Andrew D. Krahn

Background and Aims: Frequent premature ventricular complexes (PVCs) are often observed in patients undergoing ablation of atrial fibrillation (AF). However, the relationship between AF ablation and PVCs is uncertain. The purpose of this study was to examine the prevalence of frequent PVCs before and after catheter ablation of AF. Methods: This was a retrospective cohort study of patients undergoing ablation of AF at two tertiary centers. All patients undergoing initial or repeat ablation of AF were eligible. Patients were followed in AF clinics before and after ablation with routine ambulatory ECG monitoring. Results: The cohort consisted of 421 patients (mean 63 years, 33% female, 57% paroxysmal). At baseline, 18.4% and 4.7% had ≥ 1% and ≥ 5% PVCs respectively. In the 179 days post‐ablation, 9.0% developed new onset ≥ 1% PVCs, whereas 10.9% of patients had regression from ≥ 1% to < 1% PVCs. In the total follow up period of 2 years, there was a significant increase in the proportion of patients with ≥ 1% PVCs. Multivariable modeling revealed baseline PVC burden and hypertension as the only predictors of an increasing PVC burden in the post‐ablation period. Conclusion: Frequent PVCs are highly prevalent among patients undergoing AF ablation. However, there was no signal of an increase in frequent PVCs in the immediate post‐ablation period.

Background Percutaneous coronary intervention (PCI) for acute coronary syndrome (ACS) is central to modern cardiac care, yet the factors determining how many vessels are treated during a procedure (‘PCI Extensiveness’) remain poorly understood, particularly in fee-for-service systems that reward more extensive treatment. This study aimed to evaluate the association between various factors and PCI Extensiveness. Methods We conducted a multicentre retrospective study using provincial fee-for-service billing data, which pays incremental fees per vessel treated from all adult cardiac catheterisation laboratories in British Columbia, Canada (population 5.5 million). We included 72 390 cath lab encounters for presumed ST-Elevation Myocardial Infarction (STEMI) or Non-ST Elevation ACS (NSTE-ACS) between 2013 and 2020 who underwent angiogram ± PCI. Patient-specific factors (age, comorbidities, prior myocardial infarction, prior coronary interventions, ACS type and angiographic findings) were incorporated into a non-parametric machine-learning model to estimate the number of vessels treated based on case mix. Results Interventionalists varied widely in mean vessels treated per case (0.455–3.19), with remarkable internal consistency per operator across STEMI and NSTE-ACS cases (R=0.956; 95% CI 0.904 to 0.981; pConclusions In contemporary ACS care, who performs the procedure appears to be associated with how extensively a patient is treated. In a system that financially rewards more extensive treatment, this unexplained operator-level variation raises the hypothesis that compensation structures may shape treatment intensity independent of clinical need.

The promise of precision therapeutics in genetic cardiomyopathies relies on linking specific therapies to variant mechanisms. Missense variants in the cardiac splice regulator RBM20 cause a highly penetrant and arrhythmogenic dilated cardiomyopathy. Disease-causing variants in RBM20’s arginine-serine rich (RS) domain act via formation of toxic gain of function cytoplasmic granules, but this is not true for a small number of clinically adjudicated pathogenic variants in its glutamate(E)-rich domain. To better define the effects of E-rich domain variants, we developed a scalable screen based on induced pluripotent stem cell (iPSC) cardiomyocyte differentiation that identified several additional damaging variants. Several of these reduced RBM20 protein abundance and stability. We therefore hypothesized that, unlike RS domain variants, these E-rich variants might be rescued by RBM20 overexpression. To test this hypothesis, we generated induced pluripotent stem cells (iPSCs) from a patient with a pathogenic E-rich domain variant (p.E913K), and confirmed reduced RBM20 protein expression in these RBM20 ^+/p.E913K cells after differentiation to iPSC-derived cardiomyocytes (iPSC-CM, vs. engineered isogenic RBM20 ^+/+ ). These iPSC-CMs also displayed aberrant transcriptional splicing, reduced contractility, increased calcium-induced calcium release, and nuclear localization of RBM20 protein, often with more than the two expected RBM20- centric splice factories. AAV-based overexpression of RBM20 reversed some, but not all of the mis-splicing events identified in RBM20 ^+/p.E913K iPSC-CMs, and did not improve their abnormal contractility, calcium handling or supernumerary RBM20 nuclear granules. In summary, our data indicate that pathogenic E-rich domain variants reduce RBM20 protein abundance, but that their mechanism is unlikely to be explained by haploinsufficiency alone.

Background Accurate assessment of the QT interval is challenging in the presence of QRS prolongation, such as during ventricular pacing or bundle branch block. Current correction methods are heterogeneous and lack consensus. To evaluate the relationship between QRS duration and QT interval during ventricular pacing and to develop a practical correction method for QT assessment. Methods In this prospective single-centre study, 94 patients undergoing electrophysiology study for supraventricular tachycardia were included. Standardised pacing was performed at the same cycle length from the right ventricular (RV) apex, high output and low output pacing from His catheter, and coronary sinus (reference). QRS and QT intervals were measured from 12-lead ECGs. Changes in QT (QT) and QRS duration (QRS) were analysed using linear regression and mixed-effects modelling. QT correction formulas of the form QT corrected = QT N x QRS were evaluated using Bland-Altman analysis across multiple coefficients. Results A significant positive correlation between QRS and QT was observed across all pacing sites (r = 0.52-0.74, p < 0.001). In mixed-effects modelling, QRS was a strong independent predictor of QT (0.59, p < 0.001), with no significant interaction between pacing site and QRS, supporting a consistent relationship across pacing locations. Bland-Altman analysis demonstrated that correction coefficients of 0.65-0.70 minimised systematic bias compared with lower coefficients, with similar precision across models (SD 16 ms) and no evidence of proportional bias. A coefficient of 0.65 provided the most balanced performance between bias and variability. Conclusion QT prolongation during ventricular pacing is primarily driven by QRS widening and follows a consistent linear relationship across pacing sites. A simple correction using QT corrected = QT 0.65 x (QRS 100 ms) provides a practical and accurate method for QT assessment, with potential clinical applicability in patients with conduction abnormalities or ventricular pacing.

BACKGROUND: Early repolarization syndrome (ERS) is diagnosed in survivors of unexplained cardiac arrest (UCA) who exhibit a distinct ECG pattern of early repolarization (ER), defined as J-point elevation ≥0.1 mV in ≥2 contiguous inferolateral leads. UCA survivors without ER or another identifiable cause are classified as idiopathic ventricular fibrillation (IVF). This study evaluated long-term outcomes in ERS compared with IVF. METHODS: This retrospective cohort study analyzed patients from the CASPER (Cardiac Arrest Survivors with Preserved Ejection Fraction Registry) who survived UCA and had structurally normal hearts with an Implantable Cardioverter Defibrillator. Of 709 patients, 186 with explanatory diagnoses and no ER pattern were excluded. The remaining 523 were categorized as ERS (n=48), IVF (n=463), or UCA with ER plus an additional diagnosis (Dx+ER, n=12). Patients were followed for the primary outcome of appropriate Implantable Cardioverter Defibrillator therapy, and logistic regression identified predictors of arrhythmia recurrence. RESULTS: Corrected QT interval intervals were significantly shorter in ERS than in IVF (412±25 ms versus 431±41 ms; P P =0.09), with incidence rates of 3.0 and 1.5 per 100 person-years, respectively. Four deaths occurred (0.8%), with no significant difference between groups ( P =0.39). In Dx+ER, appropriate Implantable Cardioverter Defibrillator therapies occurred in 42% of patients (incidence rate, 4.5 per 100 person-years). Arrhythmia-free survival was lower in ERS than in IVF ( P =0.03). After adjusting for age, sex, and ethnicity, ER was an independent predictor of arrhythmia recurrence (odds ratio, 2.59 [95% CI, 1.33–4.85]; P =0.004). CONCLUSIONS: ERS is associated with shorter corrected QT interval intervals and reduced arrhythmia-free survival compared with IVF, with an incidence rate of 3.0 per 100 person-years. These findings underscore the importance of careful ECG review in patients with apparent UCA, to detect ER and undertake individualized risk assessment in affected individuals.

Diastolic heart failure (HF) in primary cardiomyopathy is under-recognized and often diagnosed late, particularly in children. While recent studies have advanced understanding of HF with preserved ejection fraction in older adults, the prevalence, outcomes and molecular drivers of diastolic HF in pediatric and young adult cardiomyopathy remain poorly defined, where disease is typically driven by primary myocardial disease rather than acquired co-morbidities. The Canadian Cardiomyopathy Collaborative (C3) was assembled to leverage three of Canada’s leading pediatric and adult cardiomyopathy biobank registries. Its flagship initiative, Artificial Intelligence to Model Diastolic Heart Failure (AID-HF), aims to integrate deep phenotyping - including comprehensive diastolic function assessment - with genomics, lipidomics and proteomics and apply machine learning to identify biological and clinical signatures that drive cardiac function and outcomes in cardiomyopathy. Harmonized phenotyping and multiomics protocols across registries will create a uniquely integrated national data resource and enable the goals of AID-HF i.e., earlier diagnosis and new therapeutic targets for diastolic HF in cardiomyopathy.