Risk of Heart Failure After Radiotherapy for Breast Cancer

Study Questions:

Does radiation exposure during breast cancer increase risk of heart failure (HF)?

Methods:

The study investigators conducted a population-based case-control study of incident HF in 170 female residents of Olmsted County, MN (59 cases and 111 controls) who underwent contemporary (1998-2013) radiotherapy for breast cancer utilizing computed tomography (CT) assisted radiotherapy planning. They matched controls to cases for age, tumor side, chemotherapy use, diabetes, and hypertension. Higher cancer stage often mandates more extensive radiotherapy and increases mean cardiac radiation dose (MCRD), but also may result in heightened surveillance and bias HF ascertainment. Therefore, the study investigators performed a sensitivity analysis re-matching controls to cases using the same criteria as above except matching for cancer stage rather than tumor side. They calculated MCRD in each patient from their CT images and radiotherapy plan.

Results:

Among the 945 female Olmsted County residents with breast cancer who underwent radiotherapy during 1998-2013 (median age 59), the study investigators identified 77 patients that developed new-onset validated HF after radiotherapy. Of these 77 potential cases, 60 met final entry criteria. The mean age of the study cohort at radiotherapy was 69 ± 9 years. Of HF cases, 64% (n = 38) had EF ≥50% (HF with preserved ejection fraction [HFpEF]), 31% (n = 18) had EF <50% (HF with reduced EF [HFrEF]), and 5% (n = 3) did not have EF measured. The LVEF was ≥40% in 89% (n = 50) of the 56 HF cases with an EF measurement. The mean interval from radiotherapy to HF was 5.8 ± 3.4 years. They found that the odds of HF was higher in patients with a prior history of ischemic heart disease or atrial fibrillation. The MCRD was 2.5 Gy (range 0.2-13.1 Gy) and higher in cases (3.3 ± 2.7 Gy) than controls (2.1 ± 2.0 Gy, p = 0.004). The odds ratio (95% confidence interval) for HF per log MCRD was 9.1 (3.4, 24.4) for any HF, 16.9 (3.9, 73.7) for HFpEF, and 3.17 (0.8, 13.0) for HFrEF. The increased odds of any HF or HFpEF with increasing MCRD remained significant after adjustment for HF risk factors and in sensitivity analyses matching by cancer stage rather than tumor side. Only 18.6% of patients experienced new or recurrent ischemic events between radiotherapy and onset of HF.

Conclusions:

The authors concluded that the relative risk of diastolic HF increases with increasing cardiac radiation exposure during contemporary conformal breast cancer radiotherapy and their data suggested that coronary microvascular compromise plays an important role in the pathophysiology of diastolic HF.

Perspective:

This is an important study because it suggests that despite minimizing radiation, diastolic dysfunction occurs as early as 5.8 ± 3.4 years following radiotherapy. Prospective registry studies with long-term follow-up are the next step in extending the findings of this study.


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