Challenging Cardiac Electrophysiology

is now increasingly recognized by genetic screening. Association studies have identified numerous genes that are coupled to cardiac diseases, but the functional role of mutations in these genes is often not clear. The relations between the electrophysiological changes in patients with hereditary or chronic cardiac diseases is often far from clear. This calls for an integrated type of research, combining relevant models of these diseases with elec-trophysiological studies. Additionally, a remarkable discrepancy exists between the level of detail obtained in the molecular biological and functional levels of study in some areas in cardiac elec-trophysiology. Our understanding of cardiac repolarization may serve as an example in case. In recent years the understanding of the repolarization process has soared with a multitude of the molecular biological (genetic and proteomic) studies on mutated ion channels responsible for repolarization, linking (altered) structure of the channel with altered function (Nerbonne and Kass, 2005). The literature on the hereditary Long QT syndromes is a good example of this scientific approach (Schwartz et al., 2001). The functional experiments supporting the molecular biological studies often use expression systems of human ion channels in cultured, non-cardiac, cells (Bebarova et al., 2008). The extrapolation of these results to the organ or to the organism is difficult, because not enough detailed mechanistic information is available from the more inte-grative levels of research about the genesis of the (normal and abnormal) T-wave or its relation with the arrhythmias (Opthof et al., 2009). The morphology of the T-wave, already described by Einthoven (1895) has been attributed to the reverse transmural repolarization sequence in comparison with the endo-to epi-cardial activation sequence. This mechanism is generally accepted and has been presented in many textbooks (Bayes de Luna et al., 2006). However, the exclusive causal relation between the trans-mural gradient of repolarization and the T-wave is a matter of controversy, because mapping experiments in intact hearts have demonstrated that repolarization is almost The implantable automatic defibrillator offers protection to an increasing number of patients since its application to humans by Mirowski et al. (1980). We also have gained information about the role of familial predisposition to develop ventricular fibrillation following myocardial ischemia (Dekker et al., 2006). Although these developments have contributed to improved prevention, diagnosis, and treatment of cardiac arrhythmias in the setting of ischemia and infarction and similar advances have occurred in other fields in cardiac electrophysiology, sudden arrhyth-mic death is still one of the …