Purpose: Radiation-induced cardiotoxicity is a significant concern in thoracic oncology patients. However, the basis for this disease pathology is not well characterized. We developed a novel mouse model of radiation-induced cardiotoxicity to investigate pathophysiologic mechanisms and identify clinically targetable biomarkers of cardiac injury. Experimental Design: Single radiation doses of 20, 40, or 60 Gy were delivered to the cardiac apex of female C57BL/6 mice ages 9–11 weeks, with or without adjacent lung tissue, using conformal radiotherapy. Cardiac tissue was harvested up to 24 weeks post-radiotherapy for histologic analysis. Echocardiography and Technetium-99m sestamibi single photon emission computed tomography (SPECT) at 8 and 16 weeks post-radiotherapy were implemented to evaluate myocardial function and perfusion. Mouse cardiac tissue and mouse and human plasma were harvested for biochemical studies. Results: Histopathologically, radiotherapy resulted in perivascular fibrosis 8 and 24 (P < 0.05) weeks post-radiotherapy. Apical perfusion deficits on SPECT and systolic and diastolic dysfunction on echocardiography 8 and 16 weeks post-radiotherapy were also observed (P < 0.05). Irradiated cardiac tissue and plasma showed significant increases in placental growth factor (PlGF), IL6, and TNFα compared with nonradiated matched controls, with greater increases in cardiac cytokine levels when radiotherapy involved lung. Human plasma showed increased PlGF (P = 0.021) and TNFα (P = 0.036) levels after thoracic radiotherapy. PlGF levels demonstrated a strong correlation (r = 0.89, P = 0.0001) with mean heart dose. Conclusions: We developed and characterized a pathophysiologically relevant mouse model of radiation-induced cardiotoxicity involving in situ irradiation of the cardiac apex. The model can be used to integrate radiomic and biochemical markers of cardiotoxicity to inform early therapeutic intervention and human translational studies.

Patients who underwent myocardial perfusion PET/CT and showed evidence of nonalcoholic fatty liver disease at CT showed a higher risk of coronary microvascular dysfunction, which is an independent risk factor for major adverse cardiac events. Background Cardiovascular disease is a major cause of mortality in patients with nonalcoholic fatty liver disease (NAFLD). However, the association of NAFLD with coronary microvascular dysfunction is, to our knowledge, unknown. Purpose To determine whether coronary microvascular dysfunction is more prevalent in patients with NAFLD and to determine whether coronary microvascular dysfunction predicts major adverse cardiac events (MACE) independently of NAFLD. Materials and Methods This retrospective study (2006–2014) included patients without evidence of obstructive epicardial coronary artery disease and healthy left ventricular ejection fraction (≥40%) at a clinical rest and stress myocardial perfusion PET/CT. NAFLD was defined by a mean hepatic attenuation of less than 40 HU at CT and coronary microvascular dysfunction as a coronary flow reserve (CFR) of less than 2.0. A composite of all-cause mortality, myocardial infarction, coronary revascularization, and hospitalization because of heart failure compri...