Progression to acute kidney injury (AKI) under treatment in adult congenital heart disease (ACHD) patients with heart failure is associated with poor prognosis, early detection and interventions are necessary. We aimed to explore the utility of urinary liver-type fatty acid binding protein (L-FABP) in ACHD patients hospitalized for acute decompensated heart failure (ADHF). We prospectively evaluated hemodynamic, biochemical data, and urinary biomarkers including urinary L-FABP in ACHD patients hospitalized in our institution from June 2019 to March 2022. The primary outcomes were the development of AKI and death. AKI was defined as serum creatinine level increased by 0.3 mg/dl or more within 5 days after hospitalization. A total of 104 ADHF patients aged 31 (36–51) years were enrolled. 26 cases (25% of ADHF patients) developed AKI during hospitalization and 4 died after hospital discharge. Serum creatinine (sCr), serum total bilirubin, brain natriuretic peptide (BNP), and urinary L-FABP in AKI patients were significantly higher than in non-AKI patients, whereas systemic oxygen saturation of the peripheral artery (SpO2) and estimated glomerular filtration ratio in AKI patients were lower than non-AKI patients. There was no difference in the intravenous diuretic dose on admission and during hospitalization between the two groups. In the receiver operating characteristic (ROC) analysis, the maximum area under the curve (AUC) of urinary biomarkers in AKI patients was urinary L-FABP (AUC = 0.769, p < 0.001) with a cutoff value of 4.86 µg/gCr. Urinary L-FABP level on admission was associated with a predictor for AKI development during hospitalization after adjusting for sCr, BNP and SpO2. Urinary L-FABP was a useful predictor for the development of AKI in ACHD patients hospitalized for ADHF. Monitoring of urinary L-FABP allows us to detect a high-risk patient earlier than the conventional biomarkers.

BackgroundToday most patients with congenital heart disease (CHD) can be expected to survive into adulthood. Reports regarding the number of adults with CHD in Japan are scarce. Our study aims to define the number of these adults.Material and methodsThe estimated number of infants born in Japan with major CHDs since 1947 was calculated together with mortality rates. We estimated the number of CHD survivors from data on survival rates of unoperated and postoperative patients. The number of deaths from 1968 to 1997 was analyzed using individual death certificates held by the Japanese Government.ResultsIn 1967, 163,058 patients with CHD including 53,846 adults were assumed to be alive. From 1968 to 1997, 548,360 patients with CHD were born and 82,919 died. A total of 622,800 patients, including 304,474 children (49%) and 318,326 adults (51%) were estimated to be alive in 1997. From 1997 to 2007, there has been an estimated increase of 9000 adults every year, and in 2007, 409,101 adults are estimated to be alive.ConclusionsThe prevalence in adults with CHD in Japan has explosively increased from 1967 to 2007. There were 409,101 adults with CHD in 2007 with an annual increase of 9000. These data are crucial for planning the establishment in Japan of special facilities and resources necessary for the care of these patients.

A 33-year-old male with a history of undiagnosed fever at the age of 14 years underwent coronary artery bypass grafting (CABG) and abdominal aortic replacement with a prosthetic vessel. Syncope and chest pain on exertion at the age of 19 years led to the diagnosis of complete occlusion of three major coronary branches and emergency CABG was performed. Fourteen years later, a pulsating abdominal mass was an incidental finding during an outpatient clinic visit and an abdominal aortic aneurysm was confirmed by computed tomography. Based on the recorded symptoms and examination findings, the past history of unexplained fever was suspected to be due to incomplete Kawasaki disease. Co-existing systemic arterial lesions should be sought in patients with multi-vessel coronary disease due to Kawasaki disease, although their prevalence is low.

Purpose: Cyanotic congenital heart disease (CCHD) induces secondary erythrocytosis and CCHD is thought to be one of the risk factors for cholelithiasis, but the frequency of cholelithiasis and/or gallstones in patients with CCHD is unknown. Materials and Methods: A hundred and two patients with CHD were divided into 4 groups: group A 22 CCHD without reparative surgery or with palliative surgery; group B 35 CCHD after repair who were eliminated cyanosis; group C 17 acyanotic CHD without repair; and group D 28 acyanotic CHD after repair. Gallstones were studied by abdominal ultrasonography or CT in each patient. For analysis of risk factors, patient records regarding cyanotic period, family history and past abdominal surgery were reviewed and blood pressures, lipid profiles, blood sugar and liver enzyme were evaluated. Results: Cholecystectomy due to cholelithiasis was underwent in 7 of 279 CCHD patients (2.5%). In group A, 7 patients (31%) underwent cholecystectomy, and 3 patients (18%) have gallstones. In group B, 11 patients (37%) had gallstones. In group C, nobody had gallstones, and in group D 2 patients (7%) had gallstones. SPO2 was significantly lower and red blood cell, hemoglobin, hematocrit, HbA1C and total bilirubin levels were significantly higher in group A (p 19.8, 95%CI 1.30 300.1). Conclusions: The incidence of cholelithiasis and gallstones is significantly high in CCHD regardless of repair. The most important factor related to gallstones was having CCHD even after desaturation was improved by surgical repair.

BACKGROUND:Although saphenous vein grafts (SVG) have been used from 1975 to treat coronary stenosis caused by Kawasaki disease, long-term results after more than 20 years remain unknown.METHODS AND RESULTS:From 1981 to 1997, 13 patients underwent coronary artery bypass grafting using SVG (n=20). The age at operation ranged from 2 to 20 years (median 11 years), the age at latest angiography from 15 to 36 years (median 30 years) and the postoperative follow-up period was from 10 to 26 years (median 22 years). The patency rate of the SVG was determined by postoperative angiography, graft wall morphology was graded and the late clinical course was reviewed. The patency rates at 1, 10, and 25 years after operation were 84.4%, 57.2%, and 51.5%, respectively. Irregularity of the SVG wall was slight in 3 of 7 patients with long-term patency. One patient with obesity and hyperlipidemia underwent stent implantation in the SVG because of graft stenosis.CONCLUSION:Although the patency rates for SVG are low, there are patients with long-term patency over 20 years. Obesity and hyperlipidemia in these patients should be vigorously pursued.

Background: Recently, it has been reported that frequent premature ventricular contractions (PVCs) may be associated with causing heart failure in patients with left ventricular (LV) dysfunction. However, the prognostic significance of frequent PVCs in asymptomatic patients with a normal LV function is unclear.Methods: Two hundred and thirty-nine consecutive patients presenting with frequent PVCs (>1000 beats/day) originating from the right or left ventricular outflow tract without any detectable heart disease were enrolled in the study. Structural heart disease was ruled out by echocardiography and cardiac magnetic resonance imaging, and Holter-ECG monitoring was repeated two or three times to evaluate the PVC prevalence at the initial evaluation. All patients were followed up for at least 4 years, and further observation was continued if possible.Results: During an observation period of 5.6 (1.7) years, no patients exhibited any serious cardiac events. Although there was no significant change in the mean LV ejection fraction (LVEF) and mean LV diastolic dimension (LVDd), there was a significant negative correlation between the PVC prevalence and Delta LVEF (p<0.001) and positive correlation between the PVC prevalence and Delta LVDd (p<0.001). When the development of LV dysfunction was defined as Delta LVEF>-6%, 13 patients exhibited LV dysfunction. For the prediction of the development of LV dysfunction, PVC prevalence and LVEF at the initial evaluation were independent predicting factors (p<0.01).Conclusion: Although the prognosis in patients with frequent PVCs was considered relatively benign, attention should be paid to the progression of the LV dysfunction during a long-term observation, especially in patients with a high PVC prevalence.

Objectives: To evaluate the impact of systemic ventricular (SV) morphology on mechano-electrical interaction (MEI) and compare the results with clinical profiles in Fontan patients.Background: Abnormal ventricular MEI causes systolic dysfunction of the right and left ventricles (RV, LV).Methods: We evaluated serial changes (up to 15 years post-Fontan operation) in QRS duration (QRS-d, ms), catheterization-based hemodynamics and SV performance in 77 patients and compared them with 36 referents.Results: Preoperative QRS-d was wider in the Fontan patients (86 +/- 14 vs. 64 +/- 9, p < 0.001) and steadily increased for the next 15 years (107 +/- 25 vs. 85 +/- 9, p < 0.001). QRS-d was wider in non-LV type SV patients than those with LV morphology (p < 0.05) with a positive association with age at repair (p < 0.001). SV contractility (Ees) improved in the RV and LV groups (p < 0.05), during the next 10-year Ees, ventriculoarterial coupling (Ea/Ees) and ventricular efficiency (SW/PVA) were superior in the LV group. QRS-d and its long-term change correlated with the corresponding SV volume and change (p < 0.01), respectively, while the immediate postoperative volume reduction did not result in the QRS-d shortening. QRS-d correlated with Ees, Ea/Ees, SW/PVA, and peak oxygen uptake (VO2) (p < 0.001) and QRS-d was one of the main determinants of peak VO2 (r=-0.48, p < 0.001).Conclusions: SV morphology-associated wide QRS-d compromises the MEI as well as energetic properties long-term after the Fontan operation, especially in non-LV type patients. (c) 2008 Elsevier Ireland Ltd. All rights reserved.

The 20-year clinical outcome is excellent for the children with Kawasaki disease who underwent a bypass operation using the internal thoracic artery. This operation is feasible from 1 year-old children and in our experience with more than 110 patients, the operative and hospital mortality was 0%, and the 20-year survival was 98.4%. The recent patency rate was nearly 95% for the internal thoracic artery graft regardless of the patient's age, and the 20-year patency was 87.1%. Moreover, the wall characteristics of the internal thoracic artery was quite smooth and apparently well adapting to the somatic growth of children over 20 years after the operation. In contrast, vein grafts had a lower patency of 57% at 20 years. In addition, patent vein grafts showed irregularity of the wall and in some, atherosclerotic changes were observed. Pediatric coronary bypass operation utilizing the internal thoracic artery is proved to be a golden standard treatment modality for complicated coronary artery obstructive disease due to Kawasaki disease, based upon the 20-year clinical and angiographic follow-ups.

Background Abnormal exercise-related heart rate (HR) dynamics, that is, blunted exercise HR response, lower peak HR, and delayed HR recovery after exercise, are associated with high morbidity and mortality in adults with acquired and congenital heart disease (CHID). However, the precise mechanisms underlying the abnormal HR dynamics remain unclear.Objectives The purpose of this study is to evaluate the precise contribution of cardiac autonomic nervous activity (CANA) and sinus node function on exercise-related HR dynamics in postoperative patients with CHID.Methods We analyzed our previous data in 53 postoperative patients with CHID who had undergone pharmacologic evaluation, including intrinsic HR, and compared the results with HR dynamics.Results Intrinsic HR (84% +/- 11%) was lower than the expected value and independently correlated with resting HR (P <.05). Univariate analysis demonstrated that all CANA indices significantly correlated with most HR dynamic parameters. On multivariate analysis, basal parasympathetic nervous activity significantly influenced all HR dynamics (P <.05-.0001), except for peak HR, whereas postsynaptic beta sensitivity of the sinus node significantly influenced all HR dynamics ( P <.05.001), except for early HR recovery. Resting plasma norepinephrine significantly correlated with all HR dynamics (P <.05.001), except for resting HR.Conclusions Lower resting and peak HRs are independently associated with intrinsic sinus node dysfunction and abnormal sympathetic CANA, respectively. A blunted HR increase and delayed early HR recovery are independently associated with impaired sympathetic and parasympathetic CANAs with the greater influence on a blunted exercise HR increase.

Ventricular septation (VS) and the Fontan procedure are alternatives for definitive repair in patients with double-inlet left ventricle; although VS is theoretically preferable, the current preference in practice is the Fontan procedure. However, the long-term outcomes of both procedures remain unclear. To address this issue, cardiopulmonary responses during exercise were measured in patients with double-inlet left ventricle, and the impact of the type of procedure performed, Fontan or VS, on long-term exercise capacity and late postoperative clinical profiles was assessed. Fourteen post-Fontan patients (mean age 17+/-6 years) and 13 VS patients (mean age 19+/-4 years) underwent exercise testing. Of the 13 VS patients, 5 required atrioventricular valve replacement (AVVR), and 7 required pacemaker implantation. Although no difference in peak oxygen uptake was found between the VS and Fontan patients, peak oxygen uptake was higher in VS patients without AVVR (30+/-8 ml/kg/min) than in VS patients with AVVR (19+/-1 ml/kg/min) and Fontan patients (22+/-6 ml/kg/min) (p<0.01). There was no significant difference in peak oxygen uptake between the VS patients with and without pacemaker implantation (p=0.09). The clinical profiles of the VS and Fontan patients were similar in terms of medication and freedom from tachyarrhythmias or reoperations during the follow-up period. In conclusion, the data suggest that VS without AVVR provides excellent future exercise capacity in selected patients with double-inlet left ventricle.

Central hypercapnic chemosensitivity (Chemo) influences the enhanced ventilatory and sympathetic responses in heart failure patients; however, its influence on these responses in Fontan patients is unknown.To measure Chemo and compare the results with rest and exercise ventilatory characteristics in Fontan patients.We measured Chemo (l/min/mmHg), hemodynamics, pulmonary function, cardiac autonomic nervous and neurohumoral activities and compared the results with the ventilatory response during exercise in 42 Fontan patients and 12 referents. Chemo did not differ significantly between the Fontan patients (1.5 +/- 0.9) and referents (1.3 +/- 0.4). However, a higher Chemo in addition to lower resting arterial oxygen saturation (SaO(2)) and higher dead space ventilation (Vd/Vt) independently determined a higher resting minute ventilation (VE) and, except for the Chemo, these factors also independently determined the higher resting ventilatory equivalent for carbon dioxide output (VE/VCO(2)) (p<0.05-0.001). At peak exercise, the higher Chemo as well as the higher peak Vd/Vt and aerobic exercise capacity independently determined the higher peak VE and VE/VCO(2) (p<0.01-0.001). Among cardiac autonomic and neurohumoral activities, only the higher plasma norepinephrine concentration was associated with higher Chemo in Fontan patients (r=0.40, p<0.01) and age was correlated positively with Chemo in the high Chemo (> or =2.1) Fontan patients (n=10).In addition to lower SaO(2) and higher Vd/Vt, an increased Chemo associated with sympathetic activation has a significant impact on accelerated rest and exercise ventilation in some Fontan patients, especially in adult patients.

BACKGROUND:Inflammatory cytokines have been reported to contribute to the progression of cardiac remodeling in various heart diseases and a remarkable prolongation of the monophasic action potential duration and reductions in the expression of Kv4.2 and K+ channel-interacting protein-2 (KChIP-2) in a rat autoimmune myocarditis model have been documented. In this study, the effect of tumor necrosis factor-alpha (TNF-alpha) on cultured cardiomyocytes was evaluated, focusing on the change in the voltage-gated outward K+ current and expression of related molecules.METHODS AND RESULTS:Cardiomyocytes isolated from 1-day-old Lewis rats were cultured for 72 h and treated with TNF-alpha (50 ng/ml) for an additional 48 h. The myocytes treated with TNF-alpha showed a 22% reduction in the peak K+ current, which consisted of a transient outward K+ current (Ito) and 1.4-fold enhancement of the cell-capacitance in comparison with the control. Among the cardiac ion channel related molecules evaluated in this study, Kv4.2 and KChIP-2 mRNA exhibited remarkable reductions (p < 0.05).CONCLUSIONS:Treatment with TNF-alpha induced reductions in Ito as well as cellular hypertrophy in neonatal cultured myocytes, which indicates that TNF-alpha might play a role in promoting electrical remodeling of cardiomyocytes under inflammatory conditions.

Advances in Electrocardiology 2004, pp. 64-68 (2005) No AccessHETEROGENIC PROCESS OF THE APPEARANCE OF THE ATRIAL ELECTRICAL REMODELING IN CANINE RAPID STIMULATION MODELJISHO KOJIMA, SHINICHI NIWANO, DAISUKE SATO, MASAHIKO MORIGUCHI, YUKO WAKISAKA, KAZUKO IKEDA, KIMIATSU INUO, HIDEYUKI HARA, TOHRU YOSHIDA, and TOHRU IZUMIJISHO KOJIMADepartment of Internal Medicine, Kitasato University, Kanagawa, Japan, SHINICHI NIWANODepartment of Internal Medicine, Kitasato University, Kanagawa, Japan, DAISUKE SATODepartment of Internal Medicine, Kitasato University, Kanagawa, Japan, MASAHIKO MORIGUCHIDepartment of Internal Medicine, Kitasato University, Kanagawa, Japan, YUKO WAKISAKADepartment of Internal Medicine, Kitasato University, Kanagawa, Japan, KAZUKO IKEDADepartment of Internal Medicine, Kitasato University, Kanagawa, Japan, KIMIATSU INUODepartment of Internal Medicine, Kitasato University, Kanagawa, Japan, HIDEYUKI HARADepartment of Internal Medicine, Kitasato University, Kanagawa, Japan, TOHRU YOSHIDADepartment of Internal Medicine, Kitasato University, Kanagawa, Japan, and TOHRU IZUMIDepartment of Internal Medicine, Kitasato University, Kanagawa, Japanhttps://doi.org/10.1142/9789812702234_0014Cited by:0 PreviousNext AboutSectionsPDF/EPUB ToolsAdd to favoritesDownload CitationsTrack CitationsRecommend to Library ShareShare onFacebookTwitterLinked InRedditEmail Abstract: Background: Although it is well known that rapid atrial activation causes electrical remodeling, processes of electrical remodeling at different atrial sites are still unclear. In present study, atrial electrophysiologic parameters were monitored at several atrial sites during rapid atrial stimulation for 2weeks to clarify heterogeneity of process of atrial electrical remodeling. Methods: RAA or LAA was paced with 400bpm for 2weeks. At 4atrial sites of RAA, Bachmann's bundle (BB), IVC and LAA, AERP, AERP dispersion(AERPd) and inducibility of atrial fibrillation were evaluated at several points in pacing and recovery phase. Results: AERP shortening (Δ AERP)was heterogeneous in 4atrial sites in process of atrial electrical remodeling. In RAA stimulation group, Δ AERP was larger in RAA and LA sites than other sites. In contrast, LAA stimulation group showed larger Δ AERP at BB site than others. Maximal AERPd was larger in LAA than RAA stimulation group. AF inducibility was highest at LA site in both groups, but inducibility was higher in LAA than RAA stimulation group. Conclusions: In this model, process of the atrial electrical remodeling was heterogeneous in different parts of atria. Δ AERP was largest at LA site regardless of rapid pacing site, but AERPd was larger and AF inducibility was higher in LAA stimulation group than RAA stimulation group. LA seemed to play an important role in causing AF in canine rapid stimulation model of atrial electrical remodeling. Keywords: Atrial FibrillationElectrical RemodelingElectrophysiology FiguresReferencesRelatedDetails Advances in Electrocardiology 2004Metrics History KeywordsAtrial FibrillationElectrical RemodelingElectrophysiologyPDF download

Background: We have reported that TNF-α caused down-regulation of transient outward current (Ito) as well as hypertrophy in cultured neonatal myocytes. Although TNF-α induced hypertrophy was reported to be mediated by the activation of reactive oxygen speicies (ROS), the mechanism regulating ion channel is unclear. In this study, we evaluated the effect of n-acetyl cystein (NAC), an antioxidant, on TNF-α induced reduction of Ito and Ito-related molecules, and the regulation of action potential duration (APD) in neonatal rat myocytes.

OBJECTIVE:We reported that experimental autoimmune myocarditis (EAM) rats showed dramatic changes in ventricular action potential and enhanced arrhythmogenicity in the acute phase, but mechanisms for this are still unclear. To investigate the mechanisms of cardiac remodeling in acute myocarditis and subsequent heart failure, physiological and molecular changes were evaluated along the time course of EAM.METHODS:Six-week-old Lewis rats were immunized with porcine cardiac myosin. On days 14, 21, 35 and 60 after immunization, histology, hemodynamics and electrophysiological parameters (i.e., effective refractory period (ERP), monophasic action potential duration (MAPD) and PVC inducibility) were evaluated and compared with control rats. After these studies, the expression levels of Kv(+) and L-Ca(2+) channels, ion transporters and BNP expressions in the left ventricle were examined by quantitative real time RT-PCR and Western blot analysis.RESULTS:EAM rats showed acute myocarditis with massive infiltration of the mononuclear cells on days 14 and 21. Subsequently, a chronic dilated cardiomyopathy (DCM)-like structural change was observed on day 60. Hemodynamic parameters were worse in EAM than controls. ERP and MAPD were longer in EAM than controls, with a peak on day 21, which was parallel to PVC inducibility. mRNA levels of Kv4.2, Kv1.5, KChIP2, frequenin and SERCA2a, and the protein levels of Kv4.2 and Kv1.5, were reduced, especially in the acute phase.CONCLUSIONS:The initial reduction of Ito-related molecules, such as the expression levels of Kv4.2, 1.5, frequenin and KChIP2, and the prolongation of MAPD are considered to be a key mechanism of ventricular remodeling and cause the characteristic clinical findings in EAM in the acute inflammatory phase and chronic DCM phase.