Comparison of electrocardiograms (ECG) waveforms and centralized ECG measurements between a simple 6-lead mobile ECG device and a standard 12-lead ECG.

BACKGROUND: Interval duration measurements (IDMs) were compared between standard 12-lead electrocardiograms (ECGs) and 6-lead ECGs recorded with AliveCor's KardiaMobile 6L, a hand-held mobile device designed for use by patients at home. METHODS: Electrocardiograms were recorded within, on average, 15 min from 705 patients in Mayo Clinic's Windland Smith Rice Genetic Heart Rhythm Clinic. Interpretable 12-lead and 6-lead recordings were available for 685 out of 705 (97%) eligible patients. The most common diagnosis was congenital long QT syndrome (LQTS, 343/685 [50%]), followed by unaffected relatives and patients (146/685 [21%]), and patients with other genetic heart diseases, including hypertrophic cardiomyopathy (36 [5.2%]), arrhythmogenic cardiomyopathy (23 [3.4%]), and idiopathic ventricular fibrillation (14 [2.0%]). IDMs were performed by a central ECG laboratory using lead II with a semi-automated technique. RESULTS: Despite differences in patient position (supine for 12-lead ECGs and sitting for 6-lead ECGs), mean IDMs were comparable, with mean values for the 12-lead and 6-lead ECGs for QTcF, heart rate, PR, and QRS differing by 2.6 ms, -5.5 beats per minute, 1.0 and 1.2 ms, respectively. Despite a modest difference in heart rate, intervals were close enough to allow a detection of clinically meaningful abnormalities. CONCLUSIONS: The 6-lead hand-held device is potentially useful for a clinical follow-up of remote patients, and for a safety follow-up of patients participating in clinical trials who cannot visit the investigational site. This technology may extend the use of 12-lead ECG recordings during the current COVID-19 pandemic as remote patient monitoring becomes more common in virtual or hybrid-design clinical studies.

Conversion of left atrial volume to diameter for automated estimation of sudden cardiac death risk in hypertrophic cardiomyopathy.

BACKGROUND: A subset of patients with hypertrophic cardiomyopathy (HCM) is at high risk of sudden cardiac death (SCD). Practice guidelines endorse use of a risk calculator, which requires entry of left atrial (LA) diameter. However, American Society of Echocardiography (ASE) guidelines recommend the use of LA volume index (LAVI) for routine quantification of LA size. The aims of this study were to (a) develop a model to estimate LA diameter from LAVI and (b) evaluate whether substitution of measured LA diameter by estimated LA diameter derived from LAVI reclassifies HCM-SCD risk. METHODS: The study cohort was comprised of 500 randomly selected HCM patients who underwent transthoracic echocardiography (TTE). LA diameter and LAVI were measured offline using digital clips from TTE. Linear regression models were developed to estimate LA diameter from LAVI. A European Society of Cardiology endorsed equation estimated SCD risk, which was measured using LA diameter and estimated LA diameter derived from LAVI. RESULTS: The mean LAVI was 48.5 ± 18.8 mL/m2 . The derived LA diameter was 45.1 mm (SD: 5.5 mm), similar to the measured LA diameter (45.1 mm, SD: 7.1 mm). Median SCD risk at 5 years estimated by measured LA diameter was 2.22% (interquartile range (IQR): 1.39, 3.56), while median risk calculated by estimated LA diameter was 2.18% (IQR: 1.44, 3.52). 476/500 (95%) patients maintained the same risk classification regardless of whether the measured or estimated LA diameter was used. CONCLUSIONS: Substitution of measured LA diameter by estimated LA diameter in the HCM-SCD calculator did not reclassify risk.

An autoantibody identifies arrhythmogenic right ventricular cardiomyopathy and participates in its pathogenesis.

Aims: Arrhythmogenic right ventricular cardiomyopathy (ARVC) is characterized by right ventricular myocardial replacement and life-threatening ventricular arrhythmias. Desmosomal gene mutations are sometimes identified, but clinical and genetic diagnosis remains challenging. Desmosomal skin disorders can be caused by desmosomal gene mutations or autoantibodies. We sought to determine if anti-desmosome antibodies are present in subjects with ARVC. Methods and results: We evaluated ARVC subjects and controls for antibodies to cardiac desmosomal cadherin proteins. Desmoglein-2 (DSG2), desmocollin-2, and N-cadherin proteins on western blots were exposed to sera, in primary and validation cohorts of subjects and controls, as well as the naturally occurring Boxer dog model of ARVC. We identified anti-DSG2 antibodies in 12/12 and 25/25 definite ARVC cohorts and 7/8 borderline subjects. Antibody was absent in 11/12, faint in 1/12, and absent in 20/20 of two control cohorts. Anti-DSG2 antibodies were present in 10/10 Boxer dogs with ARVC, and absent in 18/18 without. In humans, the level of anti-DSG2 antibodies correlated with the burden of premature ventricular contractions (r = 0.70), and antibodies caused gap junction dysfunction, a common feature of ARVC, in vitro. Anti-DSG2 antibodies were present in ARVC subjects regardless of whether an underlying mutation was identified, or which mutation was present. A disease-specific DSG2 epitope was identified. Conclusion: Anti-DSG2 antibodies are a sensitive and specific biomarker for ARVC. The development of autoimmunity as a result of target-related mutations is unique. Anti-DSG2 antibodies likely explain the cardiac inflammation that is frequently identified in ARVC and may represent a new therapeutic target.

Effect of Ondansetron on QT Interval in Patients Cared for in the PICU.

OBJECTIVES: There is no evidence regarding the effect of ondansetron on the QT interval in pediatric patients in the ICU. This study aimed to describe the effect of ondansetron on the corrected QT interval in patients cared for in the PICU. DESIGN: Retrospective cohort, consecutive enrollment study. SETTING: Single-center, tertiary-level, medical/surgical PICU. PATIENTS: All patients less than 8 years old who received ondansetron over an 11-month period were included. Exclusion criteria were atrial arrhythmia, bundle-branch block, known congenital long QT syndrome, and concomitant administration of proarrhythmic antiarrhythmic agents. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Overall, 210 doses of ondansetron were administered to 107 patients, with a mean age 10.5 ± 4.8 years; 49% were men. Corrected QT interval increased to 460-500 ms in 29% and to more than 500 ms in 11% of events of ondansetron administration. The mean baseline corrected QT interval even before ondansetron administration was higher for these groups (460-500 and > 500 ms; 457 ± 33 and 469 ± 45, respectively; p ≤ 0.05). In multivariate analysis, both groups were associated significantly with underlying electrolyte abnormalities (odds ratio, 2.2; 95% CI, 1.1-4.4 and odds ratio, 5.1; 95% CI, 1.8-15.7, respectively); the group with corrected QT interval more than 500 ms was also significantly associated with organ dysfunction (odds ratio, 3.2; 95% CI, 1.1-9.4). As the numbers of risk factors increased from only ondansetron to three additional QT aggravating factors (electrolyte abnormalities, administration of other QT-prolonging drugs, and organ dysfunction), the likelihood of being associated with corrected QT interval more than 500 ms increased. CONCLUSIONS: Prolonged QT interval is observed commonly in PICUs following the administration of ondansetron. Underlying risk factors, such as electrolyte abnormalities and organ dysfunction, seem to pose the highest risk of prolongation of QT interval in these patients. The awareness of prevalent risk factors for increased corrected QT interval may help identify patients at high risk for arrhythmias.

Concealed long QT syndrome and intractable partial epilepsy: a case report.

Herein, we describe a patient with concealed type 2 long QT syndrome with concomitant electroencephalogram-documented epilepsy. Although syncope in patients with long QT syndrome is common and often secondary to cerebral hypoxia after a protracted ventricular arrhythmia, this article demonstrates the importance of avoiding "tunnel vision" as patients with long QT syndrome could also have a primary seizure disorder. Identification of the etiology underlying seizurelike activity is paramount in instituting effective therapy. Furthermore, we theorize that abnormal KCHN2-encoded potassium channel repolarization in the brain could result in epilepsy and arrhythmias in long QT syndrome.