Electrophysiological mechanisms involved in the increased mortality of patients with cardiac insufficiency.

See page 1335 for the article to which this Editorial refers The study on the United Kingdom Heart failure Evaluation and Assessment of Risk Trial (UK– HEART) in this issue focuses on the relationship between QT interval, QT dispersion and mortality in patients with chronic heart failure. The paper thus focuses on dispersion of refractoriness as a main electrophysiological factor for sudden cardiac death in these patients . The study is important because much of our earlier knowledge in this field is based on retrospective and small studies, with all their limitations. One of these early publications demonstrated a strong correlation between prolonged QT, JT dispersion and sudden cardiac death. In the present study, the number of patients was sufficiently large for the statistics to be adequate. However, the number of events was small and the precise mode of death difficult, even if great efforts were made to ensure correct data. In patients with cardiac insufficiency, the ends of the T waves are often difficult to determine because of many factors of interference, among them treatment with digitalis, and there are reasons to suspect that results can vary from one investigator to another. Because of difficult T determination, QT dispersion may not help to obtain a picture of repolarization dispersion in the ventricles. This study [1] shows that heart rate corrected QT dispersion and maximum QT interval were significant univariate predictors of sudden cardiac death, but were not related to outcome in the multivariate analysis. QT dispersion not corrected for heart rate, which is the possible logical measure of ventricular dispersion, was not correlated to sudden cardiac death in the present study. At least one more prospective study is therefore needed to resolve this. Several lines of experimental and clinical evidence link malignant ventricular arrhythmias to increased dispersion of refractoriness and thus electrical heterogeneity of the heart. From a basic electrophysiological point of view, dispersion of refractoriness may be due to differences in action potential duration, differences in local activation times or a combination of both. Dispersion can be classified as adjacent (local) and maximal (the whole heart). Dispersion of repolarization has been described in detail in an earlier editorial in this journal. The end of the T wave corresponds largely with the end of the latest action potentials on the epicardial surface of the human heart. If action potentials appear late, due to prolongation or some other delaying factor, this may be a marker for large QT dispersion. This is apparent in the long QT time syndrome where large differences in action potential durations have been found. QTc as a marker for sudden cardiac death in patients with earlier myocardial infarction was recognised more than 20 years ago. Prolonged QTc and increased QT dispersion may not indicate the same electrophysiological phenomena. This was demonstrated in a recently published large prospective population study in which QTc was a marker of all-cause mortality while QT dispersion not corrected for heart rate was a predictor of cardiovascular death. The theory as to why QT dispersion is a marker of global dispersion is because the precordial leads pick up local electrical activity of the heart. The reproducibility of the method is, however, weak and it is not useful in individual patients with cardiac insufficiency, as demonstrated in the present paper. Mortality in chronic heart failure remains high, despite new drugs and new knowledge in the treatment of these patients. Angiotensinogen converting enzyme inhibitors prolong survival; however, they have until now not been shown to decrease sudden cardiac death and the prognosis still remains poor. Treatment with beta-blockers decreases mortality and the reduction seems to be mostly due to fewer sudden cardiac deaths pointing to different mechanisms of action in these two types of drug. This is well in agreement with experimental studies. It is well known that changes in potassium levels have a profound effect on cardiac electrophysiology and also on the risk of sudden cardiac death. Hypopotassaemia prolongs QTc, changes T waves and easily initiates polymorphic ventricular tachycardias. Hypopotassaemia, by influencing different potassium channels, causes an uneven prolongation of action potential duration, in addition to its effect on membrane potentials. In the present study, hypokalaemia was a significant independent risk marker of sudden cardiac death, indicating that correction of hypokalaemia is important in patients with cardiac insufficiency. The main causes of death in patients with cardiac insufficiency have been recognised as malignant ventricular arrhythmias, or pump failure. In patients with relatively good physical capacity classified as