(Circulation 1990;82:507-513) In the early embryo, the heart is a loose interwoven mesh of muscle fibers.1-3 The developing myocardium gradually condenses, and the large spaces within the trabecular meshwork flatten or disappear. Trabecular compaction is normally more complete in left ventricular than in right ventricular myocardium. Noncompaction of ventricular myocardium (sometimes referred to as "spongy myocardium") is believed to represent an arrest in endomyocardial morphogenesis.4,5 The gross anatomical appearance is characterized by numerous, excessively prominent trabeculations and deep intertrabecular recesses. Rare in any case, noncompaction is almost invariably associated with other congenital cardiac malformations.45 Isolated noncompaction of left ventricular myocardium (INVM) (i.e., without associated anomalies) is rarer still.5-7 This report represents the largest study population to date.

Loss-of-function mutations in the G4.5 gene have been shown to cause Barth syndrome (BTHS), an X-linked disorder characterized by cardiac and skeletal myopathy, short stature, and neutropenia. We recently reported a family with a severe X-linked cardiomyopathy described as isolated noncompaction of the left ventricular myocardium (INVM). Other findings associated with BTHS (skeletal myopathy, neutropenia, growth retardation, elevated urinary organic acids, and mitochondrial abnormalities) were either absent or inconsistent. A linkage study of the X chromosome localized INVM to the Xq28 region near the BTHS locus, suggesting that these disorders are allelic. We screened the G4.5 gene for mutations in this family with SSCP and direct sequencing and found a novel glycine-to-arginine substitution at position 197. This position is conserved in a homologous Caenorhabditis elegans protein. We conclude that INVM is a severe allelic variant of BTHS with a specific effect on the heart. This finding provides further structure-function information about the G4.5 gene product and has implications for unexplained cases of severe infantile hypertrophic cardiomyopathy in males.

ABSTRACT. Objective. Echocardiography can be a rapid, noninvasive, objective tool in the assessment of ventricular function and preload during resuscitation of a critically ill or injured child. We sought to determine the accuracy of bedside limited echocardiography by the emergency physician (BLEEP) in estimation of (1) left ventricular function (LVF) and (2) inferior vena cava (IVC) volume, as an indirect measure of preload.Methods. We conducted a prospective observational study of a convenience sample of patients who were admitted to our intensive care unit. All patients underwent BLEEP followed by an independent formal echocardiogram by an experienced pediatric echocardiography provider (PEP). H ypotension is observed in late decompensated shock. It occurs when compensatory mechanisms that maintain end-organ perfusion fail. Although shock can be broadly categorized into hypovolemic, cardiogenic, septic, or distributive, there is considerable overlap in clinical presentation and underlying pathophysiology. 1,2 Varying degrees of relative or absolute hypovolemia and myocardial dysfunction may exist in each category, particularly in sepsis. 3 Similarly, although hemorrhagic (hypovolemic) shock is most common in the severely traumatized patient, neurogenic shock (secondary to severe craniospinal injury), obstructive shock (from pericardial tamponade), or cardiogenic shock (secondary to myocardial contusion) may coexist in polytrauma.Critically ill or injured patients are being cared for in the emergency department (ED) with increasing frequency. Furthermore, there has been a 152% increase in the number of patients with ED length of stay of Ͼ6 hours from 1988 to 1997. 4,5 This reality necessitates provision of critical care in the pediatric ED. In a recent study of management of pediatric-neonatal septic shock referred from community hospitals to a referral urban pediatric center, 91 patients were identified during a 9-year period. 6 In a database of severely injured children who presented to the ED at a level 1 pediatric trauma center, using initial base deficit as a marker of tissue hypoperfusion and shock, 117 patients were identified during a 6-year period. 7 We are also an urban, tertiary-level regional pediatric referral center with an annual ED census of 80 000 visits. Most initial encounters of hemodynamically unstable patients mandate prompt goal-directed resuscitation. The exact cause and underlying pathophysiology of shock are not immediately evident in most clinical situations. We speculate that bedside limited echocardiography by the emergency physician (BLEEP) would be useful in 2 to

Isolated noncompaction of the left ventricular myocardium (INVM) is characterized by the presence of numerous prominent trabeculations and deep intertrabecular recesses within the left ventricle, sometimes also affecting the right ventricle and interventricular septum. Familial occurrence of this disorder was described previously. We present a family in which 6 affected individuals demonstrated X-linked recessive inheritance of this trait. Affected relatives presented postnatally with left ventricular failure and arrhythmias, associated with the pathognomonic echocardiographic findings of INVM. The usual findings of Barth syndrome (neutropenia, growth retardation, elevated urinary organic acids, low carnitine levels, and mitochondrial abnormalities) were either absent or found inconsistently. Fetal echocardiograms obtained between 24-30 weeks of gestation in 3 of the affected males showed a dilated left ventricle in one heart, but were not otherwise diagnostic of INVM in any of the cases. Four of the affected individuals died during infancy, one is in cardiac failure at age 8 months, and one is alive following cardiac transplant at age 9 months. The hearts from infants who died or underwent transplantation appeared, on gross examination, to be enlarged, with coarse, deep ventricular trabeculations and prominent endocardial fibroelastosis. Histologically, there were loosely organized fascicles of myocytes in subepicardial and midmyocardial zones of both ventricles, and the myocytes showed thin, often angulated fibers with prominent central clearing and reduced numbers of filaments. Markedly elongated mitochondria were present in some ventricular myocytes from one specimen, but this finding was not reproducible. Genetic linkage analysis has localized INVM to the Xq28 region, where other myopathies with cardiac involvement have been located.

Isolated noncompaction of the left ventricular myocardium (INVM) is characterized by the presence of numerous prominent trabeculations and deep intertrabecular recesses within the left ventricle, sometimes also affecting the right ventricle and interventricular septum. Familial occurrence of this disorder was described previously. We present a family in which 6 affected individuals demonstrated X-linked recessive inheritance of this trait. Affected relatives presented postnatally with left ventricular failure and arrhythmias, associated with the pathognomonic echocardiographic findings of INVM. The usual findings of Barth syndrome (neutropenia, growth retardation, elevated urinary organic acids, low carnitine levels, and mitochondrial abnormalities) were either absent or found inconsistently. Fetal echocardiograms obtained between 24-30 weeks of gestation in 3 of the affected males showed a dilated left ventricle in one heart, but were not otherwise diagnostic of INVM in any of the cases. Four of the affected individuals died during infancy, one is in cardiac failure at age 8 months, and one is alive following cardiac transplant at age 9 months. The hearts from infants who died or underwent transplantation appeared, on gross examination, to be enlarged, with coarse, deep ventricular trabeculations and prominent endocardial fibroelastosis. Histologically, there were loosely organized fascicles of myocytes in subepicardial and midmyocardial zones of both ventricles, and the myocytes showed thin, often angulated fibers with prominent central clearing and reduced numbers of filaments. Markedly elongated mitochondria were present in some ventricular myocytes from one specimen, but this finding was not reproducible. Genetic linkage analysis has localized INVM to the Xq28 region, where other myopathies with cardiac involvement have been located.