Hypertrophic cardiomyopathy (HCM) in childhood is characterized by marked phenotypic heterogeneity and poses significant challenges in risk stratification for sudden cardiac death (SCD). We report the case of a 9.5-year-old girl in whom transthoracic echocardiography revealed progressive extreme interventricular septal hypertrophy (up to 33 mm; Z-score > +11), marked left atrial enlargement, reduced left ventricular cavity size, and significant left ventricular outflow tract obstruction. Although repeated ambulatory Holter monitoring did not reveal ventricular arrhythmias, the patient exhibited one episode of unexplained syncope at rest. These findings placed her in a high-risk category according to contemporary pediatric risk stratification approaches. Following insufficient response to medical therapy, surgical septal myectomy was performed. Given the persistent high-risk profile, an implantable cardioverter-defibrillator was implanted for primary prevention of sudden cardiac death. This case emphasizes the importance of individualized, multimodal risk stratification in guiding management decisions in pediatric HCM, even in the absence of documented malignant arrhythmias.

Catecholaminergic polymorphic ventricular tachycardia (CPVT) is an inherited arrhythmia caused by pathogenic variants in RYR2 that increase its diastolic Ca[2+] release. Current standard of care is insufficient to protect patients from ventricular tachycardia (VT) and sudden death. We identified RYR2 interaction with a subset of MYBPC3 in cardiomyocytes, and validated this interaction by immunostaining, proximity ligation assay, and co-immunoprecipitation. Adeno-associated virus serotype 9 (AAV9)-mediated MYBPC3 overexpression reduced VT in Ryr2[R176Q/+] mice, a model of CPVT. We identified a C-terminal fragment of MYBPC3, C6C10Δ, that is sufficient for RYR2 interaction and anti-arrhythmic activity. Recombinant C6C10Δ reduced the open probability of RYR2-R176Q channels in lipid bilayer single channel recordings, and virally delivered C6C10Δ reduced VT inducibility and duration in the CPVT mouse model and in human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) harboring several different CPVT-causing RYR2 variants. In wild-type mice, MyoAAV4E-C6C10Δ did not detectably affect cardiac morphology or systolic function. However, a proportion of MyoAAV4E-C6C10Δ-treated wild-type mice exhibited inducible VT, suggesting proarrhythmic potential that warrants further study. Together, these findings demonstrate that a subset of MYBPC3 interacts with RYR2, and that this interaction may be therapeutically exploited to develop CPVT gene therapy.

BACKGROUND Pulmonary embolism is associated with increased morbidity and mortality, yet the patient can sometimes look deceptively calm at the bedside. A normal blood pressure reading does not rule out a struggling right ventricle, and patients classified as intermediate-high-risk can deteriorate quickly. A mobile right-heart thrombus (clot-in-transit) adds another layer of urgency because embolization can be sudden and unpredictable. CASE REPORT A 45-year-old woman with a previous pulmonary embolism presented with abrupt dyspnea, tachycardia, and hypoxemia shortly after stopping apixaban. Bedside transthoracic echocardiography showed marked right ventricular dilation and a mobile right atrial thrombus consistent with clot-in-transit. Computed tomography pulmonary angiography confirmed bilateral segmental/subsegmental pulmonary embolism. Although she remained normotensive, biomarker positivity and a lactate rise suggested early hypoperfusion. After immediate anticoagulation with unfractionated heparin, the Pulmonary Embolism Response Team was activated, and, after multidisciplinary discussion, we decided to treat the patient with reduced-dose systemic alteplase (50 mg over 2 hours). The patient improved rapidly without bleeding complications and was discharged on long-term anticoagulation. She remained in excellent clinical condition at her 2-month follow-up. CONCLUSIONS This case demonstrates that in pulmonary embolism, stability is more than a blood pressure reading. The presence of right ventricular strain together with a clot-in-transit can justify immediate treatment escalation. Reduced-dose systemic thrombolysis can be a reasonable option in carefully selected patients, but decisions should remain individualized.

In patients with repaired tetralogy of Fallot (rTOF), right ventricular (RV) fibrosis has been associated with ventricular tachycardia, heart failure, and sudden cardiac death. Here, we aimed to identify links between diffuse myocardial fibrosis and regional mechanical dysfunction by cardiac magnetic resonance imaging (CMR) in rTOF. Clinical CMR was extended in 17 consecutive rTOF patients (median age 20 years, 4 females) to include biventricular native T1 (nT1) mapping as indicator of diffuse fibrosis, and tissue phase mapping (TPM) for quantification of biventricular segmental, directional systolic/diastolic myocardial velocities. Patients demonstrated smaller peak velocities than healthy volunteers in both ventricles (e.g. LV-base circumferential peak-systolic velocity: median [IQR] -0.9 [1.5] vs. -3.0 [1.2] cm/s, p < 0.001). RV peak velocities were reduced even in patients with normal RV ejection fraction (e.g. RV-mid long-axis peak-diastolic velocity: -3.3 [1.2] vs. -6.9 [1.8] cm/s, p = 0.001). Global LV nT1 was higher in patients versus controls (1029 [48] vs. 993 [28] ms, p = 0.013). Within the rTOF group, fibrosis in lateral LV correlated with shorter time-to-peak-velocity (TTP), whereas fibrosis in inferior RV correlated with longer TTP. Therefore, in rTOF TPM facilitates early diagnosis of impaired systolic and diastolic myocardial function while diffuse fibrosis has differential effects on RV and LV mechanics.

Objective The perioperative cardiac risk associated with non-cardiac surgery in patients with significant coronary artery stenosis has not been fully determined. This study aimed to assess cardiac events after non-cardiac surgery in patients with or without coronary artery stenosis (CAS) based on pre-operative coronary angiography. Methods This single-center, observational study retrospectively analyzed data from 809 patients without a history of percutaneous coronary intervention or coronary artery bypass grafting who underwent coronary angiography before non-cardiac surgery for risk assessment. After excluding 94 patients who underwent preoperative coronary revascularization, 715 (215 with CAS and 500 without CAS) were assessed. The occurrence of cardiac events, including cardiac death, non-fatal myocardial infarction, the requirement for urgent revascularization, worsening heart failure, worsening angina symptoms, and ventricular tachycardia/fibrillation within 30 days of surgery, was investigated. Results The mean age of the patients was 70.3±9.7 years, and 72.7% were men. Patients with CAS were more likely to be men and had diabetes mellitus and dyslipidemia compared to those without CAS. Regarding perioperative cardiac risk, 401 (56.1%) non-cardiac surgical procedures were categorized as having a high cardiac risk, 248 (34.7%) as intermediate, and 66 (9.2%) as low. Within 30 days of non-cardiac surgery, no significant difference was observed in the occurrence of cardiac events between the patients with and without CAS (1.9% vs. 1.4%, p=0.74). Conclusion The findings suggest that significant CAS is not necessarily associated with an increased perioperative risk of cardiac events.

Ventricular tachycardia (VT) is a major cause of morbidity and mortality in patients with ischemic cardiomyopathy. Prior randomized controlled trials comparing catheter ablation (CA) with antiarrhythmic drug (AAD) therapy have reported inconsistent findings. We conducted an updated meta-analysis to compare the efficacy and safety of CA versus AAD therapy in this population. Four randomized controlled trials involving 846 patients were included. The weighted mean age was 58.7 years, the weighted mean left ventricular ejection fraction was 33.5%, and 88% of participants were male. In the AAD group, amiodarone and sotalol were used in 60% and 40% of patients, respectively. CA significantly reduced the primary composite outcome compared with AAD therapy (risk ratio [RR] = 0.85, 95% confidence interval [CI]: 0.75-0.97, P = 0.01), mainly driven by a lower incidence of treated sustained VT below the implantable cardioverter-defibrillator detection limit (RR = 0.25, 95% CI: 0.15-0.43, P < 0.01). CA also significantly reduced treatment-related adverse events (RR = 0.49, 95% CI: 0.36-0.65, P < 0.01). No significant differences were observed in all-cause mortality, appropriate implantable cardioverter-defibrillator shocks, or VT storm. In patients with ischemic cardiomyopathy and VT, CA reduces arrhythmic events and treatment-related adverse events compared with AAD therapy, although a survival benefit remains unproven.