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Although β-blockers can be used to eliminate stress-induced ventricular arrhythmias in patients with catecholaminergic polymorphic ventricular tachycardia (CPVT), this treatment is unsuccessful in ∼25% of cases. Induced pluripotent stem cell-derived cardiomyocytes (iPSC-CMs) generated from these patients have potential for use in investigating the phenomenon, but it remains unknown whether they can recapitulate patient-specific drug responses to β-blockers. This study assessed whether the inadequacy of β-blocker therapy in an individual can be observed in vitro using patient-derived CPVT iPSC-CMs. An individual with CPVT harboring a novel mutation in the type 2 cardiac ryanodine receptor (RyR2) was identified whose persistent ventricular arrhythmias during β-blockade with nadolol were abolished during flecainide treatment. iPSC-CMs generated from this patient and two control individuals expressed comparable levels of excitation-contraction genes, but assessment of the sarcoplasmic reticulum Ca2+ leak and load relationship revealed intracellular Ca2+ homeostasis was altered in the CPVT iPSC-CMs. β-adrenergic stimulation potentiated spontaneous Ca2+ waves and unduly frequent, large and prolonged Ca2+ sparks in CPVT compared with control iPSC-CMs, validating the disease phenotype. Pursuant to the patient's in vivo responses, nadolol treatment during β-adrenergic stimulation achieved negligible reduction of Ca2+ wave frequency and failed to rescue Ca2+ spark defects in CPVT iPSC-CMs. In contrast, flecainide reduced both frequency and amplitude of Ca2+ waves and restored the frequency, width and duration of Ca2+ sparks to baseline levels. By recapitulating the improved response of an individual with CPVT to flecainide compared with β-blocker therapy in vitro, these data provide new evidence that iPSC-CMs can capture basic components of patient-specific drug responses.

BackgroundArrhythmias in children are often paroxysmal, complicating the ability to capture the abnormal rhythm on routine ECG during an outpatient visit. The Alivecor Kardia Mobile (KM) device is a wireless mobile health (mHealth) device that generates a single lead ECG tracing with a FDA-approved algorithm for detection of atrial fibrillation in adults.ObjectiveThe goal of this study is to assess the accuracy of interval measurements on KM tracings by directly comparing to standard 12-lead ECGs in pediatric patients.MethodsThis single center, prospective study enrolled pediatric outpatients, age <18 years presenting for cardiology clinic visits, into 3 groups based on age: 0–5 years, 6–10 years, and 11–18 years. Patients were excluded if 12-lead ECG was not ordered during the visit. Each enrolled subject underwent standard 12-lead ECG followed by 30-second KM tracing. ECG parameters were batch read by 2 blinded pediatric electrophysiologists.ResultsThirty patients were recruited with 10 patients/group. Structural heart disease and/or conduction abnormality was present in 20 patients (67%). Majority of tracings (27/30, 90%) were of diagnostic quality on first attempt. Overall, the ΔPR was 15.2±10.8ms (r = 0.86), ΔQRS was 9.6±8ms (r = 0.86), and ΔQTc was 15.6±12.7ms (r = 0.83). There were 9 patients with ΔQTc measurements >20ms with 4/9 (44%) having a conduction disorder and 2/9 (22%) having marked sinus arrhythmia. Bland-Altman method of agreement demonstrated strong agreement for QRSd and QTc. The AF algorithm reported 4/30 (13%) false positive "possible AF" diagnoses (rhythm over-read on KM demonstrated n = 3 marked sinus arrhythmia, n = 1 sinus rhythm with aberrated PACs) resulting in a specificity of 87%.ConclusionThe Alivecor Kardia device produces accurate single lead ECG tracings in both healthy children and children with cardiac disease or rhythm abnormalities across the pediatric spectrum. This mHealth application provides an accurate, non-invasive, real-time approach for ambulatory ECG monitoring in children and adolescents.

BackgroundBased on data from studies of atrial fibrillation ablations, optimal parameters for the TactiCath (TC; St. Jude Medical, Inc) force‐sensing ablation catheter are a contact force of 20 g and a force‐time integral of 400 g·s for the creation of transmural lesions. We aimed to evaluate TC in pediatric and congenital heart disease patients undergoing ablation.Methods and ResultsComprehensive chart and case reviews were performed from June 2015 to March 2016. Of the 102 patients undergoing electrophysiology study plus ablation, 58 (57%) underwent ablation initially with a force‐sensing catheter. Patients had an average age of 14 (2.4–23) years and weight of 58 (18–195) kg with 15 patients having abnormal cardiac anatomy. Electrophysiology diagnoses for the +TC group included 30 accessory pathway–mediated tachycardia, 24 atrioventricular nodal reentrant tachycardia, and 7 other. Baseline generator settings included a power of 20 W, temperature of 40°, and 6 cc/min flow during lesion creation with 11 patients (19%) having alterations to parameters. Seventeen patients (30%) converted to an alternate ablation source. A total of 516 lesions were performed using the TC with a median contact force of 6 g, force‐time integral of 149 g·s, and lesion size index of 3.3. Median‐term follow‐up demonstrated 5 (10%) recurrences with no acute or median‐term complications.ConclusionsTactiCath can be effectively employed in the treatment of pediatric patients with congenital heart disease with lower forces than previously described in the atrial fibrillation literature. Patients with atrioventricular nodal reentrant tachycardia or atrioventricular reciprocating tachycardia may not require transmural lesions and the TC may provide surrogate markers for success during slow pathway ablation.