NEW ORLEANS, LA–Managing pediatric heart failure is increasingly multidisciplinary. In the coming decade, this will encompass the disciplines of heart transplant, mechanical circulatory support, familial cardiomyopathy, genetics, oncology, and single ventricle and neuromuscular programs.
This approach allows for enhanced collaboration and represents the portal to the heart transplant program, noted Robert E. Shaddy, MD, Children’s Hospital of Philadelphia, during ACC.11, the American College of Cardiology’s 60th Annual Scientific Session. In addition, multi-institutional approaches are necessary to perform clinical trials that can advance the field, such as the recent trial with PTC124 (or ataluren) in male patients with Duchenne muscular dystrophy aged ≥5 years, the results of which will be published soon.
One of the challenges in conducting clinical trials in children is that children do not have the same comorbidities as do a large percentage of adults. For example, “real world” adult patients with heart failure generally also have coronary artery disease, hypertension, atrial fibrillation, and left ventricular ejection fractions >40%—none of which were present in a study that included pediatric patients with a mean age of 3 years (48% male), Dr. Shaddy noted.
Karen K. Stout, MD, University of Washington Medical Center and Seattle Children’s Hospital, Seattle, said that another challenge lies in statistics: approximately 3% of children die from heart disease compared with 28% of adults ≥65 years. For that reason, more data exist for adults than for children, especially for those with heart failure. She conducted a recent literature search and found 4,725 randomized clinical trials in adults and only 319 for children.
Given the dearth of data, can trials in adults be extrapolated to children? The “pros” include the sheer number of studies in adults that include very large numbers of participants and high rates of events (including death) and that the pathophysiology is similar in many cases. “Cons” include the fact that “children aren’t little adults,” the unknown long-term sequelae of decades of medication use on growth and development, and finally the lack of overlapping etiologies.
Dr. Stout said data are clearer when older adults are compared with younger adults in their 20s and 30s. For these patients, options include modifying risk factors for future events by losing weight, exercising, controlling for blood pressure and monitoring for diabetes for those with stage A disease. For those with stage C disease there is a likely reasonable extrapolation of the usual left ventricular systolic dysfunction treatment. However, for patients with stage D disease, defined as refractory heart failure requiring specialized interventions, extrapolation of data from other adults is much more difficult.
Dr. Stout concluded by noting that while more data in children are needed, lack of data is not a license for inaction as long as therapy is well reasoned and the risks and benefits are balanced. No treatment algorithm currently exists; for this reason, individualized extrapolation requires a thorough understanding of each patient’s physiology and expected long-term outcomes.