Cardiomyocytes are resistant to radiation. However, cardiac radiation exposure causes coronary microvascular endothelial inflammation, a perturbation implicated in the pathogenesis of heart failure and particularly, heart failure with preserved ejection fraction ( HFpEF ).
Radiotherapy for breast cancer results in variable cardiac radiation exposure and may increase the risk of heart failure.
Researchers have conducted a population-based case-control study of incident heart failure in 170 female residents of Olmsted County, Minnesota ( 59 cases and 111 controls ) who underwent contemporary ( 1998-2013 ) radiotherapy for breast cancer utilizing computed tomography-assisted radiotherapy planning.
Controls were matched to cases for age, tumor side, chemotherapy use, diabetes and hypertension.
Mean cardiac radiation dose ( MCRD ) in each patient was calculated from their computed tomography images and radiotherapy plan.
Mean age at radiotherapy was 69±9 years. Of heart failure cases, 38 ( 64% ) had ejection fraction ( EF ) greater than or equal to 50% ( HFpEF ), 18 ( 31% ) had EF less than 50% ( HFrEF ) and 3 ( 5% ) did not have ejection fraction measured.
The ejection fraction was greater than or equal to 40% in 50 ( 89% ) of the 56 heart failure cases with an EF measurement.
The mean interval from radiotherapy to heart failure was 5.8±3.4 years.
The odds of heart failure was higher in patients with a prior history of ischemic heart disease or atrial fibrillation.
The MCRD was 2.5 Gy ( range 0.2 to 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 heart failure per log MCRD was 9.1 ( 3.4, 24.4 ) for any heart failure, 16.9 ( 3.9,73.7 ) for HFpEF and 3.17 ( 0.8,13.0 ) for HFrEF.
The increased odds of any heart failure or HFpEF with increasing MCRD remained significant after adjustment for heart failure 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 heart failure.
In conclusion, the relative risk of HFpEF increases with increasing cardiac radiation exposure during contemporary conformal breast cancer radiotherapy.
These data emphasize the importance of radiotherapy techniques which limit MCRD during breast cancer treatment.
Moreover, these data provide further support for the importance of coronary microvascular compromise in the pathophysiology of HFpEF. ( Xagena )
Saiki H et al, Circulation 2017