QT interval instability: An added piece for an incomplete jigsaw puzzle

Abstract

Risk stratification and prevention of sudden death may therefore be of value in certain selected groups. Heart failure represents the most common substrate for VT. Patients with reduced left ventricular ejection fraction (LVEF) are at significantly greater risk of SCD compared with those with preserved LVEF. The electrical instability caused by fibrosis and dilatation of the abnormal myocardial substrate is further triggered and exacerbated by sympathetic excitation in the presence of congestive heart failure (CHF). 3,4 Presently, the primary prevention of SCD relies on risk stratification based on LVEF and functional degree of CHF, followed by the practice of selective implantation of an implantable cardioverter-defibrillator (ICD) in patients with LVEF o35% and New York Heart Association functional class II–III CHF. Despite that several clinical trials have demonstrated clear survival benefits conferred by this strategy, 5,6 the greatest absolute number of SCD actually occurs in patients with preserved LVEF because of the much larger size of this population. 7 It is becoming apparent that additional variables other than reduced LVEF may influence the risk of SCD and that LVEF alone is insufficient in determining which patients are most likely to benefit from prophylactic ICD implantation. 8 A new risk stratification schema based on other noninvasive studies is clearly needed. In the past decades, several new parameters based on noninvasive electrophysiology studies have been proposed to predict VT in patients with cardiovascular diseases. The main rationale of these examinations is to evaluate the “electrical” factors such as abnormal background autonomic nervous activity or electrical instability of the myocardial substrate that play important roles in the generation of VT rather than the “mechanical” factors such as LVEF. Initially, these electrical parameters were designed mainly to investigate the “resting” electrical conditions without “perturbations,” for example, parameters based on standard 12-lead electrocardiogram (ECG) 9–11 or 24-hour Holter, 12 signalaveraged ECG, 13 and heart rate variability. 14 Later, other parameters based on “perturbed” conditions have been developed. These included baroreflex sensitivity, 15 heart rate recovery (HRR), 16 heart rate turbulence (HRT), 17 and T-wave alternans. 18 Although parameters based on perturbations of cardiac autonomic or electrical systems by changing blood pressure (baroreflex sensitivity), ventricular premature contraction (heart rate turbulence), or exercise (heart rate recovery and T-wave alternans) seem to have better predictive power than those measured in conditions without perturbations, these parameters either failed in some randomized trials or have low predictive value for SCD that preclude their application in clinical practice. 19,20 So far, no