Understanding the Efficacy of T-TEER in Models of Primary Tricuspid Regurgitation

Tricuspid valve regurgitation (TR) is a common valve disease that, if severe, leads to high morbidity and mortality. Until recently, many patients, even those with severe TR, remained untreated due to high operative risks. This undertreatment has been declared a “public health crisis.” The introduction of transcatheter technologies for tricuspid valve repair has reduced operative risks and offers the potential to overcome this crisis. Among them, transcatheter tricuspid edge-to-edge repair (T-TEER) has taken the lead, with many centers performing it routinely. Notably, most guidelines recommend T-TEER only for patients with secondary TR. That is, TR that is caused by other primary diseases. However, similar to other transcatheter technologies, increased confidence in the technology is slowly expanding the eligible patient populations. For example, a recent explorative study has tested the feasibility of T-TEER in patients with primary TR due to defective leaflets, including prolapsed and flail tricuspid valves. Being an explorative clinical study, efficacy-critical parameters could not be isolated and studied in a controlled setting. Without such basic scientific experiments, much remains to be understood and tested before recommending T-TEER to this increased patient population. The objective of this predoctoral fellowship application is to test the hypothesis that successful T-TEER in models of primary TR requires a defect-specific choice of procedural parameters. Therein, I explore defect type, size, and location and adjust clip location, size, and number. Confidently exploring this large parameter space is not feasible using in vitro experimentation in explanted hearts alone. To this end, I will combine experiments in porcine and human hearts and high-fidelity in silico computer simulations. I will first conduct in vitro T-TEER experiments in hearts with induced primary TR. I will use these experimental data to build and validate a baseline set of computational tricuspid valve models. Finally, from this baseline set I will produce an additional 100 “synthetic” (i.e., computer- generated) tricuspid valve models. In these models, I will conduct virtual T-TEER procedures. This approach allows testing hundreds of real and “synthetic” valve anatomies, pathologies, and procedures. Thereby, I can explore many more parameter combinations than would be possible with in vitro experiments alone. My aims are twofold: 1) experimentally test T-TEER success in prolapsed and flail tricuspid valves, 2) build, validate, and use simulations to test T-TEER success in valves with primary TR. At the conclusion of this project, I will have tested whether the efficacy of T-TEER for patients with primary TR requires defect-specific procedural parameters. Furthermore, my study will address limitations of current clinical studies, which have left critical scientific questions unanswered. My scientific findings will contribute to the current literature and inform future guidelines for T-TEER treatment selection. Project Number: 1F31HL178280-01A1 | Fiscal Year: 2025 | NIH Institute/Center: National Heart Lung and Blood Institute (NHLBI) | Principal Investigator: Collin Haese | Institution: UNIVERSITY OF TEXAS AT AUSTIN, AUSTIN, TX | Award Amount: $41,266 | Activity Code: F31 | Study Section: Special Emphasis Panel[ZRG1 F10A-R (20)] View on NIH RePORTER: https://reporter.nih.gov/project-details/1F31HL17828001A1