Fetal Cardiac Rhabdomyoma

Please also see section on fetal cardiac masses.

Please also see section on post-natal cardiac rhabdoymyoma for more information.

Quick Review

Cardiac rhabdomyomas represent the most prevalent primary cardiac tumors encountered during fetal life, accounting for the vast majority of all primary fetal cardiac masses. While these tumors are typically histologically benign, they have a profound genetic association with tuberous sclerosis complex, a disorder driven by mutations in the TSC1 or TSC2 genes. These specific mutations result in the hyperactivation and dysregulation of the mammalian target of rapamycin pathway, which acts as a central regulator for cell growth, proliferation, and survival. This pathway dysregulation promotes the abnormal proliferation of cells within the myocardial tissue, ultimately leading to the formation of the echogenic rhabdomyomas that are often detected prenatally during the second trimester through fetal imaging.

Most cardiac rhabdomyomas appear as multiple well-defined masses situated within the ventricles or septal walls of the heart. Although a large proportion of these lesions eventually regress spontaneously after birth, their size and anatomical location can significantly impact fetal physiology and cardiac function in-utero. Large tumors or those strategically positioned can cause significant morbidity by obstructing the left or right ventricular outflow tracts, leading to impaired blood flow and potential heart failure. Furthermore, these tumors can interfere with the heart's electrical system, serving as substrates for arrhythmias such as supraventricular tachycardia. In severe cases, these complications may progress to hydrops fetalis or result in fetal demise.

The emergence of pharmacological fetal therapy using mammalian target of rapamycin inhibitors, such as sirolimus and everolimus, has provided a promising non-invasive alternative to complex postnatal surgeries or premature delivery for managing symptomatic tumors. These therapeutic agents function by blocking the activity of the mammalian target of rapamycin complex 1, thereby inhibiting the abnormal cellular proliferation and angiogenesis that drive the growth of rhabdomyomas. Clinical evidence from several studies and case reports suggests that sirolimus can effectively promote the regression of these tumors in-utero when the drug is administered orally to the pregnant person. This approach relies on the transplacental transfer of the medication from the maternal circulation to the fetus, with some evidence suggesting that the transfer may be preferentially unidirectional.

In clinical practice, the prenatal administration of sirolimus has been associated with significant tumor regression and improvements in fetal complications like heart failure and outflow tract obstruction. Reported cases indicate that achieving maternal therapeutic trough levels, which are often targeted between 5 and 15 ng/mL, can lead to a rapid reduction in tumor volume and the normalization of fetal cardiac function. For instance, some fetuses have shown marked improvements in ventricular ejection fractions and the resolution of pericardial effusions within just a few weeks of starting maternal therapy. Despite these successes, it has been observed that the cessation of treatment before delivery can sometimes result in the rebound growth of the rhabdomyomas, requiring clinicians to carefully plan the timing of therapy termination relative to birth.

While the therapeutic benefits of sirolimus are promising, its use during pregnancy necessitates a careful evaluation of the risk-benefit ratio for each individual case. Potential maternal side effects include hyperlipidemia, alterations in glucose metabolism such as gestational diabetes, and rare but serious complications like interstitial pneumonitis, which may clinically manifest as a progressive dry cough. Neonatal outcomes following prenatal exposure are generally favourable, with many reports showing normal Apgar scores and developmental trajectories in early childhood. Nevertheless, a multidisciplinary approach involving specialists in maternal-fetal medicine, pediatric cardiology, and neonatology is essential to manage the complexities of maternal dosing, serial fetal echocardiography, and long-term surveillance for both the mother and the infant.