Effect and Complications of Everolimus Use for Giant Cardiac Rhabdomyomas with Neonatal Tuberous Sclerosis

Abstract

Most cardiac rhabdomyomas with tuberous sclerosis (TS) are asymptomatic and spontaneously regress. However, some cases require surgical intervention due to arrhythmia and severe obstruction of cardiac inflow or outflow. We report herein a neonatal case of giant cardiac rhabdomyomas with TS and insufficient pulmonary blood flow from the right ventricle. Lipoprostaglandin E1 was necessary to maintain patency of the ductus arteriosus. We used everolimus, a mammalian target of rapamycin inhibitor, to diminish the cardiac rhabdomyomas. After treatment, the rhabdomyomas shrank rapidly, but the serum concentration of everolimus increased sharply (maximum serum trough level: 76.1 ng/mL) and induced complications including pulmonary hemorrhage, liver dysfunction, and acne. After the everolimus level decreased, the complications resolved. Everolimus may be a viable treatment option for rhabdomyomas, but its concentration requires close monitoring to circumvent complications associated with its use.

Treatment of Cardiac Rhabdomyomas with mTOR Inhibitors in Children with Tuberous Sclerosis Complex—A Systematic Review

“…One study classified as “other” was excluded as it was a notifying article about the planned randomized study of everolimus in CRs treatment [ 23 ]. Overall, 30 reports were included in the systematic review [ 24 , 25 , 26 , 27 , 28 , 29 , 30 , 31 , 32 , 33 , 34 , 35 , 36 , 37 , 38 , 39 , 40 , 41 , 42 , 43 , 44 , 45 , 46 , 47 , 48 , 49 , 50 , 51 , 52 , 53 ]. Three of the included articles partially duplicated the case reports [ 24 , 34 , 53 ].…”

“…In 7 studies, authors reported more or less precise size of CR in more than one time point [ 24 , 26 , 36 , 43 , 46 , 47 , 52 ]. The reliable calculation of the correlation between treatment duration and CR reduction was impossible due to data reporting discrepancy and the risk of bias.…”

“…Most of the adverse effects were reported as mild. However, one neonate experienced a pulmonary hemorrhage on the third day of everolimus therapy that was probably associated with highly exceeded everolimus serum concentration [ 43 ]. One patient died during the treatment, however, the child was in a critical condition since birth [ 40 ].…”

Literature review of international mammalian target of rapamycin inhibitor use in the non-surgical management of haemodynamically significant cardiac rhabdomyomas

“…Having examined the series of published cases using mammalian target of rapamycin inhibitors for haemodynamically significant rhabdomyomas, these agents are clearly efficacious with all cases showing reduction in size or full resolution of cardiac rhabdomyoma. [10][11][12][13][14][15][16][17][18][19][20][21][22][23][26][27][28][29][30]32,33 However, these drugs are not without risk, and standardised dosing and treatment duration regimens remain to be defined. From the published case reports to date, there is no general consensus on dose of mammalian target of rapamycin inhibitors (variations from 0.1 mg OD to 0.25 mg BD twice per week to 0.5 mg BD twice per week).…”

Efficacy of Everolimus Low-Dose Treatment for Cardiac Rhabdomyomas in Neonatal Tuberous Sclerosis: Case Report and Literature Review

“…Everolimus has been successfully used off-label in pediatric case reports of symptomatic CRs associated with TSC [ 7 , 8 , 9 ]. The optimal dosage for neonates is still unknown and is currently under debate [ 3 , 5 , 10 , 11 , 12 , 13 , 14 , 15 , 16 , 17 , 18 , 19 , 20 , 21 ].…”