Cardiac Restitution, Ion Channels, and Racehorses: A Naturally Occurring Model of Sudden Cardiac Death in Athletes

Sudden cardiac death is the second most common cause of athletic mortality in both elite human and equine athletes. Racehorses perform at extremely high exercise intensities with maximal heart rates and aerobic capacities exceeding those of human athletes. A predisposition to life-threatening arrhythmias unmasked by athletic activity, is suspected to underlie sudden cardiac death in both species and predicting risk is critical for the health and safety of athletes. Cardiac restitution ratio (CRR) is used as a measure of arrhythmia risk at rest in humans and represents the ability of cardiomyocytes to recover between successive action potentials. CRR can be calculated as QT/TQ on an electrocardiogram (ECG) and has never been investigated during high intensity exercise. The objectives are to characterize changes in the QT interval and CRR in normal racehorses to establish a risk threshold and to identify unique ion channels in the equine myocardium that may be involved in accommodation of the cardiac action potential to changes in heart rate. It is hypothesized that CRR will be highest during exercise periods when sudden cardiac death most frequently occurs, and that the horse will exhibit differences in myocardial ion channel expression. Over 3800 cardiac cycles obtained from ECGs of 42 racehorses were analysed using custom software to calculate RR interval, QT interval, and CRR. Instantaneous heart rate ranged from 26 beats per minute at rest to 293 during racing. Interquartile ranges (median) of QT interval and CRR during maximal effort were 176-198 ms (186 ms) and 2.1-3.3 (2.5), respectively. CRR was highest during race exercise; the first 30 seconds of cardiac deceleration following the race; and sporadically during non-race exercise, corresponding to periods when sudden death most frequently occurs. Preliminary multivariable regression analyses revealed numerous significant associations for both QT interval and CRR, including with exercise period, RR interval, racing gait, sex, and age. Apparently healthy horses during exercise routinely displayed CRRs exceeding the described arrhythmogenic threshold of 1, established in humans. Left ventricular free wall myocardium was obtained from horses of typical racing breeds. A combined proteomic approach using mass spectrometry and immunoblotting revealed presence of several ion channels not known or not known to be significant to the ventricular action potential in humans, including Kv1.5 and Kir6.2, and different primary isoforms of sodium and calcium channels. These findings identify unique aspects of myocardial electrophysiology in horses with potential implications for sudden cardiac death in human athletes. Funding graciously provided by Equine Guelph. This abstract was presented at the American Physiology Summit 2025 and is only available in HTML format. There is no downloadable file or PDF version. The Physiology editorial board was not involved in the peer review process.