Predicting the hemodynamic response to mitral valve interventions with pressure-volume analysis

The proposed K23 development award will enable Dr. Michael Brener to become an independent investigator in the field of valvular heart disease (VHD). Dr Brener is an interventional cardiologist and plans to use this training to conduct research where invasive hemodynamics are acquired to better diagnose and manage individuals with VHD. A team of thought leaders with expertise mentoring early career investigators will guide Dr. Brener to develop his skillset in the field of research using cardiovascular imaging, deep learning for analysis of longitudinal, hemodynamic, and imaging data, and prospective trial design. Focused coursework, experiential learning, and mentored meetings will supplement conduct of the proposed research, which focuses on mitral regurgitation (MR). MR is the most common form of VHD and represents a significant public health concern. A minimally invasive technique called mitral transcatheter edge-to-edge repair (mTEER) was recently shown to reduce mortality and heart failure (HF) hospitalizations for patients with functional MR (FMR), which is a form of MR that arises as a byproduct of left ventricular (LV) dysfunction. However, patient selection for this procedure is challenging because the standard of care diagnostic studies fail to adequately capture the extent of LV dysfunction in the context of FMR. The proposed research uses a novel technique, traditionally employed in preclinical studies, called pressure-volume (PV) analysis to provide a more accurate representation of LV function. The specific aims of the proposed research are to (1) identify new echocardiographic measures of LV systolic function (LVSF) in individuals with severe FMR that are correlated with PV loop derived measures of LVSF, (2) characterize the association between baseline LVSF and changes in LV function immediately after mTEER using PV analysis, and (3) assess the relationship between immediate changes in LV function after mTEER and a sustained, longitudinal hemodynamic response as determined by an implantable device called a wireless pulmonary artery pressure sensor (wPAP-S). These aims will be accomplished within the framework of the randomized controlled CardioClip trial, where 60 individuals with FMR will undergo mTEER and be randomized to the usual post-procedural care vs. implantation of a wPAP-S. The data generated by the proposed research will provide the granular hemodynamic foundation needed to better understand LV function in FMR and elucidate the physiologic underpinnings for changes in patient- reported outcomes and clinical events after mTEER. These efforts will help Dr. Brener transition to research independence and provide much-needed evidence to change clinical practice by addressing critical knowledge gaps in VHD and help reduce VHD-associated mortality. Project Number: 1K23HL177311-01A1 | Fiscal Year: 2025 | NIH Institute/Center: National Heart Lung and Blood Institute (NHLBI) | Principal Investigator: Michael Brener | Institution: COLUMBIA UNIVERSITY HEALTH SCIENCES, NEW YORK, NY | Award Amount: $172,800 | Activity Code: K23 | Study Section: NHLBI Mentored Patient-Oriented Research Study Section[MPOR (MA)] View on NIH RePORTER: https://reporter.nih.gov/project-details/1K23HL17731101A1