No abstract

Background: Heart rate-corrected QT interval (QTc) prolongation, whether secondary to drugs, genetics including congenital long QT syndrome (LQTS), and/or systemic diseases including SARS-CoV-2-mediated COVID19, can predispose to ventricular arrhythmias and sudden cardiac death. Currently, QTc assessment and monitoring relies largely on 12-lead electrocardiography. As such, we sought to train and validate an artificial intelligence (AI)-enabled 12-lead electrocardiogram (ECG) algorithm to determine the QTc, and then prospectively test this algorithm on tracings acquired from a mobile ECG (mECG) device in a population enriched for repolarization abnormalities. Methods: Using over 1.6 million 12-lead ECGs from 538,200 patients, a deep neural network (DNN) was derived (n = 250,767 patients for training and n = 107,920 patients for testing) and validated (n = 179,513 patients) to predict the QTc using cardiologist over-read QTc values as the gold standard. The ability of this DNN to detect clinically-relevant QTc prolongation (e.g. QTc ≥ 500 ms) was then tested prospectively on 686 genetic heart disease (GHD) patients (50% with LQTS) with QTc values obtained from both a 12-lead ECG and a prototype mECG device equivalent to the commercially-available AliveCor KardiaMobile 6L. Results: In the validation sample, strong agreement was observed between human over-read and DNN-predicted QTc values (-1.76 ± 23.14 ms). Similarly, within the prospective, GHD-enriched dataset, the difference between DNN-predicted QTc values derived from mECG tracings and those annotated from 12-lead ECGs by a QT expert (-0.45 ± 24.73 ms) and a commercial core ECG laboratory [+10.52 ms ± 25.64 ms] was nominal. When applied to mECG tracings, the DNN's ability to detect a QTc value ≥ 500 ms yielded an area under the curve, sensitivity, and specificity of 0.97, 80.0%, and 94.4%, respectively. Conclusions: Using smartphone-enabled electrodes, an AI-DNN can predict accurately the QTc of a standard 12-lead ECG. QTc estimation from an AI-enabled mECG device may provide a cost-effective means of screening for both acquired and congenital LQTS in a variety of clinical settings where standard 12-lead electrocardiography is not accessible or cost-effective.

The properties of the inward rectifier K current (IK1) and the delayed rectifier K current (IK) were studied in single feline myocytes isolated from the right ventricle of normal cats and cats with experimentally induced right ventricular hypertrophy (RVH). IK1 demonstrated time-dependent decay during hyperpolarizations and showed inward rectification with a prominent negative-slope region between -30 and -10 mV. Both IK1 and IK was carried primarily by K ions. The activation of IK during depolarizations followed a monoexponential time course, whereas the deactivation of IK tail currents was either mono- or biexponential depending on the repolarization potential. IK showed marked rectification at positive potentials. A comparison of these currents in normal and hypertrophy myocytes revealed that in RVH the magnitude of IK1 is increased, whereas the magnitude of IK is decreased. IK showed steeper rectification, had slower activation, and had more rapid deactivation in RVH. These abnormalities of the IK may contribute to the prolongation of action potential duration, which characterizes pressure-overload cardiac hypertrophy.

The magnitude and kinetics of the slow inward calcium current (Isi) were compared in single right ventricular myocytes that were isolated from normal cats and cats with right ventricular hypertrophy. Peak inward current density was greater in hypertrophy than normal myocytes (-20.4 +/- 15.3 vs. -10.4 +/- 8.8 microA/cm2, P less than 0.05). When we blocked early outward currents with intracellular CsCl, however, the peak magnitude of Isi was shown to be similar in hypertrophy and normal myocytes (-16.4 +/- 11.2 vs. -12.7 +/- 3.0 microA/cm2, P = NS). The increased net inward current in hypertrophy was thus due to a decrease in Cs-sensitive early outward current rather than an increase in the magnitude of Isi. The fast component of inactivation of Isi was similar in hypertrophy and normal myocytes, but the slow component was delayed in hypertrophy (slow time constant; tau slow = 75.9 +/- 14.7 ms vs. tau slow = 60.6 +/- 4.9 ms, P less than 0.05). These abnormalities of Isi may contribute to the prolonged duration of the action potential and of contraction in hypertrophied myocardium, but a defect in excitation-contraction coupling distal to Isi appears to produce the diminished magnitude of contraction.

No abstract