Closed-loop drug infusion for control of heart-rate trajectory in pharmacological stress tests

The diagnosis of coronary artery disease (CAD) is an important task in the management of cardiology patients. Recently, the use of pharmacological stress testing has become available as an alternative to exercise stress testing (ETT). A new system (device-drug combination) was developed specifically for the diagnosis of coronary artery disease. The system uses a novel catecholamine, arbutamine, which is infused intravenously to increase heart rate (HR) and cardiac contractility in order to evoke signs of ischemia. The development of a closed-loop control algorithm for the delivery of this drug and a pharmacodynamic (PD) model representing the HR response to arbutamine infusions are presented. Model parameters are estimated from clinical data on normal volunteers and patients. Based on this mathematical model, a rule-based control algorithm is designed. The structure of the control algorithm is discussed and testing of the algorithm based on simulations and animal and human trials are summarized. Results from clinical trials shows that the algorithm controls the HR increase according to a selected trajectory. The automated delivery of the drug can provide the cardiologist with an efficient, effective, and safe method for administering a pharmacological stress test.