Experts Define Research Gaps in Pediatric Heart Failure

How and why hearts of children with congenital heart disease go from performing normally to failing is unknown. In addition, there’s no universally accepted score for pediatric heart failure (HF) or even a standard definition of the condition, hampering clinicians’ ability to optimize patient care.

Those are some of the key takeaways from the first published review of research gaps in pediatric HF, according to Shahnawaz Amdani, MD, Section Head of Pediatric Heart Function and Transplant at Cleveland Clinic. Dr. Amdani was lead author of the review recently published in the Journal of Cardiac Failure.

“Children with heart failure are not small adults, and giving them the medications we use for adults is not the solution,” says Dr. Amdani. “To improve these kids’ lives over the long term, a concerted effort needs to be made to advance the science of pediatric heart failure over the next decade.”

Two years ago, the American Heart Association, American College of Cardiology and Heart Failure Society of America updated guidelines for managing adult HF. However, the International Society for Heart and Lung Transplantation guidelines for managing pediatric HF have not been updated in 10 years.

Says Dr. Amdani, “In pediatric heart failure medicine, we’re at least two decades behind our adult colleagues, and we risk losing countless young lives if we wait another 20 years to close key research gaps.”

Panel determines top research priorities

The recent review underscores gaps identified by international experts with diverse backgrounds and extensive research and publication histories as well as clinical experience. Each participant proposed eight to 10 research priorities in their own area of expertise. The priorities then were ranked by the whole panel, based on novelty, feasibility and impact.

“Funders often ask scientists to emphasize the novelty, significance and impact of the research they are proposing, which is why we focused on those factors,” notes Dr. Amdani. “Our white paper and the tables in it represent a framework created by experts that research organizations now can reference.”

The panel cited these top priorities for pediatric HF — for both scientists and funding agencies:

• Developing a Fontan failure score
• Identifying novel biomarkers of heart failure progression
• Assessing the safety, validity and efficacy of invasive hemodynamic monitoring
• Developing checklists and systems for safe discharge of pediatric HF patients, thereby reducing readmissions, morbidity and mortality
• Developing medical and device therapies geared for pediatric HF patients

The panel notes that defining HF in Fontan patients, a growing part of the pediatric HF population, would allow for Fontan-specific interventions. Says Dr. Amdani of work already underway at Cleveland Clinic, “We have developed a Failing Fontan score, and we’re in the process of evaluating how well this score predicts outcomes.”

Regarding biomarkers, the experts cite mitochondrial dysfunction and intestinal hypoperfusion and/or congestion as promising but understudied areas for assessment in children. They believe that methods of estimating fluid overload in this population are lacking as is clinical evidence to support choices of inotropic agents.

In adult HF management, invasive hemodynamic monitoring has been well studied, but few studies exist in pediatric populations. The panel also recommends studies about the impact of daily rounding checklists on medication titration and improving physician-patient communication.

“Most importantly, however, we’re lacking a basic understanding of pediatric heart failure and medicines that are used to treat this deadly disease,” says Dr. Amdani. “That may come as a surprise to clinicians treating adults, where evidence in those areas is well established. We need studies to identify the best way to care for children in decompensated heart failure and how to deploy appropriate management strategies, whether that’s a ventricular assist device or a heart transplant.”

How to ensure equity for pediatric HF patients

When formulating future studies, the panel underscores the need to ensure equity for pediatric HF patients and to support the next generation of experts in this area of medicine.

“All children with heart failure must have access to lifesaving therapies, and females and underrepresented minorities need to be better represented in future clinical trials,” says Dr. Amdani. “The kind of effort we envision will require a significant science and funding commitment, a willingness to foster younger researchers, and multicenter collaboration.”