Utility of urinary liver-type fatty acid-binding protein as a prognostic marker in adult congenital heart patients hospitalized for acute heart failure.

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.

Prevalence of adult patients with congenital heart disease in Japan.

BACKGROUND: Today 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 METHODS: The 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. RESULTS: In 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. CONCLUSIONS: The 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 young adult who had undergone coronary artery bypass grafting and abdominal aortic replacement with prosthetic vessel later after incomplete Kawasaki disease.

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.

Systemic ventricular morphology-associated increased QRS duration compromises the ventricular mechano-electrical and energetic properties long-term after the Fontan operation.

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 (VO(2)) (p<0.001) and QRS-d was one of the main determinants of peak VO(2) (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.

Long-term results of saphenous vein graft for coronary stenosis caused by Kawasaki disease.

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.

[Pediatric coronary artery bypass grafting for Kawasaki disease: 20-years' outcome].

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.

Comparison of late post-operative cardiopulmonary responses in the Fontan versus ventricular septation for double-inlet left ventricular repair.

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.

Heart rate dynamics during and after exercise in postoperative congenital heart disease patients. Their relation to cardiac autonomic nervous activity and intrinsic sinus node dysfunction.

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 (CHD). 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 CHD. METHODS: We analyzed our previous data in 53 postoperative patients with CHD 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.

Impact of central hypercapnic chemosensitivity on enhanced ventilation in patients after the Fontan operation.

BACKGROUND: 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. OBJECTIVES: To measure Chemo and compare the results with rest and exercise ventilatory characteristics in Fontan patients. METHODS AND RESULTS: 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). CONCLUSIONS: 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.

Tumor necrosis factor-alpha downregulates the voltage gated outward K+ current in cultured neonatal rat cardiomyocytes: a possible cause of electrical remodeling in diseased hearts.

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.

Structural and electrical ventricular remodeling in rat acute myocarditis and subsequent heart failure.

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.

Prediction of clinical recurrence of atrioventricular-nodal reentrant tachycardia (AVNRT) after successful slow pathway ablation.

BACKGROUND: Even after successful slow pathway (SP) ablation for atrioventricular-nodal reentrant tachycardia (AVNRT), there may be clinical recurrence in certain patients and it is clinically important to be able to predict that. METHODS AND RESULTS: In 97 patients with common type AVNRT, the effective refractory period (ERP) of the fast pathway (FP), SP-ERP, and prolongation of the atrio-His (AH) interval (AH) at the time of jump-up phenomenon were investigated. In patients with residual SP, parameters were re-evaluated in a similar manner. SP was successfully ablated and AVNRT was not inducible in all the patients, but residual SP was observed in 54 of the 97 patients, and there was late clinical recurrence in 10 patients (10/54 patients with residual SP and 0/43 without residual SP, p=0.002). The changes in FP-ERP before and after ablation (DeltaFP-ERP) did not differ between recurrent and non-recurrent patients. Among the patients with residual SP, DeltaSP-ERP did not differ between the groups. However, the changes in DeltaAH before and after ablation (DeltaDeltaAH) were larger in non-recurrent (24+/-30 ms) than in the recurrent patients (4+/-7 ms, p=0.042). CONCLUSIONS: In patients with AVNRT, the residual SP and changes in DeltaAH after successful SP ablation might be useful indices of clinical recurrence.

Monitoring the progression of the atrial electrical remodeling in patients with paroxysmal atrial fibrillation.

It is important to clarify how electrical remodeling develops in clinical cases of paroxysmal atrial fibrillation (PAF), because it has been suggested that this electrophysiological phenomenon promotes an increase in the frequency of PAF. In the present study, the f-f interval during PAF was analyzed from the ambulatory ECG recordings of 21 patients with PAF (total PAF duration >2/24 h with normal atrial size) to monitor the atrial electrophysiological changes. The patients were clinically followed-up for 6 months without any antiarrhythmic drugs. Before and after the follow-up period 24-h Holter monitoring was carried out and the duration of both the PAF and the f-f intervals during the PAF episode were evaluated. In selected cases, the atrial effective refractory period (ERP) was evaluated in an electrophysiologic study before and after the follow-up period. The total PAF duration was prolonged from 187+/-50 to 223+/-79 min (p=0.034) and the f-f interval was shortened from 0.14+/-0.03 to 0.12+/-0.02 ms (p=0.003). There was an inverse relationship between the changes in total PAF duration and f-f interval (p=0.027). The ERP was shortened from 214+/-15 to 194+/-5 ms (n=5, p=0.025) and there was a direct correlation between the changes in ERP and f-f interval (p=0.048). In clinical cases, the prolongation of the PAF was related to the shortening of the f-f interval during the PAF episodes and to the shortening of the atrial ERP. Electrical remodeling plays a role in promoting the development of the atrial fibrillation in patients with PAF.