Korean Circ J.  2021 Sep;51(9):733-751. 10.4070/kcj.2021.0153.

Hypertrophic Cardiomyopathy in Infants from the Perspective of Cardiomyocyte Maturation

• Seok H
• Oh JH

• KMID: 2519834
• DOI: http://doi.org/10.4070/kcj.2021.0153

Abstract

Hypertrophic cardiomyopathy (HCM) is characterized by ventricular wall hypertrophy with diastolic dysfunction. Pediatric HCM is distinguished from the adult in many aspects. Most children with HCM do not present clinically until the adolescent period, even when they are born with genetic mutations. Some infants with early-onset HCM present with massive progressive myocardial hypertrophy in the first few months of life, which is often fatal. The mortality of pediatric HCM peaks during the infantile and adolescent periods. These periods roughly correlate with children's growth spurt. Non-sarcomeric causes of HCM are more frequent in pediatric HCM, while sarcomeric causes are more common in adults. From the perspective of cardiac development, the fetal heart has immature cardiomyocytes, which are characterized by proliferation and exit their cell cycles with a decreased regenerative property after birth. In the perinatal period, there is a dynamic change in maturation of cardiomyocytes from immature to mature cells. Infants who are treated with steroids or born to mothers with diabetes or hyperthyroidism often show phenotypes of HCM, which gradually resolve. With remarkable advancement of molecular biology, understanding on maturation of cardiomyocytes has increased. Neonates undergo abrupt environmental changes during the transitional circulation, which is affected by oxygen, metabolic and hormonal fluctuations. Derangement in physiological transition to the normal postnatal environment may influence maturation of proliferative immature cardiomyocytes during early infancy. This article reviews updates of infantile HCM and recent molecular studies related to maturation of cardiomyocytes from the clinical point of view of identifying distinct characteristics of infantile HCM.

Keyword

Cardiomyopathy; Hypertrophic; Cardiomyocytes; Maturation; Infant

Figure

• 

  Figure 1 Echocardiographic images of a case of infantile HCM. Images were taken at 13 weeks after birth in a neonate who was born at the gestational age of 27+2 weeks to a mother with gestational DM. This neonate was treated with corticosteroids for severe BPD of a premature infant. Images were captured with a modified parasternal long-axis view owing to a limited transthoracic window with severe BPD. Massive diffuse LV wall hypertrophy (LV wall thickness z score: >10.0) in the systolic (A) and diastolic phase (B) can be seen.BPD = bronchopulmonary dysplasia; DM = diabetes mellitus; HCM = hypertrophic cardiomyopathy; LV = left ventricle.

• 

  Figure 2 Echocardiographic images of an 8-month-old infant with ACAD9 gene mutation. The patient had a birth weight of 2.9 kg at 37 weeks of gestation and showed developmental delay. Antenatal sonography showed non-specific findings. These images show a diffuse hypertrophied left ventricular wall on the parasternal long-axis view (A) and apical four-chamber view (B) with a thick interventricular septum (z score: 10.0).ACAD9 = acyl-COA dehydrogenase 9.

• 

  Figure 3 Gross specimen of fatal fulminant infantile HCM (left) shows diffuse hypertrophy of the ventricular wall without prominent fibrosis. Microscopic findings of the myocardium (right) show hypertrophy of cardiomyocytes with nuclear enlargement and hyperchromasia. The nuclei predominantly show a typical box shape (bar = 50 μm) (reproduced with permission from Seo HS, et al. Korean Circ J 2013;43:54–6).HCM = hypertrophic cardiomyopathy.

• 

  Figure 4 Proliferative hyperplastic immature cardiomyocytes versus non-proliferative hypertrophic postnatal mature cardiomyocytes and phenotypes of infantile HCM and late-onset HCM.HCM = hypertrophic cardiomyopathy.*Footnote areas are referred from Bergmann et al.10)

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