Human heterotaxy syndrome is characterized by a wide variety of cardiac and extracardiac congenital malformations that are primarily induced by disorders of the left-right axis determination during ...early embryonic development. The cellular and molecular mechanisms of the left-right asymmetry have been extensively investigated in the past decade and the developmental mechanisms of the syndrome have been considerably elucidated. Medical and surgical management and treatment of heterotaxy syndrome have advanced as well. However, prognosis of the disease still remains unsatisfactory because the syndrome is often associated with a combination of complicated congenital heart diseases. Management of heterotaxy patients, particularly those who have undergone the Fontan procedure, is now one of the most important issues in pediatric and adult congenital heart disease clinics. In this review, we focus on the recent advances in knowledge of the genetic and molecular pathogenesis of heterotaxy syndrome, as well as its clinical features, management, and prognosis. (Circ J 2012; 76: 2066–2075)
Background:Congenital heart disease (CHD) is often diagnosed prenatally using fetal echocardiography, but few studies have evaluated the accuracy of these fetal cardiac diagnoses in detail. We ...investigated the discrepancy between pre- and postnatal diagnoses of CHD and the impact of discrepant diagnoses.Methods and Results:This retrospective study at a tertiary institution included data from the medical records of 207 neonates with prenatally diagnosed CHD admitted to the cardiac neonatal intensive care unit between January 2011 and December 2016. Pre- and postnatal diagnoses of CHD differed in 12% of neonates. Coarctation of the aorta and ventricular septal defects were the most frequent causes of discrepant diagnosis. Unexpected treatments were added to 38% of discrepant diagnostic cases. However, discrepant diagnoses did not adversely affect the clinical course. The 9% of the 207 neonates who required invasive intervention within 24 h of delivery were accurately diagnosed prenatally.Conclusions:Pre- and postnatal diagnoses differed in only a few neonates, with differences not adversely affecting the clinical course. Neonates who required invasive intervention immediately after delivery were accurately diagnosed prenatally. Prenatal diagnosis thus seems to contribute to improved prognosis in neonates with CHD.
Background Elevated central venous pressure (CVP), low cardiac output and mild hypoxia are common early and late after Fontan operation. However, the association of these characteristics with late ...mortality is unclear. We aimed to elucidate the hemodynamic determinants of mortality after Fontan operation. Method We evaluated early (group Early; 0.5 to 5 years postoperatively, n = 387) and late (group Late; ≥15 years postoperatively, n = 161) Fontan hemodynamics that included CVP (mmHg), cardiac index (CI; L/min/m2 ), systemic ventricular end-diastolic volume index (EDVI; ml/m2 ), ejection fraction (EF; %), and arterial blood oxygen saturation (SaO2 ; %). We examined the effect of these variables on 5-year all-cause mortality. Results Mortality was higher in group Late than in group Early (17 vs. 11, P < .0001). In both Groups, higher CVP (hazard ratio HR:1.46 and 1.38, respectively, P < .001–0.0001) and lower SaO2 (HR: 1.12, P < .001 for both) were associated with increased mortality. Greater EDVI (HR per 20: 1.73) and lower EF (HR per 10%: 3.38) were associated with increased mortality only in group Early ( P < .0001 for both). In contrast, only in group Late was higher CI associated with increased mortality (HR: 2.50, 95% confidence interval: 1.30–4.55, P < .01). Seven patients in group Late with both high CVP (≥14) and CI (≥3.0) had the highest mortality (HR: 18.1, 5.55–52.4, P < .0001). Conclusions Elevated CVP and low SaO2 correlate with mortality in both early and late Fontan survivors. EDVI and EF are associated with mortality only in the earlier cohort, whereas interestingly, elevated cardiac output is associated with increased mortality in the later cohort.
The objective of this study was to assess the utility of 3D printed heart models of congenital heart disease for preoperative surgical simulation.
Twenty patient-specific 3D models were created ...between March 2015 and August 2017. All operations were performed by a young consultant surgeon who had no prior experience with complex biventricular repair. All 15 patients with balanced ventricles had outflow tract malformations (double-outlet right ventricle in 7 patients, congenitally corrected transposition of great arteries in 5, transposition of great arteries in 1, interrupted aortic arch Type B in 1, tetralogy of Fallot with pulmonary atresia and major aortopulmonary collateral arteries in 1). One patient had hypoplastic left heart complex, and the remaining 4 patients had a functional single ventricle. The median age at operation was 1.4 (range 0.1-5.9) years. Based on a multislice computed tomography data set, the 3D models were made of polyurethane resins using stereolithography as the printing technology and vacuum casting as the manufacturing method.
All but 4 patients with a functional single ventricle underwent complete biventricular repair. The median cardiopulmonary bypass time and aortic cross-clamp time were 345 (110-570) min and 114 (35-293) min, respectively. During the median follow-up period of 1.3 (0.1-2.5) years, no mortality was observed. None of the patients experienced surgical heart block or systemic ventricular outflow tract obstruction.
Three-dimensional printed heart models showed potential utility, especially in understanding the relationship between intraventricular communications and great vessels, as well as in simulation for creating intracardiac pathways.
Background Liver cancer (LC) is a serious late complication after the Fontan operation. However, the incidence, predictors, and prognosis remain unknown. The purpose of our study was to determine ...these clinical characteristics. Methods and Results We assessed liver function in 339 consecutive patients who had undergone the Fontan procedure from 2005 to 2019. LC was histologically diagnosed in 10 patients after a median period of 2.9 years (range: 0.3-13.8; median age: 29.9 years range: 14.4-41.5 years; overall median post-Fontan procedure follow-up: 25.6 years range: 13-32.1 years), and the annual incidence was 0.89%. Over the entire post-Fontan follow-up period, the annual incidences of new-onset LC in the second, third, and fourth decades were 0.14%, 0.43%, and 8.83%, respectively. The patients with LC had longer follow-up periods, higher levels of AFP (α-fetoprotein), and higher values of liver fibrosis indices (
<0.01-0.0001). Moreover, all indices were predictive of new-onset LC (
<0.01-0.0001). The LC treatments were surgical resection (n=3), transarterial chemoembolization (n=3), radiofrequency ablation (n=2), and hospice care (n=2). During a median follow-up of 9.4 months, 4 patients died; the survival rate at 1 year was 60%, and it was better among asymptomatic patients (
<0.01). Conclusions The LC incidence rapidly increased ≥30 years after the Fontan procedure, and liver fibrosis indices and AFP were predictive of new-onset LC. These LC-predictive markers should be monitored closely and mandatorily for early LC detection and better prognosis.
Exercise training is recommended for its possible favorable effects on Fontan pathophysiology. This study aimed to elucidate the impact of pediatric exercise capacity trajectory, which may mimic the ...effect of exercise training, on late adult Fontan pathophysiology.
Since 1990, 97 Fontan patients had consecutively undergone two serial cardiopulmonary exercise tests (CPX1 and CPX2) during childhood (ages 8 ± 2 and 14 ± 2 years) and one during adulthood (CPX3; age 23 ± 5 years). The changes in peak oxygen uptake (PVO2: % of normal value) from CPX1 to CPX2 (1-dPVO2) and from CPX2 to CPX3 (2-dPVO2) were calculated, and then the patients were divided into four subgroups according the 1-dPVO2 and 2-dPVO2.
In their adulthood, when compared with groups with negative 1-dPVO2, the central venous pressure, plasma brain natriuretic peptide level, and renal resistive index were lower, whereas liver synthetic function, body fat-free percentage, and PVO2 were higher in those with positive 1-dPVO2 (p < 0.05–0.0001). However, these favorable associations of 2-d-PVO2 with adult Fontan pathophysiology were not observed, except for the PVO2. After CPX3, 13 unexpected events occurred, and the risk was 76% lower in the groups having positive 1-dPVO2 than in those with negative 1-dPVO2 (hazard ratio, 0.24; 95% confidence interval, 0.09–0.62; p = 0.0035).
A positive exercise capacity trajectory during childhood predicts better adult Fontan pathophysiology, including better prognosis. Thus, prescription of exercise could be a promising strategy in the management of pediatric Fontan patients.
•Pediatric exercise capacity trajectory had impact on adult Fontan physiology.•Post-pediatric exercise capacity trajectory poorly predicts adult Fontan status.•The earlier exercise training starts, the better adult Fontan outcome becomes.
Background:Tenascin-C (TN-C) is an extracellular matrix glycoprotein that is heavily upregulated at sites of inflammation. We conducted a retrospective study to assess the utility of TN-C as a novel ...biomarker to predict the risk of developing coronary artery lesions (CAL) and resistance to intravenous immunoglobulin (IVIG) in patients with Kawasaki disease (KD).Methods and Results:We collected blood samples of 111 KD patients (IVIG-responder: 89, IVIG-resistant: 22; CAL: 8) and 23 healthy controls, and measured the serum levels of TN-C. TN-C levels on admission were significantly higher in patients than in healthy controls and in patients during convalescence after IVIG administration (69.6 vs. 20.4 vs. 39.7 ng/ml, respectively; P<0.001), and correlated positively with C-reactive protein (P<0.001), neutrophil (percentage; P=0.005), and ALT (P<0.001), and negatively with platelet count (P=0.023) and sodium level (P=0.025). On admission, TN-C levels in patients who later developed CAL were significantly higher than in those without CAL (P=0.010), and significantly higher in IVIG-resistant subjects than in IVIG-responders (P=0.003). The accuracy of TN-C testing for the prediction of IVIG resistance was comparable to that of the Kobayashi score.Conclusions:Serum TN-C could be a biomarker for predicting the risk of developing CAL and IVIG resistance during the acute phase of KD. (Circ J 2016; 80: 2376–2381)
Background:Heart failure (HF) is an important complication in adults with congenital heart disease (CHD), but because only a few studies have focused on acute HF hospitalization in adults with CHD, ...we study aimed to define the clinical characteristics of such patients and examine the differences in acute HF between adults with CHD and acquired heart disease.Methods and Results:We retrospectively evaluated 50 adults with CHD admitted for treatment of acute HF and compared their data with those from Japanese HF registries. Patient mean age was 37±15 years and 58% were male. In total, 86% of the patients had complex forms of CHD and 62% had undergone corrective surgery, including the Fontan procedure; 66% of patients showed right heart hemodynamic abnormality. In-hospital mortality was 4%, which was comparable to the Japanese HF registries. Survival rate was 93% at 1 year and 75% at 3 years, which was similarly poor to the rates of HF secondary to acquired heart disease.Conclusions:We clarified the clinical characteristics of adults with CHD requiring HF hospitalization. Young adults with complex CHD were hospitalized for management of acute right HF. Short-term and mid-term outcomes were similarly poor compared with acute HF secondary to acquired heart disease.
Objective: Stereolithographic biomodelling is a technique where photosensitive liquid resin is polymerised with a pinpoint laser beam controlled by three-dimensional (3D) datasets. This study was ...designed to assess whether a stereolithographic biomodelling technique is applicable for precise anatomical diagnosis and simulation surgery of complicated congenital heart disease. Methods: Twelve stereolithographic biomodels were manufactured with multislice computed tomography (MSCT)-based 3D datasets. They were made of photosensitive liquid epoxy or urethane. Results: All the solid epoxy and rubber-like urethane biomodels reproduced the complex anatomical structures of the arteries and veins in congenital heart diseases. Furthermore, the rubber-like urethane biomodels allowed the surgeon to cut and suture, thus facilitating the simulation of the surgical operation. Conclusions: Stereolithographic biomodelling is a promising technique for the preoperative practice and simulation of individual surgery. This technique would be useful in the planning of novel and innovative surgical procedures of congenital heart disease.
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