Side effects on cardiac ion channels are one major reason for new drugs to fail during preclinical evaluation. Herein we propose a simple optogenetic screening tool measuring extracellular field potentials (FP) from paced cardiomyocytes to identify drug effects over the whole physiological heart range, which is essential given the rate-dependency of ion channel function and drug action. Human induced pluripotent stem cell-derived cardiomyocytes were transduced with an adeno-associated virus to express Channelrhodopsin2 and plated on micro-electrode arrays. Global pulsed illumination (470 nm, 1 ms, 0.9 mW/mm2) was applied at frequencies from 1 to 2.5 Hz, which evoked FP simultaneously in all cardiomyocytes. This synchronized activation allowed averaging of FP from all electrodes resulting in one robust FP signal for analysis. Field potential duration (FPD) was ~25% shorter at 2.5 Hz compared to 1 Hz. Inhibition of hERG channels prolonged FPD only at low heart rates whereas Ca2+ channel block shortened FPD at all heart rates. Optogenetic pacing also allowed analysis of the maximum downstroke velocity of the FP to detect drug effects on Na+ channel availability. In principle, the presented method is well scalable for high content cardiac toxicity screening or personalized medicine for inherited cardiac channelopathies.

An 87-year-old woman presenting with myocardial infarction and ST-segment elevation in the electrocardiogram suffered from pericardial effusion due to left ventricular rupture. After ruling out obstructive coronary artery disease and aortic dissection, she underwent cardiac surgery showing typical infarct-macerated myocardial tissue in situ. This case shows that even etiologically unclear and small-sized myocardial infarctions can cause life-threatening mechanical complications.

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An amendment to this paper has been published and can be accessed via a link at the top of the paper.

To the editor Sudden cardiasc death (SCD) is a relevant complication after myocardial infarction (MI) and in patients suffering from heart failure with reduced ejection fraction. 1 Current guidelines recommend an implantable cardioverter-defibrillator (ICD) implantation earliest 40 days after MI and 90 days after revascularization in patients with left ventricular ejection fraction (LVEF) < 35% on optimal guidelinedirected medical therapy. 2 The wearable cardioverter defibrillator (WCD) may be considered as a bridging to protect patients against SCD until decision for permanent ICD implantation. 3 In our recently published data, we investigated clinical outcome and adherence in a smaller cohort. 4 To analyze gender differences, we investigated in a multicenter−multinational setting (nine centers) a large patient cohort treated with WCD (n = 1596) Table 1.Data from a total of 1596 patients (332 females, 20.8% and 1264 males, 79.2%) regarding indication for wearing WCD, WCD shocks, adherence, and clinical outcome after termination of WCD use at mean follow-up of 20.6 ± 20.3 months were analyzed. Both