The inverse problem of electrocardiography or electrocardiographic imaging (ECGI) is a technique for reconstructing electrical information about cardiac surfaces from noninvasive or non-contact recordings. ECGI has been used to characterize atrial and ventricular arrhythmias. Although it is a technology with years of progress, its development to characterize atrial arrhythmias is challenging. Complications can arise when trying to describe the atrial mechanisms that lead to abnormal propagation patterns, premature or tachycardic beats, and reentrant arrhythmias. This review addresses the various ECGI methodologies, regularization methods, and post-processing techniques used in the atria, as well as the context in which they are used. The current advantages and limitations of ECGI in the fields of research and clinical diagnosis of atrial arrhythmias are outlined. In addition, areas where ECGI efforts should be concentrated to address the associated unsatisfied needs from the atrial perspective are discussed. Graphical abstract

Pulmonary vein isolation (PVI) is the most successful treatment for atrial fibrillation (AF) nowadays. However, not all AF patients benefit from PVI. In this study, we evaluate the use of ECGI to identify reentries and relate rotor density in the pulmonary vein (PV) area as an indicator of PVI outcome. Rotor maps were computed in a set of 29 AF patients using a new rotor detection algorithm. The relationship between the distribution of reentrant activity and the clinical outcome after PVI was studied. The number of rotors and proportion of PSs in different atrial regions were computed and compared retrospectively in two groups of patients: patients that remained in sinus rhythm 6 months after PVI and patients with arrhythmia recurrence. The total number of rotors obtained was higher in patients returning to arrhythmia after the ablation (4.31 ± 2.77 vs. 3.58 ± 2.67%, p = 0.018). However, a significantly higher concentration of PSs in the pulmonary veins was found in patients that remained in sinus rhythm (10.20 ± 12.40% vs. 5.19 ± 9.13%, p = 0.011) 6 months after PVI. The results obtained show a direct relationship between the expected AF mechanism and the electrophysiological parameters provided by ECGI, suggesting that this technology offers relevant information to predict the clinical outcome after PVI in AF patients.

Anthracyclines are widely used in the treatment of many solid cancers, but their efficacy is limited by cardiotoxicity. As the number of pediatric cancer survivors continues to rise, there has been a concomitant increase in people living with anthracycline-induced cardiotoxicity. Accordingly, there is an ongoing need for new models to better understand the pathophysiological mechanisms of anthracycline-induced cardiac damage. Here we generated induced pluripotent stem cells (iPSCs) from two pediatric oncology patients with acute cardiotoxicity induced by anthracyclines and differentiated them to ventricular cardiomyocytes (hiPSC-CMs). Comparative analysis of these cells (CTX hiPSC-CMs) and control hiPSC-CMs revealed that the former were significantly more sensitive to cell injury and death from the anthracycline doxorubicin (DOX), as measured by viability analysis, cleaved caspase 3 expression, oxidative stress, genomic and mitochondrial damage and sarcomeric disorganization. The expression of several mRNAs involved in structural integrity and inflammatory response were also differentially affected by DOX. Functionally, optical mapping analysis revealed higher arrythmia complexity after DOX treatment in CTX iPSC-CMs. Finally, using a panel of previously identified microRNAs associated with cardioprotection, we identified lower levels of miR-22-3p, miR-30b-5p, miR-90b-3p and miR-4732-3p in CTX iPSC-CMs under basal conditions. Our study provides valuable phenotype information for cellular models of cardiotoxicity and highlights the significance of using patient-derived cardiomyocytes for studying the associated pathogenic mechanisms.