Circulation. Arrhythmia and electrophysiology最新文献

Background: To address the unmet need for a smaller pacemaker for babies, a specially modified implantable pulse generator was developed containing a Medtronic Micra subassembly in a polymer header connecting to a bipolar epicardial lead. The aim of this study was to report midterm follow-up data and outcomes of patients who underwent implantation of this device.

Methods: Deidentified data were collected from 12 of 15 sites in the United States implanting the pediatric implantable pulse generator between March 2022 and February 2024. All 29 patients at these 12 sites within this timeframe were included in the analysis.

Results: The median age at implant was 15 days (range, 0 days to 3 years, including 1 outlier). The median weight was 2.3 kg (range, 1.3-11.4 kg). Gestational age was 28.5 weeks to term, with 23 (79%) patients born prematurely. Of those with anatomic information, 25% had congenital heart disease. The average duration of implant was 325 days (73-808days). The most recent lead impedance mean was 612 ohms (450-840 ohms), ventricular capture threshold mean was 1 V @ 0.4 ms (range, 0.38-2.75 V), and R-wave sensing mean was 12.5 mV (3.6-20 mV). There were 7 generator explants (24%), removed at 6.5 to 31 months of age.

Conclusions: The pediatric implantable pulse generator can be safely implanted in neonates and infants. This multicenter report demonstrates that the devices remain stable, with effective pacing, normal electrical parameters, and battery longevity aligned with projections. This novel pediatric pacemaker provides a viable alternative to standard-size generators and addresses a vital unmet need for these small patients.

Background: The strongest genetic risk factors for atrial fibrillation (AF) are DNA variants on chromosome 4q25 near the transcription factor gene PITX2. Mice deficient in Pitx2 (Pitx2^+/-) have increased AF susceptibility, although the molecular mechanism(s) remains controversial. Pitx2 encodes a transcription factor that activates an antioxidant response to promote cardiac repair. Increased reactive oxygen species causing oxidation of polyunsaturated fatty acids generates reactive lipid dicarbonyl moieties that adduct to proteins and other macromolecules to promote cellular injury. We tested the hypothesis that oxidative stress, and specifically isolevuglandins, the most reactive lipid dicarbonyls identified, are increased in the setting of Pitx2 deficiency to promote proarrhythmic remodeling and AF.

Methods: Pitx2^+/- and Pitx2^+/+ wild-type littermate control mice were treated orally with vehicle, the lipid dicarbonyl scavenger 2-hydroxybenzylamine, or an inactive control compound at weaning, until study at age 16 to 18 weeks.

Results: Pitx2^+/- mice demonstrated increased P wave duration indicative of slowed atrial conduction, as well as increased inducible AF burden and sustained AF, compared with wild type, and these abnormalities were prevented by 2-hydroxybenzylamine. Both reactive oxygen species and isolevuglandin protein adducts were elevated in Pitx2^+/- atria with reduced expression of reactive oxygen species-protective genes. High-resolution respirometry demonstrated impaired mitochondrial function in Pitx2^+/- atria, with disruption of mitochondrial integrity and cell-cell junctions with connexin lateralization, as well as decreased mitochondrial biogenesis gene expression. Proarrhythmic ionic current remodeling in Pitx2^+/- atrial myocytes included elevated resting membrane potential, abbreviated action potential duration, and reduced maximum phase 0 upstroke velocity compared with wild type. Most of these abnormalities were ameliorated or prevented by 2-hydroxybenzylamine.

Conclusions: These results demonstrate a critical role for lipid dicarbonyl mediators of oxidative stress in the proarrhythmic remodeling and AF susceptibility that occurs with Pitx2 deficiency, implying the possibility of genotype-specific therapy to prevent AF.

Background: The safety of subcutaneous implantable cardioverter defibrillator (S-ICD) recipients who lead active lifestyles and engage in recreational sports is unknown. We aimed to evaluate the association between lifestyle and recreational sports and the occurrence of arrhythmia- and device-related complications, appropriate and inappropriate shocks in S-ICD recipients.

Methods: We assessed a cohort of young-adult (15-65 years) S-ICD patients, evaluated their physical activity with IPAQ (International Physical Activity Questionnaire), and assessed the association between lifestyle and recreational sports on S-ICD safety and shocks.

Results: We enrolled 602 S-ICD recipients (77% males; age, 46±14 years). According to the IPAQ, patients were categorized as inactive subjects (26.4%), moderately active subjects (45.2%), or highly active subjects (28.4%). Among moderately/highly active subjects, 163 (27.1%) were recreational athletes. During follow-up (47.3 [interquartile range, 27.0-67.6] months), 23 patients (3.8%) reached the safety end point of arrhythmia- or device-related complications, with moderately and highly active subjects showing in multivariate analysis similar incidence compared with inactive subjects (P=0.59 and P=0.83, respectively). Forty-four patients had 87 appropriate shocks. In multivariate analysis, moderately and highly active subjects showed a nonsignificantly lower incidence of appropriate shocks compared with inactive subjects (P=0.12 and P=0.11, respectively). Consistently, there was a nonsignificant lower incidence of appropriate shocks in athletes versus nonathletes (P=0.06). Thirty-nine patients had 46 inappropriate shocks. Moderately and highly active subjects had similar incidence of inappropriate shocks compared with inactive subjects (P=0.92 and P=0.88, respectively).

Conclusions: Young S-ICD patients often lead active lifestyles and participate in sports. Higher activity levels were not associated with increased implantable cardioverter defibrillator-related complications or increased risk of implantable cardioverter defibrillator shocks.

Background: Population genomic screening for desmosome variants associated with arrhythmogenic right ventricular cardiomyopathy (ARVC) may facilitate early disease detection and protective intervention. The validated ARVC risk calculator offers a novel means to risk stratify individuals with diagnosed ARVC, but predicted risk in the context of genomic screening identification has not been explored.

Methods: Individuals harboring a pathogenic/likely pathogenic variant in a desmosome gene (PKP2, DSP, DSG2, or DSC2) were identified through the Geisinger MyCode Genomic Screening and Counseling program. The ARVC risk calculator was applied to patients with a subsequent evaluation of right ventricular function. This predicted risk was compared with outcomes in the first 5 years (range, 0.3-5.0 years) after genetic result return.

Results: Of 254 individuals with a clinically confirmed pathogenic/likely pathogenic desmosome variant, 113 (median age, 56 [interquartile range, 42-66]; 71% female) had cardiac imaging in follow-up and no prior sustained ventricular arrhythmia (VA). Eighty-two (73%) had no ARVC task force criteria (TFC) besides the variant (possible diagnosis), 22 (19%) had a single additional minor criterion (borderline diagnosis), and 9 (8%) met criteria for definite diagnosis. The median 5-year predicted VA risk was 3.9% (2.3%-6.6%), notably lower than that of the calculator derivation cohort (20.6%). The risk of fast VA was 1.6% (1.0%-2.9%). The predicted VA risk was higher in individuals with any nongenetic ARVC task force criteria (6.3% [2.5-13.2%]) versus those without (3.7% [2.2-5.6%]; P=0.01), and in individuals with DSP variants (6.1% [3.9-7.8%] versus PKP2 3.4% [2.2-5.3%]; P=0.01). Over a median 3.0 years of follow-up (≤5 years only), no sustained VA events were observed in this cohort.

Conclusions: The predicted 5-year risk of VA in individuals ascertained via population genomic screening for desmosome variants is low (3.9%; 1.6% for fast VA) but may vary by affected gene and ARVC task force criteria burden.

Background: Remote monitoring offers an effective and safe method for monitoring patients with cardiovascular implantable electronic devices. The downside of remote monitoring is the overflow of the data. Since many of the remote monitoring transmissions are nonactionable, optimizing alert transmissions could partly overcome this problem.

Methods: We collected data on the number and the causes of all alert-, scheduled-, and patient-initiated transmissions as well as actions initiated by these transmissions in 2023. According to our strategy, all clinically nonrelevant alerts were turned off. The trend of alert transmissions and the proportion of actionable scheduled transmissions are presented. The patient safety was monitored by analyzing the premortem alerts and changes to alert settings in deceased patients, as well as the rate of actionable scheduled or patient-initiated transmissions during follow-up.

Results: During the study period 8182 transmissions were generated from 3732 cardiovascular implantable electronic devices. Of these, 2306 (28%) were alert transmissions, of which 57% (n=1290) were considered clinically nonrelevant. The rate of alerts decreased by 44% from January to December (0.07 versus 0.04 per device per month, P=0.001). Of the 3335 scheduled transmissions, 11% (364) were actionable, and the proportion of actionable scheduled transmissions remained unchanged during the follow-up period (P=0.08). Notably, none of the deaths were linked to the adjustment of alert settings.

Conclusions: Our data indicated that active evaluation of the clinical relevance of all alert transmissions and deactivation of clinically nonrelevant alerts reduce the remote monitoring workload. However, long-term follow-up is needed to ensure that patient safety is not compromised.

Background: Sudden cardiac death is the most common cause of death in childhood hypertrophic cardiomyopathy (HCM). Recently, 2 risk scores have been developed to estimate the 5-year risk of sudden cardiac death. We aimed to assess their respective performances in an independent cohort.

Methods: All patients with HCM aged <18 years from a single center were retrospectively included between 2003 and 2023. HCM Risk-Kids and PRIMaCY risk scores were calculated at diagnosis and during follow-up. The primary composite outcome included sustained ventricular arrhythmia, appropriate implantable cardioverter defibrillator (ICD) therapy, aborted cardiac arrest, or sudden cardiac death.

Results: A total of 100 primary prevention children were included (7.1±5.6 years, 59.0% males), with a mean follow-up of 8.6±5.5 years. Overall, 13 (13.0%) patients experienced the primary composite outcome. When only considering events during the 5 first years, Harrel C index was 0.52 (95% CI, 0.27-0.77) for HCM Risk-Kids (≥6%) and 0.70 (95% CI, 0.59-0.80) for PRIMaCY (>8.3%), with 1 patient potentially treated by ICD for every 25 ICDs implanted for HCM Risk-Kids and 1 for every 14 ICDs implanted for PRIMaCY. When risk scores were repeated and all primary outcomes during follow-up were considered, 12 of 13 (92.3%) events were correctly identified using both risk scores, with 1 patient potentially treated by ICD for every 5.6 ICDs implanted for HCM Risk-Kids and 1 for every 5.3 ICDs implanted for PRIMaCY. Among 44 (44.0%) patients implanted with an ICD, all primary prevention patients who had ≥1 appropriate ICD therapy during follow-up had an HCM Risk-Kids ≥6% and PRIMaCY >8.3% at implantation.

Conclusions: In this independent evaluation, our findings suggest imperfect discrimination between low and high-risk patients using the HCM Risk-Kids and PRIMaCY risk scores, with predicted risks tending to be overestimated compared with the actual observed events. The performance or risk scores was substantially improved by periodic reassessment during follow-up.

Background: Patients with arrhythmogenic mitral valve prolapse syndrome are at increased risk for life-threatening ventricular arrhythmias, but studies have been limited by small sample sizes. We sought to assemble an international arrhythmogenic mitral valve prolapse syndrome registry to delineate the clinical, imaging, and treatment characteristics of patients with arrhythmogenic mitral valve prolapse syndrome who survived sudden cardiac arrest (SCA) or had sustained ventricular tachycardia (VT) or ventricular fibrillation.

Methods: In this descriptive registry, we characterized patients with arrhythmogenic mitral valve prolapse syndrome who survived SCA, sustained VT, or ventricular fibrillation. Deidentified data were abstracted locally and combined centrally.

Results: We included 148 patients who had SCA or VT/ventricular fibrillation. Patients had a mean age of 43.7±15.4 years; 68% were women, 73% had bileaflet prolapse, 65% had mitral annular disjunction, 67% had nonsustained VT, and 59% had inferolateral T-wave inversions. Syncope (n=54, 48%) and anterolateral T-wave inversion (n=26, 22%) were relatively common. Catheter ablation was performed in 50 (35%) patients for premature ventricular complexes and in 18 (17.7%) patients for VT. Sites of origin for arrhythmias were commonly in the papillary muscles, fascicles, mitral annulus, and inferior/inferolateral left ventricle.

Conclusions: In this international descriptive registry of patients with arrhythmogenic mitral valve prolapse syndrome and SCA, patients were young, women, and had bileaflet mitral valve prolapse, mitral annular disjunction, inferolateral T-wave inversions, and nonsustained VT. A history of syncope and anterolateral T-wave inversions was relatively common in patients who survived SCA or sustained VT/ventricular fibrillation.