Cancer-Related Cardiac Dysfunction Increases Risk of Heart Complications During Pregnancy

In cancer survivors who become pregnant, the incidence of left-ventricular (LV) dysfunction or heart failure (HF) during pregnancy is low. But in those with a history of cancer therapeutics-related cardiac dysfunction (CTRCD), the odds of pregnancy-related LV dysfunction and HF are significantly higher — 47.4-fold higher — compared to that in women without CTRCD, according to a systemic review and meta-analysis published in JACC: CardioOncology.

“The increasing number of female cancer survivors with reproductive potential raises concern about cardiac complications associated with pregnancy,” wrote Mark Nolan, MBBS, PhD, of University of Toronto, Toronto, Ontario, Canada, and fellow researchers. “Prior studies examining maternal adverse cardiac events in cancer survivors are individually limited by small sample size and single-center recruitment, and some were dependent on self-reported events. Drawing definitive conclusions from each study in isolation to guide management may be challenging,” they added.

Changes during pregnancy — including plasma volume expansion, increased heart rate, higher cardiac output, increased myocardial wall stress, and increased oxidative stress — can take a toll and may be poorly tolerated, especially by women with a history of CTRCD.

“Furthermore, up to one-third of patients with prior cancer treatment, regardless of a CTRCD history, can have subclinical LV systolic dysfunction which can be unmasked by the hemodynamic stress of pregnancy,” explained Nolan and colleagues.

Therefore, they conducted a systematic search of MEDLINE and EMBASE from inception through January 2020, and identified 6 studies, which included 1,137 women with 2,016 pregnancies that primarily occurred in childhood cancer survivors. Median age at cancer diagnosis was 12.1 years, and median age at first pregnancy was 21.8 years. Median follow-up since cancer diagnosis was 24.8 years. In all, 66.5% of patients had been treated with anthracycline.

LV dysfunction or HF during pregnancy or in the 12 months immediately after delivery occurred in 33 cancer survivors (2.9%), of whom 51.5% had previous CTRCD, and 97.0% had previous treatment with anthracycline.

With pregnancy, the total weighted incidence of LV dysfunction or HF with pregnancy was 1.7% (95% CI: 0.9%-2.7%). In women with a history of CTRCD, this was 28.4% (95% CI: 14.6%-43.9%) while in those without CTRCD, it was 0.24% (95% CI: 0%-0.81%). Thus, patients who had a history of pre-pregnancy CTRCD had a significantly higher odds of LV dysfunction or HF during pregnancy or within 12 months of delivery (OR: 47.4; 95% CI: 17.9-125.8).

Nolan and fellow researchers found no cases of maternal or fetal pregnancy-related mortality. In three studies, however, the incidence of spontaneous abortion was 15.1%, 10.8%, and 6.0%.

Interstudy heterogeneity was low (Cochran Q: 4.2; P=0.53; I²=17.5%).

Based on results from the individual studies, the potential predictors of LV dysfunction or HF during pregnancy or in the 12 months after delivery included lower pre-pregnancy LV systolic function, younger age at cancer diagnosis, longer time from cancer treatment to first pregnancy, and cumulative anthracycline dose.

“[T]he present authors believe those with a history of CTRCD should receive close cardiac surveillance during pregnancy at a center with expertise in cardiac disease in pregnancy. Women without prior CTRCD may benefit from a baseline assessment of LV function, and in the absence of LV systolic dysfunction, these women can be reassured that they are at low risk of developing LV dysfunction or HF during pregnancy with follow-up determined on an individual basis,” concluded Nolan and fellow researchers.

Study limitations include the limited number of events, a lack of interstudy heterogeneity, and inconsistencies in CTRCD definition and cardiac imaging, as well as a lack of information regarding cardiac medications taken by patients with a history of CTRCD or cessation of such treatment during pregnancy. Most studies included pediatric, adolescent, and young adult cancer survivors. Nolan and colleagues were also unable to assess the effects of radiotherapy or types of cancer treatments on outcomes.

In an accompanying editorial, Melissa M. Hudson, MD, and Matthew J. Ehrhardt, MD, MS, of St. Jude Children’s Research Hospital, Memphis, TN, stressed the importance of increased vigilance and further studies of pregnancy in cancer survivors.

“This topic is relatively understudied and is of substantial clinical importance in view of the increasing numbers of long-term survivors with preserved reproductive potential, the large proportion (estimated at 60%) exposed to anthracycline chemotherapy and/or chest-directed radiation therapy, and the clinical implications for obstetrical management,” they wrote.

“All but 1 event occurred in women exposed to anthracycline therapy, precluding subgroup analysis of treatment factors contributing to risk of cancer therapy-related cardiac dysfunction that could be used to stratify the risk of perinatal care. Until further information is available, vigilance is advised in assessing women treated with any potentially cardiotoxic agent or modality,” they concluded.

1. The incidence of pregnancy-related cardiac dysfunction in cancer survivors is low (1.7%), according to results of a recent systematic review/meta-analysis.

2. However, be aware that pregnant women with a history of cancer-therapeutics-related cardiac dysfunction are a high-risk population and require cardiac surveillance.

E.C. Meszaros, Contributing Writer, BreakingMED™

Cat ID: 41

Topic ID: 83,41,730,116,935,41,192,925