Sex differences among subcutaneous implantable cardioverter-defibrillator recipients: a propensity-matched, multicentre, international analysis from the i-SUSI project.

AIMS: Women have been historically underrepresented in implantable cardioverter-defibrillator (ICD) trials. No data on sex differences regarding subcutaneous ICDs (S-ICD) carriers have been described. Aim of our study was to investigate sex-related differences among unselected S-ICD recipients. METHODS AND RESULTS: Consecutive patients enrolled in the multicentre, international i-SUSI registry were analysed. Comparisons between sexes were performed using a 1:1 propensity matching adjusted analysis for age, body mass index (BMI), left ventricular function, and substrate. The primary outcome was the rate of appropriate shocks during follow-up. Inappropriate shocks and other device-related complications were deemed secondary outcomes. A total of 1698 patients were extracted from the i-SUSI registry; 399 (23.5%) were females. After propensity matching, two cohorts of 374 patients presenting similar baseline characteristics were analysed. Despite similar periprocedural characteristics and a matched BMI, women resulted at lower risk of conversion failure as per PRAETORIAN score (73.4% vs. 81.3%, P = 0.049). Over a median follow-up time of 26.5 [12.7-42.5] months, appropriate shocks were more common in the male cohort (rate/year 3.4% vs. 1.7%; log-rank P = 0.049), while no significant differences in device-related complications (rate/year: 6.3% vs. 5.8%; log-rank P = 0.595) and inappropriate shocks (rate/year: 4.3% vs. 3.1%; log-rank P = 0.375) were observed. After controlling for confounders, sex remained significantly associated with the primary outcome (aHR 1.648; CI 0.999-2.655, P = 0.048), while not resulting predictor of inappropriate shocks and device-related complications. CONCLUSION: In a propensity-matched cohort of S-ICD recipients, women are less likely to experience appropriate ICD therapy, while not showing higher risk of device-related complications. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT0473876.

Underlying reasons for sex difference in survival following out-of-hospital cardiac arrest: a mediation analysis.

AIMS: Previous studies have indicated a poorer survival among women following out-of-hospital cardiac arrest (OHCA), but the mechanisms explaining this difference remain largely uncertain.This study aimed to assess the survival after OHCA among women and men and explore the role of potential mediators, such as resuscitation characteristics, prior comorbidity, and socioeconomic factors. METHODS AND RESULTS: This was a population-based cohort study including emergency medical service-treated OHCA reported to the Swedish Registry for Cardiopulmonary Resuscitation in 2010-2020, linked to nationwide Swedish healthcare registries. The relative risks (RR) of 30-day survival were compared among women and men, and a mediation analysis was performed to investigate the importance of potential mediators. Total of 43 226 OHCAs were included, of which 14 249 (33.0%) were women. Women were older and had a lower proportion of shockable initial rhythm. The crude 30-day survival among women was 6.2% compared to 10.7% for men [RR 0.58, 95% confidence interval (CI) = 0.54-0.62]. Stepwise adjustment for shockable initial rhythm attenuated the association to RR 0.85 (95% CI = 0.79-0.91). Further adjustments for age and resuscitation factors attenuated the survival difference to null (RR 0.98; 95% CI = 0.92-1.05). Mediation analysis showed that shockable initial rhythm explained ∼50% of the negative association of female sex on survival. Older age and lower disposable income were the second and third most important variables, respectively. CONCLUSION: Women have a lower crude 30-day survival following OHCA compared to men. The poor prognosis is largely explained by a lower proportion of shockable initial rhythm, older age at presentation, and lower income.

Impact of preventive substrate catheter ablation on implantable cardioverter-defibrillator interventions in patients with ischaemic cardiomyopathy and infarct-related coronary chronic total occlusion.

AIMS: Primary prevention patients with ischaemic cardiomyopathy and chronic total occlusion of an infarct-related coronary artery (CTO) are at a particularly high risk of implantable cardioverter-defibrillator (ICD) therapy occurrence. The trial was designed to evaluate the efficacy of preventive CTO-related substrate ablation strategy in ischaemic cardiomyopathy patients undergoing primary prevention ICD implantation. METHODS AND RESULTS: The PREVENTIVE VT study was a prospective, multicentre, randomized trial including ischaemic patients with ejection fraction ≤40%, no documented ventricular arrhythmias (VAs), and evidence of scar related to the coronary CTO. Patients were randomly assigned 1:1 to a preventive substrate ablation before ICD implantation or standard therapy with ICD implantation only. The primary outcome was a composite of appropriate ICD therapy or unplanned hospitalization for VAs. Secondary outcomes included the primary outcome's components, the incidence of appropriate ICD therapies, cardiac hospitalization, electrical storm, and cardiovascular (CV) mortality. Sixty patients were included in the study. During the mean follow-up of 44.7 ± 20.7 months, the primary outcome occurred in 5 (16.7%) patients undergoing preventive substrate ablation and in 13 (43.3%) patients receiving only ICD [hazard ratio (HR): 0.33; 95% confidence interval (CI): 0.12-0.94; P = 0.037]. Patients in the preventive ablation group also had fewer appropriate ICD therapies (P = 0.039) and the electrical storms (Log-rank: P = 0.01). While preventive ablation also reduced cardiac hospitalizations (P = 0.006), it had no significant impact on CV mortality (P = 0.151). CONCLUSION: Preventive ablation of the coronary CTO-related substrate in patients undergoing primary ICD implantation is associated with the reduced risk of appropriate ICD therapy or unplanned hospitalization due to VAs.

A review regarding the article 'Health inequalities in cardiopulmonary resuscitation and use of automated electrical defibrillators in out-of-hospital cardiac arrest'.

Out-of-hospital cardiac arrest (OHCA) is a major cause of mortality worldwide, with a high incidence and low survival rate. Prompt cardiopulmonary resuscitation (CPR) and automated external defibrillator (AED) use are major contributors in the "chain of survival" for OHCA. the response of a community plays a key role in determining the outcomes in OHCA. The outcomes of OHCA are affected by health inequalities in bystander CPR and AED use, due to factors such as differences in sex, ethnicity, and socioeconomic status amongst others. Literature shows patients from lower socio-economic backgrounds are more likely to have risk factors for a cardiac arrest and are therefore more likely to have OHCA. Studies have also reported lower rates of bystander AED use in females compared to males. Targeting deprived areas with tailored training and access to AEDs can be beneficial in improving CPR outcomes in communities. Due to the physical nature of CPR maneuvers, age and frailty of the patient can both impact the outcome of the resuscitation. Environmental factors affecting AED use include availability, visibility, accessibility, support, extra equipment, training materials, staffing, and awareness. Education should focus on areas such as conducting BLS on both male and female patients, recognizing cardiac arrest, tailoring BLS to difference ages as well as provision for training in different languages, including sign language. Like some other countries, CPR training is now being implemented in the school curriculum.

Implantable cardioverter-defibrillator lead failure and revision following transcutaneous bicaval valve (TricValve®) implantation.

INTRODUCTION: Tricuspid regurgitation is associated with significant morbidity and mortality, and occurs at a higher rate in patients with cardiovascular implantable electronic devices. Percutaneous strategies for managing tricuspid regurgitation are evolving, including the development of bicaval valve implantation which has been successfully used in patients with pacing leads. METHODS AND RESULTS: We present the first documented case of lead failure following TricValve® implantation, a dedicated self-expanding system for bicaval valve implantation, and the first successful lead revision procedure in this setting. CONCLUSION: The case illustrates important considerations in undertaking percutaneous intervention in patients with cardiovascular implantable electronic devices, and their ongoing management.

Time-trend treatment effect of cardiac resynchronization therapy with or without defibrillator on mortality: a systematic review and meta-analysis.

AIMS: This study aimed to investigate the impact of cardiac resynchronization therapy with a defibrillator (CRT-D) on mortality, comparing it with CRT with a pacemaker (CRT-P). Additionally, the study sought to identify subgroups, evaluate the time trend in treatment effects, and analyze patient characteristics, considering the changing indications over the past decades. METHODS AND RESULTS: PubMed, CENTRAL, and Embase up to October 2021 were screened for studies comparing CRT-P and CRT-D, focusing on mortality. Altogether 26 observational studies were selected comprising 128 030 CRT patients, including 55 469 with CRT-P and 72 561 with CRT-D device. Cardiac resynchronization therapy with defibrillator was able to reduce all-cause mortality by almost 20% over CRT-P [adjusted hazard ratio (HR): 0.85; 95% confidence interval (CI): 0.76-0.94; P < 0.01] even in propensity-matched studies (HR: 0.83; 95% CI: 0.80-0.87; P < 0.001) but not in those with non-ischaemic aetiology (HR: 0.95; 95% CI: 0.79-1.15; P = 0.19) or over 75 years (HR: 1.08; 95% CI 0.96-1.21; P = 0.17). When treatment effect on mortality was investigated by the median year of inclusion, there was a difference between studies released before 2015 and those thereafter. Time-trend effects could be also observed in patients' characteristics: CRT-P candidates were getting older and the prevalence of ischaemic aetiology was increasing over time. CONCLUSION: The results of this systematic review of observational studies, mostly retrospective with meta-analysis, suggest that patients with CRT-D had a lower risk of mortality compared with CRT-P. However, subgroups could be identified, where CRT-D was not superior such as non-ischaemic and older patients. An improved treatment effect of CRT-D on mortality could be observed between the early and late studies partly related to the changed characteristics of CRT candidates.

Association between basic life support and survival in sports-related sudden cardiac arrest: a meta-analysis.

AIMS: To evaluate the association of basic life support with survival after sports-related sudden cardiac arrest (SR-SCA). METHODS AND RESULTS: In this systematic review and meta-analysis, a search of several databases from each database inception to 31 July 2021 without language restrictions was conducted. Studies were considered eligible if they evaluated one of three scenarios in patients with SR-SCA: (i) bystander presence, (ii) bystander cardiopulmonary resuscitation (CPR), or (iii) bystander automated external defibrillator (AED) use and provided information on survival. Risk of bias was evaluated using Risk of Bias in Non-randomized Studies of Interventions. The primary outcome was survival at the longest follow up. The meta-analysis was conducted using the random-effects model. The Grading of Recommendations Assessment, Development, and Evaluations (GRADE) approach was used to rate certainty in the evidence. In total, 28 non-randomized studies were included. The meta-analysis showed significant benefit on survival in all three groups: bystander presence [odds ratio (OR) 2.55, 95% confidence interval (CI) 1.48-4.37; I2 = 25%; 9 studies-988 patients], bystander CPR (OR 3.84, 95% CI 2.36-6.25; I2 = 54%; 23 studies-2523 patients), and bystander AED use (OR 5.25, 95% CI 3.58-7.70; I2 = 16%; 19 studies-1227 patients). The GRADE certainty of evidence was judged to be moderate. CONCLUSION: In patients with SR-SCA, bystander presence, bystander CPR, and bystander AED use were significantly associated with survival. These results highlight the importance of witness intervention and encourage countries to develop their first aid training policy and AED installation in sport settings.

Defibrillation Strategies for Refractory Ventricular Fibrillation.

BACKGROUND: Despite advances in defibrillation technology, shock-refractory ventricular fibrillation remains common during out-of-hospital cardiac arrest. Double sequential external defibrillation (DSED; rapid sequential shocks from two defibrillators) and vector-change (VC) defibrillation (switching defibrillation pads to an anterior-posterior position) have been proposed as defibrillation strategies to improve outcomes in patients with refractory ventricular fibrillation. METHODS: We conducted a cluster-randomized trial with crossover among six Canadian paramedic services to evaluate DSED and VC defibrillation as compared with standard defibrillation in adult patients with refractory ventricular fibrillation during out-of-hospital cardiac arrest. Patients were treated with one of these three techniques according to the strategy that was randomly assigned to the paramedic service. The primary outcome was survival to hospital discharge. Secondary outcomes included termination of ventricular fibrillation, return of spontaneous circulation, and a good neurologic outcome, defined as a modified Rankin scale score of 2 or lower (indicating no symptoms to slight disability) at hospital discharge. RESULTS: A total of 405 patients were enrolled before the data and safety monitoring board stopped the trial because of the coronavirus disease 2019 pandemic. A total of 136 patients (33.6%) were assigned to receive standard defibrillation, 144 (35.6%) to receive VC defibrillation, and 125 (30.9%) to receive DSED. Survival to hospital discharge was more common in the DSED group than in the standard group (30.4% vs. 13.3%; relative risk, 2.21; 95% confidence interval [CI], 1.33 to 3.67) and more common in the VC group than in the standard group (21.7% vs. 13.3%; relative risk, 1.71; 95% CI, 1.01 to 2.88). DSED but not VC defibrillation was associated with a higher percentage of patients having a good neurologic outcome than standard defibrillation (relative risk, 2.21 [95% CI, 1.26 to 3.88] and 1.48 [95% CI, 0.81 to 2.71], respectively). CONCLUSIONS: Among patients with refractory ventricular fibrillation, survival to hospital discharge occurred more frequently among those who received DSED or VC defibrillation than among those who received standard defibrillation. (Funded by the Heart and Stroke Foundation of Canada; DOSE VF ClinicalTrials.gov number, NCT04080986.).

Implantable Cardioverter Defibrillators in Infants and Toddlers: Indications, Placement, Programming, and Outcomes.

BACKGROUND: Limited data exist regarding implantable cardioverter defibrillator (ICD) usage in infants and toddlers. This study evaluates ICD placement indications, procedural techniques, programming strategies, and outcomes of ICDs in infants and toddlers. METHODS: This is a single-center retrospective review of all patients ≤3 years old who received an ICD from 2009 to 2021. RESULTS: Fifteen patients received an ICD at an age of 1.2 years (interquartile range [IQR], 0.1-2.4; 12 [80%] women; weight, 8.2 kg [IQR, 4.2-12.6]) and were followed for a median of 4.28 years (IQR, 1.40-5.53) or 64.2 patient-years. ICDs were placed for secondary prevention in 12 patients (80%). Diagnoses included 8 long-QT syndromes (53%), 4 idiopathic ventricular tachycardias/ventricular fibrillations (VFs; 27%), 1 recurrent ventricular tachycardia with cardiomyopathy (7%), 1 VF with left ventricular noncompaction (7%), and 1 catecholaminergic polymorphic ventricular tachycardia (7%). All implants were epicardial, with a coil in the pericardial space. Intraoperative defibrillation safety testing was attempted in 11 patients (73%), with VF induced in 8 (53%). Successful restoration of sinus rhythm was achieved in all tested patients with a median of 9 (IQR, 7.3-11.3) J or 0.90 (IQR, 0.68-1.04) J/kg. Complications consisted of 1 postoperative chylothorax and 3 episodes of feeding intolerance. VF detection was programmed to 250 (IQR, 240-250) ms with first shock delivering 10 (IQR, 5-15) J or 1.1 (IQR, 0.8-1.4) J/kg. Three patients (20%) received appropriate shocks for ventricular tachycardia/VF. No patient received an inappropriate shock. There were 2 (13%) ventricular lead fractures (at 2.6 and 4.2 years post-implant), 1 (7%) pocket-site infection, and 2 (13%) generator exchanges. All patients were alive, and 1 patient (7%) received a heart transplant. CONCLUSIONS: ICDs can be safely and effectively placed for sudden death prevention in infants and toddlers with good midterm outcomes.

Echocardiography-guided Cardiac Implantable Electronic Device Implantation to Reduce Device Related Tricuspid Regurgitation: A Prospective Controlled Study.

BACKGROUND: Endocardial leads of permanent pacemakers (PPM) and implantable defibrillators (ICD) across the tricuspid valve (TV) can lead to tricuspid regurgitation (TR) or can worsen existing TR with subsequent severe morbidity and mortality. OBJECTIVES: To evaluate prospectively the efficacy of intraprocedural 2-dimentional-transthoracic echocardiography (2DTTE) in reducing/preventing lead-associated TR. METHODS: We conducted a prospective randomized controlled study comparing echocardiographic results in patients undergoing de-novo PPM/ICD implantation with intraprocedural echo-guided right ventricular (RV) lead placement (Group 1, n=56) versus non-echo guided implantation (Group 2, n=55). Lead position was changed if TR grade was more than baseline in Group 1. Cohort patients underwent 2DTTE at baseline and 3 and/or 6 months after implantation. Excluded were patients with baseline TR > moderate or baseline ≥ moderate RV dysfunction. RESULTS: The study comprised 111 patients (74.14 ± 11 years of age, 58.6% male, 19% ICD, 42% active leads). In 98 patients there was at least one follow-up echo. Two patients from Group 1 (3.6%) needed intraprocedural RV electrode repositioning. Four patients (3.5%, 2 from each group, all dual chamber PPM, 3 atrial fibrillation, 2 RV pacing > 40%, none with intraprocedural reposition) had TR deterioration during 6 months follow-up. One patient from Group 2 with baseline mild-moderate aortic regurgitation (AR) had worsening TR and AR within 3 months and underwent aortic valve replacement and TV repair. CONCLUSIONS: The rate of mechanically induced lead-associated TR is low; thus, a routine intraprocedural 2DTTE does not have a significant role in reducing/preventing it.

Significantly less inappropriate shocks in ischemic patients compared to non-ischemic patients: The S-ICD experience of a high volume single-center.

BACKGROUND: The subcutaneous cardioverter-defibrillator (S-ICD) continues to be preferentially used in relatively young patients, with less advanced heart disease. OBJECTIVE: We, therefore, studied the short and long-term efficacy and safety of the S-ICD in subgroups of patients, which are underreported at present. METHODS: A total of 218 patients between November 2010 and February 2019 undergoing S-ICD with a follow up of at least 6 months implantation were included in a prospective registry. Mean follow up was 38 months. RESULTS: The most common indication for S-ICD implantation was ischemic cardiomyopathy (n = 106, 49%). Complication rate needing invasive intervention was 9% (n = 21). Appropriate shock rate in patients with an S-ICD was 3.5%/year. A total of 30 inappropriate shocks (IAS) occurred in 19 patients (8.7%; 2.7%/year). The proportion of appropriate and inappropriate shock rates in patients with different cardiomyopathies shows remarkable variances. There were significant more IAS (3.6%/year vs. 1.7%/year, p = .048) in patients with non-ischemic cardiomyopathy versus patients with ischemic cardiomyopathy. Multivariate analysis identified, besides type of cardiomyopathy, atrial fibrillation (AF) as predictor for IAS. CONCLUSION: In this real-world prospective registry we analyzed S-ICD performance in the more traditional ICD patient. Patients with ischemic cardiomyopathy had significantly less inappropriate therapy compared to patients with non-ischemic cardiomyopathy and appear to be appropriate patients for this type of device.

Health status measured by Kansas City Cardiomyopathy Questionnaire-12 in primary prevention implantable cardioverter defibrillator patients with heart failure.

BACKGROUND: Self-reported health status as measured by the Kansas City Cardiomyopathy Questionnaire (KCCQ) in patients with primary prevention implantable cardioverter defibrillators (ICDs) has mainly been reported from randomized trials. However, these studies are often limited to short follow-up and are subject to selection bias. The aim of this study was to assess KCCQ-12 in patients with primary prevention ICD due to either ischemic or nonischemic heart failure. METHODS: This cross-sectional observational study included all patients in Region Gävleborg, Sweden, who because of primary prevention due to heart failure, had an ICD or underwent device replacement between 2007 and 2017. After validation using medical records patients were sent and returned the KCCQ-12 by regular mail. RESULTS: A total of 118 questionnaires were analyzed (response rate 71.1%). The mean age was 70.9 ± 9.8 years, and a minority was female (n = 20, 16.9%). The mean overall summary score was 71.5 ± 22.4, there was no significant difference between ischemic and nonischemic heart failure (69.5 ± 23.1 vs. 74.4 ± 21.3; p = 0.195). Atrial fibrillation at baseline was associated with lower score for the domains Symptom frequency (70.2 ± 23.2 vs. 82.2 ± 19.2; p = 0.006) and Social limitation (62.1 ± 26.0 vs. 75.6 ± 26.6; p = 0.006) as well as the overall summary score (63.9 ± 21.3 vs. 74.8 ± 22.2; p = 0.004). CONCLUSION: In a real-world setting, primary prevention ICD patients with heart failure report an acceptable disease-specific health status at long-term follow-up. Ischemic and nonischemic etiology showed similar health status whereas atrial fibrillation was associated with worse outcome.

Comparative Effectiveness of Implantable Defibrillators for Asymptomatic Brugada Syndrome: A Decision-Analytic Model.

Background Optimal management of asymptomatic Brugada syndrome (BrS) with spontaneous type I electrocardiographic pattern is uncertain. Methods and Results We developed an individual-level simulation comprising 2 000 000 average-risk individuals with asymptomatic BrS and spontaneous type I electrocardiographic pattern. We compared (1) observation, (2) electrophysiologic study (EPS)-guided implantable cardioverter-defibrillator (ICD), and (3) upfront ICD, each using either subcutaneous or transvenous ICD, resulting in 6 strategies tested. The primary outcome was quality-adjusted life years (QALYs), with cardiac deaths (arrest or procedural-related) as a secondary outcome. We varied BrS diagnosis age and underlying arrest rate. We assessed cost-effectiveness at $100 000/QALY. Compared with observation, EPS-guided subcutaneous ICD resulted in 0.35 QALY gain/individual and 4130 cardiac deaths avoided/100 000 individuals, and EPS-guided transvenous ICD resulted in 0.26 QALY gain and 3390 cardiac deaths avoided. Compared with observation, upfront ICD reduced cardiac deaths by a greater margin (subcutaneous ICD, 8950; transvenous ICD, 6050), but only subcutaneous ICD improved QALYs (subcutaneous ICD, 0.25 QALY gain; transvenous ICD, 0.01 QALY loss), and complications were higher. ICD-based strategies were more effective at younger ages and higher arrest rates (eg, using subcutaneous devices, upfront ICD was the most effective strategy at ages 20-39.4 years and arrest rates >1.37%/year; EPS-guided ICD was the most effective strategy at ages 39.5-51.3 years and arrest rates 0.47%-1.37%/year, and observation was the most effective strategy at ages >51.3 years and arrest rates <0.47%/year). EPS-guided subcutaneous ICD was cost-effective ($80 508/QALY). Conclusions Device-based approaches (with or without EPS risk stratification) can be more effective than observation among selected patients with asymptomatic BrS. BrS management should be tailored to patient characteristics.