Fig. 1: Focal, automatic EAs can be effectively suppressed with pharmacotherapy.
a, Study timeline for phase 1 large-animal experiments in which 19 swine were randomized to four treatment groups (vehicle, vehicle + AA, PSC-CM, PSC-CM + AA) following percutaneously induced MI. A further two animals underwent sham infarction and vehicle injection. BD, twice a day; EPS, electrophysiological study. b, Representative CMR reconstruction (created with ADAS 3D) merged with an epicardial voltage map, used to choose and annotate border and infarct zone injection sites (black circles). BZ, border zone; col, color; img, image; IZ, infarct zone; RZ, remote zone; Uni, unipolar voltage. c, Plot depicting the percentage of time per day that each cell (red), cell and drug (blue) or vehicle (pink) recipient spent in ventricular arrhythmia over the course of the study protocol. d, Representative endocardial activation map during EA localizing arrhythmia origin to focal sites of cell injections (white, early activation; purple, late activation; star, site of earliest activation). e, Representative EA persisting through burst pacing, suggesting an automatic mechanism rather than a re-entrant mechanism. f, Dose-dependent suppression of PSC-CM contraction rate using amiodarone (dark purple) and ivabradine (light purple) in vitro (drug concentrations of 0–100 µM, n = 3 biologically independent experiments for each group, presented as mean ± s.e.m.). g, Telemetry strip from a representative cell recipient exhibiting a run of EA with spontaneous onset and offset. h, Telemetry strip from representative cell and anti-arrhythmic recipients showing a predominantly sinus rhythm with occasional ventricular ectopic beats. i–k, Arrhythmia parameters from day 0 to day 28 for each subject, grouped by treatment allocation (vehicle, n = 5; vehicle + AA, n = 4; PSC-CM, n = 5; PSC-CM + AA, n = 5; biologically independent animals; data are presented as mean ± s.e.m.). Significant reduction in arrhythmia burden (i) (**P = 0.008, Mann–Whitney test, two-tailed), number of days with arrhythmia (j) (***P = 0.0002, unpaired t-test, degrees of freedom (df) = 8, two-tailed) and peak arrhythmia heart rate (k) (**P = 0.002, unpaired t-test, df = 8, two-tailed) in cell recipients treated with anti-arrhythmics.
