CASE REPORT Fetal Cardiac Rhabdomyoma

CASE REPORT
Fetal Cardiac Rhabdomyoma: A Case Report
Abduljalil, Rawan*. Quraish, Abida**
ABSTRACT
Background: Fetal cardiac rhabdomyoma is the most common cardiac tumor which is diagnosed antenatally. It has a strong association with tuberous sclerosis.
Case: We described a case of cardiac rhabdomyoma which was diagnosed at 22 weeks gestation through an anomaly scan. Scan showed multiple masses related to the ventricular myocardium with no obstruction to blood inflow or outflow from the ventricles. At birth, the diagnosis of cardiac rhabdomyoma with tuberous sclerosis was confirmed. Repeated echocardiographyat three months of life showed slightly decrease in the tumor with no deterioration of the cardiovascular status.

Conclusion: Most common cardiac tumor in children is rhabdomyoma, which may disappear spontaneously in the majority of patients over the long term. Most of them do not require treatment. They vary in clinical status from absence of symptoms to heart failure and respiratory distress which requires surgical intervention. All these children, even asymptomatic ones, need regular serial follow-ups including echocardiographs.
KEYWORDS
Fetal cardiac tumor, Rhabdomyoma, Tuberous sclerosis, Autosomal dominant.______________________________________________________________________________________
INTRODUCTION
Antenatal diagnosis of cardiac rhabdomyoma was first reported by De Vore et al. in 1982.(1) It presented in up to 90% of cardiac tumors in pediatrics populations.(2) The incidence of congenital cardiac tumors was 1 in 20,000 births(3), were the reported prevalence were 0.25% in autopsies and 0.08% among the live born.(3,4)
Rhabdomyomas are hamartomas benign smooth muscle that derived from embryonic myoblasts.
Echocardiography has been established as the primary diagnostic tool for the evaluation of cardiac tumors.(5) Predominantly localized within the ventricles but can be found in the vessels which may lead to obstruction of cardiac valves or inflow/outflow tracts.

They are typically asymptomatic but may also cause atrial or ventricular arrhythmias, sinus node dysfunction, congestive heart failure and heart block.

Some studies reported the high correlation between cardiac rhabdomyomas and positive tuberous sclerosis around 50 to 80%.(1,6,7) Most of the patients with Tuberous sclerosis complex (TSC) have inactivating mutations in either TSC1 or TSC2 gene, resulting in activation of mechanistic target of rapamycin (mTOR), which is responsible for a proliferative cellular response and cell activation.(8)
The better prognosis is when it detected prenatally, and most of them asymptomatic; regressing spontaneously during the first few months after birth. Were as obstruction to the inflow or outflow tract indicated poor prognosis. The risk of fetal death is 4-6%.(1)
As recommended, these cases suppose to be delivered in centers were pediatric cardiology and surgery facilities available. After delivery, infants are advised for regular follow-up with serial echocardiograms. Surgical resection of tumor is not usually done unless it causes severe arrhythmias, valvular obstruction, or congestive heart failure.(9)
Recent literatures suggested that early therapy with a mechanistic target of rapamycin (mTOR) inhibitors may cause regression of the tumor size, as well as preventing the development of tuberous sclerosis manifestations.(10,11)
CASE REPORT
A 19 years old primigravida Bahraini female, of a first degree consanguineous marriage and spontaneous conception, had a regular antenatal follow-up in Bahrain Defence Hospital. She is a known case of bicornuate uterus diagnosed through early pregnancy. Her last menstrual period was on 12 June 2017 with an early scan showed expected date of delivery 18 March 2018. There was no major illness in the past, no history of any congenital anomalies in the family. Has a laser cosmetic therapy for upper lip mole.

The patient did an anomaly scan which showed a single fetus with microcephaly and intraventricular rhabdomyoma.

Antenatal fetal echo study confirmed multiple masses related to the ventricular myocardium, the largest of which measured 18x12mm in the left ventricle, the other two masses measured 14x8mm and 15x7mm related to the posterior interventricular septum. There was no obstruction to blood inflow or outflow from the ventricles. The presence of multiple cardiac tumors consistent with rhabdomyoma most likely secondary to tuberous sclerosis. The pregnancy may allow going term and may have normal vaginal delivery.

The patient came in early labor at thirty-seven weeks gestation with breech presentation, delivered by emergency lower segment caesarian section; a live male baby of 2.48 kg with an Apgar score of nine and ten at one and five minutes after delivery respectively.

Patient’s postnatal course was uneventful and was discharged on third day postpartum.

At day 1 of life, the infant developed tachypnea and desaturation kept on nasal continuous positive airway pressure (CPAP) but still oxygen requirement is high so intubated and kept on PTV mode still not maintaining then shifted to High-frequency osculatory ventilation (HFO). He needed nitric oxide along with a norepinephrine for Persistent pulmonary hypertension (PPHTN), weaned gradually as kept on room air since day nine of life.

Fetal US brain done showed both cerebral hemispheres are of normal morphology and echo pattern. No abnormal focal echogenicity. Unremarkable appearances of the ventricular system with no evidence of hydrocephalus. No detectable intracerebral, intraventricular or subarachnoid hemorrhage now.

Tuberous sclerosis was confirmed.

Fetal echo has done after birth showed a large rhabdomyoma attached to the intraventricular septum to the left ventricle side measured 18x14mm, additional two large ones at the atrioventricular groove measured 5x4mm and 3.5x5mm and right ventricle apex measured 10×6.9mm. A multiple rhabdomyoma was seen at the left ventricle/right ventricle free wall and intraventricular septum. No vessel obstruction. PFO shunt seen with a right to left flow. Trivial mitral regurgitation with mild tricuspid regurgitation. PDA shunt 2-3mm seen with right to left flow. Normal aortic arch, no coarctation of the aorta. Ejection fraction 71%. Good biventricular systolic function. No pericardial effusion.

The infant upon discharge was in stabled condition. Discharged on day 16 of life with a weight of 2.375 kg, and has been managed as an outpatient in pediatric and pediatric cardiology clinic at our hospital.

After delivery, examination by a pediatric cardiologist confirmed that the infant had a cardiac tumor and the cardiac function of the infant was diagnosed as normal.
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Figure 1 Figure 2 Figure 3
Figure 1: Large rhabdomyoma attached to the intraventricular septum to the left ventricle side measured 18x12mm.

Figure 2: There is no obstruction to blood inflow or outflow from the ventricles.

Figure 3: Is a basal cut that shows three tumors.29718001263650045720012636500
Figure 4 Figure 5
Figure 4 and 5: Ultrasound of the brain showed both cerebral hemispheres are of normal morphology and echo pattern. No abnormal focal echogenicity.

Stayed at the hospital for approximately 3 weeks duration and discharged in stable condition.

At 1 month of age, readmitted with an episode of cyanosis and uprolling of eyes lasted for few seconds. Discharged after 5 days in stable condition.

At 2 months of age, readmitted as having decreased activity to rule out sepsis. During admission developed supraventricular tachycardia which aborted with adenosine, admitted 1 day in ICU. Discharged after 3 days in stable condition.

Repeated echo at age of 3 months; the largest tumor slightly reduced in size while the others almost remain the same size.

DISCUSSION:
Cardiac rhabdomyomas accounts for the majority of cardiac tumors in pediatrics populations, the majority are asymptomatic, associated with tuberous sclerosis complex and regress spontaneously during the first few months after birth.
A case reported by Kwiatkowska et al.,(12); newborn with multiple giant cardiac tumors; largest measured 33x30mm with no obstruction to both inflow and outflow heart tracks. During 3 months follow-up, the infant remains asymptomatic. In this study, stated that asymptomatic infants need close follow-up with serial imaging and electrocardiography as they are at risk of a sudden unsuspected death.

Kwiatkowska et al.,(13) studied 30 children with cardiac tumors. Most of them did not need cardiac surgery except 3 cases due to severe hemodynamically disturbance. All of them confirmed association with tuberous sclerosis. There was only one death during the follow-up period.

A study performed by Chen et al., (14) on total 53 pregnant women with fetal cardiac tumor(s). Thirty-seven out of fifty-three were having multiple cardiac tumors, where as the rest had a single cardiac tumor. This study concludes that there is no significant difference between single and multiple tumors regarding the degree of fetal heart damage.

Helen et al., (10) reported a neonate case with a single rhabdomyoma obstructing the left ventricular outflow tract of diameter 1.3 cm2. Everolimus was used for 6 months duration 0.5mg twice weekly which showed a significant reduction in the tumor size. The drug was tapered gradually to prevent a rebound increase on the tumor size and prevented late side effects of the drug.

Hoshal et al., (11) reported a 2 days old neonate, the tumor was obstructing the outflow tract of the right ventricle and infiltrated into the left ventricle. Everolimus was started after a successful cardiopulmonary resuscitation. It results in a successful reduction of tumor size within 2 months of therapy.

Another case report by Demir et al.,(15) of a neonatal cardiac rhabdomyoma using Everolimus. The tumor regressed to a smaller size after 75 days of therapy.

Our case was the first case reported at Bahrain Defence Hospital Bahrain, which was diagnosed antenatally. Was regularly followed up which showed regression of tumor size without any medical or surgical treatment. Other studies reported using Everolimus drug for regression of tumor size.
REFERENCES:
1. Bader, Rima S., et al. “Fetal Rhabdomyoma: Prenatal Diagnosis, Clinical Outcome, and Incidence of Associated Tuberous Sclerosis Complex.” Journal of the American College of Cardiology, vol. 41, no. 6, 2003, pp. 483–484., doi:10.1016/s0735-1097(03)82645-1.

2. Grebenc, Mary L., et al. “Primary Cardiac and Pericardial Neoplasms: Radiologic-Pathologic Correlation.” RadioGraphics, vol. 20, no. 4, 2000, pp. 1073–1103., doi:10.1148/radiographics.20.4.g00jl081073.

3. Bejiqi, Ramush, et al. “Prenatally Diagnosis and Outcome of Fetuses with Cardiac Rhabdomyoma – Single Centre Experience.” Open Access Macedonian Journal of Medical Sciences, 2017, doi:10.3889/oamjms.2017.040.

4. Kulkarni, Akhil M., el al. “Multiple Intracardiac Rhabdomyomas, an Antenatal Clue to the Diagnosis of Tuberous Sclerosis.” RGUHS J Med Sciences, 2013, Vol 3 / Issue 1
5. Sciacca, Pietro, et al. “Rhabdomyomas and Tuberous Sclerosis Complex: Our Experience in 33 Cases.” BMC Cardiovascular Disorders, vol. 14, no. 1, Sept. 2014, doi:10.1186/1471-2261-14-66.

6. Chao, A. S., et al. “Outcome of Antenatally Diagnosed Cardiac Rhabdomyoma: Case Series and a Meta-Analysis.” Ultrasound in Obstetrics and Gynecology, vol. 31, no. 3, 2008, pp. 289–295., doi:10.1002/uog.5264.

7. Chen, Jian, et al. “Fetal Cardiac Tumors: Fetal Echocardiography, Clinical Outcome and Genetic Analysis in 53 Cases.” Ultrasound in Obstetrics ; Gynecology, June 2018, doi:10.1002/uog.19108.
8. Franz, David Neal. “Everolimus: an MTOR Inhibitor for the Treatment of Tuberous Sclerosis.” Expert Review of Anticancer Therapy, vol. 11, no. 8, 2011, pp. 1181–1192., doi:10.1586/era.11.93.

9. Venugopalan P, Babu JS, Al-Bulushi A: Right atrial rhabdomyoma acting as the substrate for Wolff-Parkinson-White syndrome in a 3-month-old infant. Acta Cardiol 2005, 60:543–545.10. Bornaun, Helen, et al. “Regression of Cardiac Rhabdomyomas in a Neonate after Everolimus Treatment.” Case Reports in Pediatrics, vol. 2016, 2016, pp. 1–3., doi:10.1155/2016/8712962.

11. Hoshal, Steven G., et al. “Regression of Massive Cardiac Rhabdomyoma on Everolimus Therapy.” Pediatrics International, vol. 58, no. 5, 2015, pp. 397–399., doi:10.1111/ped.12816.

12. Kwiatkowska, J., Ciemny, S., ; Koz?owski, D. (2017). Giant cardiac tumors in the newborn – an unusual image. Folia Morphologica. doi:10.5603/fm.a2017.0119
13. Kwiatkowska, J et al. “Cardiac tumors in children: A 20-year review of clinical presentation, diagnostics and treatment.” 2018, doi: 10.17219/acem/62121
14. Chen, Jian, et al. “Fetal Cardiac Tumors: Fetal Echocardiography, Clinical Outcome and Genetic Analysis in 53 Cases.” Ultrasound in Obstetrics ; Gynecology, June 2018, doi:10.1002/uog.19108.
15. Demir, H. A., et al. “Everolimus: A Challenging Drug in the Treatment of Multifocal Inoperable Cardiac Rhabdomyoma.” Pediatrics, vol. 130, no. 1, 2012, doi:10.1542/peds.2011-3476.

In a study by Beghetti et al. 41% of cardiac rhabdomyomas cases were associated with TSC2 , in contrast to the data reported by Holley et al., who stated that the incidence was 91%.21 Despite the considerable discrepancies in the frequency of coexisting rhabdomyiomas and TSC, both Beghetti et al. and Holley et al. emphasize that the seizures were a leading symptom of TSC.

2. Beghetti M, Gow RM, Haney I, Mawson J, Williams WG, Freedom RM. Pediatric primary benign cardiac tumors: A 15-year review. Am Heart J. 1997;134:1107–1114.

21. Holley DG, Martin GR, Brenner JI, et al. Diagnosis and management of fetal cardiac tumors: A multicenter experience and review of published reports. J Am Coll Cardiol. 1995;26:516–20.

Beghetti et al.2 reported partial or complete spontaneous regression in 54% of 44 analyzed patients. In the present study, spontaneous resolution of the tumor occurred in 12 out of 16 children with a confirmed diagnosis of tuberous sclerosis (75%) in a mean time of 4 years, based on repeated echo examinations.3 In the rest of the study group there was no progression on echo and/or MRI visualization, and no further indication for a cardiac surgery.

2. Beghetti M, Gow RM, Haney I, Mawson J, Williams WG, Freedom RM. Pediatric primary benign cardiac tumors: A 15-year review. Am Heart J. 1997;134:1107–1114.

3. Kwiatkowska, J ., Waldoch, A ., Meyer-Szary, J ., Potaz, P ., Grzybiak, M . (2016). Cardiac tumors in children: A 20-year review of clinical presentation, diagnostics and treatment. Doi: 10.17219/acem/62121
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Magnetic resonance imaging (MRI) is more helpful in the diagnosis of brain lesions.

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