Prominent atrial fibrosis and its correlation with atrial tachyarrhythmia and dilated atrium long after classic Fontan surgery.

BACKGROUND: The progression of atrial fibrosis long after Fontan surgery is unclear. This study aimed to evaluate the degree of atrial fibrosis long after the classic Fontan procedure and to investigate the factors associated with atrial fibrosis. METHODS: We obtained atrial free wall specimens resected at Fontan conversion from 43 patients (Fontan group) and studied the degree of atrial fibrosis, along with its association with atrial tachycardia/fibrillation (AT/AF) and other clinical parameters, compared with those of the control group without heart disease (n=6). RESULTS: The time after the initial Fontan procedure was 19.9 (15.9-25.3) years. Atrial fibrosis (%) was more common in the Fontan group than in the control group [24.3 (20.9-35.0)% vs. 6.2 (5.6-7.5)%, p<0.001]. The severity of atrial fibrosis was mild in 16% (n=7), moderate in 54% (n=23), and severe in 30% (n=13) of cases. Atrial fibrosis (%) was more common in the persistent/permanent AT/AF group than in the no AT/AF (p<0.001) and paroxysmal AT/AF (p<0.001) groups. The maximum atrial diameter on computed tomography (CT) (mm) significantly correlated with atrial fibrosis (%) (r=0.52, p<0.001). The maximum diameter of the right atrium (≥75 mm) on CT was a significant risk factor for severe atrial fibrosis on multivariate logistic analysis (hazard ratio=10.22, 95% confidence interval=1.04-254.8, p=0.04). CONCLUSIONS: Atrial fibrosis was prominent long after classic Fontan surgery, especially in patients with non-paroxysmal AT/AF and dilated right atrium.

Induced Pluripotent Stem Cell-Derived Cardiomyocytes with SCN5A R1623Q Mutation Associated with Severe Long QT Syndrome in Fetuses and Neonates Recapitulates Pathophysiological Phenotypes.

The SCN5A R1623Q mutation is one of the most common genetic variants associated with severe congenital long QT syndrome 3 (LQT3) in fetal and neonatal patients. To investigate the properties of the R1623Q mutation, we established an induced pluripotent stem cell (iPSC) cardiomyocyte (CM) model from a patient with LQTS harboring a heterozygous R1623Q mutation. The properties and pharmacological responses of iPSC-CMs were characterized using a multi-electrode array system. The biophysical characteristic analysis revealed that R1623Q increased open probability and persistent currents of sodium channel, indicating a gain-of-function mutation. In the pharmacological study, mexiletine shortened FPDcF in R1623Q-iPSC-CMs, which exhibited prolonged field potential duration corrected by Fridericia's formula (FPDcF, analogous to QTcF). Meanwhile, E4031, a specific inhibitor of human ether-a-go-go-related gene (hERG) channel, significantly increased the frequency of arrhythmia-like early after depolarization (EAD) events. These characteristics partly reflect the patient phenotypes. To further analyze the effect of neonatal isoform, which is predominantly expressed in the fetal period, on the R1623Q mutant properties, we transfected adult form and neonatal isoform SCN5A of control and R1623Q mutant SCN5A genes to 293T cells. Whole-cell automated patch-clamp recordings revealed that R1623Q increased persistent Na+ currents, indicating a gain-of-function mutation. Our findings demonstrate the utility of LQT3-associated R1623Q mutation-harboring iPSC-CMs for assessing pharmacological responses to therapeutic drugs and improving treatment efficacy. Furthermore, developmental switching of neonatal/adult Nav1.5 isoforms may be involved in the pathological mechanisms underlying severe long QT syndrome in fetuses and neonates.

Impact of preoperative electrophysiological intervention on occurrence of peri/postoperative supraventricular tachycardia following Fontan surgery.

BACKGROUND: Little is known about the effects of preoperative electrophysiological study (EPS) and catheter ablation (CA) in Fontan surgery candidates with supraventricular tachycardia (SVT). OBJECTIVE: The purpose of this study was to investigate the clinical impact of EPS-guided intervention in Fontan surgery candidates with preceding SVT events. METHODS: A total of 109 consecutive patients with a history of SVT before Fontan surgery were divided into 3 groups: 44 in whom EPS with CA was attempted (CA group); 21 in whom EPS without CA was attempted (EPS group); and 44 in whom EPS was not performed (N group). The incidence and diagnosis of SVT, acute success rate of CA, and risk factors of peri/postoperative SVT were retrospectively investigated. RESULTS: The total incidence of SVT within 1 year after Fontan surgery was 34% (n = 37), with 91% of cases occurring within 1 month. Among the 71 SVT incidences diagnosed with EPS, 31 were atrioventricular reentrant tachycardias (AVRTs) involving twin atrioventricular nodes, 12 were atrioventricular nodal reentrant tachycardias, 12 were atrial tachycardias, 7 were orthodromic AVRTs via the accessory pathway, 7 were atrial flutters, and 2 were junctional tachycardias. The acute success rate of CA was 91% (48/53). The rate of peri/postoperative atrioventricular reciprocating SVT was significantly lower in the CA group than in the N or EPS group (11% vs 43% or 43%; P <.05). No/unsuccessful CA significantly increased the risk of peri/postoperative SVT in multivariate analysis (odds ratio 4.43; 95% confidence interval 1.69-11.59). CONCLUSION: Preoperative CA reduces peri/postoperative SVT occurrence in Fontan surgery candidates at high risk for SVT.

Transvenous shock-only implantable cardioverter defibrillator after an atrio-pulmonary Fontan surgery.

A 42-year-old woman with tricuspid atresia who underwent a Fontan surgery (atrio-pulmonary connection) was admitted to our hospital due to symptomatic ventricular tachycardia (VT). A defibrillation lead was implanted in a distal site of a coronary vein since there was no usual entry to the ventricle. Ventricular pacing was impossible due to the high threshold, however, good sensing was obtained. Three years later, she felt palpitations and a subsequent shock therapy while climbing stairs. The cardioverter data showed that an appropriate cardioversion therapy successfully converted VT to normal rhythm.

Statement for electrophysiological procedures under the COVID-19 pandemic from the Japanese heart rhythm society task force.

COVID-19 is a global catastrophe with markedly reduced health and economy of human civilization. Heart rhythm disorder has also been impacted by this disease. This statement is the universal criteria for EP procedures in the new era, which we will face during COVID-19 pandemic. We described the methods of triage based on the severity of disease, the regional state of pandemic and supply of medical resources. This guidance will be the universal criteria for EP procedures in the new era, which we will face during and after the COVID-19 pandemic.

Electrophysiological features and radiofrequency catheter ablation of accessory pathways associated with atrioventricular discordance.

INTRODUCTION: Although a high prevalence of the presence of an accessory pathway (AP) associated with atrioventricular (AV) discordance has been reported, a case series of its characteristics and the results of catheter ablation (CA) have not been sufficiently documented. METHODS AND RESULTS: We retrospectively examined 11 consecutive patients with atrioventricular discordance who underwent CA for atrioventricular reciprocating tachycardia (AVRT) via an AP and planned cardiac surgery after CA. Orthodromic AVRTs were induced in 10 patients via AP, but no antidromic/duodromic AVRT was induced in any of the cases. A total of 13 APs were identified, and all of them were located around the anatomical tricuspid valve (TV) annulus, including two Ebsteinoid valves. The APs were predominantly located posteriorly, posterolaterally, and posteroseptally on the TV in nine patients (82%). Two patients (18%) had multiple APs or a single broad AP. Four (36%) and three (27%) patients showed twin AVNs and other supraventricular tachycardias (SVTs) except AVRT via the AP. Ten patients (91%) had acute successful CA in the first session, except for one patient with multiple APs who required the third session to eliminate all APs before the planned Fontan surgery. There were no major complications associated with CA. Seven of eight patients who underwent cardiac surgery after CA did not experience peri-/postoperative SVT. CONCLUSION: APs in patients with AV discordance are usually associated with the anatomical TV annulus. CA of an AP in AV discordance is highly effective and recommended to reduce the risk of SVT. The coexistence of twin AVNs and other SVTs should be considered during CA of an AP in AV discordance.

Successful staged tricuspid valve replacement following cardiac resynchronization therapy in a congenitally corrected transposition of the great arteries.

Simple tricuspid valve surgery for complex heart disease with systemic right ventricular dysfunction is a high-risk procedure; however, staged tricuspid valve surgery following cardiac resynchronization therapy seems to be a beneficial method to expect reverse systemic ventricular remodeling.

Prevalence and risk factors of sleep apnea in adult patients with congenital heart disease.

BACKGROUND: Although sleep apnea is an important disorder associated with cardiac events, data regarding its prevalence and risk factors in adult patients with congenital heart disease are limited. METHODS: In this study, patients underwent a sleep study in the hospital. Indications for admission were classified as heart failure, diagnostic catheterisation, interventional catheterisation, or arrhythmia. The prevalence, characteristics, and risk factors of sleep apnea using a type-3 portable overnight polygraph in adult patients with congenital heart disease were evaluated. RESULTS: There were 104 patients [median age: 36 (interquartile range: 28-48) years] who were admitted for heart failure 34% (n = 36), diagnostic catheterisation 26% (n = 27), interventional catheterisation 18% (n = 19), or arrhythmia 22% (n = 23). The prevalence of sleep apnea, defined as a respiratory disturbance index ≥5, was 63% (n = 63), with a distribution of 37%, 16%, and 10% for mild (5≤ respiratory disturbance index <15), moderate (15≤ respiratory disturbance index <30), and severe (respiratory disturbance index ≥30) sleep apnea, respectively. A large majority of the sleep apnea cases were categorised as obstructive sleep apnea (92%, n = 58). The respiratory disturbance index ≥15 group had a significantly higher proportion of male patients and higher body mass index, noradrenaline level, and aortic blood pressure than the group without sleep apnea (respiratory disturbance index <5). Multivariable analysis showed that New York Heart Association class ≥II (OR, 4.36; 95% CI, 1.09-20.87) and body mass index ≥25 (OR, 4.29; 95% CI, 1.32-15.23) were independent risk factors for a respiratory disturbance index ≥15. CONCLUSION: Our results showed a high prevalence of sleep apnea in adult patients with congenital heart disease. Its unique haemodynamics may be associated with a high prevalence of sleep apnea. Congestive heart failure and being overweight are important risk factors for sleep apnea. Management of heart failure and general lifestyle improvements will be important for controlling sleep apnea symptoms in these patients.

Acute and Long-Term Outcomes of Transvenous Cardiac Pacing Device Implantation in Patients With Congenital Heart Disease.

Background: Little is known about the acute/long-term outcomes of implantation of cardiac implantable electronic devices (CIED) using a transvenous approach for patients with congenital heart disease (CHD). Methods and Results: We retrospectively investigated the acute/long-term results and complications associated with transvenous CIED implantation in 140 patients with CHD. We implanted 77 pacemakers, 51 implantable cardioverter defibrillators (ICD), and 12 cardiac resynchronization therapy (CRT) devices. Although we successfully implanted pacemakers and ICD in all patients, we could not place a coronary sinus (CS) lead in 25% of the patients requiring CRT devices due to coronary vein anomalies associated with corrected transposition of the great arteries (cTGA). Overall complication rate, lead failure rate, and incidence of device infection were 16%, 9%, and 0.7%, respectively. There was no significant difference in overall complication rates between the simple (n=22) and complex CHD (n=118) groups (14% vs. 16%). The 10-year lead survival for the ICD leads (77%) was significantly lower than for the pacemaker leads (91%, P=0.0065). Conclusions: The outcomes of transvenous CIED in patients with CHD seemed acceptable, although there was a relatively high incidence of complications. CS lead placement for cTGA may be hindered by coronary vein anomalies. Lead survival tended to be lower for ICD than for pacemakers in these patients.

Prevalence and risk factors of sleep apnoea in adult patients with CHD.

BACKGROUND: Although sleep apnoea is an important disorder associated with cardiac events, data regarding its prevalence and risk factors in adult patients with CHD are limited. METHODS: In this study, patients underwent a sleep study in the hospital. Indications for admission were classified as heart failure, diagnostic catheterisation, interventional catheterisation, or arrhythmia. The prevalence, characteristics, and risk factors of sleep apnoea using a type 3 portable overnight polygraph in adult patients with CHD were evaluated. RESULTS: This study comprised 104 patients of median age 36 years with interquartile range of 28-48 years, admitted for heart failure 34% (n = 36), diagnostic catheterisation 26% (n = 27), interventional catheterisation 18% (n = 19), or arrhythmia 22% (n = 23). The prevalence of sleep apnoea, defined as a respiratory disturbance index ≥5, was 63% (n = 63), with a distribution of 37, 16, and 10% for mild (5≤ respiratory disturbance index <15), moderate (15⩽ respiratory disturbance index <30), and severe (respiratory disturbance index ≥30) sleep apnoea, respectively. A large majority of the sleep apnoea cases were categorised as obstructive sleep apnoea (92%, n = 58). The respiratory disturbance index ≥15 group had a significantly higher proportion of male patients and higher body mass index, noradrenaline level, and aortic blood pressure than the group without sleep apnoea (respiratory disturbance index <5). Multi-variable analysis showed that NYHA class ≥II, whose odds ratio 4.36, 95% confidence interval 1.09-20.87, and body mass index ≥25, whose odds ratio 4.29, 95% confidence interval 1.32-15.23, were independent risk factors for a respiratory disturbance index ≥15. CONCLUSION: Our results showed a high prevalence of sleep apnoea in adult patients with CHD. Its unique haemodynamics may be associated with a high prevalence of sleep apnoea. Congestive heart failure and being overweight are important risk factors for sleep apnoea. Management of heart failure and general lifestyle improvements are important for controlling sleep apnoea symptoms in these patients.

Thoracic endovascular aortic repair of a late aortic aneurysm after patch repair of an interrupted aortic arch.

We reported a successful case of thoracic endovascular aortic repair of a late aortic aneurysm after patch repair of an interrupted aortic arch and favourable outcome 4 years after the procedure.

Long-Term Efficacy of Implantable Cardioverter Defibrillator in Repaired Tetralogy of Fallot　- Role of Anti-tachycardia Pacing.

BACKGROUND: Tetralogy of Fallot (TOF) is one of the common congenital heart diseases (CHD) in implantable cardioverter defibrillator (ICD) recipients, but few studies have reported the long-term outcomes of and the anti-tachycardia pacing (ATP) efficacy in repaired TOF.Methods and Results:Twenty-one repaired TOF patients with an ICD implanted between April 2003 and March 2015 were investigated retrospectively. ICD therapy and clinical outcome were analyzed. Mean patient age was 39±11 years; 62% were male; and mean age at repair surgery was 9.4±6.8 years. During a median follow-up of 5.6 years (range, 2.6-8.4 years), no patients died. Appropriate ATP were delivered in 11 patients (52%), with appropriate shocks in 5 patients (24%) and inappropriate shocks in 5 patients (24%). The success rate of ATP was 98% for fast ventricular tachycardia (VT; cycle length ≤320 ms) and 98% for slow VT (cycle length >320 ms). ATP effectiveness increased from 81.5% with the first ATP attempt to 93.7% with the second ATP attempt, to 97.5% with the third ATP attempt, and to 98.6% with the fourth or successive ATP attempt (P<0.0001, Cochran-Armitage trend test). CONCLUSIONS: ATP was highly effective in repaired TOF regardless of VT cycle length. Multiple ATP attempts could have an important role in VT termination, and the novel subcutaneous ICD without ATP capability should be used carefully.

Blood coagulation abnormalities and the usefulness of D-dimer level for detecting intracardiac thrombosis in adult Fontan patients.

BACKGROUND: Coagulation abnormality is associated with a high incidence of intracardiac thrombus (ICT) and systemic thromboembolism in Fontan patients. The biomarker for detecting ICT is currently unknown. METHODS: We retrospectively investigated the underlying coagulation abnormality and useful biomarkers to screen for ICT in adult Fontan patients. We measured various biomarkers of blood coagulation, fibrinolysis, and platelet activity in 122 Fontan patients (Fontan group: median age [P25-P75]: 27 [20-34] years) and compared them to those in 50 patients with atrial septal defect (ASD group: 31 [24-40] years). RESULTS: Regardless of whether the patient had ICT, the Fontan group showed significantly lower levels of antithrombin III, thrombomodulin, and α2-antiplasmin; lower protein C and protein S activities; and significantly higher levels of thrombin-antithrombin complex and α2-plasmin inhibitor complex than the ASD group. Among various biomarkers, D-dimer level measured by using latex immunoassay was significantly higher in the patients with ICT (thrombus group: n=21) than in the patients without ICT (non-thrombus group: n=101). Fifteen (26%) of 57 patients on warfarin achieved prothrombin time international normalized ratios (PT-INRs) of >2. The proportion of patients with PT-INRs of >2 tended to be lower in the thrombus group than in the non-thrombus group (13% vs 31%). Persistent atrial arrhythmia and D-dimer level were significant risk factors associated with ICT formation in the multivariate analysis (persistent atrial arrhythmia: hazard ratio [HR], 6.89; 95% confidence interval [CI], 1.44-34.5; D-dimer: HR, 0.29; 95% CI, 0.13-0.50). Receiver-operating characteristic curve analysis revealed that the appropriate cutoff D-dimer level for screening for ICT was 1.8µg/mL (area under the curve, 0.94), with a negative predictive value of 95%. CONCLUSIONS: In the adult Fontan patients, blood coagulation abnormalities existed regardless of the absence of ICT. D-dimer level may be a useful biomarker for screening for ICT in adult Fontan patients.

Prognostic value of multiple biomarkers for cardiovascular mortality in adult congenital heart disease: comparisons of single-/two-ventricle physiology, and systemic morphologically right/left ventricles.

Although there are many biomarkers for heart failure, limited data are available regarding their prognostic value in adult congenital heart disease (ACHD). We investigated the potential of various biomarkers to predict ACHD mortality in a single-center, retrospective cohort study. Blood levels of neurohormones [angiotensin II, endothelin-1 (ET-1), norepinephrine (NE), aldosterone, and plasma renin activity]; inflammatory biomarkers [high-sensitivity C-reactive protein (hs-CRP), high-sensitivity tumor necrosis factor, soluble TNF receptor type I and II (sTNF-RI and sTNF-RII), and interleukin-6 (IL-6)]; and brain natriuretic peptide (BNP) were measured in 103 ACHD patients (median age 28 years). Subjects were divided into patients with single-ventricle physiology (SV group, n = 61) and those with two-ventricle physiology (TV group, n = 42); and into patients with a systemic right ventricle (SRV group, n = 25) and those with a systemic left ventricle (SLV group, n = 78). During a median follow-up period of 6.5 years, 12 patients (11 %) died of acute decompensated heart failure (ADHF). Predictive biomarkers, which are related to the New York Heart Association class and cardiothoracic ratio, were as follows: elevated levels of BNP, ET-1, sTNF-RI, NE, and IL-6 in the overall patient group; IL-6, NE, hs-CRP, BNP, and ET-1 in the TV group; BNP and ET-1 in the SV group; BNP, NE, hs-CRP, sTNF-RI, IL-6, and ET-1 in the SLV group. Elevated levels of ET-1 in SRV groups were slightly although not significantly associated with these. Various clinical biomarkers are associated with ADHF mortality in ACHD patients. The most prominent mortality predictors in biomarker profiles may vary according to differences in ventricular physiology and systemic ventricle morphology.

High prevalence of cardiovascular risk factors in children and adolescents with Williams-Beuren syndrome.

BACKGROUND: A high incidence of cardiovascular (CV) risk factors has been reported in adults with Williams-Beuren syndrome (WS). However, the prevalence of these factors in children and adolescents with WS is unknown. Therefore, the purpose of this study was to evaluate the prevalence of CV risk factors in these patients. METHODS: Thirty-two WS patients aged <18 years were enrolled in the study. Oxidized low-density lipoprotein levels (n = 32), oral glucose tolerance test results (n = 20), plasma renin and aldosterone levels (n = 31), 24-h ambulatory blood pressure (ABP; n = 24), carotid artery intima-media thickness (IMT; n = 15), and brachial artery flow-mediated dilatation (FMD; n = 15) were measured and analyzed. RESULTS: The lipid profile revealed hypercholesterolemia in 22% and elevated oxidized low-density lipoprotein levels in 94% of the patients. Glucose metabolism abnormalities were found in 70% of the patients. Insulin resistance was observed in 40% of the patients. High plasma renin and aldosterone levels were detected in 45 and 39% of the patients, respectively. A mean systolic blood pressure above the 90th percentile was noted in 29% of patients. High IMT (>0.65 mm) and low FMD (<9%) were detected in 80 and 73% of patients, respectively. CONCLUSION: In patients with WS, CV risk factors are frequently present from childhood. In children with WS, screening tests for the early detection of CV risk factors and long-term follow-up are required to determine whether long-term exposure to these factors increases the risk for CV events in adulthood.

Incidence, Clinical Course, and Risk Factors of Amiodarone-Induced Thyroid Dysfunction in Japanese Adults With Congenital Heart Disease.

BACKGROUND: Although amiodarone (AMD)-induced thyroid dysfunction (AITD) is an important complication of AMD therapy, little is known about AITD in adult Japanese patients with congenital heart disease (CHD). METHODS AND RESULTS: We retrospectively studied 131 adult patients with CHD who were on low-dose AMD (median, 150 mg/day). The median patient age was 28 years, and the median follow-up was 44 months. The incidence, clinical course, and risk factors of AITD, including AMD-induced thyrotoxicosis (AIT) and AMD-induced hypothyroidism (AIH), were evaluated. The total incidence of AITD was 30% (AIT: 18%, n=24; AIH: 12%, n=16). Approximately 67% of patients with AIT displayed deterioration of tachyarrhythmia, and 38% patients underwent steroid therapy. Although thyroid function and symptoms associated with AIT improved within 6 months after diagnosis in most patients with AIT (92%), 1 patient died suddenly during an acute phase of AIT. No patient with AIH exhibited deterioration of tachyarrhythmia, and 9 patients underwent thyroid hormone replacement therapy. Cox multivariate analysis identified no independent risk factor for AIT, whereas liver dysfunction (hazard ratio 2.573; 95% confidence interval 1.102-5.795) was an independent risk factor for AIH. CONCLUSIONS: AITD commonly occurred in adult Japanese patients with CHD even though they were on a low-dose AMD regimen. Risk factors for AITD may vary according to ethnicity and diet.

Relationships among red cell distribution width, anemia, and interleukin-6 in adult congenital heart disease.

BACKGROUND: Red cell distribution width (RDW) is known to be associated with anemia and mortality in cardiovascular diseases, while anemia itself is related to increased mortality. RDW may also be related to cytokine activation. We investigated the potential of RDW to predict anemia-adjusted mortality in patients with adult congenital heart disease (ACHD) and we evaluated the relationships among RDW, anemia, and interleukin-6 (IL-6). METHODS AND RESULTS: This was a single-center, retrospective cohort study. Blood RDW and IL-6 levels were measured in 144 patients with ACHD (median age [interquartile range (IQR)], 28 [22-36] years), 84% in New York Heart Association class I/II. During a mean 4.8-year follow-up, 21 (15%) patients died of cardiovascular causes. Elevated RDW (>15.0%) correlated significantly with mortality risk in a univariate analysis (RDW hazard ratio [HR]: 1.570; 95% confidence interval [CI]: 1.208-2.040 per 1 standard deviation increase; P=0.001). Elevated RDW levels correlated significantly with increased anemia-adjusted mortality (adjusted RDW HR: 1.912; 95% CI: 1.369-2.670; P<0.001). The high RDW group had significantly elevated serum IL-6 levels (RDW >15%, median [IQR], 3.7 [0.9-13.9] pg/ml vs. RDW ≤15%, 1.4 [0.8-2.5 pg/ml]; P=0.001), as did patients with anemia (anemia, 1.9 [0.9-5.2] pg/ml vs. no anemia, 1.4 [0.8-2.5 pg/ml]; P=0.021). CONCLUSIONS: Elevation of RDW may be related with increased IL-6 and anemia-adjusted cardiovascular mortality in patients with ACHD.