New Treatment Option For Severe HCM in Children Shows Promise

Trametinib, a mitogen-activated protein kinase (MEK) inhibitor, may reduce morbidity and mortality in children with severe hypertrophic cardiomyopathy (HCM) caused by pathogenic variants in the RAS/ mitogen-activated protein kinase (MAPK) signaling pathway, according to a study published in JACC: Basic to Translational Science.

The study, which involved 61 children with severe RAS-HCM, compared 30 children receiving trametinib to 31 children receiving standard care. The results showed a significant reduction in the outcome of death, cardiac transplantation or the need for cardiac surgery in the trametinib group. No life-threatening adverse events were observed, although dermatologic and mucous membrane side effects were common but manageable.

"This study provides crucial evidence that targeted therapies like trametinib could dramatically improve the outlook for children suffering from severe HCM," said Gregor Andelfinger, MD, PhD, co-author of the study. "It underscores the importance of developing genotype-specific therapies for RASopathies and other rare diseases."

Study limitations include potential biases due to its design and incomplete data collection for the control group. Additionally, the trametinib group included patients with prior heart surgeries, which could affect the results. The shorter follow-up for the trametinib group may also underestimate long-term side effects.

In a related editorial comment, Daphne T. Hsu, MD, FACC, explains that the study is "Promising But Not Yet the Promised Land." She notes that "Important questions regarding the pharmacokinetics and pharmacodynamics of trametinib in infants, the appropriate timing and duration of treatment, and the short- and long-term safety of the MEK inhibition in the developing child must be answered to understand the potential benefit of trametinib in this scenario."

"Given the rarity of this condition and the lack of existing therapies for these children, we felt it was important to publish this paper, with the hope that it will advance the field by providing a foundation for future randomized clinical trials to definitively evaluate the safety and efficacy of trametinib in children with HCM," adds Douglas L. Mann, MD, FACC, editor-in-chief of JACC: Basic to Translational Science.

Clinical Topics: Cardiac Surgery, Invasive Cardiovascular Angiography and Intervention, Cardiac Surgery and Heart Failure, Heart Transplant

Keywords: Cardiac Surgical Procedures, Heart Transplantation, Mitogen-Activated Protein Kinase Kinases