A Newborn Presenting with Alternating Bradycardia and Tachycardia

A male infant is delivered to a healthy 36-year-old primigravida. The family history is unremarkable. At 26 weeks of gestation, fetal arrhythmia was suspected. A fetal cardiac ultrasound conducted at 27 weeks revealed isolated premature atrial contractions that were not observed during subsequent evaluations at 29 and 33 weeks. No structural cardiac abnormalities were identified. The mother’s medications were limited to prenatal vitamins. Prenatal maternal laboratory results were within normal limits, including negative Group B Streptococcus screening, nonreactive rapid plasma regain, negative HIV and hepatitis B surface antigen tests, rubella immunity, toxoplasmosis nonimmunity, and normal thyroid function.Because of fetal bradycardia, the infant was delivered by cesarean section at 39 weeks of gestation. Cord blood gas analysis yielded unremarkable results (pH 7.27, bicarbonate 25 mEq/L, base excess −3 mmol/L, lactate 1.7 mmol/L). Apgar scores were 8 and 9 at 1 and 5 minutes, respectively, with no requirement for resuscitation.At birth, the infant exhibited bradycardia with a heart rate of 90 bpm that rapidly progressed to tachycardia. Cardiac monitoring identified supraventricular tachycardia (SVT) with a heart rate ranging from 220 to 260 bpm. The condition was unresponsive to intravenous adenosine (administered at 1 × 100 μg/kg and 2 × 200 μg/kg), necessitating transfer to the neonatal intensive care unit (NICU). During transportation, spontaneous reversion of SVT to sinus bradycardia was observed.On admission to the NICU, the newborn was in good general condition. His heart rate was 109 bpm, blood pressure measured 55/28 mm Hg, respiratory rate was 30 breaths per minute, and peripheral oxygen saturation was 98%. Cardiac auscultation revealed normal S1 and S2 sounds without murmurs and capillary refill time was less than 3 seconds. Pulses in the upper and lower extremities were palpable and symmetrical. The remainder of the physical examination yielded no significant findings. Laboratory investigations, including a complete blood count, chemistry panel, and C-reactive protein levels, were within normal limits. Blood cultures were negative.Electrocardiography demonstrated sinus bradycardia with a heart rate of 109 bpm and no additional abnormalities for the patient’s age. The chest radiograph was normal. Echocardiography (Figure 1) revealed multiple intracardiac echogenic lesions. On the same day, a cranial ultrasound (cUS) (Figure 2) identified multiple subcortical echogenic areas and subependymal nodules.Differential diagnosis for intracardiac echogenic lesions includes rhabdomyoma, fibroma, myxoma, metastatic tumor, thrombus, and teratoma.Neonatal cardiac tumors are a rare occurrence, with the majority being histologically benign. Rhabdomyomas represent the most prevalent form of benign cardiac tumors, followed by teratomas and fibromas.1 The clinical presentation is influenced by the size and anatomical location of the tumor, with manifestations observed during either the fetal or postnatal period. Tumors may compromise blood flow, interfere with myocardial function, or precipitate rhythm disturbances, potentially leading to diagnosis or resulting in adverse outcomes such as stillbirth or sudden death.1Each type of tumor exhibits distinct phenotypic characteristics, with echocardiography serving as the primary diagnostic tool for evaluation. The identification of multiple homogenous, echogenic masses within the ventricles is indicative of rhabdomyoma. Teratomas, the second most common cardiac tumor, are typically present as heterogeneous, encapsulated cystic lesions. Fibromas are most frequently localized within the ventricular septum and may occasionally demonstrate central calcifications. Notably, there was no significant risk of thrombus formation in this patient, and myxomas often present as pedunculated, mobile masses. Cardiac rhabdomyomas are closely associated with tuberous sclerosis, with up to 90% of infant cases exhibiting this correlation.2 The capability to perform bedside cUS facilitated the identification of cortical tubers and subependymal nodules, thereby fulfilling 2 major criteria for the clinical diagnosis of tuberous sclerosis complex (TSC) in accordance with the guidelines established by the International Tuberous Sclerosis Complex Consensus Group (Table 1). This diagnosis was established shortly after the neonate’s admission to the NICU.3TSC occurs in approximately 1 in 6000 live births.3 TSC is an autosomal dominant multisystem disorder caused by pathogenic variants in the TSC1 or TSC2 genes, with 75% of cases representing simplex cases (single occurrence within a family). These cases are more frequently associated with TSC2 variants.4 The TSC1 and TSC2 genes encode the proteins hamartin and tuberin, respectively, which are involved in the mammalian target of rapamycin (mTOR) signaling pathway.4 Affected organs may include the brain, kidneys, heart, liver, lungs, retina, and skin, with a broad phenotypic spectrum encompassing seizures, neurodevelopmental impairment, renal failure, and arrhythmias.3,4Neurologic manifestations such as epilepsy, cognitive impairment, and autism represent significant sources of morbidity and play a crucial role in determining the long-term prognosis of TSC. Approximately 80% of children with TSC develop epilepsy before the age of 2 years, often presenting as infantile spasms or West Syndrome.5 Clinical seizures are typically preceded by asymptomatic epileptiform activity detected on electroencephalography (EEG), followed by electrographic seizures without overt clinical manifestations.6 Recent evidence indicates that initiating antiseizure medication (ASM) on detection of these EEG abnormalities before clinical seizure onset improves epilepsy-related outcomes. The term “antiseizure medication” is now preferred over “antiepileptic drugs” to reflect the symptomatic nature of these therapies, thereby mitigating undue expectations regarding their curative potential. The International League Against Epilepsy has endorsed this terminology to ensure clearer communication among health care providers, patients, and caregivers.7Cardiac rhabdomyomas, although histologically benign, may lead to heart failure depending on their size, number, and anatomical location. This occurs when ventricular inflow or outflow is obstructed or severe arrhythmias develop. Additionally, cardiac rhabdomyomas may directly induce arrhythmias through extensive intramural infiltration involving the cardiac conduction system, resulting in SVT, sinus node dysfunction, ventricular tachycardia, or complete heart block.8 Although spontaneous regression of cardiac rhabdomyomas typically occurs within the first few years of life, surgical or medical interventions may be necessary in life-threatening scenarios.9,10 The mTOR inhibitor everolimus has been approved for the treatment of brain subependymal giant cell astrocytomas, renal angiomyolipomas, pulmonary lymphangioleiomyomatosis, and, more recently, cardiac rhabdomyomas.5 However, monitoring for side effects such as omega-3–responsive transient hypertriglyceridemia, self-limited diarrhea, decreased CD/CD8 ratio, and decreased lymphocyte percentages are important.Molecular diagnosis of TSC is established by identifying a heterozygous pathogenic variant in either TSC1 or TSC2, irrespective of clinical presentation. Molecular confirmation enhances diagnostic accuracy and provides essential information for genetic counseling. Pathogenic variants in TSC2 are generally associated with more severe phenotypes compared with TSC1, including increased risks of renal malignancy, intellectual disability, autism spectrum disorder, and infantile spasms. Genetic analysis enables reproductive counseling and facilitates options such as preimplantation genetic testing to prevent disease transmission. Additionally, predictive testing for asymptomatic at-risk family members is made possible.A comprehensive evaluation of the patient revealed an achromic patch in the right eye and a retinal hamartoma in the left eye (Figure 3). Renal ultrasonography and dermatologic examinations yielded normal results. EEG monitoring performed at 48 hours of life identified 2 epileptiform foci and abnormal baseline activity, prompting initiation of vigabatrin (100 mg/kg/d). Brain magnetic resonance imaging (MRI) conducted on day 5 corroborated the cUS findings (Figure 4).The patient experienced initial stability; however, by the seventh day of life, frequent episodes of SVT were observed with heart rates approximating 280 beats per minute, although hemodynamic stability was preserved. Low-dose propranolol and flecainide were initiated for anti-arrhythmic therapy, but adequate control of the tachyarrhythmia was not achieved. Dose escalation was precluded by baseline bradycardia. Consequently, everolimus was introduced on day 17 (0.25 mg twice weekly), achieving target serum levels between 5 and 15 ng/ml.During the two-month hospitalization, the patient exhibited a transient elevation in serum triglycerides, which resolved without intervention. Additionally, a febrile urinary tract infection necessitated a 7-day course of intravenous antibiotics, during which everolimus therapy was temporarily suspended. The patient was discharged at 2 months of age, receiving vigabatrin and everolimus under the supervision of a multidisciplinary team encompassing pediatric ophthalmology, general pediatrics, pediatric neurology, neurosurgery, pediatric cardiology, nephrology, radiology, dermatology, psychiatry, psychology, and genetics, in accordance with Portuguese guidelines for TSC diagnosis and management.11By 3 months of age, complete regression of cardiac rhabdomyomas was achieved (Figure 5) with the restoration of an age-appropriate heart rate. Although SVT episodes persisted, the normalization of baseline heart rate allowed for dose adjustments of anti-arrhythmic medications, resulting in effective tachyarrhythmia control by 5 months of age. Flecainide was discontinued at 10 months, followed by propranolol at 11 months.At 12 months, the patient demonstrated normal developmental progress, with unremarkable video EEG recordings conducted at 6-week intervals. Brain MRI identified no additional lesions apart from cortical tubers and subependymal nodules. Genetic testing confirmed the presence of a de novo heterozygous pathogenic variant in TSC2 (NM_000548.4): c.658C>T p.(Gln220*).Cardiac rhabdomyomas represent a significant cause of arrhythmias and are associated with TSC in up to 90% of infant cases.Approximately 80% of children diagnosed with TSC will develop epilepsy before the age of 2 years.Recent evidence indicates that the initiation of preventive ASM before the manifestation of clinical seizures may enhance neurological outcomes by mitigating the risk of refractory epilepsy, intellectual disability, and autism spectrum disorder.Early diagnosis of TSC facilitates not only the administration of epileptogenic preventive ASM but also enables more precise monitoring and targeted therapeutic interventions.Everolimus may serve as a potential therapeutic option for the management of arrhythmias associated with cardiac rhabdomyomas.American Board of Pediatrics Neonatal-Perinatal Content SpecificationRecognize signs of cardiac arrhythmia in the neonate.Understand neonatal seizure outcomes.