Introduction
Takotsubo cardiomyopathy is named for echocardiographic features that look like the “tako-tsubo” (octopus trap). This condition is also known as stress cardiomyopathy or broken heart syndrome and is classically associated with older women after experiencing a significant emotional stress such as the loss of a spouse. Reference Sendi, Martinez, Chegondi and Totapally1 Although rare, estimated incidence in paediatrics is ∼ 3.1 per 100,000 discharges. Reference Sendi, Martinez, Chegondi and Totapally1 Within the paediatric population, it is more typically seen in adolescent males with preceding physical triggers and/or psychiatric history. Reference Sendi, Martinez, Chegondi and Totapally1,Reference Vazirani, Rodriguez-Gonzalez and Castellano-Martinez2
Patient presentation
Our patient is an 11-year-old male with cerebral palsy, developmental delay, seizures (history of placement of ventriculoperitoneal shunt and vagal nerve stimulator), obstructive sleep apnoea with continuous positive airway pressure dependence, and neuromuscular scoliosis who presented for a scheduled posterior spinal fusion. For 2 days prior to surgery, he received gabapentin pre-treatment and was noted by parents to have increased sleepiness and sinus bradycardia on home monitor. He underwent anaesthetic induction with inhaled sevoflurane followed by intravenous propofol, fentanyl, rocuronium, and ketamine with resultant bradycardia and profound hypotension. He became pulseless and received two minutes of chest compressions and two doses of epinephrine during the code with return of spontaneous circulation. The posterior spinal fusion was aborted, and he was admitted to the paediatric ICU (PICU) on an epinephrine infusion. CT head ruled out intracranial process, and CT angiography of the chest ruled out pulmonary embolism as the cause of the cardiac arrest. Transthoracic echocardiogram demonstrated normal left ventricular size, but severe hypokinesis of the septum and walls from the mid-ventricle to the apex with systolic dysfunction, with an overall left ventricular ejection fraction of 36% and moderately diminished right ventricular systolic function (Figure 1). He subsequently underwent cardiac CT, which showed normal coronary arteries. His initial electrocardiogram had non-specific ST segment and T wave abnormalities (Figure 2), and troponin was mildly elevated at 50 ng/L (normal range < 31 ng/L). His troponin peaked ∼1200 ng/L and then down trended to normal at 19.9 ng/L by day 6. A repeat echocardiogram 2 days post-arrest had no regional wall abnormalities with significant improvement in left ventricular systolic function with ejection fraction of 54% and only mildly diminished right ventricular systolic function.
Initial echocardiogram obtained the day of cardiac arrest—apical four-chamber view. ( a ) In diastole, the left ventricle and right ventricle have normal size and appropriate filling. ( b ) In systole, the basal portion of the heart is seen contracting inward normally (red arrows) with apical portion without normal contractility giving an appearance like an octopus trap.
Electrocardiogram. ( a ) Electrocardiogram obtained the day of cardiac arrest. There are non-specific ST segment and T wave abnormalities throughout the electrocardiogram. Of note, the spikes noted throughout are related to the patient’s vagal nerve stimulator that was initially placed secondary to an underlying neurologic disorder. ( b ) Electrocardiogram that shows normalization of the ST segment and T wave abnormalities.
During his PICU stay, he required inotropic support with milrinone, epinephrine, and norepinephrine. All inotropic support was discontinued by day 7 of hospitalization, and he received only supportive cardiac care for the remainder of the admission. Eight days after his arrest, his echocardiogram had completely normalized with normal biventricular size and systolic function. He remained admitted for an additional 24 days due to non-cardiac complications. He was discharged without any cardiac medications and has since been followed in our heart failure clinic with continued normal left ventricular systolic function without regional wall abnormalities. He had not had any prior cardiac workup, and genetic testing to evaluate for a unifying diagnosis of chronic comorbidities was declined by family; however, they consented to cardiomyopathy-specific genetic testing, which was negative for variants in known cardiomyopathy genes. His family history was also negative for any known cardiomyopathy.
Conclusion
The underlying pathophysiology of Takotsubo cardiomyopathy has not been fully elucidated; however, it is believed to be related to an exaggerated sympathetic stimulation leading to catecholamine release. Reference Sendi, Martinez, Chegondi and Totapally1 Further, the mechanism behind the apical region dysfunction with preservation of basal function is not understood with current theories including coronary vasoconstriction from sympathetic tone, coronary microspasm leading to abnormal flow, or direct myocyte injury from elevated catecholamines. Reference Sendi, Martinez, Chegondi and Totapally1 We believe our patient experienced relative gabapentin toxicity, which coupled with anaesthetic induction and decreased systemic vascular resistance resulted in cardiac arrest. He then had a robust response to appropriate resuscitative epinephrine dosing with systolic blood pressures reaching as high as 200 mmHg. This response may be due to dysregulated vascular tone and the catecholamine effect, which is like the stress response described in Takotsubo cardiomyopathy. This has been described in other case reports in patients with significant stress pre-surgery subsequently combined with the physical stress from anaesthesia and surgery as well as in patients that receive high-dose epinephrine for anaphylaxis, etc. Reference Khalili, Dabbous, Taha, Naji, Bahjah and Beresian4,Reference Ouerghi, Boukhris, Grall, Desprets and Quercy5,Reference Y-Hassan6,Reference Patrick and Tobias7 There has only been one case report in an adult with gabapentin-induced cardiomyopathy, but none in children. Reference Tellor, Ngo-Lam, Badran, Armbruster and Schwarze3
The mechanism of action of gabapentin is poorly understood but postulated as binding to the α2δ-subunit of voltage-gated calcium channels, thereby inhibiting the influx of intracellular calcium, causing a decrease in the release of excitatory neurotransmitters. We believe the mechanism of hypotension is via presynaptic inhibition, resulting in decreased sympathetic output and subsequent systemic vasodilation, which has been previously described. Reference Patrick and Tobias7 The appropriate dose of epinephrine then had an exaggerated blood pressure response by an acute increased systemic vascular resistance because the vascular receptors were not blocked directly, but rather, vasodilation was through gabapentin’s central presynaptic inhibition. This exacerbated response to catecholamines, in this case exogenous epinephrine, would be consistent with other mechanisms of Takotsubo, where there is an acute sympathetic output resulting in cardiac dysfunction. There is no standardized treatment regimen for Takotsubo and remains based on each individual patient’s presentation and focuses on supportive treatment until the left ventricular function normalizes, Reference Hernadez8 which was similar to what was done with our patient. Given the acute onset of cardiac dysfunction after resuscitation in our patient, we considered post-cardiac arrest syndrome leading to myocardial dysfunction or “stun” as an aetiology of his significantly depressed function. Although a well-described and transient phenomenon, post-cardiac arrest dysfunction tends to have a shorter duration compared to Takotsubo, with many studies showing recovery within 24–48 hours, and the dysfunction is global. Reference Neumar, Nolan, Adrie, Aibiki, Berg and Bottiger9 Our patient had a more prolonged recovery time, requiring 8 days before his left ventricular ejection fraction had normalized, and he had preservation of his basal function, which is not seen in post-cardiac arrest dysfunction but is characteristic of Takotsubo. This case highlights the importance of consideration of potential, rare drug interactions and the sequelae of an extremely rare presentation of cardiomyopathy in a paediatric patient.
Supplementary material
The supplementary material for this article can be found at https://doi.org/10.1017/S1047951125101625.
Financial support
This research received no specific grant from any funding agency, commercial, or not-for-profit sectors.
Competing interests
The authors declare none.
Ethical standard
The authors assert that all procedures contributing to this work comply with the ethical standards of the relevant national guidelines on human experimentation and with the Helsinki Declaration of 1975, as revised in 2008, and due to the nature of being a case report, IRB approval was not needed. Informed consent was obtained from the patient’s parents due to patient being a minor at time of publication.
