated the feasibility of integrating SPECT/CT with EAM performed retrospectively for characterization of anatomical substrates during VT ablation procedures.

Performance and acute procedural outcomes of the EnSite Precision™ cardiac mapping system for electrophysiology mapping and ablation procedures: results from the EnSite Precision™ observational study.

BACKGROUND: The EnSite Precision™ cardiac mapping system (Abbott) is a catheter navigation and mapping system capable of displaying the three-dimensional (3D) position of conventional and sensor-enabled electrophysiology catheters, as well as displaying cardiac electrical activity as waveform traces and dynamic 3D maps of cardiac chambers. The EnSite Precision™ Observational Study (NCT-03260244) was designed to quantify and characterize the use of the EnSite Precision™ cardiac mapping system for mapping and ablation of cardiac arrhythmias in a real-world environment and evaluate procedural outcomes. METHODS: A total of 1065 patients were enrolled at 38 centers in the USA and Canada between 2017 and 2018 and were followed for 12 months post procedure for arrhythmia recurrence, medication use, and quality-of-life changes. Eligible subjects were adults undergoing a cardiac electrophysiology mapping and radiofrequency ablation procedure using the EnSite Precision™ System. RESULTS: A final cohort of 925 patients (64.3 years of age, 30.2% female) were analyzed. The primary procedural indication was atrial flutter in 48.1% (445/925), atrial fibrillation in 46.5% (430/925), and other arrhythmias in 5% (50/925). Electroanatomic mapping was performed in 81.5% (754/925) of patients. Mapping was stable throughout 79.8% (738/925) of procedures with initial mapping time of 8.6 min (IQR 4.7-15.0). Average mapping efficiency created with AutoMap or TurboMap was 164.9 ± 365.7 used points per minute. Median number of mapping points collected and used was 1752.5 and 811.0, respectively. Only 335/925 (36.2%) required editing and 66.0% (221/335) of these patients required editing of less than 10 points. Fluoroscopy was utilized in most cases (n = 811/925, 87.4%) with fluoroscopy time of 11.0 min (IQR 6.0-18.0). Overall median procedure time was 101.0 min (IQR 59.0-152.0). Acute procedural success was high for both atrial fibrillation (n = 422/430, 98.1%) and atrial flutter (n = 434/445, 97.5%). CONCLUSION: In a real-world study analysis, use of the EnSite Precision™ mapping system was associated with high procedural stability, short mapping times, high point density requiring infrequent editing, low fluoroscopy time, and high prevalence of acute procedural success.

Right ventricular function and its coupling to pulmonary circulation predicts exercise tolerance in systolic heart failure.

AIMS: Right ventricular (RV) dysfunction, pulmonary hypertension, and exercise intolerance have prognostic values, but their interrelation is not fully understood. We investigated how RV function alone and its coupling with pulmonary circulation (RV-PA) predict cardio-respiratory fitness in patients with heart failure and reduced ejection fraction (HFrEF). METHODS AND RESULTS: The Evaluation of Resynchronization Therapy for Heart Failure (EARTH) study included 205 HFrEF patients with narrow (n = 85) and prolonged (n = 120) QRS duration undergoing implantable cardioverter defibrillator implantation. All patients underwent a comprehensive evaluation with exercise tolerance tests and echocardiography. We investigated the correlations at baseline between RV parameters {size, function [tricuspid annular plane systolic excursion (TAPSE), RV fractional area change (RV-FAC), and RV myocardial performance index (RV-MPI)], pulmonary artery systolic pressure (PASP), and tricuspid regurgitation}; left ventricular ejection fraction (LVEF), left ventricular end-diastolic volume index (LVEDVi), and left atrial volume index (LAVi); and cardiopulmonary exercise test (CPET) [peak VO2 , minute ventilation/carbon dioxide production (VE/VCO2 ), 6 min walk distance (6MWD), and submaximal exercise duration (SED)]. We also studied the relationship between RV-PA coupling (TAPSE/PASP ratio) and echocardiographic parameters in patients with both data available. Univariate and multivariate linear regression models were used. Patients enrolled in EARTH (overall population) were mostly male (73.2%), mean age 61.0 ± 9.8 years, New York Heart Association class II-III (87.8%), mean LVEF of 26.6 ± 7.7%, and reduced peak VO2 (15.1 ± 4.6 mL/kg/min). Of these, 100 had both TAPSE and PASP available (TAPSE/PASP population): they exhibited higher BNP, wider QRS duration, larger LVEDVi, with more having tricuspid regurgitation compared with the 105 patients for whom these values were not available (all P < 0.05). RV-FAC (ß = 7.5), LAVi (ß = -0.1), and sex (female, ß = -1.9) predicted peak VO2 in the overall population (all P = 0.01). When available, TAPSE/PASP ratio was the only echocardiographic parameter associated with peak VO2 (ß = 6.8; P < 0.01), a threshold ≤0.45 predicting a peak VO2  ≤ 14 mL/kg/min (0.39 for VO2  ≤ 12). RV-MPI was the only echocardiographic parameter associated with ventilatory inefficiency (VE/VCO2 ) and 6MWD (ß = 21.9 and ß = -69.3, respectively, both P ≤ 0.01) in the overall population. In presence of TAPSE/PASP, it became an important predictor for those two CPET (ß = -18.0 and ß = 72.4, respectively, both P < 0.01), together with RV-MPI (ß = 18.5, P < 0.01) for VE/VCO2 . Tricuspid regurgitation predicted SED (ß = -3.2, P = 0.03). CONCLUSIONS: Right ventricular function assessed by echocardiography (RV-MPI and RV-FAC) is closely associated with exercise tolerance in patients with HFrEF. When the TAPSE/PASP ratio is available, this marker of RV-PA coupling becomes the stronger echocardiographic predictor of exercise capacity in this population, highlighting its potential role as a screening tool to identify patients with reduced exercise capacity and potentially triage them to formal peak VO2 and/or evaluation for advanced HF therapies.

Impact of Choice of Prophylaxis on the Microbiology of Cardiac Implantable Electronic Device Infections: Insights From the Prevention of Arrhythmia Device Infection Trial (PADIT).

BACKGROUND: The Prevention of Arrhythmia Device Infection Trial (PADIT) investigated whether intensification of perioperative prophylaxis could prevent cardiac implantable electronic device (CIED) infections. Compared with a single dose of cefazolin, the perioperative administration of cefazolin, vancomycin, bacitracin, and cephalexin did not significantly decrease the risk of infection. Our objective was to compare the microbiology of infections between study arms in PADIT. METHODS: This was a post hoc analysis. Differences between study arms in the microbiology of infections were assessed at the level of individual patients and at the level of microorganisms using the Fisher exact test. RESULTS: Overall, 209 microorganisms were reported from 177 patients. The most common microorganisms were coagulase-negative staphylococci (CoNS; 82/209 [39.2%]) and S. aureus (75/209 [35.9%]). There was a significantly lower proportion of CoNS in the incremental arm compared with the standard arm (30.1% vs 46.6%; P = .04). However, there was no significant difference between study arms in the frequency of recovery of other microorganisms. In terms of antimicrobial susceptibility, 26.5% of microorganisms were resistant to cefazolin. CoNS were more likely to be cefazolin-resistant in the incremental arm (52.2% vs 26.8%, respectively; P = .05). However, there was no difference between study arms in terms of infections in which the main pathogen was sensitive to cefazolin (77.8% vs 64.3%; P = .10) or vancomycin (90.8% vs 90.2%; P = .90). CONCLUSIONS: Intensification of the prophylaxis led to significant changes in the microbiology of infections, despite the absence of a decrease in the overall risk of infections. These findings provide important insight on the physiopathology of CIED infections. TRIAL REGISTRATION: NCT01002911.

Gain in real-world cardiac resynchronization therapy efficacy with SyncAV dynamic optimization: Heart failure hospitalizations and costs.

BACKGROUND: SyncAV, a device-based cardiac resynchronization therapy (CRT) algorithm, promotes electrical optimization by dynamically adjusting atrioventricular intervals. OBJECTIVE: The purpose of this study was to evaluate the impact of SyncAV on heart failure hospitalizations (HFHs) and related costs in a real-world CRT cohort. METHODS: Patients with SyncAV-capable CRT devices followed by remote monitoring and enrolled in Medicare fee-for-service for at least 1 year preimplant and up to 2 years postimplant were studied. Patients with SyncAV OFF were 4:1 matched to those with SyncAV ON on preimplant HFH rate, demographics, comorbidities, disease etiology, and left bundle branch block. HFHs were determined from the primary diagnosis of inpatient hospitalizations, and the cost for each event was the sum of Medicare, supplemental insurance, and patient payment. RESULTS: After 4:1 propensity score matching, 3630 patients were studied (mean age 75 ± 8 years; 1386 [38%] female), including 726 (25%) patients with SyncAV ON. The pre-CRT HFH rate was 0.338 HFH events per patient-year. Overall, CRT diminished the HFH rate to 0.204 events per patient-year (P < .001). SyncAV elicited a larger reduction in HFH rate (SyncAV ON: hazard ratio [HR] 0.52; 95% confidence interval [CI] 0.41-0.66; P < .001 and SyncAV OFF: HR 0.68; 95% CI 0.59-0.77; P < .001). After 2 years, the HFH rate was lower in the SyncAV ON group than in the SyncAV OFF group (0.143 HFHs per patient-year vs 0.193 HFHs per patient-year; HR 0.70; 95% CI 0.55-0.89; P = .003) and fewer HFHs were followed by 30-day HFH readmissions (4.41% vs 7.68%; P = .003) and 30-day all-cause hospital readmissions (7.04% vs 10.01%; P = .010). The total 2-year HFH-associated costs per patient were lower with SyncAV ON (difference $1135; 90% CI $93-$2109; P = .038). CONCLUSION: This large, real-world, propensity score-matched study demonstrates that SyncAV CRT is associated with significantly reduced HFHs and associated costs, incremental to standard CRT.

Canadian Registry of Electronic Device Outcomes: remote monitoring outcomes in the Abbott battery performance alert-a multicentre cohort.

AIMS: Cardiac implantable electronic devices with device advisories have the potential of device malfunction. Remote monitoring (RM) of devices has been suggested to allow the identification of abnormal device performance and permit early intervention. We sought to describe the outcomes of patients with and without RM in devices subject to the Abbott Premature Battery Depletion (PBD) advisory with data from a Canadian registry. METHODS AND RESULTS: Patients with an Abbott device subject to the PBD advisory from nine implantable cardioverter defibrillator (ICD) implanting centres in Canada were included in the registry. The use of RM was identified from baseline and follow-up data in the registry. The primary outcome was detection of PBD and all-cause mortality. A total of 2666 patients were identified with a device subject to the advisory. In all, 1687 patients (63.2%) had RM at baseline. There were 487 deaths during follow-up. At a mean follow-up of 5.7 ± 0.7 years, mortality was higher in those without a remote monitor compared with RM at baseline (24.7% vs. 14.5%; P < 0.001). Pre-mature battery depletion was identified in 36 patients (2.1%) with RM vs. 7 (0.7%) without RM (P = 0.004). Time to battery replacement was significantly reduced in patients on RM (median 5 vs. 13 days, P = 0.001). CONCLUSION: The use of RM in patients with ICD and cardiac resynchronization therapy under advisory improved detection of PBD, time to device replacement, and was associated with a reduction in all-cause mortality. The factors influencing the association with mortality are unknown and deserve further study.

Canadian Registry of Electronic Device Outcomes (CREDO): The Abbott ICD Premature Battery Depletion Advisory, a Multicentre Cohort Study.

BACKGROUND: Premature or rapid battery depletion may compromise the performance and reliability of an implantable cardioverter defibrillator (ICD), potentially resulting in harm or death to patients. We sought to describe the outcomes and clinical management of devices included in the Abbott ICD Premature Battery Depletion Advisory, using data from a Canadian registry. METHODS: This prospective observational study includes patients with an Abbott device subject to the advisory, from 9 centres in Canada. The incidence and outcomes related to device revision owing to premature battery depletion were identified and adjudicated by a committee. RESULTS: There were 2678 patients enrolled with a device subject to the advisory. Devices were implanted between 2010 and 2017; follow-up time was 5.7 ± 0.7 years. Device revision occurred in 222 patients (8.3%). Revision for premature battery depletion occurred in 43 patients (1.6%). Devices were revised at physician discretion on notice of the advisory in 16 patients (0.6%), and at patient request in 5 patients (0.2%). A total of 63 (2.4%) devices reached routine end of battery life. A further 95 (3.5%) patients underwent revision for other reasons. There were no reported major complications or adverse events with device revision owing to the advisory. There were no deaths attributed to premature battery depletion. CONCLUSIONS: The rate of premature battery depletion associated with the Abbott ICD Premature Battery Depletion Advisory is low. There were no clinically adverse events identified that were associated with the battery performance of devices under advisory.

CONTEXTE: L'épuisement prématuré ou rapide de la pile pourrait compromettre le rendement et la fiabilité d'un défibrillateur cardioverteur implantable (DCI), et risque d'être dommageable ou mortel pour les patients. Nous avons voulu décrire les issues et la gestion clinique des dispositifs mentionnés dans l'avis d'Abbott sur l'épuisement prématuré de la pile de DCI, en utilisant des données tirées d'un registre canadien. MÉTHODOLOGIE: L'étude observationnelle prospective a été menée auprès de patients porteurs d'un dispositif Abbott faisant l'objet de l'avis, dans neuf établissements au Canada. La fréquence des révisions de dispositif dues à l'épuisement prématuré de la pile et les issues qui y sont associées ont été recensées et évaluées par un comité. RÉSULTATS: Ont été inscrits à l'étude 2 678 patients porteurs d'un dispositif faisant l'objet de l'avis. Les dispositifs avaient été mis en place entre 2010 et 2017; la durée du suivi avait été de 5,7 ± 0,7 ans. Une révision de dispositif a été effectuée chez 222 patients (8,3 %). Elle a été motivée par un épuisement prématuré de la pile chez 43 patients (1,6 %). Une révision de dispositif a été faite à la discrétion du médecin, après réception de l'avis, chez 16 patients (0,6 %) et à la demande de cinq patients (0,2 %). Au total, la pile de 63 (2,4 %) dispositifs avait atteint la fin de sa durée de vie habituelle. D'autres raisons ont entraîné une révision chez 95 autres patients (3,5 %). Aucune complication majeure et aucun effet indésirable n'ont été signalés avec les dispositifs révisés par suite de l'avis. Il n'y a eu aucun décès attribué à un épuisement prématuré de la pile. CONCLUSIONS: Le taux d'épuisement prématuré de la pile de DCI associé à l'avis d'Abbott est faible. Il n'y a pas eu d'incidents cliniques jugés liés au rendement de la pile des dispositifs faisant l'objet de l'avis.

Post-operative pain following cardiac implantable electronic device implantation: insights from the BRUISE CONTROL trials.

AIMS: Post-operative pain following cardiac implantable electronic device (CIED) insertion is associated with patient dissatisfaction, emotional distress, and emergency department visits. We sought to identify factors associated with post-operative pain and develop a prediction score for post-operative pain. METHODS AND RESULTS: All patients from the BRUISE CONTROL-1 and 2 trials were included in this analysis. A validated Visual Analogue Scale (VAS) was used to assess the severity of pain related to CIED implant procedures. Patients were asked to grade the most severe post-operative pain, average post-operative pain, and pain on the day of the first post-operative clinic. Multivariable regression analyses were performed to identify predictors of significant post-operative pain and to develop a pain-prediction score. A total of 1308 patients were included. Multivariable regression analysis found that the presence of post-operative clinically significant haematoma {CSH; P value < 0.001; odds ratio (OR) 3.82 [95% confidence interval (CI): 2.37-6.16]}, de novo CIED implantation [P value < 0.001; OR 1.90 (95% CI: 1.47-2.46)], female sex [P value < 0.001; OR 1.61 (95% CI: 1.22-2.12)], younger age [<65 years; P value < 0.001; OR 1.54 (95% CI: 1.14-2.10)], and lower body mass index [<20 kg/m2; P value < 0.05; OR 2.05 (95% CI: 0.98-4.28)] demonstrated strong and independent associations with increased post-operative pain. An 11-point post-operative pain prediction score was developed using the data. CONCLUSION: Our study has identified multiple predictors of post-operative pain after CIED insertion. We have developed a prediction score for post-operative pain that can be used to identify individuals at risk of experiencing significant post-operative pain.

Electrical synchronization achieved by multipoint pacing combined with dynamic atrioventricular delay.

PURPOSE: Multipoint pacing (MPP) improves left ventricular (LV) electrical synchrony in cardiac resynchronization therapy (CRT). SyncAV automatically adjusts atrioventricular delay (AVD) according to intrinsic AV intervals and may further improve synchrony. Their combination has not been assessed. The objective was to evaluate the improvement in electrical synchrony achieved by SyncAV combined with MPP in an international, multicenter study. METHODS: Patients with LBBB undergoing CRT implant with a quadripolar lead (Abbott Quartet™) were prospectively enrolled. QRS duration (QRSd) was measured by blinded observers from 12-lead ECG during: intrinsic conduction, BiV pacing (conventional biventricular pacing, nominal static AVD), MPP (2 LV cathodes maximally spaced, nominal static AVD), BiV + SyncAV, and MPP + SyncAV. All SyncAV offsets were individualized for each patient to yield the narrowest QRSd during BiV pacing. QRSd changes were compared by ANOVA and post hoc Tukey-Kramer tests. RESULTS: One hundred and three patients were enrolled (65.7 ± 12.1 years, 67% male, 37% ischemic, EF 26.4 ± 6.5%, PR 190.3 ± 39.1 ms). Relative to intrinsic conduction (QRSd of 165 ± 16 ms), BiV reduced QRSd by 11.9% to 145 ± 18 ms (P < 0.001 vs intrinsic), and MPP reduced QRSd by 13.3% to 142 ± 19 ms (P < 0.001 vs intrinsic). However, enabling SyncAV with a patient-optimized offset nearly doubled this QRSd reduction. BiV + SyncAV reduced QRSd by 22.0% to 128 ± 13 ms (P < 0.001 vs BiV), while MPP + SyncAV reduced QRSd further by 25.6% to 122 ± 14 ms (P < 0.05 vs BiV + SyncAV). CONCLUSION: SyncAV can significantly improve acute electrical synchrony beyond conventional CRT, with further improvement achieved by superimposing MPP.

Pulmonary Vein Stenosis After Atrial Fibrillation Ablation: Insights From the ADVICE Trial.

BACKGROUND: Pulmonary vein (PV) stenosis is a complication of atrial fibrillation (AF) ablation. The incidence of PV stenosis after routine post-ablation imaging remains unclear and is limited to single-centre studies. Our objective was to determine the incidence and predictors of PV stenosis following circumferential radiofrequency ablation in the multicentre Adenosine Following Pulmonary Vein Isolation to Target Dormant Conduction Elimination (ADVICE) trial. METHODS: Patients with symptomatic AF underwent circumferential radiofrequency ablation in one of 13 trial centres. Computed tomographic (CTA) or magnetic resonance (MRA) angiography was performed before ablation and 90 days after ablation. Two blinded reviewers measured PV diameters and areas. PVs with stenosis were classified as severe (> 70%), moderate (50%-70%), or mild (< 50%). Predictors of PV stenosis were identified by means of multivariable logistic regression. RESULTS: A total of 197 patients (median age 59.5 years, 29.4% women) were included in this substudy. PV stenosis was identified in 41 patients (20.8%) and 47 (8.2%) of 573 ablated PVs. PV stenosis was classified as mild in 42 PVs (7.3%) and moderate in 5 PVs (0.9%). No PVs had severe stenosis. Both cross-sectional area and diameter yielded similar classifications for severity of PV stenosis. Diabetes was associated with a statistically significant increased risk of PV stenosis (OR 4.91, 95% CI 1.45-16.66). CONCLUSIONS: In the first systematic multicentre evaluation of post-ablation PV stenosis, no patient acquired severe PV stenosis. Although the results are encouraging for the safety of AF ablation, 20.8% of patients had mild or moderate PV stenosis, in which the long-term effects are unknown.

Infections Associated with Resterilized Pacemakers and Defibrillators.

BACKGROUND: Access to pacemakers and defibrillators is problematic in places with limited resources. Resterilization and reuse of implantable cardiac devices obtained post mortem from patients in wealthier nations have been undertaken, but uncertainty around the risk of infection is a concern. METHODS: A multinational program was initiated in 1983 to provide tested and resterilized pacemakers and defibrillators to underserved nations; a prospective registry was established in 2003. Patients who received reused devices in this program were matched in a 1:3 ratio with control patients who received new devices implanted in Canada. The primary outcome was infection or device-related death, with mortality from other causes modeled as a competing risk. RESULTS: Resterilized devices were implanted in 1051 patients (mean [±SD] age, 63.2±18.5 years; 43.6% women) in Mexico (36.0%), the Dominican Republic (28.1%), Guatemala (26.6%), and Honduras (9.3%). Overall, 85% received pacemakers and 15% received defibrillators, with one (55.5%), two (38.8%), or three (5.7%) leads. Baseline characteristics did not differ between these patients and the 3153 matched control patients. At 2 years of follow-up, infections had occurred in 21 patients (2.0%) with reused devices and in 38 (1.2%) with new devices (hazard ratio, 1.66; 95% confidence interval, 0.97 to 2.83; P = 0.06); there were no device-related deaths. The most common implicated pathogens were Staphylococcus aureus and S. epidermidis. CONCLUSIONS: Among patients in underserved countries who received a resterilized and reused pacemaker or defibrillator, the incidence of infection or device-related death at 2 years was 2.0%, an incidence that did not differ significantly from that seen among matched control patients with new devices in Canada.

Mortality Risk Increases With Clustered Ventricular Arrhythmias in Patients With Implantable Cardioverter-Defibrillators.

OBJECTIVES: This study sought to examine the adverse prognosis associated with ventricular arrhythmia clusters that falls outside the current electrical storm definition. BACKGROUND: Electrical storm is most frequently defined as a cluster of ≥3 episodes of ventricular arrhythmia (VA) in a 24-h period. This definition has been associated with adverse cardiovascular outcomes and mortality, but the effect of lesser and greater clustering of arrhythmias has not been described. METHODS: Among all patients in the Resynchronization in Ambulatory Heart Failure trial, 14,515 implantable cardioverter-defibrillator-detected events with data available were rigorously adjudicated in blinded fashion. Arrhythmia incidence was examined for clustering, defined as 2 or more VA events occurring within 3 months. The prognostic importance of clustering was analyzed by varying the cluster length and number of events used to define a cluster. Mortality rates of groups with clustered arrhythmias were compared to patients with no arrhythmia or with unclustered arrhythmia. RESULTS: The trial included 1,764 patients, among whom 465 patients had two or more VA episodes within 3 months, whereas 406 had unclustered arrhythmias. Compared to patients with no arrhythmia, patients experiencing unclustered VA had increased risk of death (hazard ratio [HR]: 1.45; 95% confidence interval [CI]: 1.09 to 1.93; p = 0.011), whereas the risk was even higher in patients with clustered arrhythmia (HR: 2.68; 95% CI: 2.13 to 3.36; p < 0.0001). Mortality risk increased with higher VA burden (number of VAs in a cluster) and shorter cluster length. This was observed in all groups tested, including the cluster with the least VA burden in the longest cluster length tested (2 VA episodes occurring within 3 months) (mortality HR: 2.85; 95% CI: 1.95 to 4.17; p < 0.0001). Although clustered arrhythmias terminated with antitachycardia pacing were associated with increased mortality, clusters terminated with implantable cardioverter-defibrillator shocks were associated with still higher mortality risk. CONCLUSIONS: Significant adverse prognostic association of clustered VAs is observable with even 2 VA events within 3 months and increases with higher cluster density.

Dynamic atrioventricular delay programming improves ventricular electrical synchronization as evaluated by 3D vectorcardiography.

BACKGROUND: Optimal timing of the atrioventricular delay in cardiac resynchronization therapy (CRT) can improve synchrony in patients suffering from heart failure. The purpose of this study was to evaluate the impact of SyncAV™ on electrical synchrony as measured by vectorcardiography (VCG) derived QRS metrics during bi-ventricular (BiV) pacing. METHODS: Patients implanted with a cardiac resynchronization therapy (CRT) device and quadripolar left ventricular (LV) lead underwent 12­lead ECG recordings. VCG metrics, including QRS duration (QRSd) and area, were derived from the ECG by a blinded observer during: intrinsic conduction, BiV with nominal atrioventricular delays (BiV Nominal), and BiV with SyncAV programmed to the optimal offset achieving maximal synchronization (BiV + SyncAV Opt). RESULTS: One hundred patients (71% male, 40% ischemic, 65% LBBB, 32 ±â€¯9% ejection fraction) completed VCG assessment. QRSd during intrinsic conduction (166 ±â€¯25 ms) was narrowed successively by BiV Nominal (137 ±â€¯23 ms, p < .05 vs. intrinsic) and BiV + SyncAV Opt (122 ±â€¯22 ms, p < .05 vs. BiV Nominal). Likewise, 3D QRS area during intrinsic conduction (90 ±â€¯42 mV ∗ ms) was reduced by BiV Nominal (65 ±â€¯39 mV ∗ ms, p < .05 vs. intrinsic) and further by BiV + SyncAV Opt (53 ±â€¯30 mV ∗ ms, p = .06 vs. BiV Nominal). CONCLUSION: With VCG-based, patient-specific optimization of the programmable offset, SyncAV reduced electrical dyssynchrony beyond conventional CRT.

Risk Factors for Infections Involving Cardiac Implanted Electronic Devices.

BACKGROUND: Cardiac implantable electronic device infection is a major complication that usually requires device removal. PADIT (Prevention of Arrhythmia Device Infection Trial) was a large cluster crossover trial of conventional versus incremental antibiotics. OBJECTIVES: This study sought to investigate independent predictors of device infection in PADIT and develop a novel infection risk score. METHODS: In brief, over 4 6-month periods, 28 centers used either conventional or incremental prophylactic antibiotic treatment in all patients. The primary outcome was hospitalization for device infection within 1 year (blinded endpoint adjudication). Multivariable logistic prediction modeling was used to identify the independent predictors and develop a risk score for device infection. The prediction models were internally validated with bootstrap methods. RESULTS: Device procedures were performed in 19,603 patients, and hospitalization for infection occurred in 177 (0.90%) within 1 year of follow-up. The final prediction model identified 5 independent predictors of device infection (prior procedures [P], age [A], depressed renal function [D], immunocompromised [I], and procedure type [T]) with an optimism-corrected C-statistic of 0.704 (95% confidence interval: 0.660 to 0.744). A PADIT risk score ranging from 0 to 15 points classified patients into low (0 to 4), intermediate (5 to 6) and high (≥7) risk groups with rates of hospitalization for infection of 0.51%, 1.42%, and 3.41%, respectively. CONCLUSIONS: This study identified 5 independent predictors of device infection and developed a novel infection risk score in the largest cardiac implantable electronic device trial to date, warranting validation in an independent cohort. The 5 independent predictors in the PADIT score are readily adopted into clinical practice. (Prevention of Arrhythmia Device Infection Trial [PADIT Pilot]; NCT01002911).