Optimization of Right and Left Ventricular Coupling During Mechanical Circulatory Support

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PROJECT SUMMARY Cardiogenic shock, a devastating outcome of decompensated heart disease, has both increased in incidence and maintained remarkably high mortality rates near 50%. Mechanical circulatory support is emerging with the unique ability to decouple cardiac supply and demand to sustain end-organ perfusion while reducing cardiac work. However, methods to guide device selection and titration are limited. One aspect of this which remains understudied is the importance of interactions between the left and right ventricles and their power over patient tolerance to device support. This is particularly critical as >40% of patients with left-sided support have been reported to experience right heart failure after device initiation, making this a major limitation to clinical utility. Thereby, this research employs a mechanistic approach to define the nature of right-left ventricular coupling in health and cardiogenic shock and its governance of mechanical circulatory support outcomes. We will employ a novel porcine model of graded left and right ventricular collapse to determine metrics critical to right and left heart adaptability individually, and those which contextualize the two to assess ventricular coupling. We will use this understanding to assess the biventricular response to two forms of clinical mechanical support. First, we will test a percutaneous left ventricular assist device, which employs a mechanism of continuously unloading the left ventricle to increase forward flow from the heart. The second technology will be veno-arterial extracorporeal membrane oxygenation support, which increases perfusion through venous withdrawal and retrograde return into the systemic circulation; this mechanism is particularly notable for unloading and reducing stress on the right heart and pulmonary circulation. Controlled stimulus provided by each technology will allow for assessment of the dynamic response according to ventricular coupling state. This project implements mechanistic analysis of the ability of each ventricle to respond to stress, as well as dynamic assessment (rather than classic static metrics) of ventricular-ventricular interactions (including serial interactions through the pulmonary circulation, parallel interactions through shared intracardiac structures, and synchronous interactions in time). In doing so, this work will provide insight into the governing factors over the response to mechanical support, allowing for improvements in device selection and titration, and ultimately improve outcomes from the devasting consequences of cardiogenic shock. I am excited to conduct this work with MIT Professor Elazer Edelman and to couple the research with a rigorous training plan which will allow me to grow as a scientist, communicator, and teacher. I am blessed to be at an institution and laboratory which provides all resources to complete this novel work and creates a research environment and training program that supports me in advancing towards independent translational research.