An integrated mathematical cardiorenal model demonstrated that losartan produces a larger reduction in left ventricular mass than atenolol because heart rate lowering with beta blockers limits the reduction in peak systolic wall stress.
A novel integrated cardiorenal mathematical model mechanistically explains the clinically observed superiority of ARBs over beta-blockers in regressing left ventricular hypertrophy.
Cardiac and renal function are inextricably connected through both hemodynamic and neurohormonal mechanisms, and the interaction between these organ systems plays an important role in adaptive and pathophysiologic remodeling of the heart, as well as in the response to renally acting therapies. Insufficient understanding of the integrative function or dysfunction of these physiological systems has led to many examples of unexpected or incompletely understood clinical trial results. Mathematical models of heart and kidney physiology have long been used to better understand the function of these organs, but an integrated model of renal function and cardiac function and cardiac remodeling has not yet been published. Here we describe an integrated cardiorenal model that couples existing cardiac and renal models, and expands them to simulate cardiac remodeling in response to pressure and volume overload, as well as hypertrophy regression in response to angiotensin receptor blockers and beta-blockers. The model is able to reproduce different patterns of hypertrophy in response to pressure and volume overload. We show that increases in myocyte diameter are adaptive in pressure overload not only because it normalizes wall shear stress, as others have shown before, but also because it limits excess volume accumulation and further elevation of cardiac stresses by maintaining cardiac output and renal sodium and water balance. The model also reproduces the clinically observed larger LV mass reduction with angiotensin receptor blockers than with beta blockers. We further provide a mechanistic explanation for this difference by showing that heart rate lowering with beta blockers limits the reduction in peak systolic wall stress (a key signal for myocyte hypertrophy) relative to ARBs.
Hallow et al. (2021) studied Left ventricular hypertrophy. Losartan (simulated) vs. Atenolol (simulated) was evaluated on Left ventricular mass reduction. An integrated mathematical cardiorenal model demonstrated that losartan produces a larger reduction in left ventricular mass than atenolol because heart rate lowering with beta blockers limits the reduction in peak systolic wall stress.