Author + information
- Shiying Liu, MD,
- Nazanin Aghel, MD,
- Linda Belford, BScN, MN,
- Candice K. Silversides, MD,
- Mark Nolan, MBBS,
- Eitan Amir, MD, PhD,
- Cynthia Maxwell, MD and
- Paaladinesh Thavendiranathan, MD, MSc∗ (, )@tgwhf@UHN@UHN_Research
- ↵∗Division of Cardiology, Ted Rogers Program in Cardiotoxicity Prevention, Peter Munk Cardiac Center, and Division of Maternal-Fetal Medicine and Pregnancy and Heart Disease Research Program, University Health Network and Mount Sinai Hospital, University of Toronto, 200 Elizabeth Street, Toronto, Ontario M5G 2C4, Canada
Cancer treatment can lead to cardiac disease in female cancer survivors of child-bearing age. We evaluated the incidence of cardiac decompensation during pregnancy in cancer survivors and evaluated the effect of a cardiotoxicity history on the risk of decompensation.
We retrospectively identified consecutive female cancer survivors previously exposed to potentially cardiotoxic treatments (chemotherapy and/or radiation therapy to the thorax) seen in high-risk pregnancy clinics between 2005 and 2015 at Mount Sinai Hospital (Toronto, Ontario, Canada). Women with unknown type and duration of cancer treatment or other familial cardiomyopathies were excluded. Data were abstracted through chart review. Prior history of cardiotoxicity was defined as a reduction in left ventricular ejection fraction (LVEF) to <50% after completion of cancer therapy with or without congestive heart failure (CHF) symptoms. For patients exposed to anthracyclines, we collected doxorubicin-equivalent doses. The primary outcome was a composite of adverse maternal cardiac events including: cardiac death, clinical CHF (defined as signs or symptoms requiring addition or dose escalation of a diuretic agent or hospital admission for diuresis), acute coronary syndrome, and sustained arrhythmia (>30 s duration or symptomatic). All outcomes were assessed during pregnancy and up to 16 weeks postpartum and confirmed by a cardiologist. We also collected data on obstetric and perinatal events.
We included 78 women who had 94 pregnancies (90 singletons and 4 twin pregnancies). These women received cancer therapy as children, adolescents, or young adults. A total of 55 women received anthracyclines, while 23 received nonanthracycline chemotherapy and/or radiation therapy only. Among the 94 pregnancies, 15 (16%) occurred in 13 women with a prior history of cardiotoxicity. Baseline characteristics of patients with and without prior cardiotoxicity are summarized in Table 1. In anthracycline-treated patients with available data (24 of 55 patients, 42%), the median cumulative anthracycline dose was 290 mg/m2 (range 90 to 500 mg/m2). Of the 13 women with prior cardiotoxicity, 12 were treated with anthracyclines. At the first antenatal visit, 5 had normal LVEF, 5 had mildly reduced LVEF (41% to 50%), 2 had moderately reduced LVEF (37% and 40%), and 1 had LVEF of 25% (nonanthracycline treatment) measured by biplane Simpson’s method. All women except 1 from the cardiotoxicity group were in New York Heart Association functional class I.
Primary outcomes occurred in 5 pregnancies (5.3%) in 4 women and consisted exclusively of CHF. The incidence of CHF was 31% (4 of 13) (95% confidence interval: 13% to 58%) and 0% (0 of 65) (95% confidence interval: 0% to 6%) in women with and without a history of cardiotoxicity, respectively (p < 0.001) (Table 1). Among women with (n = 4) and without CHF (n = 74) during pregnancy, there was no difference in the age at cancer diagnosis (28 ± 4 years vs. 25 ± 11 years; p = 0.790), age at pregnancy (35 ± 4 years vs. 34 ± 5 years; p = 0.680), cancer type, or exposure to anthracyclines (75% vs. 70%; p = 0.840), respectively. Women with CHF during pregnancy were more likely to have had a history of cardiotoxicity before pregnancy (100% vs. 12%; p = 0.007), LV systolic dysfunction at first antenatal visit (75% vs. 8%; p = 0.004), or be on cardiac medications (50% vs. 8%; p = 0.026) compared with those without CHF. There were no maternal or neonatal deaths. Obstetric and perinatal outcomes are summarized in Table 1 and were similar to that reported in prior studies of cancer survivors (1).
The reported incidence of CHF associated with pregnancy in cancer survivors has varied from 0.0% to 5.4% (2–5). However, there has been significant variation in study methods, making interpretation of incidence rates difficult. Some studies did not have pre- and post-pregnancy cardiac assessment (5), relied on self-reporting of peripartum CHF (3), or included events before and well after pregnancy (4). In comparison, our study examines outcomes in consecutive pregnancies of cancer survivors, adjudicates outcomes based on clinical criteria, and provides information for pre-conception counseling.
We found that the risk of developing CHF during pregnancy is rare in female cancer survivors without a history of cardiotoxicity. These women can be reassured that they are at a very low risk of developing CHF during pregnancy. Women who have a history of cardiotoxicity have an approximately 1 in 3 chance of developing CHF during pregnancy and should receive close cardiac surveillance during pregnancy at a center with expertise in cardiac disease in pregnancy.
Please note: Dr. Thavendiranathan is supported by the Canadian Institutes of Health Research New Investigator Award. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose.
- 2018 American College of Cardiology Foundation
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