Isolated noncompaction of myocardium associated with calcification in the interventricular septum.

We describe a 12-year-old male with isolated noncompaction of the myocardium and associated abnormal calcification in the basal interventricular septum, and we present a review of the literature. The patient has been healthy and free of symptoms. The electrocardiogram showed abnormal Q waves in III, V1, V2, and ST elevation in V1-V3. Exercise testing demonstrated ST depression in V4 and V5. Myocardial scintigraphic examination showed a regional reduction in iodine-1,2,3-beta-methyl-iodophenylpentadecanoic acid uptake in the basal interventricular septum. Since coronary angiography demonstrated normal coronary vessels and the trabeculations were not prominent in this region, we hypothesize that coronary microcirculatory dysfunction may cause subendocardial infarction associated with calcification in the same area.

Isolated noncompaction of the ventricular myocardium: ultrafast computed tomography and magnetic resonance imaging.

This study was undertaken to evaluate the feasibility of ultrafast computed tomography (CT) and magnetic resonance imaging (MRI) for anatomical and pathophysiological diagnosis of isolated noncompaction of the left ventricular myocardium (INVM) compared with other imaging modalities including thallium myocardial imaging. Six patients, three sets of siblings, ranging in age from 13 to 18 years, were included in this study. Two-dimensional echocardiograms revealed numerous prominent trabeculations and deep intertrabecular recesses in one or more ventricular wall segments in all cases. Thallium-201 myocardial imaging disclosed a hypoperfusion area corresponding to the zones where noncompacted ventricular myocardium was localized. Ultrafast CT showed early defects of varying degrees and rate enhancement of the noncompacted ventricular myocardium, implying fibrosis in this area. MRI disclosed inner zones of noncompacted myocardium distinguishable from thin outer zones of compacted myocardium. T2-weighted imaging revealed high intensity areas at the apex of the left ventricle, suggesting disturbed microcirculation due to fibrosis, thrombus formation, and hypokinesis. Cine MRI revealed hypokinesis of the noncompacted ventricular wall during the cardiac cycle. In conclusion, ultrafast CT and MRI provide high-resolution imaging of noncompacted myocardium, and also pathophysiological details regarding this rare disease.

Dipyridamole stress ultrasonic myocardial tissue characterization in patients with Kawasaki disease.

Dipyridamole stress integrated backscatter (IBS) was used for evaluation of myocardial ischemia or damage in 31 children with coronary artery lesions caused by Kawasaki disease, in comparison with thallium-201 myocardial imaging. All patients underwent echocardiography at rest and after dipyridamole stress at the anterior interventricular septum, posterior wall (PW), and inferior wall (INF). At rest, no significant difference was seen in cyclic variation (CV) of IBS in the regions with normal or abnormal distribution on Tl-201 imaging. But in the regions showing abnormal distribution after stress, CV decreased significantly. A delayed study after stress showed the recovery of CV to the level at rest in all patients. Sensitivity of abnormal cyclic variation integrated backscatter was 75% in the PW and 91% in the INF, and specificity was 91% in the PW and 90% in the INF, compared with the results of thallium-201 imaging. Dipyridamole stress IBS can provide sensitive detection of myocardial ischemia or damage in Kawasaki disease.

Novel gene mutations in patients with left ventricular noncompaction or Barth syndrome.

BACKGROUND: Mutations in the gene G4.5 result in a wide spectrum of severe infantile cardiomyopathic phenotypes, including isolated left ventricular noncompaction (LVNC), as well as Barth syndrome (BTHS) with dilated cardiomyopathy (DCM). The purpose of this study was to investigate patients with LVNC or BTHS for mutations in G4.5 or other novel genes. METHODS AND RESULTS: DNA was isolated from 2 families and 3 individuals with isolated LVNC or LVNC with congenital heart disease (CHD), as well as 4 families with BTHS associated with LVNC or DCM, and screened for mutations by single-strand DNA conformation polymorphism analysis and DNA sequencing. In 1 family with LVNC and CHD, a C-->T mutation was identified at nucleotide 362 of alpha-dystrobrevin, changing a proline to leucine (P121L). Mutations in G4.5 were identified in 2 families with isolated LVNC: a missense mutation in exon 4 (C118R) in 1 and a splice donor mutation (IVS10+2T-->A) in intron 10 in the other. In a family with cardiomyopathies ranging from BTHS or fatal infantile cardiomyopathy to asymptomatic DCM, a splice acceptor mutation in exon 2 of G4.5 (398-2 A-->G) was identified, and a 1-bp deletion in exon 2 of G4.5, resulting in a stop codon after amino acid 41, was identified in a sporadic case of BTHS. CONCLUSIONS: These data demonstrate genetic heterogeneity in LVNC, with mutation of a novel gene, alpha-dystrobrevin, identified in LVNC associated with CHD. In addition, these results confirm that mutations in G4.5 result in a wide phenotypic spectrum of cardiomyopathies.

Magnetic resonance imaging for early detection of Takayasu arteritis.

The patient was a 15-year-old girl with suspected Takayasu arteritis. Magnetic resonance (MR) imaging, using the fast low angle shot (FLASH) technique, revealed aneurysmal dilation of the aortic root and irregular thickening of the aortic wall. Three-dimensional (3-D) contrast-enhanced MR angiography successfully demonstrated narrowing of the left carotid and left subclavian arteries. In addition, 2-dimensional (2-D) FLASH MR imaging clearly visualized narrowing of two right renal arteries and the left renal artery. These were angiographically evident. Thus, MR imaging is particularly useful for early detection of subtle arteritic changes and involvement of stenotic lesions in branch vessels in the early phase of Takayasu arteritis.

Neutrophils and mononuclear cells express vascular endothelial growth factor in acute Kawasaki disease: its possible role in progression of coronary artery lesions.

Kawasaki disease (KD) is a syndrome of systemic vasculitis of unknown etiology that is complicated by coronary artery lesions (CAL), leading occasionally to cardiac ischemic sequelae. To examine whether vascular endothelial growth factor (VEGF) is responsible for CAL in KD, we determined serum VEGF levels by ELISA and peripheral blood mononuclear cell (PBMC) and neutrophil VEGF expression by immunoblot analysis. Significantly increased levels of VEGF were demonstrated in acute KD as well as in other vasculitis syndromes (p < 0.0001). In the 10 KD patients with CAL, serum VEGF levels were maximal approximately 2 wk post-onset when CAL generally develops and were significantly higher than in 20 patients without CAL (mean, 474 and 241 pg/mL, respectively; p = 0.00015). During the same period, immunoblot analysis revealed maximal VEGF expression in PBMC, corresponding to serum VEGF levels in most patients and being particularly marked in patients with CAL (p < 0.01). Neutrophils expressed VEGF only in the early stage of acute KD and declined rapidly in the majority of KD patients regardless of the presence of CAL, showing a strikingly different expression pattern than that for PBMC. Predominant VEGF expression by PBMC was also demonstrated in patients with other vasculitis syndromes and only faintly in normal controls. The results suggest that VEGF is generated dynamically in KD, presumably reflecting its disease activity. Neutrophil-derived VEGF may play a role in regulating early vascular responses, whereas PBMC-derived VEGF may contribute to later vascular injury and remodeling.

Changes in T-cell receptor subsets after cardiac surgery in children.

T cells are divided into two subsets, alphabeta and gammadelta, according to the T-cell receptor (TCR) expressed. Recent findings indicate that gammadelta T cells serve as the first defense against microbial pathogens, and represent a link between innate and acquired immunity. We conducted a study to investigate the changes in circulating TCR subsets after cardiac surgery in children. Blood samples from 24 children who underwent cardiac surgery with cardiopulmonary bypass (CPB) were collected serially to analyze TCR subsets by flow cytometry. The alphabeta T cells reached a nadir on postoperative day (POD) 1, but recovered to pre-CPB levels on POD 3. On the other hand, the gammadelta T cells decreased after CPB and did not recover to pre-CPB levels even after POD 7. The alphabeta/gammadelta T-cell ratio was increased after POD 3. In children, gammadelta T cells recover more slowly than alphabeta T cells after cardiac surgery. These changes in TCR subsets may contribute to postoperative immunosuppression.

Total anomalous pulmonary venous connection with bronchogenic cyst in neonatal period.

Here, we report a case of a two-day-old neonate with total anomalous pulmonary venous connection to the innominate vein and a bronchogenic cyst arising from the trachea. Antenatal echocardiography had delineated both cardiac and extracardiac lesions, and a repeated examination on the day of birth disclosed progressive enlargement in the cyst in a manner so as to obstruct the innominate vein. On the second day of life, the patient underwent complete correction of the cardiac lesion and total excision of the cyst. The patient recovered uneventfully and was discharged on the thirteenth postoperative day.

Anomalous origin of the main stem of the left coronary artery from the non-facing sinus of valsalva associated with sudden death in a young athlete.

A young female athlete is described with anomalous origin of the main stem of the left coronary artery from the non-facing sinus of Valsalva who sustained myocardial infarction and died suddenly after physical exertion. Autopsy findings illustrated the mechanistic importance of acute angle take-off of the left main coronary artery and a slit-like orifice, which was likely compressed and obstructed by acute expansion of the aortic wall. This rare type of coronary anomaly has been regarded as having little clinical significance, but it can lead to sudden cardiac death under physical exertion.

Clinical features of isolated noncompaction of the ventricular myocardium: long-term clinical course, hemodynamic properties, and genetic background.

OBJECTIVES: A nationwide survey was conducted to clarify the clinical features of isolated noncompaction of the ventricular myocardium (INVM) in Japanese children in comparison with features previously described in patients with INVM. BACKGROUND: Isolated noncompaction of the ventricular myocardium is a rare disorder characterized by an excessively prominent trabecular meshwork. It is accompanied by depressed ventricular function, systemic embolism and ventricular arrhythmia. METHODS: A questionnaire specifically designed for this study was sent to 150 hospitals in Japan where a pediatric cardiology division exists. RESULTS: Twenty-seven patients were diagnosed by two-dimensional echocardiography, their ages ranging from one week to 15 years at presentation, with follow-up lasting as long as 17 years. The gross anatomical appearance and the extension of noncompacted myocardium predominantly at the apex observed on two-dimensional echocardiograms were similar to observations reported previously. Dissimilarities included a greater number of asymptomatic patients at initial presentation, a longer clinical course with gradually depressed left ventricular function, no systemic embolism, and rare ventricular tachycardia in the Japanese children. Cardiac catheterization disclosed normal left ventricular end-diastolic volume and increased left ventricular end-diastolic pressure in most cases, consistent with restrictive hemodynamics. A higher incidence of Wolff-Parkinson-White syndrome was found in the children, whereas left bundle branch block was rarer than reported in adults. Familial recurrence was high (44%) and included many women. CONCLUSIONS: In Japanese children, INVM can be found by screening examinations at asymptomatic stage, and it might have a longer dinical course with gradually depressed left ventricular function and restrictive hemodynamics. The pattern of familial recurrence we observed implies that INVM is a distinctive clinical entity with a heterogeneous genetic background.

Automatic border detection identifies subclinical anthracycline cardiotoxicity in children with malignancy.

BACKGROUND: Anthracycline drugs for cancer therapy often cause functional myocardial impairment even in relatively low doses. We investigated the left ventricular function in asymptomatic anthracycline-treated children by automatic border detection (ABD) to assess its clinical usefulness for unmasking latent anthracycline-induced myocardial damage. METHODS AND RESULTS: Thirty-four children (0.7 to 17.6 years old) during or after anthracycline chemotherapy (26 to 1100 mg/m2) for malignancy (Chemo group) were studied, and 40 children (2.8 to 15.6 years old) without cardiac involvement served as normal control subjects (Control group). All patients underwent complete echocardiographic examination, including M-mode, Doppler, and ABD. Conventional echocardiography disclosed no difference between groups with regard to ejection fraction and the ratio of early to late transmitral flow velocity. In marked contrast, an investigation using ABD revealed that the Chemo group appeared to have some anthracycline-induced myocardial damage. In the apical 4-chamber view, peak filling rate in the Chemo group [2.3+/-0.4 end-diastolic area (EDA)/s] was significantly lower than that in the Control group (3.1+/-0.5 EDA/s) (P<0.0001), and time to peak filling rate in the Chemo group (106+/-31 ms) was clearly prolonged compared with that in the Control group (74+/-22 ms) (P<0.0001). CONCLUSIONS: Echocardiographic ABD may be a sensitive and useful noninvasive approach for evaluating subclinical anthracycline cardiotoxicity.

A novel method for indexing echocardiographic left ventricular mass in infants, children and adolescents: evaluation of obesity-induced left ventricular hypertrophy.

BACKGROUND: Measurement of left ventricular mass (LVM) is important to the diagnosis of left ventricular hypertrophy in children with various cardiovascular diseases. The purpose of this study was to determine the most appropriate method for standardization of LVM and to evaluate obesity-induced left ventricular hypertrophy in children across the entire age range, from infancy through adolescence. METHODS: We studied 928 children and adolescents (527 males, 401 females), aged 0-17 years, who were classified into two groups by degree of obesity. Left ventricular mass was calculated by M-mode echocardiography using the formula of Devereux et al. and was indexed using body size (body length, bodyweight or body surface area) raised to a non-integer power using logarithmic transformation of measurements in children without obesity. RESULTS: The body length, bodyweight and body surface area exponents were 1.85, 0.88 and 1.15, respectively, in males, and 1.72, 0.82 and 1.08, respectively, in females. Whereas indexing of left ventricular mass by body length both in males and in females revealed significant differences between the two groups, indexing using bodyweight or body surface area exponents did not manifest left ventricular hypertrophy induced by obesity. CONCLUSION: It is suggested that applying body length exponents 1.85 in males and 1.72 in females is an appropriate method for indexation of LVM in children and adolescents. This method is particularly useful for the evaluation of left ventricular hypertrophy in children.

A novel technique using biplane cine magnetic resonance imaging to evaluate left ventricular volume in children.

The purpose of the study is to determine the feasibility of a novel simplified technique using cine magnetic resonance imaging (MRI) to assess left ventricular (LV) volume and ejection fraction (EF) validated by comparison with biplane LV angiography. Previous MRI studies to assess LV volumes have used multiple axial planes, which are compromised by partial volume effects and are time consuming to acquire and analyze. Accordingly, we developed a simplified imaging approach using biplane cine MRI and imaging planes aligned with the intrinsic cardiac axes of the LV. We studied 20 children (aged 4 months to 10 years) with various heart diseases. The accuracy of cine MRI was compared with that of LV angiography in all patients. LV volumes were calculated using Simpson's rule algorithm, for both MRI and LV angiography. LV volumes determined from MRI were slightly underestimated but correlated reasonably well with angiographic volumes (LVEDV: Y = 0.88X + 1.58, r = 0.99, LVESV: Y = 0.73X + 1.03, r = 0.98). Most importantly, even in patients who had abnormal ventricular curvature such as in tetralogy of Fallot, MRI determined LV volumes correlated well with angiographic values. The MR study was completed within 35 min in all patients. In conclusion, simplified biplane cine MRI, using the intrinsic LV axis planes, permits noninvasive assessment of LV volumes in views comparable to standard angiographic projections and appears practical for clinical use in childhood heart disease since the scan and analysis times are relatively short.

Evaluation of pulmonary blood supply by multiplanar cine magnetic resonance imaging in patients with pulmonary atresia and severe pulmonary stenosis.

The purpose of this study was to assess the capability of multiplanar cine magnetic resonance imaging (MRI) for evaluating pre- and post-operative pulmonary circulation in patients with pulmonary atresia and severe pulmonary stenosis. Seventy-three multiplanar cine MRIs were performed in 30 patients, aged 1 month to 7 years (mean age, 27 months). The morphology and size of the central pulmonary arteries (PA), source of the major aortopulmonary collateral arteries (MAPCA), patency of Blalock-Taussig (BT) shunt vessels, and the post-operative pulmonary circulation were assessed. The accuracy of cine MRI was compared with that of angiography in all patients. The PA was visualized to the first hilar branch in 21 patients, but not in 8 patients in whom the central PA was absent. On follow-up MRI, PA growth was measured, and the results showed excellent correlation with the results obtained by angiography. In 17 patients who had undergone 23 BT shunt operations, cine MRI correctly demonstrated all patient shunts and 5 of 6 stenotic lesions. Multiplanar cine MRI provided excellent detail of the peripheral PA in all patients, 7 of 8 peripheral pulmonary stenoses, 3 of 4 nonconfluent pulmonary arteries, and 2 of 3 PA obstructions. Although the sources of MAPCA were identified in 7 of 9 patients, the distal connection of the MAPCA was not detected in all patients. Seven patients were reexamined after pulmonary plasty; they exhibited normal pulmonary flow patterns. Multiplanar cine MRI provides high-resolution imaging of PA with dynamic visualization of flow and is an effective noninvasive technique for evaluating pre- and post-operative patients with pulmonary atresia and severe pulmonary stenosis.

Evaluation of left ventricular volume using automatic border detection in children: a comparison with conventional off-line echocardiographic quantification.

BACKGROUND: Evaluation of the clinical usefulness of the one-line automatic border detection system for determination of left ventricular volume in children in comparison to the conventional off-line method. METHODS: Eighty consecutive patients in whom clear images were obtained by two-dimensional echocardiography were studied. Using the Hewlett-Packard Sonos 2500 with a 3.5 or 5.5 Mhz phased array transducer, all patients were studied in the apical four-chamber imaging plane for automatic border detection and apical four-chamber and two-chamber imaging planes for manual tracing. Left ventricular end-diastolic and end-systolic volumes were measured and compared using the bi-plane Simpson method. RESULTS: Left ventricular end-diastolic volumes obtained by automatic border detection correlated well but were slightly underestimated compared to those obtained by manual tracing (r = 0.98). Left ventricular end-systolic volumes obtained by automatic border detection also correlated well with those obtained by manual tracing (r = 0.96). Left ventricular ejection fractions compared favorably. However, left ventricular volumes obtained using the classical Pombo M-mode echocardiography showed poorer correlation with those obtained by manual tracing methods. CONCLUSIONS: Automatic border detection is a promising method for real-time estimation of left ventricular volume. In patients with good endocardial tracking, automatic border detection can be used for routine studies of cardiovascular disease, even in children.

Chronic effects of oral prostacyclin analogue on thromboxane A2 and prostacyclin metabolites in pulmonary hypertension.

Abnormal biosynthesis of thromboxane and prostacyclin has been implicated in patients with primary pulmonary hypertension and secondary pulmonary hypertension associated with congenital heart disease, and could be involved in the pathogenesis of pulmonary vascular disease. The chronic effects of an oral prostacyclin analogue, beraprost sodium, on thromboxane and prostacyclin biosynthesis and on pulmonary circulation were investigated in 15 children with pulmonary hypertension. The plasma concentrations of thromboxane B2 and 6-keto-prostaglandin F1 alpha were measured, as was the urinary excretion of 11-dehydro-thromboxane B2 and 2,3-dinor-6-keto-prostaglandin F1 alpha, which are stable metabolites of thromboxane A2 and prostacyclin, respectively. In patients with pulmonary hypertension, the plasma concentration of thromboxane B2 and the ratio of thromboxane B2 to 6-keto-prostaglandin F1 alpha were greater than in healthy controls: 210 +/- 49 versus 28 +/- 4 pg/mL (P < 0.05) and 32.6 +/- 8.9 versus 5.7 +/- 1.8 (P < 0.01), respectively. After 3 months of administration of beraprost, the plasma concentration of thromboxane B2 and the ratio of thromboxane B2 to 6-keto-prostaglandin F1 alpha were reduced significantly: 210 +/- 49 to 98 +/- 26 pg/mL (P < 0.01) and 32.6 +/- 8.9 to 18.0 +/- 6.7 (P < 0.05), respectively. In contrast, the plasma concentrations of 6-keto-prostaglandin F1 alpha in patients were slightly but not significantly higher than in controls, and did not change significantly after administration of beraprost. The concentrations of 11-dehydro-thromboxane B2 and 2,3-dinor-6-keto-prostaglandin F1 alpha in urine correlated significantly with thromboxane B2 and 6-keto-prostaglandin F1 alpha, respectively, in plasma. Beraprost improved the imbalance of thromboxane and prostacyclin biosynthesis and has a potential efficacy for preventing the progressive development of pathological changes in pulmonary vasculature.

Analysis of serum cytokine levels in primary biliary cirrhosis patients and healthy adults.

By using commercially available ELISA kits, serum IL-6 and TNF-alpha levels in healthy adults, and the levels of various cytokines in patients with primary biliary cirrhosis or chronic viral liver diseases, were investigated. IL-6 levels of healthy subjects were distributed in a wide range, and the distribution pattern was similar to those of the patients. TNF-alpha levels tended to be low in females in their 30s, but there were no abnormalities in the patients. Characteristic findings, in the primary biliary cirrhosis patients, were an increase of IFN-gamma and IL-2 levels, and a decrease of GM-CSF levels (P < 0.05). IL-8 levels were higher in the patients than in the healthy subjects (P < 0.05), and the increase was remarkable in chronic viral liver disease patients. We believe that measurement of serum cytokine levels as a clinical immunological test is highly useful. Further development of simpler, more rapid, and more sensitive analysis methods is desired.