Description of Research Expertise

Cardiotoxicity from cancer therapy is detectable, preventable and treatable. This is the focus of Dr. Ky’s research program. Cancer therapies are becoming increasingly effective at killing cancer, but these treatments also have toxic side effects, resulting in a growing population of cancer patients and survivors with heart disease. In our lab, we are studying innovative strategies to understand the changes in heart function that occur with common cancer therapies, and how we can apply these methods to understand an individual patient’s risk of developing heart disease and heart failure. Our goals are to bring these exciting research findings to the clinic and continue our mission of delivering state-of-the-art, evidence-based medicine to cancer patients and survivors regionally and nationally. We highlight 3 recent discoveries from our lab below.

How breast cancer therapy affects heart function. In a recent paper published in Circulation, we rigorously and comprehensively define the precise changes that occur with heart function over time in breast cancer patients treated with doxorubicin, trastuzumab and radiation. We found that with these cancer therapies, there are modest, but persistent declines in heart function, even at 3 years post treatment exposure. We also determined that afterload, or blood pressure, is a major determinant of this adverse remodeling. These findings might suggest that aggressive blood pressure control is critical in mitigating a patient’s risk of developing heart dysfunction. We have proposed new trials to test this hypothesis.

How innovative new imaging tools can predict heart damage with cancer therapy. We are also interested in discovering new strategies to predict the risk of subsequent heart damage in cancer patients. In two separate manuscripts published in the Journal of American College of Cardiology Imaging, we have used 2-dimensional and 3-dimensional ultrasound techniques in order to more precisely and deeply understand how the heart functions. We have discovered that early changes in 2D and 3D circumferential strain, or deformation, are associated with the risk of developing cardiotoxicity with anthracyclines.

How simple blood tests – using new markers – can predict heart damage with cancer therapy. We are also studying the role of new blood markers of oxidative stress – and how they can predict who will develop heart damage with anthracycline chemotherapy. These findings were published in the Journal of the American College of Cardiology. We are now testing in a clinical trial how these blood markers can be used to understand why statins might protect the heart and who may benefit the most from statins when receiving anthracycline chemotherapy.

Selected Publications

Makhlin I, Demissei BG, D'Agostino R, Hundley WG, Baleanu-Gogonea C, Wilcox NS, Chen A, Smith AM, O'Connell NS, Januzzi J, Lesser GJ, Scherrer-Crosbie M, Ibanez B, Tang WHW, Ky B.: Statins Do Not Significantly Affect Oxidative Nitrosative Stress Biomarkers in the PREVENT Randomized Clinical Trial Clinical Cancer Research. : 2024.

Hammoud RA, Liu Q, Dixon SB, Onerup A, Mulrooney DA, Huang I, Jefferies JL, Rhea IB, Krull KR, Ness KK, Ehrhardt MJ, Hudson MM, Ky B, Bhakta N, Sapkota Y, Yasui Y, Armstrong GT.: The growing burden of cardiovascular disease and increased risk for subsequent major adverse cardiovascular events (MACE) in survivors of childhood cancer: a prospective longitudinal analysis from the St. Jude Lifetime Cohort Study The Lancet Oncology 25 (6): 811-822,2024.

Kim K, Kim MM, Skoufos G, Diffenderfer ES, Motlagh SAO, Kokkorakis M, Koliaki I, Morcos G, Shoniyozov K, Griffin J, Hatzigeorgiou AG, Metz JM, Lin A, Feigenberg SJ, Cengel KA, Ky B, Koumenis C, Verginadis II.: FLASH Proton Radiation Therapy Mitigates Inflammatory and Fibrotic Pathways and Preserves Cardiac Function in a Preclinical Mouse Model of Radiation-Induced Heart Disease Int J Radiat Oncol Biol Phys : 2024.

Leger KJ, Robison N, Narayan HK, Smith AM, Tsega T, Chung J, Daniels A, Chen Z, Englefield V, Demissei BG, Lefebvre B, Morrow G, Dizon I, Gerbing RB, Pabari R, Getz KD, Aplenc R, Pollard JA, Chow EJ, Tang WHW, Border WL, Sachdeva R, Alonzo TA, Kolb EA, Cooper TM, Ky B: Rationale and design of the Children's Oncology Group study AAML1831 integrated cardiac substudies in pediatric acute myeloid leukemia therapy. Front Cardiovasc Med : 2023.

Yegya-Raman N, Ho Lee S, Friedes C, Wang X, Iocolano M, Kegelman TP, Duan L, Li B, Berlin E, Kim KN, Doucette A, Denduluri S, Levin WP, Cengel KA, Cohen RB, Langer CJ, Kevin Teo BK, Zou W, O'Quinn RP, Deasy JO, Bradley JD, Sun L, Ky B, Xiao Y, Feigenberg SJ.: Cardiac radiation dose is associated with inferior survival but not cardiac events in patients with locally advanced non-small cell lung cancer in the era of immune checkpoint inhibitor consolidation. Radiother Oncol : 2023.

Avula V, Sharma G, Kosiborod MN, Vaduganathan M, Neilan TG, Lopez T, Dent S, Baldassarre L, Scherrer-Crosbie M, Barac A, Liu J, Deswal A, Khadke S, Yang EH, Ky B, Lenihan D, Nohria A, Dani SS, Ganatra S.: SGLT2 Inhibitor Use and Risk of Clinical Events in Patients With Cancer Therapy-Related Cardiac Dysfunction. JACC Heart Fail. : 2023.

Narayan V, Liu T, Song Y, Mitchell J, Sicks J, Gareen I, Sun L, Denduluri S, Fisher C, Mankowski J, WOjtowicz, Vadakara J, Haas N, Margulies KB, Ky B.: Early Increases in Blood Pressure and Major Adverse Cardiovascular Events in Renal Cell Carcinoma and Thyroid Cancer Patients Treated with VEGFR Tyrosine Kinase Inhibitors J Natl Compr Canc Netw 21 (10): 1039-1049,2023.

Neilan TG, Quinaglia T, Onoue T, Mahmood SS, Drobni ZD, Gilman HK, Smith A, Heemelaar J, Brahmbhatt P, Ho JS, Sama S, Svoboda J, Neuberg DS, Abramson JS, Hochberg EP, Barnes JA, Armand P, Jacobsen ED, Jacobson CA, Kim AI, Soumerai JD, Han Y, Friedman RS, Lacasce AS, Ky B, Landsburg D, Nasta S, Kwong RY, Jerosch-Herold M, Redd RA, Hua L, Januzzi JL, Asnani A, Mousavi N, Scherrer-Crosbie M.: Atorvastatin for Anthracycline-Associated Cardiac Dysfunction: The STOP-CA Randomized Clinical Trial JAMA 330 (6): 2023.

Sun L, Brody R, Candelieri D, Lynch JA, Cohen RB, Li Y, Getz KD, Ky B.: Risk of Cardiovascular Events Among Patients With Head and Neck Cancer JAMA Otolaryngol Head Neck Surg 149 (8): 2023.

Bottinor W, Flamand Y, Haas N, O'Neill A, DiPaolo R, Subramanian P, Cella D, Hundley WG, Wagner L, Salsman J, Ky B.: Cardiovascular Implications of Vascular Endothelial Growth Factor Inhibition Among Adolescents/Young Adults in ECOG-ACRIN E2805 J Natl Compr Canc Netw 21 (7): 2023.

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Academic Contact Information

Hospital of the University of Pennsylvania
11-105 Smilow Center for Translational Research
3400 Civic Center Boulevard
Philadelphia, PA 19104
Phone: 215-573-6606
Patient appointments: 800-789-7366