Toshikatsu Yagihara

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.

Early and late stroke after mitral valve replacement with a mechanical prosthesis: risk factor analysis of a 24-year experience

OBJECTIVE We evaluated risk factors for mortality and stroke after mechanical mitral valve replacement between May 1977 and December 2001. METHODS Early and late mortality and stroke were assessed. Potential predictors of mortality and stroke were entered into a Cox proportional hazards model. Actuarial survival and freedom from stroke were determined by a log-rank test. RESULTS Mitral valve replacement was performed in 812 patients. Concomitant procedures included left atrial appendage closure in 493 (61%) patients, tricuspid annuloplasty-replacement in 348 (43%) patients, maze procedure in 185 (23%) patients, plication of the left atrium in 148 (18%) patients, and other procedures in 151 (19%) patients. Five-year actuarial survival was 91.1% +/- 2.3%. Freedom from stroke at 8 years was significantly better in patients with sinus rhythm versus atrial fibrillation (P <.001). Ninety-nine percent of patients with mitral valve replacement combined with a maze procedure were free from stroke, whereas only 89% of patients with mitral valve replacement alone were free from stroke at 8 years after surgical intervention. Seventy-two patients had late stroke; sixty-five patients (90%) were in atrial fibrillation, and 47 (65%) patients had the left atrial appendage closed. Multivariate analysis showed that late atrial fibrillation (odds ratio, 3.39; 95% confidence interval, 1.72-6.67; P =.0001) and omission of the maze procedure (odds ratio, 3.40; 95% confidence interval, 1.14-10.14; P =.003) were the significant risk factors for late stroke. CONCLUSIONS Persistent atrial fibrillation was the most significant risk factor for late stroke after mechanical mitral valve replacement. Restoration of sinus rhythm with a maze procedure nearly eliminated the risk of late stroke, whereas neither closure of the left atrial appendage nor therapeutic anticoagulation prevented this complication.

Activation of cardiac progenitor cells through paracrine effects of mesenchymal stem cells

Mesenchymal stem cells (MSC) transplantation has been proved to be promising strategy to treat the failing heart. The effect of MSC transplantation is thought to be mediated mainly in a paracrine manner. Recent reports have suggested that cardiac progenitor cells (CPC) reside in the heart. In this study, we investigated whether MSC had paracrine effects on CPC in vitro. CPC were isolated from the neonatal rat heart using an explant method. MSC were isolated from the adult rat bone marrow. MSC-derived conditioned medium promoted proliferation of CPC and inhibited apoptosis of CPC induced by hypoxia and serum starvation. Chemotaxis chamber assay demonstrated that MSC-derived conditioned medium enhanced migration of CPC. Furthermore, MSC-derived conditioned medium upregulated expression of cardiomyocyte-related genes in CPC such as beta-myosin heavy chain (beta-MHC) and atrial natriuretic peptide (ANP). In conclusion, MSC-derived conditioned medium had protective effects on CPC and enhanced their migration and differentiation.

Overview of Late Outcome of Medical and Surgical Treatment for Takayasu Arteritis

Takayasu arteritis (TA), which is a nonspecific inflammatory disease of unknown origin, causes various types of aortoarterial stenosis/occlusion or dilatation (Figure). Historically, Mikito Takayasu, a Japanese ophthalmologist, described a peculiar wreathlike arteriovenous anastomosis around the papillae of the retina (Takayasu disease) in 1908.1 In the first necropsy case reported in 1940, this ophthalmologic finding was related to cervical vessel occlusion.2,3 Subsequently, this nonspecific panarteritis that affects the intima and the adventitia of the aorta and its main branches was called Takayasu arteritis . Its clinical manifestations are varied and related to the vessel that presents the stenotic or occlusive lesions, such as the aortic arch (pulseless disease),4 descending thoracic or abdominal aorta (atypical coarctation),5 renal arteries,6 coronary arteries,7 and pulmonary arteries. Aortic aneurysm8 and aortic valve regurgitation with ascending aortic dilatation9 may also develop in some instances. Pharmacological treatment with corticosteroids is usually the initial treatment. Some patients require surgical treatment such as bypass grafting and graft replacement or endovascular repair including percutaneous transluminal angioplasty (PTA) and stent grafting, even in the active phase or in the inactive chronic phase with adequate control of the inflammation. Since the 1960s, acceptable early and midterm outcomes of medical and/or surgical treatment have been published. However, the long-term outcome, including that of recently developed endovascular treatment, has not been discussed. In this article, we describe an overview, particularly focusing on the late outcome of treatment for TA. Figure. Three-dimensional computed tomographic findings of an active phase of Takayasu arteritis (21 years, female). Three-dimensional computed tomographic findings include multiple stenotic lesions on the carotid and subclavian arteries (A), aneurysmal dilatation of the ascending aorta to the aortic arch and of the main pulmonary artery (B), aneurysmal dilatation of the descending aorta, stenosis of the right renal …

Extent of aortopulmonary collateral blood flow as a risk factor for Fontan operations

Between November 1987 and January 1990, 33 patients (tricuspid atresia, 9 patients; mitral atresia, 3; single ventricle, 15; others, 6) underwent Fontan operations. The rate of blood flow returning to the heart during aortic cross-clamping was measured as an indication of the extent of development of aortopulmonary collateral arteries. Percent cardiac return (calculated by dividing the blood flow rate returning to the heart by the cardiopulmonary bypass blood flow rate and expressing the value as a percentage), were 1% to 9%, 7 patients; 10% to 19%, 11; 20% to 29%, 9; 30% to 39%, 4; 40% to 49%, 1; and 50% to 59%, 1 patient. Percent cardiac return showed a significant correlation with postoperative mean systemic venous pressure (r = 0.6, p < 0.01). In those patients in whom percent cardiac return was more than 33%, the mean systemic venous pressure after operation was high (more than 17 mm Hg), and none of these patients survived. To predict percent cardiac return preoperatively, the conventional indices of systemic ventricular volume, pulmonary artery area index, arterial blood oxygen saturation, pulmonary blood flow index, and pulmonary vascular resistance were analyzed. None of these showed significant correlation with percent cardiac return. However, all the patients who had a high percent cardiac return (more than 30%) also had both high arterial blood oxygen saturation (more than 75% in room air) and small pulmonary artery area index (less than 55%). In addition, the age at operation showed good correlation (r = 0.6, p < 0.01) to percent cardiac return.(ABSTRACT TRUNCATED AT 250 WORDS)

Double switch operation in cardiac anomalies with atrioventricular and ventriculoarterial discordance

Since June 1987, 10 of 19 consecutive patients with atrioventricular and ventriculoarterial discordance (average age 4 +/- 2 years) had undergone a double switch operation with the morphologically left ventricle used as a systemic ventricle. There were two combinations of procedures. Atrial switch combined with arterial switch was used in two patients who had a normal pulmonary valve. Atrial switch combined with ventriculoarterial switch by Rastellis procedure was used in eight patients with pulmonary stenosis or atresia and a large ventricular septal defect. One early death and two late deaths have occurred in a postoperative follow-up period of up to 4 years. Subsequent problems were mainly related to the results of atrial switch procedures in patients who had a small atrium because of low pulmonary flow, especially in patients with apicocaval juxtaposition. Our experience suggested that the double switch operation would open a new era of definitive surgical treatment in half of the patients with atrioventricular and ventriculoarterial discordance.

What factors affect ventricular performance after a Fontan-type operation

Postoperative conditions after a Fontan-type operation, particularly as they affect results in the early term, are thought to depend on factors such as the state of pulmonary circulation and ventricular function. In this study, we attempted to determine the factors that influence ventricular characteristics in the middle term after Fontan-type procedures. Catheterization was performed at a mean of 15 months after operation in 57 patients with univentricular atrioventricular connection who underwent the operation between 1.0 and 22.6 years of age. End-diastolic volume, end-systolic volume, ejection fraction, and end-diastolic pressure of the systemic ventricle were analyzed together with an estimation of the systemic flow index. These parameters were influenced significantly by the presence of atrioventricular valve insufficiency. The morphologically left ventricle showed a better ejection fraction than did the morphologically right ventricle, whereas the systemic flow index was greater in patients undergoing total cavopulmonary connection than in those receiving an atriopulmonary connection. Young age was significantly associated with a better postoperative contractility, whereas the potential for impaired ventricular compliance was suggested in several patients undergoing operation after 4 years of age. On the basis of our results, we conclude that total cavopulmonary connection performed at a young age should be the surgical procedure of choice and that atrioventricular insufficiency must be treated properly at, and even after, the initial definitive repair.

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.