Translational Research in Advanced Heart Failure
Amrut Ambardekar, MD, associate professor of cardiology, is leading translational research efforts around artificial heart pumps. By using tissue collected at the time of left ventricular assist device (LVAD), implantation and subsequently at cardiac transplantation, we can answer fundamental questions related to the cellular and molecular pathophysiology of heart failure and of the non-pulsatile blood flow that results from modern continuous-flow LVADs. Our goals for this work include reducing patient complications during LVAD therapy and promoting myocardial recovery to ultimately reduce the need for cardiac transplantation. Dr. Ambardekar also oversees the Division’s Human Cardiac Tissue Biobank, which has collected more than 1500 myocardial tissue samples for collaborative research projects.
Recent Research Highlights: Vascular Complications in Patients with Continuous-Flow LVADs
Changes within the vascular system are uniquely relevant to current LVAD patients as the pumps used today result in continuous-flow where the aortic valve does not open or close, and there is no palpable pulse. The long-term effects of this lack of pulsatility on the aorta and the possibility that non-pulsatile blood flow during LVAD support may result in a reduction in aortic compliance (essentially rapidly aging the aorta) had not been explored. In our seminal work in this area, we have helped established that non-pulsatile flow can rapidly increase aortic fibrosis with a subsequent increase in vascular stiffness that may contribute to adverse clinical outcomes in this patient population. We have subsequently confirmed that such vascular fibrosis is also present within the coronary arteries. Further work is underway to investigate the time course for these vascular changes and if modulation of flow by restoration of pulsatility can attenuate these vascular fibrotic changes.
Alterations in vascular properties that result from the unique physiology of blood flow from continuous-flow left ventricular assist devices (CF-LVADs) may contribute to the pathogenesis of many common CF-LVAD complications.
In heart failure patients with continuous-flow left ventricular assist device (CF-LVAD) support (right), coronary arteries showed evidence of remodeling and fibrosis compared to patients without a CF-LVAD (left).
A, Healthy patient: in normal physiology, the aorta acts a reservoir to store 50% of the stroke volume during systole. In diastole, elastic recoil pushes the stored volume of blood to the peripheral vasculature to maintain continuous perfusion of the periphery throughout the cardiac cycle. The aortic pressure waveform has pressure on the y axis and time on the x axis. The dicrotic notch (arrow) signals the end of systole and beginning of diastole. The slope of the aortic upslope reflects myocardial contractility. The slope of the diastolic waveform is a reflection of aortic compliance and the area under the diastolic portion is a measure of coronary blood flow. B, Patient with vascular disease: in conditions that increase arterial stiffness such as aging or atherosclerosis, the aorta is less compliant of blood
volume. This decrease in vessel elasticity results in decreased storage of stroke volume in the aorta, increased forward flow in systole, and increased systolic blood pressure (*). In diastole (arrow signifies the dicrotic notch), the slope of the pressure waveform shows a steeper decline as a result of this decrease in stored volume within the stiff vessel resulting in a lower diastolic pressure. The resultant wide pulse pressure is a commonly observed marker of vascular stiffness. C, Patient with a continuous-flow left ventricular assist device (CF-LVAD): the interactions between stroke volume and vessel compliance with CF-LVAD are challenging to assess,
in large part, because of the lack of a true systole and diastole with nonpulsatile flow. In addition, the flow from the CF-LVAD outflow graft in the ascending aorta may influence the fluid dynamics within more distal portions of the vessel. It is known that CF-LVAD therapy is associated with increased aortic stiffness and aortic dilation, but the systemic effects of these changes remain under active investigation.