Abstract Body: Current breast cancer diagnosis and treatment protocols achieve survival rates of>80% at 10 years.However, long-term cancer survivors have>4-fold higher incidence of cardiovascular complications, including heart failure.Early potentially reversible changes that may underlie downstream irreversible loss of mechanical function are unknown.Therefore, we aimed to test the feasibility of a noninvasive cardiac phenotyping protocol in patients undergoing treatment for breast cancer with doxorubicin, without or with immune checkpoint inhibitors, including multiparametric proton cardiac magnetic resonance(CMR) imaging and novel metabolic carbon13MR.
A comprehensive set of studies included conventional 1HCMR,as well as metabolic 13CCMR using hyperpolarized(HP)[1-13C] pyruvate, following an oral glucose load. 13CCMR with HP[1-13C] pyruvate allows the detection of downstream metabolites of injected pyruvate within the myocardium: bicarbonate from mitochondrial oxidation and lactate from anaerobic cytosolic metabolism.HP[1-13C]pyruvate was prepared using dynamic nuclear polarization in a commercial polarizer.Imaging and spectroscopy(MRS) of hyperpolarized pyruvate was conducted using a 13C transmit/receive Helmholtz loop-pair coil on a 3Tscanner.13C data were acquired from a short-axis slice, ECG-triggered in end-systole. ProtonCMR images were analyzed using Circle, and 13CCMR images were analyzed using MATLAB. The left ventricular mid-myocardium and blood pool were segmented for metabolite quantitation.
Baseline cardiac studies were performed in a consecutive series of 25 women treated for breast cancer. Of these 14(56%) were Caucasian, 3(12%) were Hispanic, 5(20%) Black, and 3(12%) Asian, with ages ranging 46±11 years.Patients received standard-of-care treatment plans based on the tumor type: 11 patients were treated with dose-dense anthracycline and cyclophosphamide, and 14 also received pembrolizumab. The comprehensive baseline phenotyping protocol is planned to be repeated after standard of care therapy in all patients. Baseline data are presented in Table1, with values reported as mean±standard deviation.
Noninvasive cardiac phenotyping, including dynamic detection of metabolic substrate utilization is feasible,without showing significant adverse effects,and is well tolerated in a diverse group of patients.Completion of this protocol post-oncological therapy may allow to detect early changes in cardiac function due to chemo-and immunotherapy in susceptible patients.