Evaluation of cardiovascular health in sarcoma survivors.

Abstract

e21579 Background: Heart disease is the most common and serious chronic illness observed in sarcoma survivors treated with doxorubicin. Now the commonest heart disease in theses survivors is coronary artery disease (CAD). We established a Sarcoma Survivorship Program to include patients at high risk of chronic illness including exposure to doxorubicin who are at least 2 years free of disease post treatment. Methods: Every 6 months patients electronically complete NIH’s PROMIS (Patient-Reported Outcomes Measurement Information System) questionnaires (on Anxiety, Depression, Mobility, Pain Interference, Sleep Disturbance, and Physical Function). Detailed family history is documented. Chemotherapy doses are abstracted from original medical records. Data collected includes: blood pressure, lipid profile, high-sensitivity C-reactive protein (hs-CRP), basic metabolic panel, chemistries, renal and pulmonary function, expert echocardiography. All patients signed an IRB approved informed consent. Results: All patients had normal left ventricular ejection fractions (median = 60%) yet 8 (N = 24) patients had an elevated hs-CRP suggesting increased risk of early CAD. 10 patients had untreated hypertension. More than half of our patients have a BMI > 25 and self-declare that they do not exercise. Our high rate of family history of heart disease (58%) raises the issue of genetic predisposition both to heart disease and sarcoma. We compared standardized cardiac risk assessments with mediastinal calcification and epicardial fat on serial chest CT scans. A 39 y.o. man had a coronary calcium score > 400 Agatston units and scattered calcifications were found in 4 additional patients under the age of 40. Conclusions: This survivorship phase of oncologic care represents a unique opportunity to improve the health and quality of life for sarcoma survivors as well as a new focus for translational research to understand mechanisms driving premature aging and chronic heart disease. We assess cardiomyocyte function (cell viability, organization, fibrosis, electrical coupling and contractility) for survivors and matched sibling controls with cells from skin biopsy using 3D bioengineering techniques to culture and mature the phenotype from human stem cells.