Can Radiation Treatments for Cancer Cause Lower Ejection Fraction?
Yes, radiation therapy to the chest can cause reduced ejection fraction, though the mechanism and clinical significance vary depending on radiation dose, volume of heart exposed, and time since treatment.
Mechanisms of Radiation-Induced Cardiac Dysfunction
Radiation causes cardiac injury primarily through microvascular endothelial damage rather than direct cardiomyocyte injury, as cardiomyocytes are highly radioresistant 1, 2. This endothelial inflammation leads to:
- Myocardial fibrosis from radiation effects on supporting vasculature 3
- Coronary microvascular rarefaction with subsequent oxidative stress 2
- Combined dilated and restrictive cardiomyopathy patterns, particularly when radiation is combined with anthracyclines 3
The pathophysiology differs from chemotherapy-induced cardiotoxicity—radiation more commonly causes heart failure with preserved ejection fraction (HFpEF) rather than reduced ejection fraction 1, 2.
Clinical Evidence for EF Reduction
Magnitude and Timing
- In esophageal cancer patients receiving 50.4 Gy with platinum-based chemotherapy, median ejection fraction declined from 59% to 54% (p=0.01), though this was not clinically significant 4
- The latency between radiation exposure and clinically evident cardiac disease is often prolonged, ranging from 1 year to 10-30 years after treatment 3
- Mean interval from radiotherapy to heart failure was 5.8 years in breast cancer patients 1
Dose-Response Relationship
Radiation dose is the strongest predictor of cardiac dysfunction 3:
- Risk factors include doses >30-35 Gy, dose per fraction >2 Gy, and large volume of irradiated heart 3
- In breast cancer patients, mean cardiac radiation dose was significantly higher in those who developed heart failure (3.3 Gy) versus controls (2.1 Gy, p=0.004) 1
- The odds ratio for heart failure per log increase in mean cardiac radiation dose was 9.1 for any heart failure 1
Type of Cardiac Dysfunction
Critical distinction: Radiation more commonly causes HFpEF rather than reduced EF 1, 2:
- Of heart failure cases after breast radiotherapy, 64% had EF ≥50% (HFpEF) while only 31% had reduced EF 1
- The odds ratio for HFpEF per log mean cardiac radiation dose was 16.9 compared to only 3.17 for heart failure with reduced EF 1
- Experimental models confirm radiation causes diastolic dysfunction with preserved EF, characterized by increased LV stiffness, impaired relaxation, and elevated filling pressures 2
Combined Effects with Chemotherapy
Radiation significantly amplifies anthracycline cardiotoxicity 3:
- Childhood cancer survivors exposed to both anthracyclines and chest radiation have a 15-fold increased risk of developing congestive heart failure 3
- Prior mediastinal irradiation is an established risk factor for anthracycline-induced cardiotoxicity 3
- The combination can result in both dilated and restrictive cardiomyopathy patterns 3
Surveillance Recommendations
Baseline cardiac assessment is mandatory before initiating radiotherapy that exposes the heart 3, 5:
- Baseline echocardiogram with LVEF measurement is recommended for all patients receiving chest radiation, particularly with cardiovascular risk factors, age >60 years, or previous cardiovascular disease 3, 5
- Doppler-derived diastolic indices (E/A ratio, deceleration time, isovolumic relaxation time) are more sensitive than EF for detecting early radiation-induced dysfunction 3
- Long-term surveillance is essential given the prolonged latency period 3
Clinical Pitfalls
Do not rely solely on EF measurements to detect radiation cardiotoxicity 3, 1:
- EF may remain preserved despite significant diastolic dysfunction 1, 2
- Evaluate diastolic parameters and consider tissue Doppler imaging for early detection 3
- Be aware that volume depletion can cause isolated LVEDV declines that reduce EF without true myocardial dysfunction 6
Recognize the long latency period: Cardiac complications may not manifest for 10-15 years after radiation, requiring lifelong surveillance 3.