Shigeyuki Echigo

Stratification of Pediatric Heart Failure on the Basis of Neurohormonal and Cardiac Autonomic Nervous Activities in Patients With Congenital Heart Disease

Background—Stratification of pediatric patients with congenital heart disease (CHD) has been based on their hemodynamics and/or functional capacity. Our purpose was to compare cardiac autonomic nervous activity (CANA) and neurohormonal activities (NHA) with postoperative status in stable CHD patients with biventricular physiology. Methods and Results—We divided 379 subjects (297 CHD patients, 28 dilated cardiomyopathy patient, and 54 control subjects) into 4 subgroups according to New York Heart Association (NYHA) class (1.3±0.7) and measured various CANA and NHA indices. Stepwise decreases in baroreflex sensitivity (BRS), heart rate variability (HRV), adrenergic imaging, and vital capacity (VC) were observed in proportion to functional capacity in normal to NYHA II patients (P <0.001). However, there were no differences in these indices between NYHA II and III+IV groups, whereas a stepwise proportional increase in NHA indices was observed in these groups (P <0.001). Natriuretic peptides differentiated all NYHA classes. BRS, HRV, and VC were greater in the adult patients than in the child patients (P <0.05 to 0.01), although the functional class in adult patients was lower. Cardiac surgeries resulted in low BRS and VC, and the VC reduction independently determined a small HRV. Even if functional class and ejection fraction were comparable, CANA and brain natriuretic peptide were lower in CHD patients than in dilated cardiomyopathy patients (P <0.05 to 0.001). Conclusions—CANA and NHA indices are useful to stratify mild and severe heart failure in stable postoperative CHD patients, respectively. However, careful attention should be paid to age- and surgery-related influences on these indices.

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.

Heart rate recovery after exercise and cardiac autonomic nervous activity in children.

To investigate the difference in heart rate (HR) recovery after exercise between children and young adults, we administered a constant load of light exercise intensity and progressive treadmill exercise tests to nine children (aged 9 to 12 y, group A) and eight young adults (six male and two female, aged 17 to 21 y, group B) who had a history of Kawasaki disease without significant coronary arterial lesions. HR after both exercise protocols was analyzed. The low-frequency (LF) and high-frequency (HF) components of HR variability were measured, and LF/HF was calculated (log LF, log HF, log L/H). Arterial baroreflex sensitivity was assessed by the phenylephrine method. There were no differences between groups A and B in resting HR, peak HR, peak oxygen uptake, and decreases in systolic blood pressure during the recovery period. HR 1 and 2 min after peak exercise and 1 min after constant-load exercise was significantly lower in group A than in group B (p < 0.05), and the changes in HR from peak values after both exercise tests were also greater in group A than in group B (p < 0.05–0.01). Although no difference in arterial baroreflex sensitivity was observed, log HF was significantly higher in group A than in group B (p < 0.01), and log L/H was significantly lower in group A than in group B (p < 0.05). The value of log HF correlated inversely with the decrease in HR immediately after both exercise protocols (p < 0.05–0.01). Although log L/H correlated with the decrease in HR after peak exercise (p < 0.05–0.0005), the early decline in HR after constant-load exercise did not correlate with log L/H. Arterial baroreflex sensitivity did not correlate with the decrease in HR at any recovery time. These data suggest that the early phase of HR recovery after light to severe exercise is influenced by the cardiac parasympathetic nervous activity at rest and that the greater central cholinergic modulation of HR in children than in young adults may be responsible in part for childrens faster HR recovery after exercise.

Influence of ventricular morphology on aerobic exercise capacity in patients after the Fontan operation

OBJECTIVES This study investigated the influences of ventricular morphology, hemodynamics and clinical findings on exercise capacity in patients after the Fontan operation. BACKGROUND Determinants of exercise capacity after the Fontan operation remain unclear. METHODS Peak oxygen uptake (PVo2) was determined in 105 patients by exercise test and compared to hemodynamics and clinical findings. Patients were divided into three groups based on ventricular morphology: those with a right ventricle (group RV), a biventricle (group BV) and a left ventricle (group LV). RESULTS Ten patients with atrioventricular valve regurgitation (AVVR) or hypoxia exhibited a low PVo2. After excluding these patients, although PVo2 did not correlate with hemodynamics, except ventricular ejection fraction (p < 0.02), it correlated with age at the Fontan operation and exercise test (p < 0.002). The PVo2 was higher in group LV (63+/-9%) than in groups RV (55+/-9%) and BV (55+/-12%) (p < 0.01), while an inverse correlation between PVo2 and age at operation was demonstrated only in group RV (p < 0.05). Groups RV or BV and age at exercise test were associated with a lower PVo2, whereas group LV was an independent predictor of a higher PVo2 (p < 0.01). During 4.2 years of follow-up, a decrease in peak heart rate was related to a decrease in PVo2 (p < 0.05). The PVo2 decreased in group RV (p < 0.01). CONCLUSIONS In addition to AVVR, hypoxia, and heart rate response, ventricular morphology is related to exercise capacity. Early Fontan operation may be beneficial in terms of exercise capacity, especially in the group RV patients.

Abnormalities of Neurohormonal and Cardiac Autonomic Nervous Activities Relate Poorly to Functional Status in Fontan Patients

Background—Impaired cardiac autonomic nervous activities and increased neurohumoral activities (CANA, NHA) characterize Fontan patients. However, the clinical significance of these changes is not clearly understood. Our purpose was to clarify the clinical significance of the CANA and NHA in stable Fontan patients. Methods and Results—We divided 22 atriopulmonary connection (APC) and 75 total cavopulmonary connection (TCPC) patients into 4 subgroups according to New York Heart Association (NYHA) class (1.8±0.6) and measured various CANA and NHA indices. All NHA indices were elevated in the symptomatic patients (P<0.001). Natriuretic peptides were higher in the APC than in the TCPC patients, and the hemodynamics showed no correlation with brain natriuretic peptide in the APC patients. Low arterial oxygen saturation and impaired hemodynamics greatly influenced all elevated NHA indices (P<0.01), except for plasma renin activity, in the TCPC patients. Impaired CANA indices did not relate to NYHA class, although surgeries were associated with lower heart rate variability. In addition to poor correlation between NHA and CANA, age and ventricular morphology had no impact on all CANA and NHA indices, except for high norepinephrine in right ventricular Fontan patients. Conclusions—Although symptomatic Fontan patients exhibit higher NHA, CANA is not related to either NYHA class or NHA. APC itself is responsible for higher natriuretic peptides, and arterial oxygen desaturation has a great impact on elevated NHA in the TCPC patients. These characteristics of the NHA and CANA differ from those of heart failure patients with biventricular physiology.

Late death after arterial switch operation for transposition of the great arteries

Fifty-nine patients survived for more than 1 month after an arterial switch operation (ASO). Diagnoses in these patients included transposition of the great arteries in 27, transposition of the great arteries with ventricular septal defect in 28, and double-outlet right ventricle in four. There were six late deaths (10%) during the follow-up period, and all of them occurred suddenly and unexpectedly. Four of the six late deaths were in patients who had undergone ASO in the neonatal period. Late deaths occurred from 40 days to 10 months after the operation. Autopsies were performed in all six patients. The cause of these late deaths was acute myocardial infarction. Five patients died of subendocardial infarction resulting from stenosis of the left main coronary artery. On pathologic examination, a fibrocellular intimal thickening was noted at the proximal region of the right and left coronary arteries, which resulted in 80% stenosis on average.

Coronary Artery Dilatation Exceeding 4.0 mm During Acute Kawasaki Disease Predicts a High Probability of Subsequent Late Intima-Medial Thickening

We used intravascular ultrasound (IVUS) to compare the degree of coronary artery dilatation during the acute phase of Kawasaki disease with the extent of intima-medial thickening more than 10 years later. We wanted to determine if there was a threshold degree of dilatation that was highly predictive of later thickening. Twenty-eight patients with a mean age of 17.3 ± 1.7 years were studied; the mean interval from the initial selective coronary angiography to the IVUS study was 15.0 ± 1.6 years. We measured the maximum intima-medial thickness of selected coronary arterial segments in IVUS images and measured the largest diameters of the corresponding coronary arterial segments in the initial coronary angiograms. A significant correlation was found between the initial diameters of the coronary arteries and the intima-medial thickness more than 10 years later in the right coronary, the left anterior descending coronary, and the left circumflex arteries. The coefficient of correlation was 0.77 (n = 120, p < 0.0001), and for the bifurcation of the left coronary artery it was 0.50 (n = 26, p < 0.01). For this study, abnormal intima-medial thickness was defined as more than 0.40 mm. When the initial coronary arterial dilatation exceeded 4.0 mm, the sensitivity was 28/31 (90%) and the specificity was 87/89 (98%) in the right coronary, the left anterior descending coronary, and the left circumflex arteries. For the bifurcation of the left coronary artery, the sensitivity was 14/21 (67%) and the specificity was 5/5 (100%).

Coagulation profile, hepatic function, and hemodynamics following Fontan-type operations.

We analyzed retrospectively the relationship between coagulation profile, and either hepatic function or hemodynamics, in patients who had undergone a Fontan-type procedure, comparing them, first, with a control group of 12 patients without significant hemodynamic abnormality, and, second, with a group of 14 patients who had not undergone a Fontan procedure, but whose mean right atrial pressure exceeded 8 mmHg. Follow-up catheterization had been performed in all 30 patients submitted to the Fontan-type operation. Prothrombin time, and factor XIII, were significantly lower in those who had undergone the Fontan procedure than in the other groups. Those submitted to the Fontan operation also had lower levels of protein C than controls, and their levels of plasminogen were lower than the patients with high right atrial pressure. Both aspartate aminotransferase and alanine aminotransferase were higher in those undergoing the Fontan procedure than in the other groups, while gamma-glutamyltranspeptidase in these patients was higher than in the control group. Mean right atrial pressure was highest in those undergoing the Fontan procedure, while cardiac index was lowest. Prothrombin time was correlated to some extent with aspartate aminotransferase, mean right atrial pressure, and cardiac index. Protein C correlated with both aspartate aminotransferase and mean right atrial pressure, while factor XIII correlated with alanine aminotransferase, mean right atrial pressure, and cardiac index. Aspartate aminotransferase, alanine aminotransferase, and gamma-glutamyltranspeptidase, parameters of hepatic function, correlated significantly with mean right atrial pressure. In those who had undergone the Fontan procedure, decreased synthesis of pro-and anti-coagulant factors is a risk factor for both thrombosis and bleeding. Abnormal hemodynamics, in the absence of a right sided pumping chamber, may predispose to subclinical hepatic dysfunction, leading to selective disturbances of protein synthesis.

Guidelines for catheter intervention in coronary artery lesion in Kawasaki disease.

Abstract The Research Committee of Ministry of Health, Labour and Welfare ‘Study of treatment and long‐term management in Kawasaki disease’ reported the guidelines for catheter intervention in coronary artery lesion in Kawasaki disease in this paper. The contents include: (i) background and natural history of coronary artery lesion in Kawasaki disease; (ii) indication of catheter intervention; (iii) types of procedure, and their indication and care; (iv) institute and backup system; (v) the management after procedure, evaluation and follow up; and (vi) prospects, especially in relation to bypass surgery.

Changes in causes of sudden deaths by decade in patients with coronary arterial lesions due to Kawasaki disease

Over a 25-year period, we encountered 12 patients who died suddenly with coronary arterial lesions due to Kawasaki disease. We report their clinical course, and analyze the happenings of their deaths. Of the 12 patients, 10 were dead on arrival at hospital. Their age at death ranged from 13 months to 27 years, with a median of 16 years, and the interval from the onset of Kawasaki disease to death ranged from 2 months to 24 years. In 4 patients, death was found to be due to myocardial infarction, while in the remaining 8, it could not be determined. In 7 patients, coronary angiograms obtained less than 4 months after the acute onset of Kawasaki disease showed lesions bilaterally, most being giant aneurysms. Myocardial infarction had occurred in 6 patients prior to their death. In 1 patient of the late 1970s, who collapsed after running, cardiac sequels had not been suspected prior to autopsy. During the 1980s, 3 infants with bilateral giant aneurysms died within a year of the initial onset of Kawasaki disease, with acute myocardial infarction being the cause in 2 of them. In the late 1990s, and the 2000s, 5 patients died suddenly with left ventricular dysfunction, their ejection fractions being less than 40 percent more than 20 years after the initial onset of Kawasaki disease. Prior to their sudden deaths, they had had no cardiac events for many years, but had suffered previous myocardial infarctions. Multifocal premature ventricular contractions, and non-sustained ventricular tachycardia, are probable risk factors in such patients. Careful follow-up, checking for ventricular arrhythmia, is needed to prevent sudden death in patients suffering left ventricular dysfunction in the setting of Kawasaki disease.