Steven Goldman

Steven Goldman

Professor, BIO5 Institute
Professor, Medicine - (Research Scholar Track)
Research Scientist
Primary Department
Department Affiliations
Contact
(520) 626-2939

Work Summary

Work Summary
Our lab has a new treatment for heart failure. We have a biodegradable graft seeded with adult human cells that we put on the surface of the heart. The potential is to regenerate new heart muscle

Research Interest

Research Interest
Research in my laboratory over the last 30 years has focused on chronic heart failure (CHF), its pathophysiology and the development of new treatments for CHF. We have developed clinically relevant animal models of heart failure that allow us to explore the translational potential of new treatments. Our work initially examined the role of afterload reduction and neurohormal blockade. More recently we have been working with cell-based therapy for CHF using bioengineered scaffolds to prevent left ventricular (LV) remodeling and restore function in the damaged heart. Our most effective scaffold is a biodegradable vicryl mesh with embedded viable neonatal fibroblasts that secrete angiogenic growth factors. This patch increases myocardial blood flow, improves LV systolic function, and reverses LV remodeling if implanted at the time of an acute myocardial infarction. In CHF, this patch still improves myocardial blood flow but does not improve LV function or reverse LV remodeling. Thus, we have an effective delivery system for cell based therapy for CHF that increases myocardial blood flow and provides structural support for new cell growth. We are now focusing on seeding this patch with human inducible pluripotent stem cells in the cardiac lineage, the seeded cardiomyocytes align, communicate, contract in a spontaneous and rhythmic fashion. When implanted in rats with CHF, they improve LV function. We are exploring this patch seeded with human inducible cardiac pluripotent stem cells to treat patients with CHF. Keywords: induced pluripotent stem cells

Publications

Desai, A., Choi, B., Dudley, S. C., Kittles, R., Machado, R. F., Garcia, J. G., Hillery, C., Indik, J. H., Goldman, S., Juneman, E. B., Groth, J., Nair, N., Rutledge, C., Kanady, J., Fleming, I., Batai, K., Weigand, K., Shi, G., Kim, T. Y., , Gupta, G., et al. (2018). IL-18 is a novel mediator of prolonged QTc and ventricular arrhythmias associated with Sickle Cell Disease. Proceedings of the National Academy of Sciences.
BIO5 Collaborators
Joe GN Garcia, Steven Goldman
Brilakis, E. S., Banerjee, S., Edson, R., Shunk, K., Goldman, S., Holmes, D. R., Bhatt, D. L., Rao, S. V., Smith, M. W., Sather, M., Colling, C., Kar, B., Nielsen, L., Conner, T., Wagner, T., Rangan, B. V., Ventura, B., Lu, Y., Holodniy, M., & Shih, M. C. (2017). Rationale and design of the Drug-Eluting Stents vs Bare-Metal Stents in Saphenous Vein Graft Angioplasty (DIVA) Trial. Clinical cardiology, 40(11), 946-954.

VA Cooperative Studies Program #571 (DIVA) was designed to evaluate the efficacy of drug-eluting stents (DES) for reducing aortocoronary saphenous vein bypass graft (SVG) failure when compared with bare-metal stents (BMS) in participants undergoing stenting of de novo SVG lesions. Participants undergoing clinically indicated stenting of de novo SVG lesions were randomized in a 1:1 ratio to DES or BMS. Randomization was stratified by presence/absence of diabetes mellitus and the number of target SVG lesions (1 vs ≥2) within each participating site. At sites that did not routinely administer 12-months of dual antiplatelet therapy after SVG stenting participants without acute coronary syndromes received 1 month of open-label clopidogrel, followed by 11 months of clopidogrel for those assigned to DES and 11 months of placebo for those assigned to BMS. The primary endpoint was the 12-month incidence of target-vessel failure (defined as the composite of cardiac death, target-vessel myocardial infarction, or target-vessel revascularization). Secondary endpoints included the incidence of other clinical endpoints and the incremental cost-effectiveness of DES relative to BMS. Due to lower-than-anticipated target-vessel failure rates, target enrollment was increased from 519 to 762. The study had randomized 599 participants when recruitment ended in December 2015. The DIVA trial will provide clarity on the appropriate stent type for de novo SVG lesions.

Gaudino, M., Alexander, J. H., Bakaeen, F. G., Ballman, K., Barili, F., Calafiore, A. M., Davierwala, P., Kappetein, P., Lorusso, R., Mylotte, D., Pagano, D., Ruel, M., Schwann, T., Suma, H., Taggart, D. P., Tranbaugh, R. F., Fremes, S., & Goldman, S. (2017). Randomized comparison of the clinical outcome of single versus multiple arterial grafts: the ROMA trial-rationale and study protocol. European journal of cardio-thoracic surgery : official journal of the European Association for Cardio-thoracic Surgery, 52(6), 1031-1040.

The primary hypothesis of the ROMA trial is that in patients undergoing primary isolated non-emergent coronary artery bypass grafting, the use of 2 or more arterial grafts compared with a single arterial graft (SAG) is associated with a reduction in the composite outcome of death from any cause, any stroke, post-discharge myocardial infarction and/or repeat revascularization.

Shanmugasundaram, M., Ram, V., Jayasuria, S., Dewar, J., Nguyen, J., Boyella, R., & Goldman, S. (2011). The Effect of IVUS Guidance on Clinical Outcomes in Percutaneous Revascularization compared to Coronary Artery Bypass Grafting among High Risk Patients with Left Main Coronary Artery Disease. Journal of Investigative Medicine, 59(1), 888-217.
Hayward, R. A., Reaven, P. D., Wiitala, W. L., Bahn, G. D., Reda, D. J., Ge, L., McCarren, M., Duckworth, W. C., Emanuele, N. V., & , V. I. (2015). Follow-up of glycemic control and cardiovascular outcomes in type 2 diabetes. The New England journal of medicine, 372(23), 2197-206.

The Veterans Affairs Diabetes Trial previously showed that intensive glucose lowering, as compared with standard therapy, did not significantly reduce the rate of major cardiovascular events among 1791 military veterans (median follow-up, 5.6 years). We report the extended follow-up of the study participants.