Conduction system hamartoma is a benign hamartomatous lesion arising from Purkinje and Purkinje-like cells of the heart. We aimed to investigate the cases that we detected during postmortem histopathological examination. The histopathology reports of the cases autopsied between 2012 and 2022 were reviewed retrospectively. The cases were evaluated in terms of histopathological features, demographic data, autopsy findings, causes of death, microbiological results, and accompanying cardiac anomalies. There was a total of 4 cases. The female-to-male ratio was 3/1. The mean age of the cases was 5.8 months. The heart weight was found within the normal range when evaluated according to age and gender. Microscopy revealed sharply demarcated cell groups or layers with histiocyte-like cells with foamy cytoplasm. Congenital heart disease and lung infection were given as causes of death in all cases. The lesion, which was previously called histiocytoid cardiomyopathy and many different names, is known as "conduction system hamartoma" in the latest World Health Organization classification (5th edition). Being aware of this entity that causes fatal arrhythmias and sudden cardiac deaths is important for pathologists. Autopsy findings should be evaluated by taking extra samples from the heart if necessary, especially in suspected cases below 2 years of age.

Hypertrophic cardiomyopathy in the neonate has a diverse genetic background, and non-sarcomeric variants may not be identified on commercial genetic testing panels. NDUFB11 is an X-linked mitochondrial Complex I protein and is known to cause histiocytoid cardiomyopathy but has not been described in female infants with hypertrophic cardiomyopathy. We present this first reported case of obstructive hypertrophic cardiomyopathy in a female neonate secondary to a pathogenic variant in NDUFB11. A term female neonate presented following a prenatal diagnosis of biventricular hypertrophy and growth restriction. She developed lactic acidosis after birth and whole-genome sequencing identified a de novo variant in the mitochondrial Complex I gene, NDUFB11 (c.391G>A, p.Glu131Lys). There was progression of left ventricular hypertrophy and obstruction, with rapid development of heart failure symptoms. She was unresponsive to beta-blocker medical therapy and was not suitable for advanced mechanical support. There was subsequent clinical deterioration resulting in death by 3 months of age. Hemizygous variants in NDUFB11 have been associated with hypertrophic cardiomyopathy in male infants previously, and skewed X-linked inactivation likely resulted in the presentation described here in a female infant. This variant was not identifiable by commercial cardiomyopathy panels. We highlight the importance of rapid whole-genome sequencing in cases of infantile hypertrophic cardiomyopathy and the importance of genetic diagnosis in guiding prognosis and care for these individuals.

Histiocytoid cardiomyopathy (HC) is an arrhythmogenic disorder, usually involving children under two years of age with a strong Caucasian and female predominance. The disease is fatal in the vast majority and diagnosis is nearly always established at autopsy, but this is only possible with adequate myocardial sampling. Meticulous gross and histological examination of the heart in collaboration with a cardiovascular-trained pathologist maximises the opportunity to make specific diagnoses (and therefore rule out the differentials of SIDS, SUDC and child abuse), guide genetic testing, and inform potentially life-saving medical interventions for blood relations. We present a typical HC case presenting as sudden death, without prodrome, in a previously healthy 18-month-old boy. The disease is characterised histologically by discrete groups of enlarged, polygonal histiocyte-like cells with distinct margins and abundant faintly eosinophilic foamy cytoplasm. Cells often contain coarse granules, microvacuoles and irregular, round nuclei. In our case, dysplastic fascicles were predominantly located immediately deep to the endocardium of the left ventricle. We report our own autopsy findings with histological images, and discuss the expected clinical, morphological and ultrastructural features of the disease.

Histiocytoid cardiomyopathy is a rare infancy cardiac disorder manifesting as severe cardiac arrhythmias or dilated cardiomyopathy. There is no specific treatment for these arrhythmias. This is the first report of infantile histiocytoid cardiomyopathy whose refractory ventricular arrhythmias were successfully controlled by high-dose carvedilol. A 4-month-old girl presented with asystole, and recurrent ventricular tachycardias. From the histological findings and clinical symptoms, she was diagnosed as histiocytoid cardiomyopathy. Sedatives were the most effective therapy for her arrhythmia, but the cardiac sympathetic denervation was not effective enough. Finally, her ventricular arrhythmias were controlled with high-dose carvedilol, and she was discharged on hospitalization Day 393. Carvedilol is the only beta blocker that directly acts on the ryanodine receptor (RyR2) and inhibits store-overload-induced Ca2+ release (SOICR) in myocardium at high dosage. The arrhythmias did not disappear with bisoprolol, landiolol, or verapamil, but high-dose carvedilol was effective. This clinical course suggested that the arrhythmias in histiocytoid cardiomyopathy might be related with SOICR. High-dose carvedilol might be a key drug for patients with histiocytoid cardiomyopathy.

Histiocytoid cardiomyopathy (HICMP) is a rare mitochondrial cardiomyopathy associated with recurrent life-threatening arrhythmias and variable degrees of systolic dysfunction. Successful heart transplantation for HICMP has been described, but there has been no published experience with biventricular assist device (BiVAD) support for intractable arrhythmias in HICMP. We report a 13 month old girl with left ventricular noncompaction and preserved systolic function who presented in cardiogenic shock secondary to incessant ventricular arrhythmias. After failed attempts at chemical and electrical cardioversion, she underwent BiVAD implantation as bridge to transplantation. Her BiVAD course was complicated by mechanical inflow obstruction during sinus rhythm, necessitating left-sided cannulation revision from an apical to atrial inflow cannula. This maneuver resolved the obstruction and the patient was transitioned to Berlin EXCOR (Berlin Heart Inc, The Woodlands, TX) BiVADs. On Berlin pumps, she had intermittent pauses (no fill/no eject) while in sinus rhythm, felt to be due to competition from intrinsic ejection. Despite these pauses, the patient experienced an uneventful remainder of her BiVAD course (205 days total) with minimal fibrin deposition and no device-related complications. BiVAD can support pediatric patients with hemodynamically significant arrhythmias to transplantation. Atrial cannulation strategy may be preferred in cases of preserved systolic function, ventricular noncompaction, and frequent rhythm changes.