Latino Studies at New York University

K. Melissa Hallow

Novartis Pharmaceuticals

December 6, 2011

The Cardiovascular-Renal Simulator (CVR-sim): a large scale mechanistic model for evaluating the effects of antihpertensive agents on chronic heart failure

Dr. K. Melissa Hallow is a scientist in the modeling and simulation group at Novartis Pharmaceuticals.  Her background is in vascular bioloy with special emphasis on the link between the local mechanical environment and inflammatory markers in athereosclerotic plaques.  While at Novartis, Dr. Hallow has been a leading part of a joint Novartis-Entelos team building a large-scale physiological model of blood pressure regulation, the Cardiovascular-Renal Simulation platform (CVR-Sim), including the focus on the Renin-Angiotensin-Aldosterone-System (RAAS).  The majority of the talk will be dedicated to how the heart failure module was scoped and developed.  In particular, the process involves constructing a model of normal cardiac vascular function with sufficient level of detail representation, in turn expanded to capture ventricular composition and geometry, resulting from myocyte hypertrophy and death, fibrosis and dilatation.  Finally, this basic physiology model gets transitioned to one of pathophysiology by linking it to known disease drivers, such as hypertension, coronary artery disease and diabetes.  The resulting model can capture normal function, as well as the hemodynamic changes observed in heart failure patients.  By adjusting various parameters (e.g. contractility), one can build in representation of heart failure patients with various degree of severity in their disease, consistent with observations in clinical trials under various therapeutic interventions.