Cardiac dysfunction from cancer therapies increases risk for pregnancy-related HF
Women who had a history of cardiac dysfunction related to cancer therapeutics had a 47.4-fold increased risk for HF or left ventricular dysfunction during pregnancy or within 12 months after delivery, according to a systematic review.
“Our data should prompt physicians to ask the question about prior history of cardiotoxicity and triage their pregnancy-related cases based on this response,” Dinesh Thavendiranathan, MDSM, cardiologist, associate professor of medicine and director of the Ted Rogers Program in Cardiotoxicity Prevention at Toronto General Hospital at the University of Toronto, told Healio. “We also provide an algorithm in the paper that physicians can use in the care of cancer survivors going through pregnancy.”
Pregnancy in cancer survivors
In the study published in JACC: CardioOncology, Mark Nolan, MBBS, PhD, advanced cardiac imaging and cardio-oncology fellow at University of Toronto, and colleagues analyzed data from 2,016 pregnancies of 1,137 women (median age at cancer diagnosis, 12 years; median age at first pregnancy, 22 years) from six studies.
Studies included in this review were retrospective or prospective with 10 or more patients with one or more pregnancies. These women underwent prior cancer treatment with potentially cardiotoxic therapeutics and were followed up from their diagnosis of cancer until at least their first pregnancy for HF or LV systolic dysfunction.
Most of the included studies focused on women who were pediatric, adolescent and young adult cancer survivors.
“The number of pediatric, adolescent and young adult cancer survivors is increasing at a rapid pace,” Thavendiranathan said in an interview. “These patients are at high risk of having subclinical heart dysfunction. ... Pregnancy causes lots of changes to the cardiovascular system and can stress the system. Therefore, one that already has mild abnormalities could deteriorate and result in further cardiac dysfunction and heart failure.”
Five of the six studies were retrospective with a median follow-up of 24.8 years since cancer diagnosis.
During follow-up, 2.9% of patients had HF or LV dysfunction during pregnancy or up to 1 year after delivery.
The overall total weighted incidence of HF or LV dysfunction with pregnancy was 1.7% (95% CI, 0.9-2.7). Women with a history of cancer therapeutics-related cardiac dysfunction had a total weighted incidence of 28.4% (95% CI, 14.6-43.9) compared with 0.24% for those without a history of cardiac dysfunction (95% CI, 0-0.81). This equates to a number needed to harm of 4 and an OR of 47.4 (95% CI, 17.9-125.8).
Low interstudy heterogeneity was observed (I2 = 17.5%). Meta-regression did not result in any significant contribution toward interstudy heterogeneity when cumulative anthracycline dose (r = 0.01; P = .18), publication year (r = 0.06; P = .96) and number of patients enrolled (r = 0.002; P = .07) were included as study level variables.
“We need to understand other factors that help us understand each cancer survivor’s risk of developing heart dysfunction related to pregnancy,” Thavendiranathan told Healio. “This would be based on advanced heart imaging methods, blood work and clinical history. We need studies that identify these patients at the onset of pregnancy, collect relevant information and follow them during pregnancy to develop risk models. These risk models along with the findings of this paper can help us institute a precision medicine approach to the care of these women.”
Need for collaboration
In a related editorial, Melissa M. Hudson, MD, director of the cancer survivorship division, co-leader of the cancer control and survivorship program and The Charles E. Williams Endowed Chair of Oncology-Cancer Survivorship at St. Jude Children’s Research Hospital in Memphis, Tennessee, and Matthew J. Ehrhardt, MD, MS, assistant member of faculty at St. Jude Children’s Research Hospital, wrote: “Considering the relative rarity of this outcome, international collaboration is encouraged to track cardiomyopathy events among clinically well-characterized survivor cohorts to advance understanding about management that will optimize maternal and fetal outcomes.”
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Dinesh Thavendiranathan, MDSM, can be reached at dinesh.thavendiranathan@uhn.ca.
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