Abstract

Background: Significant right ventricular dysfunction with elevated central venous pressure is associated with poor survival in heart failure patients with reduced ejection fraction (HFrEF). Heart transplant is often the only option for this group of patients, as they are not candidates for left ventricular assist device therapy. Medical management of HFrEF involves lowering the systemic afterload with vasodilators. While this therapy is very effective in isolated left ventricular dysfunction, in patients with biventricular dysfunction and high venous pressure, vasodilation can lead to low organ perfusion pressure, resulting in organ dysfunction. Organ perfusion pressure is calculated as the difference between mean arterial pressure and central venous pressure. We hypothesized that combining intra-aortic balloon pump (IABP) counter-pulsation with vasodilator therapy might be a good clinical option for stabilizing these patients while awaiting a heart transplant. Methods: To understand the hemodynamics of vasodilator and IABP therapy in biventricular heart failure, we used a closed-loop multiscale model of the entire cardiovascular system, including a one-dimensional model of the arterial tree coupled with a lumped model of the heart and IABP counter-pulsation. In addition, a baroreceptor model was also used to capture the physiological changes secondary to ventricular dysfunction realistically. Results: Our mathematical model accurately captures the features of the aortic pressure waveform with IABP support (Figure 1) and the hemodynamic consequences of the onset of right ventricular dysfunction (Table 1). Biventricular dysfunction leads to lower cardiac output and organ perfusion pressure when compared with isolated left ventricular dysfunction. Vasodilation during biventricular dysfunction increases the cardiac output but reduces the organ perfusion pressure further. IABP counter-pulsation increases cardiac output along with higher mean arterial pressure and hence higher organ perfusion pressure. The best results are seen when vasodilators are used in conjunction with IABP, where a “sweet spot” of maximal increase in cardiac output with the best possible organ perfusion pressure is obtained, and this combined additive effect of IABP counter-pulsation and vasodilation is also reflected across the renal vasculature (Table 1). Conclusion: Vasodilation with high venous pressure can lead to low organ perfusion pressure and consequent organ dysfunction. Fine-tuning IABP counter-pulsation and vasodilator seems to confer a substantial hemodynamic benefit in this setting.Figure 1. Simulated aortic pressure waveform with IABP support

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