Action potential dynamics explain arrhythmic vulnerability in human heart failure: a clinical and modeling study implicating abnormal calcium handling

Journal of the American College of Cardiology
Sanjiv M NarayanNatalia A Trayanova

Abstract

The purpose of this study was to determine whether abnormalities of calcium cycling explain ventricular action potential (AP) oscillations and cause electrocardiogram T-wave alternans (TWA). Mechanisms explaining why heart failure patients are at risk for malignant ventricular arrhythmias (ventricular tachycardia [VT]/ventricular fibrillation [VF]) are unclear. We studied whether oscillations in human ventricular AP explain TWA and predict VT/VF, and used computer modeling to suggest potential cellular mechanisms. We studied 53 patients with left ventricular ejection fraction 28 +/- 8% and 18 control subjects. Monophasic APs were recorded in the right ventricle (n = 62) and/or left ventricle (n = 9) at 109 beats/min. Alternans of AP amplitude, computed spectrally, had higher magnitude in study patients than in controls (p = 0.03), particularly in AP phase II (p = 0.02) rather than phase III (p = 0.10). The AP duration and activation restitution (n = 11 patients) were flat at 109 beats/min and did not explain TWA. In computer simulations, only reduced sarcoplasmic reticulum calcium uptake explained our results, causing calcium oscillations, AP amplitude alternans, and TWA that were all abolished by calcium clamping. On prospecti...Continue Reading

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Related Concepts

Nerve Impulses
Calcium
In Silico
Sarcoplasmic Reticulum
Stroke Volume
Systole
Ventricular Fibrillation
Nested Case-Control Studies
Sudden Cardiac Arrest
Tachycardia, Ventricular

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