Inappropriate Shocks Research Articles

Abstract 4148089: Comparative Efficacy of Carvedilol versus Metoprolol in Patients with Implantable Cardioverter Defibrillators and Ventricular Arrhythmias: A Systematic Review and Meta-Analysis

Background: Ventricular arrhythmias are major causes of morbidity and mortality in patients with cardiovascular disease. Implantable cardioverter-defibrillators (ICDs) are commonly used to prevent sudden cardiac death in these patients. However, patients with ICDs frequently experience recurrent arrhythmias and inappropriate shocks, which can impact their quality of life. Beta-blockers, specifically carvedilol and metoprolol, are commonly prescribed to manage these arrhythmias. This meta-analysis aims to compare the impact of both medications in this patient population. Methods: A comprehensive literature search was conducted to identify relevant studies comparing carvedilol to metoprolol in patients with ventricular arrhythmias or ICDs. Study outcomes included all-cause mortality, recurrent ventricular arrhythmia, and inappropriate ICD shocks. Effect estimates are presented as hazard ratios (HR) with 95% confidence intervals (CI). Results: 1,453 studies were identified through database search. After full-text screening, a total of 5 studies involving 9,292 patients were included. We found no significant difference in the incidence of recurrent ventricular arrhythmias between carvedilol and metoprolol (HR = 0.99, 95% CI [0.75, 1.32], P = 0.97). Additionally, Carvedilol showed a trend toward reduction of all-cause mortality (HR = 0.83, 95% CI [0.68, 1.03], P = 0.09). On the other hand, Carvedilol was associated with a statistically significant reduction of inappropriate ICD shocks (HR = 0.61, 95% CI [0.48, 0.78], P < 0.001). Conclusion: Carvedilol may offer additional benefits over metoprolol in managing patients with ventricular arrhythmias or ICDs, particularly in minimizing the incidence of inappropriate ICD shocks. However, no significant difference was found in terms of all-cause mortality and recurrent ventricular arrhythmia incidence. Further research is needed to confirm these findings and guide clinical decision-making.

Abstract 4141488: Initial Real-World Experience with a Novel Wearable Cardioverter Defibrillator

Background: The wearable cardioverter defibrillator (WCD) can reduce sudden cardiac death; effectiveness depends on adherence. A novel WCD designed for sex specific comfort and noise immunity has reported improved compliance. Hypothesis: Patient compliance with the WCD maximizes device utility in treating significant arrhythmia. Aims: Report WCD patient compliance and efficacy in a cohort with balanced gender representation. Evaluate WCD performance in minimizing noise artifact leading to false alarms and unnecessary shocks. Methods: Retrospective analysis of patients prescribed the ASSURE WCD at the Cleveland Clinic. Clinical data was collected via medical chart review. All device-detected arrhythmia episodes were manually adjudicated by a Board-certified Electrophysiologist. Detected rhythms that persist, result in an audible alarm notifying that a shock is imminent. A conscious patient can manually divert a shock. An alarm was deemed true and shock appropriate if the underlying rhythm was sustained VT/VF. Results: Fifty-five patients were fitted with a WCD. Median daily use 22 hr/day (IQR 13,24) and median duration of use 43 days (IQR 8,79). Female representation was 49%, significantly greater than prior reports of WCD experience. 4 episodes of sustained VT/VF were detected in 4 patients. A single shock terminated VT/VF in 2, while spontaneous termination of VT/VF occurred in the other 2 patients who diverted shocks. One shock for hemodynamically unstable atrial fibrillation with heart rate >200bpm was delivered and deemed necessary. No deaths occurred while wearing a WCD. Of 163 recorded episodes, 62 (38%) persisted and triggered an alarm (Figure 1). 10 patients experienced a median of 1 (IQR 1,9.5) alarm during the WCD wear period. The majority (97%) of alarms were associated with a significant tachyarrhythmia, with only 3% due to noise artifact. No inappropriate, unnecessary shocks were delivered. Discussion: Patient compliance with the ASSURE WCD was high in this real-world observational study with equal representation of both sexes. The WCD effectively terminated sustained hemodynamically significant tachyarrhythmias, emitted few false alarms due to noise and resulted in no unnecessary and inappropriate shocks.

ATrial arrhythmias in inhEriTed aRrhythmIa Syndromes: results from the TETRIS study.

Little is known about the distribution and clinical course of patients with inherited arrhythmia syndrome (IAS) and concomitant atrial arrhythmias (AAs). 1) to characterize the distribution of AAs in patients with IAS and 2) evaluate the long-term clinical course of these patients. An international multicenter study was performed and involved 28 centers in 16 countries. Inclusion criteria were: 1) IAS and 2) ECG documentation of AAs. The primary endpoint was a composite of sudden cardiac death, sustained VAs or appropriate ICD interventions. Strokes, inappropriate ICD shocks due to AAs, and the occurrence of sinus node dysfunction were assessed. A total of 522 patients with IAS and AAs were included. Most patients were diagnosed with Brugada syndrome (n=355, 68%) and long-QT syndrome (n=93, 18%). The remaining patients (n=71, 14%) presented with short-QT syndrome, early repolarization syndrome (ERS), catecholaminergic polymorphic ventricular tachycardia (CPVT), progressive cardiac conduction diseases, or idiopathic ventricular fibrillation. Atrial fibrillation (AF) was the most prevalent AA (82%), followed by atrial flutter (9%) and atrial tachycardia (9%). AA was the first clinical manifestation of IAS in 52% of patients. More than one type of AAs was documented in 23% of patients. Nine patients (3%) experienced VA before the diagnosis of IAS, due the use of anti-arrhythmic medications taken for the AA. The incidence of the primary endpoint was 1.4% per year, with a twofold increase observed in patients who experienced their first AA before the age of 20 (OR 2.2, p=0.043). This was consistent across the different forms of IAS. Inappropriate ICD shock due to AAs were reported in 2.8% of patients, strokes in 4.4% and sinus node dysfunction in 9.6%. Among patients with IAS and AAs, AA is the first clinical manifestation in about half of the cases, with more than one form of AAs present in one-fourth of the patients. The occurrence of AA earlier in life may be associated with a higher risk of ventricular arrhythmias. The occurrence of stroke and sinus node dysfunction is not-infrequently in this cohort.

Rates of and Indications for Subcutaneous ICD Extraction: A Multihospital Healthcare System Analysis.

The subcutaneous implantable cardioverter defibrillator (S-ICD) is an alternative to a transvenous ICD in patients who meet the criteria for ICD implantation without concurrent need for cardiac pacing. The objective of this study is to examine the rates of and indications for S-ICD removal and extraction. A retrospective analysis of all patients who underwent S-ICD implantation between 2010 and 2022 at a single multihospital healthcare system was performed. The primary endpoint was S-ICD removal or extraction. Patient and device characteristics were abstracted from the electronic medical record. Univariate and multivariate analyses were completed to determine factors associated with S-ICD extraction. A total of 372 patients (69.5% male; 48.6 ± 14.4 years old) underwent S-ICD implantation during the study period. There were 22 (5.9%) patients (81.8% male; 52.1 ± 13.2 years old) who underwent S-ICD extraction over a median follow-up period of 4.4 [2.0-6.5] years. The median length of time between implantation and extraction was 39.6 [8.3-64.6] months. The most common indications for S-ICD extraction were the need for bradycardia pacing (frequency among extractions, 18.2%), infection (22.7%), and inappropriate shocks due to oversensing (22.7%). A smoking history and higher body mass index were independently associated with S-ICD extraction. The overall rate of S-ICD extraction over 4.4 [2.0-6.5] years was 5.9%, with the most common indications for extraction being the need for bradycardia pacing, infection, and inappropriate shocks due to oversensing. A smoking history and high body mass index are associated with increased rates of S-ICD extraction. With appropriate patient selection for the S-ICD, the need to remove the device after implantation is low.

Long-term clinical outcomes of remote monitoring for implantable cardioverter-defibrillators in Singapore.

Remote monitoring (RM) for cardiac implantable electronic devices is on the rise and has been shown to reduce the burden of in-clinic follow-up visits. We aimed to investigate the long-term clinical outcomes of RM versus no RM. This was a prospective, single-centre cohort study of consecutive patients with an implantable cardioverter-defibrillator (ICD) or cardiac resynchronisation therapy-defibrillator (CRT-D) followed up from 2018 to 2023. Patients who received non-ICD devices were excluded. In general, RM was offered to all patients, but uptake depended on patient preference. For data analysis, patients were stratified according to whether RM was used. The primary outcome was all-cause mortality; secondary outcomes were hospitalisation for heart failure and device therapy (shocks and electrical storm). Of 551 patients, 284 (51.5%) received RM and 267 (49.5%) did not. Baseline demographics were similar between the two arms. All-cause mortality was significantly lower in RM versus non-RM patients (hazard ratio [HR] 0.45, 95% confidence interval [CI] 0.33-0.60, P <0.001), as was hospitalisation for heart failure (HR 0.39, 95% CI 0.25-0.59, P <0.001); these remained significant after adjustment for baseline covariates. More patients on RM received appropriate antitachycardia pacing (ATP) (17.6% vs. 10.7%, P = 0.035) and appropriate shocks (24.1% vs. 14.7%, P = 0.017). The incidences of inappropriate ATP, inappropriate shocks and electrical storm were similar. More patients on RM underwent pulse generator change (34.1% vs. 10.1%, P <0.001). Remote monitoring was associated with significantly lower mortality in both ICDs and CRT-Ds and in primary and secondary indications, as well as fewer heart failure hospitalisations. This supports current guidelines recommending the use of RM in all patients with ICD or CRT-D.

Equal performance of the subcutaneous and transvenous implantable cardioverter defibrillator across all age groups in the PRAETORIAN trial

Abstract Introduction The subcutaneous ICD (S-ICD) is developed to overcome lead-related complications and systemic infections, inherent to transvenous ICD (TV-ICD) therapy. In the PRAETORIAN trial the S-ICD proved to be non-inferior to the TV-ICD with regard to inappropriate shocks (IAS) and complications. However, the S-ICD is still mainly the preferred choice in young patients with a long life expectancy and therefore higher risk for lead-related complications. We aimed to evaluate the impact of age on complications and IAS between the S-ICD and TV-ICD. Methods The PRAETORIAN trial is an investigator-initiated, international, multicenter, randomized, two-arm noninferiority trial that was conducted in the United States and Europe. In total 849 patients with a class I or IIa indication for ICD therapy and no pacing indication were randomized to receive an S-ICD (N=426) or TV-ICD (N=423) and followed for a median of 49 months. We compare the occurrence of complications and IAS between increasing quartiles of age. Results Quartile 1 (Q1) consisted of 203 patients aged &amp;lt;55 (109 S-ICD, 94 TV-ICD), Q2 of 199 patients aged 55-62 (100 S-ICD, 99 TV-ICD), Q3 of 232 patients aged 63-69 (111 S-ICD, 121 TV-ICD) and Q4 of 215 patients aged ≥70 (106 S-ICD, 109 TV-ICD). Between the quartiles, there were no significant differences in occurrence of device-related complications (P = 0.32) or IAS (P = 0.66). In Q1, there were 15 (7.4%) complications (5 S-ICD, 10 TV-ICD) and 13 (6.4%) IAS (7 S-ICD, 6 TV-ICD), compared to 20 (10.1%) complications (7 S-ICD, 13 TV-ICD) and 17 (8.5%) IAS (9 S-ICD, 8 TV-ICD) in Q2, 22 (9.5%) complications (12 S-ICD, 10 TV-ICD) and 19 (8.2%) IAS (11 S-ICD, 8 TV-ICD) in Q3 and 18 (8.4%) complications (7 S-ICD, 11 TV-ICD) and 21 (9.8%) IAS (14 S-ICD, 7 TV-ICD) in Q4 (Figure 1.). Figure 2. shows forest plots of the hazard ratios per quartile. Conclusions The S-ICD performed equal to the TV-ICD with regard to IAS and complications between quartiles of age, making the S-ICD a good alternative across all age groups.

Comparison of ICD implantation approach in children. The IChilDren study

Abstract Background Without dedicated device, implantable cardioverter defibrillators (ICD) implantation in children is a real challenge for physicians. Types of implantation include transvenous, surgical and subcutaneous-ICD approach, but with a lack of reliable data comparing their respective efficacy and safety. Objective We here aim to compare the results of these 3 ICD implantation approaches in children. Methods Consecutive children (&amp;lt;16yo) implanted with an ICD from 2005 to 2021 in 19 french tertiary centers of the French Pediatric and Congenital heart disease network, were retrospectively enrolled in the study. The primary endpoints were the occurrence of lead failure, device infection or inappropriate shock. Results Among 306 patients (mean age 12,6 yo), 34% received a transvenous ICD, 28% a S-ICD and 38% a surgical ICD. During a median follow-up of 4.7 years, endpoints occurred in 24.2% of the total population, more often in the surgical group (p&amp;lt;0.05). After adjustment for age, ICD type and stratification by heart disease, there was an excess risk of lead failure or infection with the surgical ICD compared with the S-ICD (HR 7.54, 95% CI 1.73;32.91, p&amp;lt;0.05). However, when inappropriate shocks were included, the difference was reduced (HR 2.28, 95% CI 1.03;5.04, p&amp;gt;0.05). In addition, no significant difference between transvenous and surgical ICDs was observed in the multivariate analysis. Conclusions We demonstrate a high rate of complication in children implanted with an ICD. The transvenous and surgical approaches are quite similar. S-ICD appears as a promising approach with the lowest serious adverse event rate. Limitation of inappropriate shock remain the main challenge of this technique.Late complications

Remote monitoring of implantable cardioverter defibrillators: a systematic review and meta-analysis of randomised controlled trials

Abstract Background Remote monitoring (RM) of implantable cardioverter defibrillators (ICD) has been widely adopted as the standard follow-up strategy [1]. Observational data [2,3] has suggested morbidity and mortality reduction associated with RM compared to traditional in-person ICD follow-up, however, randomised controlled trials (RCTs) demonstrate heterogeneous results. Purpose To assess the impact of RM of ICDs on morbidity and mortality through a systematic review and meta-analysis of RCTs comparing RM versus in-person follow-up. Methods PubMed, Embase, Cochrane Central Register of Controlled Trials (CENTRAL) and reference lists were searched for RCTs evaluating RM compared to in-person follow-up of patients with ICDs or cardiac resynchronisation therapy with defibrillator (CRT-D) devices. Meta-analyses of all-cause mortality, cardiovascular (CVD) hospitalisation and inappropriate ICD shock rates were performed. Results Literature search identified 1011 relevant publications, out of which 15 RCTs [4-18] involving a total of 7579 patients (13 RCTs reporting mortality rate, 7 RCTs reporting CVD hospitalisation rate, 6 RCTs reporting inappropriate ICD shock rate) met the inclusion criteria. Pooled analyses demonstrated that RM is not associated with a significant reduction in all-cause mortality (OR 0.95; 95% CI 0.78-1.16; p=0.60)(Figure 1, panel a) or odds of CVD hospitalisation (OR 0.95; 95% CI 0.72-1.25; p=0.70) (Figure 1, panel b). RM was, however, shown to be associated with significantly lower odds of receiving an inappropriate ICD shock compared to the control group (OR 0.63; 95% CI 0.46-0.88; p=0.006) (Figure 1, panel c). The IN-TIME study (the only RCT that independently reached statistical significance in terms of RM effect on mortality) enrolled patients exclusively with a Biotronik ICD or CRT-D; this raised the question as to whether the choice of vendor had an impact on mortality. Our subgroup analysis of the Biotronik device studies demonstrated that there was no significant all-cause mortality benefit (OR 0.87, 95% CI 0.59-1.27; p=0.46). Conclusions This meta-analysis of 15 RCTs including 7579 patients suggests that RM of ICDs is associated with a reduction in inappropriate ICD shocks, without a significant reduction in mortality or CVD hospitalisation when compared to in-person follow-up. Further studies comparing different RM processing and alert response models are warranted.

Effectiveness of contemporary risk stratification in patients with hypertrophic cardiomyopathy: a pilot study

Abstract Introduction Risk stratification and primary prevention of sudden cardiac death (SCD) in patients with hypertrophic cardiomyopathy (HCM) is a challenging discipline. When using current stratification systems, there is always a compromise between sensitivity and specificity. Objective In our pilot study, we sought to determine the incidence of SCD and the effectiveness of stratification systems, i.e., the ESC HCM Risk-SCD score and the system of individual major risk factors (RF) according to ACC/AHA in patients followed in an expert center. Methods Patients with HCM were risk-stratified and followed for 10 ± 8 years at the referral HCM center. Results Five hundred and five patients were stratified, and 71 (14%) were implanted with a cardioverter-defibrillator (ICD) based on risk stratification. ICD patients were stratified at age 39 ± 17 years, of which 26 (35%) were women, maximal left ventricular wall thickness (MLWT) was 23 ± 7 mm, and left atrial dimension (LA) 46 ± 7 mm. During follow-up, 12 (17%) patients had ≥ 1 appropriate ICD therapy at age 46 ± 19 years. Patients with ≥ 1 appropriate ICD therapy had an average 5-year ESC score of 1.8 ± 0.4% and an average ACC/AHA major RF of 1.4 ± 0.8, MLWT 25 ± 6 mm, LA 47 ± 7 mm. None of the ICD patients died of SCD. Five (7%) patients suffered from ICD complications, including 4 (6%) inappropriate shock, and one patient experienced infective endocarditis requiring system extraction. During follow-up, 118 (23%) patients died, of which 28 (6%) from HCM-related causes, 12 (2%) from stroke, 11 (2%) from advanced heart failure, one perioperatively (myectomy) and 4 (1%) patients died suddenly (SCD). The mean age of SCD patients at the time of stratification was 59 ± 14 years; all were male, MLWT 18 ± 5 mm, LA 49 ± 2 mm, mean ESC score 2.0 ± 0.9%, and three (75%) had no RF present according to ACC/AHA. The ESC HCM Risk-SCD score was markedly less sensitive (sensitivity 56%; 95% CI 21-86) but more specific (specificity 98%; 95% CI 96-99) than the ACC/AHA approach (sensitivity 77%; 95% CI 46-95; and specificity 71%; 95% CI 67-75) (Figure). Conclusion With current risk stratification, albeit imperfect, SCD is rare in HCM patients managed at an expert center.

Outcomes and complications of transvenous implantable cardioverter defibrillator systems in the pediatric population: a systematic review and meta-analysis

Abstract Background Implantable cardioverter defibrillators (ICDs) are an important therapy for prevention of sudden cardiac death (SCD). Data on transvenous (TV) ICD therapy rates, complications, and system survival in children ≤ 21 years is limited by absolute numbers and inclusion of adults with congenital heart disease. Purpose To determine ICD therapy rates and complications in pediatric patients ≤ 21 years of age. Methods A systematic review and meta-analysis were conducted following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. Medline, Embase, PubMed Ahead-of-Print and in-process records, and Cochrane Database of Systematic Reviews were searched for full-text articles on pediatric ICD. Articles were assessed for inclusion by two authors via a consensus process; the exclusion criteria included: case reports, review articles, abstracts, editorials, articles not in English, articles solely on epicardial or subcutaneous leads, articles on unrelated topics, articles with &amp;lt;50% ICD leads, and articles with any patients &amp;gt;21 years old. Data were extracted by 1 author and verified by a 2nd author. Meta-analysis of aggregate data was performed, where possible. Random effects models were used for pooled inferences. All reported rates are annualized rates based on reported follow-up times in each study. Results Of 1325 articles, 23 met all inclusion and no exclusion criteria (Figure) representing 1700 patients implanted from 1987-2020. The average age of patients was 12.8 years (95% confidence interval [CI]: 11.9 – 13.7) with weight of 51.1 kg (95% CI: 42.2 – 60.0) (Table). Primary prevention was the indication in 56.4 % (95% CI: 45.0% – 67.7%). Only 14.8% (95% CI: 10.6% – 19.0%) of the patients had congenital heart disease while 22.6% (95% CI: 15.8% – 29.3%) had long QT syndrome. The annualized rate of appropriate shock was 7.0% (95% CI: 5.6% – 8.8%) and the rate of inappropriate shock was 4.8% (95% CI: 3.8% – 6.0%). Annualized rates of reported adverse events included lead failure: 2.3% (95% CI: 1.6% – 3.3%) and infection: 0.8% (95% CI: 0.4% – 1.6%), which could have led to system revision: 4.4% (95% CI: 2.1% – 9.4%). The all-cause mortality rate was 0.8% (95% CI: 0.6% – 1.2%) across 17 studies. In 9 studies with 719 patients, the heart transplant rate was 1.6% (95% CI: 0.6% – 3.9%). Conclusion In this first systematic review and meta-analysis of ICDs in pediatric patients, ICD therapy was effective for prevention of SCD with a 7.0% annualized rate of appropriate ICD shocks. This is comparable to the annualized rate of appropriate ICD shock for secondary prevention of SCD in adult randomized controlled trials. Most common adverse events in the pediatric population were lead failure and system revision. Further refinements in patient selection criteria for implantation and improvements in lead and device technology are needed for pediatric patients.FigureTable

Atrial cardiomyopathy resulting from loss of plakophilin-2 expression: Response to adrenergic stimulation and implications for the exercise response.

Atrial arrhythmias occur in 20-40% of patients with arrhythmogenic right ventricular cardiomyopathy (ARVC) and are associated with an increased risk of sustained ventricular arrhythmias and inappropriate implantable cardioverter-defibrillator shocks. The pathophysiology of atrial arrhythmias in ARVC remains unclear. Most cases of gene-positive ARVC are linked to pathogenic variants in the desmosomal gene plakophilin-2 (PKP2). Here, we test the hypothesis that loss of PKP2 expression leads to pro-arrhythmic changes in atrial cardiomyocytes. Atrial cells/tissue were obtained from a cardiac-specific, tamoxifen-activated model of PKP2 deficiency (PKP2cKO). By contrast to PKP2cKO ventricular myocytes, PKP2cKO atrial cardiomyocytes presented no significant differences in intracellular calcium (Ca2+ i) transient dynamics, sarcoplasmic reticulum load or action potential morphology. PKP2cKO atrial cardiomyocytes showed elevated reactive oxygen species levels, increased frequency and amplitude of Ca2+ sparks, and increased diastolic [Ca2+]i compared to control; the latter two parameters were further increased by isoproterenol exposure and reversed by exposure to ryanodine receptor blocker dantrolene. We speculate that these isoproterenol-dependent effects may impact on the exercise-related atrial arrhythmia risk in ARVC patients. Despite absence of changes in Ca2+ i transient dynamics, PKP2cKO atrial cardiomyocytes showed enhanced sarcomere shortening and impaired sarcomere relaxation. Orthogonal transcriptomic analysis of human(GTEx) and PKP2cKO atrial tissue led to identification of 41 transcripts depending on PKP2 expression. Biochemical follow-up confirmed reduced abundance of sarcomeric protein myosin binding protein C, potentially playing a role in cellular shortening and relaxation changes observed. Our findings provide novel insights into the role of PKP2 in atrial myocardium with potential implications to therapeutic management of atrial fibrillation in patients with PKP2-related ARVC. KEY POINTS: Atrial arrhythmias occur in a large group of patients with arrhythmogenic right ventricular cardiomyopathy (ARVC), a cardiac disease mostly caused by pathogenic variants in the desmosomal gene plakophilin-2 (PKP2). Exercise is considered to be an independent risk factor for arrhythmias consequent to PKP2 deficiency. Weshow that loss of PKP2 expression affects cellular calcium handling and electrophysiology differently in left atrial vs. ventricular myocardium and causes extensive atrial fibrosis. PKP2-deficient atrial cardiomyocytes present increased spontaneous sarcoplasmic reticulum calcium release events, furtherenhancedby isoproterenol exposure and reversiblebya ryanodine receptor blocker(dantrolene). In addition, PKP2-deficient atrial myocytes exhibit impaired relaxation and enhanced sarcomere shortening, most probably related to reduced abundance of myosin binding protein C. We speculate that cellular effects reported upon isoproterenol impact on the exercise-related atrial arrhythmia risk in ARVC patients. We further propose that therapeutic approaches aimed at mitigating ventricular damage may be effective to treat the atrial disease in ARVC.

AI-enabled detection of QRS fragmentation from 12-lead electrocardiogram and its clinical relevance for predicting malignant arrhythmia onset.

Electrocardiographic markers differentiating between death caused by ventricular arrhythmias and non-arrhythmic death could improve the selection of patients for implantable cardioverter-defibrillator (ICD) implantation. QRS fragmentation (fQRS) is a parameter of interest, but subject to debate. We investigated the association of an automatically quantified probability of fragmentation with the outcome in ICD patients. From a single-center retrospective registry, all patients implanted with an ICD between January 1996 and December 2018 were eligible for inclusion. Patients with active pacing were excluded. From the electronical medical record, clinical characteristics at implantation were collected and a 12-lead ECG was exported and analyzed by a previously validated machine-learning algorithm to quantify the probability of fQRS. To compare fQRS(+) and fQRS(-) patients, dichotomization was performed using the Youden index. Patients with a high probability of fragmentation in any region (anterior, inferior or lateral), were labeled fQRS(+). The impact of this fQRS probability on outcomes was investigated using Cox regression. A total of 1,242 patients with a mean age of 62.6 ± 11.5 years and a reduced left ventricular ejection fraction of 31 ± 12% were included of which 227 (18.3%) were female. The vast majority suffered from ischemic heart disease (64.3%) and were implanted in primary prevention (63.8%). 538 (43.3%) had a high probability of fragmentation in any region. Patients with a high probability of fragmentation had more frequently dilated cardiomyopathy (39.4% vs. 33.0%, p = 0.019), left bundle branch block (40.8% vs. 32.5%, p = 0.006) and a higher use of cardiac resynchronization therapy with defibrillator (CRT-D) devices (33.9% vs. 26.3%, p = 0.004). After adjustment in a multivariable Cox model, there was no significant association between the probability of global or regional fQRS and appropriate ICD therapy, inappropriate shock and short- or long-term mortality. There was no association between the automatically quantified probability of the presence of fQRS and outcome. This lack of predictive value might be due to the algorithm used, which identifies only the presence but not the severity of fragmentation.

Advancements in automated external and wearable cardiac defibrillators.

Survival statistics for out-of-hospital cardiac arrests remain unsatisfactory. Prompt defibrillation of shockable rhythms, such as ventricular fibrillation and pulseless ventricular tachycardia, is crucial for improving survival. Automated external defibrillators (AEDs) and wearable cardiac defibrillators (WCDs) seek to improve the survival rates following out-of-hospital cardiac arrests. We aim to review the indications, utility, advancements, and limitations of AEDs and WCDs, as well as their role in contemporary and future clinical practice. Recent advancements in these technologies, such as smartphone applications and drone delivery of AEDs and less inappropriate shocks and decreased size of WCDs, have increased their ubiquity and efficacy. However, implementation of this technology remains limited due to lack of resources and suboptimal patient adherence. Out of hospital cardiac arrests continue to pose a significant public health challenge. Advancements in AEDs and WCDs aim to facilitate prompt defibrillation of shockable rhythms with the goal of improving survival rates. However, they remain underutilized due to limited resources and suboptimal patient adherence. As these technologies continue to evolve to become smaller, lighter and more affordable, their utilization and accessibility are expected to improve.

Promising tools for future drug discovery and development in antiarrhythmic therapy.

Arrhythmia refers to irregularities in the rate and rhythm of the heart, with symptoms spanning from mild palpitations to life-threatening arrhythmias and sudden cardiac death (SCD). The complex molecular nature of arrhythmias complicates the selection of appropriate treatment. Current therapies involve the use of antiarrhythmic drugs (class I-IV) with limited efficacy and dangerous side effects and implantable pacemakers and cardioverter-defibrillators with hardware-related complications and inappropriate shocks. The number of novel antiarrhythmic drug in the development pipeline has decreased substantially during the last decade and underscores uncertainties regarding future developments in this field. Consequently, arrhythmia treatment poses significant challenges, prompting the need for alternative approaches. Remarkably, innovative drug discovery and development technologies show promise in helping advance antiarrhythmic therapies. Here, we review unique characteristics and the transformative potential of emerging technologies that offer unprecedented opportunities for transitioning from traditional antiarrhythmics to next-generation therapies. We assess stem cell technology, emphasizing the utility of innovative cell profiling using multi-omics, high-throughput screening, and advanced computational modeling in developing treatments tailored precisely to individual genetic and physiological profiles. We offer insights into gene therapy, peptide and peptibody approaches for drug delivery. We finally discuss potential strengths and weaknesses of such techniques in reducing adverse effects and enhancing overall treatment outcomes, leading to more effective, specific, and safer therapies. Altogether, this comprehensive overview introduces innovative avenues for personalized rhythm therapy, with particular emphasis on drug discovery, aiming to advance the arrhythmia treatment landscape and the prevention of SCD. Significance Statement Arrhythmias and sudden cardiac death account for 15-20% of deaths worldwide. However, current antiarrhythmic therapies are ineffective and with dangerous side effects. Here, we review the field of arrhythmia treatment underscoring the slow progress in advancing the cardiac rhythm therapy pipeline and the uncertainties regarding evolution of this field. We provide information on how emerging technological and experimental tools can help accelerate progress and address the limitations of antiarrhythmic drug discovery.

Assessment of Antitachycardia Pacing in Primary Prevention Patients

The emergence of novel programming guidelines that reduce premature and inappropriate therapies along with the availability of new implantable cardioverter-defibrillator (ICD) technologies lacking traditional endocardial antitachycardia pacing (ATP) capabilities requires the reevaluation of ATP as a first strategy in terminating fast ventricular tachycardias (VTs) in primary prevention ICD recipients. To assess the role of ATP in terminating fast VTs in primary prevention ICD recipients with contemporary programming. This global, prospective, double-blind, randomized clinical trial had an equivalence design with a relative margin of 35%. Superiority tests were performed at interim analyses and the final analysis if equivalence was not proven. Patients were enrolled between September 2016 and April 2021 at 134 sites in 8 countries, with the last date of follow-up on July 6, 2023. Patients were required to have an indication for a primary prevention ICD, including left ventricular ejection fraction less than or equal to 35%. Patients were randomized in a 1:1 ratio to receive ATP plus shock vs shock only. The primary end point was time to first all-cause shock. Secondary end points included time to first appropriate shock, time to first inappropriate shock, all-cause mortality, and the composite of time to first all-cause shock plus all-cause mortality. A total of 2595 patients were randomized (mean age, 63.9 years; 22.4% were females). At a mean follow-up of 38 months, first all-cause shock occurred in 129 participants in the ATP plus shock group and 178 participants in the shock only group. The hazard ratio (HR) for the primary end point was 0.72 (95.9% CI, 0.57-0.92), with P = .005 for superiority of the ATP plus shock group over the shock only group. During follow-up in an intention-to-treat analysis, the total shock burden per 100 patient-years was not statistically different, at 12.3 and 14.9, respectively (P = .70). The use of a single burst of ATP prior to shock in primary prevention ICD recipients with modern ICD detection programming prolonged the time to first all-cause ICD shock. ClinicalTrials.gov Identifier: NCT02923726.

Design of a postmarket registry for the extravascular implantable cardioverter-defibrillator: the Enlighten Study

BackgroundThe extravascular implantable cardioverter-defibrillator (EV-ICD) with substernal lead placement has been shown to terminate ventricular arrhythmias safely and effectively while being outside the vasculature. The performance of the EV-ICD system with a novel inappropriate shock reducing algorithm in a real-world setting has yet to be investigated. ObjectiveThe objective of the Enlighten Study: the EV-ICD Post Approval Registry is to provide a comprehensive measure of the safety and performance of the EV-ICD system in real-world clinical practice over the lifetime of the device. MethodsThe Enlighten Study is a global, prospective, observational, multi-center, post-approval study utilizing the manufacturer’s Product Surveillance Registry (PSR). Eligible patients implanted with an Aurora EV-ICDTM system at participating centers will be included. Follow-up clinical data will be collected approximately every 6 months throughout the lifetime of the device, enrolling a minimum of 500 patients. ResultsThe primary endpoint of the study is major system-related complication-free survival at 5-years post-implant, with a minimum threshold of >79%. The study will also characterize device performance which includes, but is not limited to, freedom from system- or procedure-related complications, performance of antitachycardia pacing, characterization of sensing and detection, inappropriate therapy, shock effectiveness, battery depletion, and system revisions. ConclusionThe Enlighten Study: the EV-ICD Post Approval Registry will examine the real-world performance of the post-market EV-ICD system. Additionally, this study will allow for a robust assessment of EV-ICD-related complications, device revisions, and extractions over chronic (>5 year) implant durations.

Performance and Safety of the Extravascular Implantable Cardioverter-Defibrillator Through Long-Term Follow-Up: Final Results From the Pivotal Study.

Substernal lead placement of the extravascular implantable cardioverter-defibrillator (EV ICD) permits both defibrillation at thresholds similar to those seen with transvenous ICDs and effective antitachycardia pacing (ATP), while avoiding the vasculature and associated complications. The global Pivotal study has shown the EV ICD system to be safe and effective through 6 months, but long-term experience has yet to be published. We aim to report the performance and safety of the EV ICD system throughout the study. The EV ICD Pivotal study was a prospective, global, single-arm, pre-market clinical study. Individuals with a class I or IIa indication for a single-chamber ICD per guidelines were enrolled. Freedom from major system- or procedure-related complications, as well as appropriate and inappropriate therapy rates, were assessed through 3 years using the Kaplan-Meier method. Anti-tachycardia pacing success was calculated using simple proportions. An implant was attempted in 316 patients [25.3% female, 53.8±13.1 years old, 81.6% primary prevention, LVEF 38.9%±15.4%]. Of 299 patients with a successful implant, 24 experienced 82 spontaneous arrhythmic episodes that were appropriately treated with either ATP only (38, 46.3%), shock only (34, 41.5%), or both (10, 12.2%) for a Kaplan-Meier-estimated rate of first any appropriate therapy of 9.2% at 3 years. Antitachycardia pacing was successful in 77.1% (37/48) of episodes, and ATP usage significantly increased from discharge to last follow-up visit (P<0.0001). Shock therapy was successful in 100% (27/27) of discrete, spontaneous ventricular arrhythmias. The inappropriate shock rates at 1 and 3 years were 9.8% and 17.5%, respectively, with P-wave oversensing the predominant cause. No major intraprocedural complications were reported and the estimated freedom from system- or procedure-related major complications was 91.9% at 1 year and 89.0% at 3 years. The most common major complications were lead dislodgement (10 events; n=9 patients, 2.8%), postoperative wound or device pocket infection (n=8, 2.5%), and device inappropriate shock delivery (n=4, 1.3%). Twenty-four system revisions were performed as a result of major complications related to the EV ICD system or procedure. From implant to study completion, the EV ICD Pivotal study demonstrated that a single integrated system with an extravascular lead placed in the substernal space maintains high ATP success, effective defibrillation, and a consistent safety profile.

Reduction of inappropriate shock rate through signal filtering (smart-pass) in patients with implantable subcutaneous cardioverter-defibrillator: a systematic review and meta-analysis.

Subcutaneous implantable cardioverter-defibrillators (S-ICD) are effective in protecting patients against sudden death but expose them to a higher risk of inappropriate shock (IAS). We performed a systematic search of studies published between January 2010 and December 2019 assessing IAS due to cardiac oversensing by the selection process (PRISMA) and identified 17 eligible articles. Fifteen studies were observational, and two studies were retrospective. For the meta-analysis, the final population included 6111 patients: 3356 without SMART pass (SP) filter (group 1) and 2755 with SP filter (group 2). 1614 shocks (appropriate shocks plus IAS) were registered (1245 in group 1 and 369 in group 2). The random effects meta-analysis estimated an overall IAS rate of 7.78% (95% confidence interval: 4.93-10.64) with substantial variability between studies (I square=96.05%, p<0.001). The IAS rate was 10.75% (95% confidence interval: 8.49-13.02) for group 1 and 3.61% (95% confidence interval: 1.36-5.86) for group 2 (p<0.001). Third-generation S-ICD technology with SP filters reduced the risk of cardiac signal-related IAS.

Incidence and risk factors for first and recurrent ICD shock therapy in patients with an implantable cardioverter defibrillator.

Advances in medical treatment and outcomes in implantable cardioverter-defibrillator (ICD) recipients incentivize a need for improved candidate selection and identification of risk factors for ICD therapy. We examined contemporary rates of and risk factors for ICD therapy. Patients with ICD for primary (PP) or secondary prevention (SP), implanted between January 2010 and December 2020, were followed for appropriate and inappropriate incident and recurrent shock. Overall, 2998 patients (mean age 61.8 ± 12.7years, 20% female, 73% ICD carriers, and 47.1% SP) were analyzed with a median follow-up of 4.3 (interquartile range (IQR) 2.1-7.4) years. A total of 426/2998 (14.2%) patients had shock; 364/2998 (12.1%) had appropriate and 82/2998 (2.7%) inappropriate shock, with annualized event rates of 2.34 (2.11-2.59) and 0.49 (0.39-0.61) per 100 person-years, respectively. Of those with shock, 133/364 (36.5%) experienced recurrent appropriate shock and 8/364 (2.2%) received recurrent inappropriate shock, with event rates of 10.57 (8.85-12.53) and 0.46 (0.20-0.92), respectively. In multivariable analyses, female sex was associated with a reduced risk of incident appropriate shock (hazard ratio 0.69 [95% confidence interval 0.52; 0.91]). Of other variables, only revascularization status was associated with recurrent appropriate shock in PP, and CRT-D with recurrent appropriate shock in the overall cohort. One in eight ICD recipients received appropriate shock 2-7years after guideline-directed implantation. More than one-third of patients with a first shock experienced recurrent shock. Few clinical variables showed potential in predicting shocks, illustrating a need for more advanced tools to select candidates for implantation.

SMART Pass automatic deactivation of subcutaneous implantable cardioverter-defibrillators

BackgroundThe SMART Pass algorithm for subcutaneous implantable cardioverter-defibrillator prevents inappropriate shocks due to oversensing. The mechanisms and significance of SMART Pass deactivation remain unclear. ObjectiveThe objective of this study was to assess whether SMART Pass deactivation is associated with inappropriate shocks and to elucidate the underlying mechanism. MethodsWe retrospectively investigated 115 patients who underwent subcutaneous implantable cardioverter-defibrillator implantation between 2016 and 2021. SMART Pass deactivation and inappropriate shocks during follow-up were assessed. The QRS amplitudes of the subcutaneous (S-ECG) and 12-lead electrocardiogram (ECG) at the time of implantation (pre) and SMART Pass deactivation (post) were measured. The patients were divided into the SP-ON group with SMART Pass consistently on and the SP-OFF group with the experience of SMART Pass deactivation. ResultsThree of 12 patients in the SP-OFF group experienced inappropriate shocks during a median follow-up of 1094 (interquartile range, 887–1502) days compared with 4 of 87 patients in the SP-ON group. Pre- and post–S-ECG QRS amplitudes were significantly lower in the SP-OFF group than in the SP-ON group (both P < .05), despite similar 12-lead ECG QRS amplitude in both groups. A significant temporary drop in the QRS amplitude of the S-ECG led to SMART Pass deactivation (pre–QRS amplitude vs amplitude at deactivation, P = .015; 95% CI, 0.3–1.9). ConclusionThe rate of inappropriate shocks was numerically higher after SMART Pass deactivation. A low QRS amplitude in S-ECG was a potential risk factor for SMART Pass deactivation. Careful follow-up and suitable management are required for managing patients with risks of SMART Pass deactivation.