Preclinical data have confirmed that human pluripotent stem cell-derived cardiomyocytes (PSC-CMs) can remuscularize the injured or diseased heart, with several clinical trials now in planning or recruitment stages. However, because ventricular arrhythmias represent a complication following engraftment of intramyocardially injected PSC-CMs, it is necessary to provide treatment strategies to control or prevent engraftment arrhythmias (EAs). Here, we show in a porcine model of myocardial infarction and PSC-CM transplantation that EAs are mechanistically linked to cellular heterogeneity in the input PSC-CM and resultant graft. Specifically, we identify atrial and pacemaker-like cardiomyocytes as culprit arrhythmogenic subpopulations. Two unique surface marker signatures, signal regulatory protein α (SIRPA)⁺CD90⁻CD200⁺ and SIRPA⁺CD90⁻CD200⁻, identify arrhythmogenic and non-arrhythmogenic cardiomyocytes, respectively. Our data suggest that modifications to current PSC-CM-production and/or PSC-CM-selection protocols could potentially prevent EAs. We further show that pharmacologic and interventional anti-arrhythmic strategies can control and potentially abolish these arrhythmias.

Background: Ventricular tachycardia (VT) storm is associated with significantly increased morbidity, mortality, and exponential healthcare utilization. Although catheter ablation (CA) may be curative, there are limited data directly comparing outcomes of early CA with initial medical therapy. Methods: We compared outcomes of patients presenting with VT storm treated with initial CA versus those treated with initial medical therapy during their first storm presentation in an observational study. Retrospective data from the host institution from January 2014 to April 2020 of 129 patients with their first VT storm presentation were analyzed (58 underwent initial CA, 71 underwent treatment with initial medical therapy). Outcomes were compared in follow-up. Results: Median time to initial CA was 6 days. Over a median follow-up of 702 days, patients who underwent initial CA compared with those treated with initial medical therapy had significantly less: (i) VA recurrence (43% versus 92%; P =0.002); (ii) VT storm recurrence (28% versus 73%; P <0.001); (iii) composite end point of death, heart transplant, VT storm recurrence, and VT-related hospitalization (47% versus 89%; P =0.002); (iv) iatrogenic complications (at 12 months: 17% versus 45%; P <0.001); (v) cardiovascular-related hospitalizations (50% versus 89%; P =0.01); (vi) total number of hospitalizations (median 1 versus 4; P <0.001); and (vi) cumulative days in hospital (median 0.5 versus 18; P <0.001). There were no intraprocedural deaths in patients treated with early CA. Conclusion: In an observational setting in which patients presenting with storm, early CA appears superior to initial medical therapy in terms of VT recurrence, storm recurrence, iatrogenic complications, cardiovascular hospitalizations, and cumulative days in hospital in follow-up.

Intracardiac echocardiography (ICE) is increasingly used to facilitate catheter ablation of ventricular arrhythmias (VA). It allows intraprocedural recognition of myocardial substrate, optimization of catheter-tissue contact, identification of anatomical barriers to ablation, and early recognition of complications. In the era where the 3-dimensionality of substrate for VA is increasingly recognized, ICE is invaluable in identifying scar topography in the endocardial, midmyocardial, and epicardial layers. ICE assists in identifying endocavitary structures that are a common source of VA in idiopathic and structural heart disease. Furthermore, as substrate imaging of the right ventricle has not been optimized with other imaging modalities, ICE offers a unique opportunity to visualize substrate in this chamber. Real-time substrate identification can be particularly useful where there are contraindications to use of other imaging modalities or the images are obscured by artefact in the presence of cardiac device leads. In this review we provide a step-by-step guide in the techniques used to image ventricular arrhythmia substrate with ICE. We also discuss the benefits and limitations of this technique in comparison to other imaging modalities.