Risk of Heart Failure with Preserved Ejection Fraction in Older Women After Contemporary Radiotherapy for Breast Cancer

Hirofumi Saiki, Ivy A Petersen, Christopher G. Scott, Kent R Bailey, Shannon M Dunlay, Randi R. Finley, Kathryn J Ruddy, Elizabeth Yan, Margaret May Redfield

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Abstract

BACKGROUND—: Cardiomyocytes are resistant to radiation. However, cardiac radiation exposure causes coronary microvascular endothelial inflammation, a perturbation implicated in the pathogenesis of heart failure (HF) and particularly, HF with preserved ejection fraction (HFpEF). Radiotherapy for breast cancer results in variable cardiac radiation exposure and may increase the risk of HF. METHODS—: We conducted a population-based case-control study of incident HF 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. RESULTS—: Mean age at radiotherapy was 69±9 years. Of HF cases, 38 (64%) had EF≥50% (HFpEF), 18 (31%) had EF<50% (HFrEF) and 3 (5%) did not have EF measured. The EF was ≥ 40% in 50 (89%) of the 56 HF cases with an EF measurement. The mean interval from radiotherapy to HF was 5.8±3.4 years. 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 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 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 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.

Original languageEnglish (US)
JournalCirculation
DOIs
StateAccepted/In press - Feb 20 2017

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Radiotherapy
Heart Failure
Breast Neoplasms
Radiation
Tomography
Neoplasms
Cardiac Myocytes
Atrial Fibrillation
Myocardial Ischemia
Case-Control Studies
Odds Ratio
Confidence Intervals
Hypertension
Inflammation
Drug Therapy

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)

Cite this

@article{faff4fd0934a4dfeb2e8015bb5184ce5,
title = "Risk of Heart Failure with Preserved Ejection Fraction in Older Women After Contemporary Radiotherapy for Breast Cancer",
abstract = "BACKGROUND—: Cardiomyocytes are resistant to radiation. However, cardiac radiation exposure causes coronary microvascular endothelial inflammation, a perturbation implicated in the pathogenesis of heart failure (HF) and particularly, HF with preserved ejection fraction (HFpEF). Radiotherapy for breast cancer results in variable cardiac radiation exposure and may increase the risk of HF. METHODS—: We conducted a population-based case-control study of incident HF 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. RESULTS—: Mean age at radiotherapy was 69±9 years. Of HF cases, 38 (64{\%}) had EF≥50{\%} (HFpEF), 18 (31{\%}) had EF<50{\%} (HFrEF) and 3 (5{\%}) did not have EF measured. The EF was ≥ 40{\%} in 50 (89{\%}) of the 56 HF cases with an EF measurement. The mean interval from radiotherapy to HF was 5.8±3.4 years. 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 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 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 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.",
author = "Hirofumi Saiki and Petersen, {Ivy A} and Scott, {Christopher G.} and Bailey, {Kent R} and Dunlay, {Shannon M} and Finley, {Randi R.} and Ruddy, {Kathryn J} and Elizabeth Yan and Redfield, {Margaret May}",
year = "2017",
month = "2",
day = "20",
doi = "10.1161/CIRCULATIONAHA.116.025434",
language = "English (US)",
journal = "Circulation",
issn = "0009-7322",
publisher = "Lippincott Williams and Wilkins",

}

TY - JOUR

T1 - Risk of Heart Failure with Preserved Ejection Fraction in Older Women After Contemporary Radiotherapy for Breast Cancer

AU - Saiki, Hirofumi

AU - Petersen, Ivy A

AU - Scott, Christopher G.

AU - Bailey, Kent R

AU - Dunlay, Shannon M

AU - Finley, Randi R.

AU - Ruddy, Kathryn J

AU - Yan, Elizabeth

AU - Redfield, Margaret May

PY - 2017/2/20

Y1 - 2017/2/20

N2 - BACKGROUND—: Cardiomyocytes are resistant to radiation. However, cardiac radiation exposure causes coronary microvascular endothelial inflammation, a perturbation implicated in the pathogenesis of heart failure (HF) and particularly, HF with preserved ejection fraction (HFpEF). Radiotherapy for breast cancer results in variable cardiac radiation exposure and may increase the risk of HF. METHODS—: We conducted a population-based case-control study of incident HF 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. RESULTS—: Mean age at radiotherapy was 69±9 years. Of HF cases, 38 (64%) had EF≥50% (HFpEF), 18 (31%) had EF<50% (HFrEF) and 3 (5%) did not have EF measured. The EF was ≥ 40% in 50 (89%) of the 56 HF cases with an EF measurement. The mean interval from radiotherapy to HF was 5.8±3.4 years. 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 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 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 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.

AB - BACKGROUND—: Cardiomyocytes are resistant to radiation. However, cardiac radiation exposure causes coronary microvascular endothelial inflammation, a perturbation implicated in the pathogenesis of heart failure (HF) and particularly, HF with preserved ejection fraction (HFpEF). Radiotherapy for breast cancer results in variable cardiac radiation exposure and may increase the risk of HF. METHODS—: We conducted a population-based case-control study of incident HF 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. RESULTS—: Mean age at radiotherapy was 69±9 years. Of HF cases, 38 (64%) had EF≥50% (HFpEF), 18 (31%) had EF<50% (HFrEF) and 3 (5%) did not have EF measured. The EF was ≥ 40% in 50 (89%) of the 56 HF cases with an EF measurement. The mean interval from radiotherapy to HF was 5.8±3.4 years. 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 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 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 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.

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U2 - 10.1161/CIRCULATIONAHA.116.025434

DO - 10.1161/CIRCULATIONAHA.116.025434

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JO - Circulation

JF - Circulation

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