With Major Statement by the American Heart Association, Pediatric Cardio-oncology Comes of Age

Led by the Miller School’s Steven E. Lipshultz, M.D., the American Heart Association has issued a major and unprecedented scientific statement on the life-threatening or quality-of-life reducing cardiovascular problems that the growing number of childhood cancer survivors are destined to face decades after their initial treatment. Published online this week in advance of print in Circulation, the official journal of the AHA, the statement underscores the growing recognition of pediatric cardio-oncology as a legitimate and essential specialty of mainstream cardiology.

“This is a game-changer,’’ said Lipshultz, the George E. Batchelor Professor of Pediatrics, George E. Batchelor Endowed Chair in Pediatric Cardiology and Director of the Batchelor Children’s Research Institute, who published the first paper describing the latent cardiac effects in survivors of childhood cancer in The New England Journal of Medicine in 1991. “Accepting that late cardiotoxic effects of cancer survivorship are important issues is a key starting point to enhancing the dissemination and implementation of evidence-based findings and legitimizing them to those caring for survivors who have not been previously trained or made aware of these emerging issues.”

Spanning 68 pages, the statement from a group of experts assembled and chaired by Lipshultz and commissioned by the AHA four years ago is titled “Long-term Cardiovascular Toxicity in Children, Adolescents, and Young Adults Who Receive Cancer Therapy: Pathophysiology, Course, Monitoring, Management, Prevention, and Research Directions,” and is targeted at all healthcare providers who care for childhood cancer survivors, including pediatric oncologists, pediatricians, adolescent and young adult specialists and general practitioners.

Over the past three decades, there have been dramatic improvements in treatment for childhood cancers, raising the survival rates to nearly 80 percent. Yet, as Lipshultz, who is also professor of pediatrics, medicine and public health sciences, and other experts have been meticulously documenting, cancer therapy-induced cardiovascular disease (CVD) has emerged as the leading cause of morbidity and mortality after childhood cancer in this population, making it a major and expanding public health concern. Today, more than 325,000 young adults in the U.S. – about one of every 500 people aged 20 to 45 years of age – is a survivor of childhood cancer, and they are eight times more likely to die from cardiac causes and 15 times more likely to experience congestive heart failure than the general population.

The statement does not provide specific recommendations, but rather summarizes a large volume of scientific evidence, based on literature searches and the knowledge and experience of the experts, that can help clinicians and childhood cancer survivors make the best clinical decisions for treating their cancer, as well as for assessing, monitoring and managing their long-term care to prevent or minimize latent cardiotoxic effects of earlier treatment.

Among the topics are the pathophysiology of cardiovascular toxicity from chemotherapeutic agents and radiation, the epidemiology, presentation and progression of cardiotoxicity, assessing and monitoring cardiac function during and after therapy, the cardiometabolic risk factors for premature atherosclerosis, cerebrovascular screening for stroke prevention, arrhythmias and conduction defects, and strategies to reduce the cardiotoxic effects of chemotherapy and radiation.

“In summary,” the authors wrote, “it is time we move beyond our current focus on the young adult years to address the entire life span of patients who survive a childhood cancer. The pediatric oncological community, in the development of new protocols, operates under the mantra, ‘maximize the cure, minimize the cost.’ As investigators focused on the long-term outcomes of cancer survivors, an equally important mantra for us is to ‘maintain the cure and maintain the quality of the cure.’ Recognizing that cardiac outcomes affect both longevity and quality of life, it is imperative that we better understand how we can prevent or slow the progression of CVD while managing the assortment of other health risks and comorbidities in this population.”

In an accompanying commentary, “A Lifelong Perspective on the Cardiovascular Toxicity of Cancer Therapy in Children,” Elske Sieswerda, of Emma Children’s Hospital/Academic Medical Center in Amsterdam, the Netherlands, and Robert G. Weintraub, M.B.B.S., of The Royal Children’s Hospital and Murdoch Children’s Research Institute in Melbourne, Australia, called the statement “a welcome addition to the literature.”

“It is a comprehensive summary of the pathophysiology, clinical course, monitoring, prevention, management and needed research in this area,’’ Sieswerda and Weintraub wrote.

“Much of the literature concerns the short- and medium-term effects of a single antineoplastic agent, but this Statement describes the risk factors associated with each therapy and the additive impact of multiple cardiotoxic agents decades after exposure,” they continued. “Many studies have identified younger age at the time of cancer therapy to be a risk factor for late cardiotoxicity, implying that myocardial damage is greatest in the immature heart. In keeping with the finding that these survivors have a lifetime during which they are at higher risk for cardiovascular events, the discussion about the interaction of traditional cardiovascular risk factors and the late effects of cancer therapy is both relevant and far-sighted.”

In addition to Lipshultz, other Miller School authors of the statement are David C. Landy, M.P.H., Ph.D., a student in UM’s M.D./Ph.D. program; Tracie L. Miller, M.D., professor of pediatrics and Director of Pediatric Clinical Research; Thomas R. Cochran, B.S.; and James Wilkinson, M.D., M.P.H., professor of pediatrics and public health sciences in the Division of Pediatric Clinical Research.

Others contributors included experts from the U.S. Food and Drug Administration, Boston Children’s Hospital, Children’s Hospital of Montefiore, St. Jude Children’s Research Hospital, the University of Rochester, Academic Medical Center, Amsterdam, the Netherlands, Memorial Sloan-Kettering Cancer Center, Stanford University, Children’s National Medical Center, Dana Farber Cancer Institute, and Washington University in St. Louis.

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