System Design for Optimizing Drug Infusions Using Cardiovascular Space Mapping for Acute Heart Failure.

ABSTRACT

Acute heart failure is caused by various factors and requires multiple drug therapies to remedy underlying causes. Due to the complexity of pharmacologic effects of cardiovascular agents, few studies have theoretically addressed the multidrug optimization problem. This paper proposes a drug infusion system for acute heart failure that controls cardiovascular performance metrics (cardiac output, left atrial pressure, and mean arterial pressure) within desired ranges as dictated by the cardiovascular parameters (systemic vascular resistance, cardiac contractility, heart rate, and stressed blood volume). The key to our system design is modeling and controlling cardiovascular parameters to yield the desired cardiovascular metrics. A 'tailored drug infusion' technique controls parameters by solving the optimization problem in order to conquer the complexity of multi-dependencies and the different dosage limits among multiple drugs. A 'cardiovascular space mapping' technique identifies the desired parameters from the desired metrics by deriving the analytical solutions of the metrics as functions of the parameters. To facilitate clinical discussions, parameters were set to realistic values in 5,600 simulated patients. Our results showed not only that the optimized drug combinations and dosages controlled the cardiovascular metrics to within the desired ranges, but also that they mostly corresponded to the recommended clinical use guidelines. An additional value of our system is that it proactively predicts the limitations of the tailored drug therapy, which supports the clinical decision of pivoting to alternative treatment strategies such as mechanical circulatory support.