Research and Publications

The Heart Failure and Transplantation Lab conducts translational science and clinical outcomes research on heart failure and related conditions. We have several ongoing research projects, and we publish our findings in numerous research journals.

Project 1: Metabolic reprogramming of donor hearts improves function

Harmful metabolic processes are well underway during cold preservation of donor hearts. We discovered a method to increase the expression of beneficial enzymes that help produce anti-inflammatory metabolites. This method helps lower oxidative stress and myocardial injury, which results in better cardiac function after transplant. Future strategies to reduce primary graft dysfunction could involve precise modulation of these cardiac metabolic pathways.

Related publications

• Metabolic reprogramming by immune-responsive gene 1 up-regulation improves donor heart preservation and function. Science Translational Medicine, 2023. 
• The secret life of human donor hearts: An examination of transcriptomic events during cold storage. Circulation: Heart Failure, 2020. 
• Commentary: The next chapter in donor heart preservation: Modulation of preservation biology by targeted molecular therapies. JTCVS Techniques, 2021. 

Project 2: Cold preservation induces changes in the physical attributes of molecular interactions in donor hearts

Hypothermic preservation is often seen as pressing the pause button on molecular processes in donor organs, with transplantation then reanimating the organ where it left off. Research from our group sheds light on how the cold preservation process itself hinders a range of molecular interactions. These mechanisms contribute to impaired donor heart function after transplant.

Related video

Watch this video showing phase separation of molecules into condensates with fluorescence recovery after photobleaching.

Project 3: Valve diseases affect LVAD outcomes

Valve diseases such as aortic and mitral valve regurgitation can influence the short-term and long-term outcomes of left ventricular assist device (LVAD) therapy. The presence of significant valve regurgitation can reduce the benefits of mechanical circulatory support and harm right heart function. Our team generates new knowledge about the interplay between valve function and circulatory support with LVADs. This helps us better manage ventricular assist device therapy.

Related publications

• Right ventricular function and residual mitral regurgitation after left ventricular assist device implantation determines the incidence of right heart failure. The Journal of Thoracic and Cardiovascular Surgery, 2020.
• Aortic valve repair versus replacement associated with durable left ventricular assist devices. The Annals of Thoracic Surgery, 2020.
• Left ventricular assist device implantation in patients with preoperative severe mitral regurgitation. ASAIO Journal, 2021.
• Cluster analysis of preoperative echocardiographic findings and outcomes following left ventricular device implantation. The Journal of Thoracic and Cardiovascular Surgery, 2019.
• Fate of preoperative moderate mitral regurgitation following left ventricular assist device implantation. Journal of Cardiac Surgery, 2021.

Project 4: Precision health approach predicts outcomes in heart failure

Our biobank houses hundreds of myocardial and serum samples from both people with heart failure and with regular heart function. This biobank has enabled us to perform omics-guided molecular phenotyping in end-stage heart failure. Our analysis revealed specific molecular signatures that can help predict outcomes from LVADs and other treatment. Mitral regurgitation resolution, for example, is predicted by expression of a specific pre-LVAD myocardial transcriptome.

Related publications

• Mitral regurgitation severity at left ventricular assist device implantation is associated with distinct myocardial transcriptomic signatures. The Journal of Thoracic and Cardiovascular Surgery, 2023.

Project 5: Big data analysis of multi-institutional clinical registries

We're using databases to discover answers for important management issues in heart failure. Data on tens of thousands of people in national and international registries allow us to harness machine learning and other advanced statistical techniques to address knowledge gaps in conditions related to heart failure. Our lab conducts detailed data analyses, and we also work closely with statisticians to gain additional insights.

Related publications

• Impact of donor blood type on outcomes after prolonged allograft ischemic times. The Journal of Thoracic and Cardiovascular Surgery, 2022.
• Determining optimal donor heart ischemic times in adult cardiac transplantation. Journal of Cardiac Surgery, 2022.
• Histidine-tryptophan-ketoglutarate solution for donor heart preservation is safe for transplantation. The Annals of Thoracic Surgery, 2020.
• Risk factors for heart transplant survival with greater than 5 h of donor heart ischemic time. Journal of Cardiac Surgery, 2021.

Current funding

Project: Targeting Mineralocorticoid Receptor Condensates to Optimize Donor Heart Preservation. This project investigates the role of phase separation of steroid receptors in determining organ preservation quality.
Principal investigator: Paul C. Tang, M.D., Ph.D.
Award: R01 (HL166140); 12/1/2022-11/30/2026

Project: Targeting Immune-Responsive Gene 1 (Irg1) and Itaconate for Cardioprotection of the Donor Hearts for Transplantation. This project uses metabolic reprogramming of donor hearts to improve cardiac performance and ischemic tolerance.
Principal investigator: Paul C. Tang, M.D., Ph.D.
Award: R01 (HL164416); 7/1/2022 -6/30/2027