Cardiac irradiation is associated with early diastolic impairment after contemporary radiotherapy

Abstract

Radiation-associated cardiac disease (RACD) remains a clinically relevant late toxicity of thoracic radiotherapy. Although contemporary radiotherapy techniques have reduced cardiac exposure, early subclinical myocardial dysfunction may still occur. The aim of this study was to investigate the association of cardiac irradiation with cardiac troponin I (cTnI) levels and cardiac function. We analyzed 298 patients with esophageal, lung, or left-sided breast cancer who underwent cardiac evaluation before cancer therapy and at 12 months later. Patients who received radiotherapy involving the heart (cardiac RT group, n=41) were compared to those without radiotherapy (no RT group, n=237). Levels of cTnI and echocardiographic parameters were assessed before therapy and after 12 months. In the cardiac RT group, correlations between total prescribed radiation dose and cardiac parameters were evaluated. Multivariable logistic regression was then performed for dose-associated diastolic indices. Baseline age, sex, and major comorbidities (hypertension, diabetes mellitus and dyslipidemia) were similar between cardiac RT and no RT groups. Cancer type distribution differed between the groups, with a higher proportion of esophageal cancer in the cardiac RT group and a higher proportion of lung and left-sided breast cancer in the no RT group. cTnI levels remained stable throughout the observation period and showed no significant association with total radiation dose in the cardiac RT group (R=0.057, P=0.812). At 12 months, left ventricular ejection fraction (LVEF) was preserved and comparable between cardiac RT and no RT groups (64.0 [61.0–67.0] vs. 65.0 [61.0–67.0]%, P=0.628). In contrast, within the cardiac RT group, total radiation dose was negatively correlated with E/A ratio (Figure A: R=-0.448, P=0.009) and septal e′ velocity (B: R=-0.389, P=0.023), whereas no significant correlations were observed for lateral e′, E/e′, LVEF, or left atrial volume index. In multivariable logistic regression analysis, age (OR 1.096, 95% CI 1.061-1.133; P<0.001), diabetes mellitus (OR 3.018, 95% CI 1.334-6.827; P=0.008), and cardiac irradiation (OR 2.458, 95% CI 1.036-5.827; P=0.041) were independently associated with reduced E/A ratio. Cardiac irradiation was associated with dose-dependent declines in diastolic indices despite stable cTnI levels and preserved LVEF. Early diastolic impairment may represent a subclinical manifestation of RACD, supporting echocardiographic surveillance and efforts to minimize cardiac radiation exposure in contemporary radiotherapy.Total radiation dose and diastolic indices