Abstract:

The modelling of the relationship between QT and RR intervals is an important issue for pharmaceuticalresearch on the way to new drugs. Pharmaceutical industries have to thoroughly investigate potential effects of their medicines on QT intervals since QT prolongation is considered as a marker of the proarrhythmia risk. As QT intervals depend on RR intervals there is an obvious interest in modelling the QT-RR relationship. Static formulas to correct QT for RR are well known, but a dynamic dependencyis mainly observed.Two models of dynamic QT-RR relationships are introduced to eliminate the heart rate dependent part out of the QT interval. These models are based on heart cell measurements and simulations and are validated by Holter ECG data.

Abstract:

Since the Dutch physiologist William Einthoven had established the electrocardiographin 1903 there has been a huge interest in ECG signals. ECG signalsare biosignals and give information on the healthy state of the patient's heart.Therefore it is used in the field of medicine and health science in cardiology.To investigate on heart diseases the QT-interval and its change is in special interest.Abnormalities like QT prolongation can cause the development of ventriculartachyarrhythmias such as Torsades de Points and ventricular fibrillationoften leading to sudden cardiac death. Drug induced QT prolongation of antiarrhythmicahas been known for many years, but in the last two decades even somenon cardiac drugs have been recognized to have an inuence on the QT-interval.As in the early 1990's an antihistamine drug was associated with Torsades dePoints and sudden cardiac death, the medical community, regulatory agenciesand pharmaceutical companies became more sensitive for drug induced QT prolongation.Since then lists of cardiac and even non cardiac drugs which seem tocause QT prolongation and increase the risk of sudden cardiac death have beenexposed. [Zar07] QT-intervals mainly change with the heart rate. To documentthe effect on QT-interval caused by a drug, QT-interval changes depending onheart rate changes have to be removed. There are many correction formulas publishedbut still the formula of Bazett is quasi-standard. But QT does not onlyreact instantaneously on changes of RR. A "memory" effect is actually observed.Four models are presented in this thesis, motivated by analysis of measured andsimulated data of action potential duration (APD) in heart cells at different basiccycle length (BCL).