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Mortality rates may be high in adult Fontan patients; however, the clinical determinants remain unclear.We conducted a prospective multicenter study of adult Fontan survivors to determine the 5-year mortality rate and clarify the determinants.We followed 600 adult Fontan survivors from 40 Japanese institutions (307 men, 28 ± 7 years old, follow-up: 18 ± 6 years). The New York Heart Association (NYHA) functional class I and II was 51% and 42%, respectively. During the follow-up period of 4.1 ± 1.6 years, 33 patients died, and the 5-year survival rate was 93.5%. The mode of death was heart failure in 11 patients (34%), arrhythmia or sudden death in 8 (24%), cancer in 5 (15%), perioperative problems and hemostatic problems in 4 each (12% for each), and infection in 1 (3%). Left isomerism, prior hospitalization, protein losing enteropathy (PLE), pulmonary arteriovenous fistulae, NYHA functional class, impaired hemodynamics, hyponatremia, hepatorenal dysfunction, and use of diuretics were associated with a high mortality rate (p 0.05-0.0001). Further, PLE (hazard ratio [HR]: 14.4), left isomerism (HR: 3.5), and NYHA (HR: 2.4) independently predicted a high 5-year high mortality (p 0.05 for all). The incidence of cancer-related mortality increased markedly with age40 years.Majority of the Japanese adult Fontan survivors had good functional status, with an acceptable 5-year survival rate. However, the significant prevalence of non-cardiac mortality highlights Fontan pathophysiology as a multi-organ disease that requires a multidisciplinary management strategy to improve the long-term outcome.

Background Fontan-associated liver disease (FALD) is an important late complication involving liver dysfunction, such as liver cirrhosis (LC) and hepatocellular carcinoma (HCC), in patients undergoing the Fontan procedure. However, the prevalence, clinical manifestation, and methods of diagnosis of FALD are still not well established.Methods and Results:This study comprised 2 nationwide surveys in Japan. First, the prevalence of LC and/or HCC in patients undergoing the Fontan procedure was determined. Second, clinical manifestations in patients with LC and/or HCC were analyzed, along with data from blood tests, echocardiography, and right heart catheterization. In the 1st survey, of the 2,700 patients who underwent the Fontan procedure, 31 were diagnosed with LC and/or HCC (1.15%), and 5 died due to liver diseases (mortality: 0.19%). In the 2nd survey, data were collected from 17 patients (12 with LC, 2 with HCC, and 3 with LC+HCC. Of these 17 patients, 5 died (mortality: 29.4%). The mean age at diagnosis of LC and HCC was 23 and 31 years, respectively. Computed tomography followed by ultrasound was most frequently used for diagnosis. Blood tests revealed low platelet counts, increased hemoglobin, aspartate aminotransferase, γ-guanosine triphosphate, and total bilirubin levels, and an elevated international normalized ratio of prothrombin time. Conclusions LC and/or HCC in patients undergoing the Fontan procedure were not rare late complications and were associated with high mortality rates.

Objective 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. Methods 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. Results 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 Conclusions 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.

Protein-losing enteropathy (PLE) is a life-threatening complication in patients following the Fontan operation. However, PLE also develops in some patients with congenital heart disease (CHD) after biventricular repair (BVR). This study compared clinical profiles of PLE patients following the Fontan operation with those after BVR. We retrospectively reviewed clinical charts of postoperative CHD patients with PLE. The study population comprised 42 PLE patients (14BVR, 28Fontan). Postoperative follow-up period until onset was significantly shorter in the Fontan group than in the BVR group (14 ± 2 vs. 8 ± 1 years, p = 0.02), while there was no difference in PLE onset age between groups. Furthermore, there were no differences in prevalence of clinically relevant arrhythmias, cardiac output, or central venous pressure between the two groups at PLE onset. Percentage of structural lesions (valve regurgitation and/or stenotic lesions) responsible for development of PLE and ventricular end-diastolic pressure were higher in the BVR group than in the Fontan group (93 vs. 50%, p

Surgical experiences of the reoperative double ventricular outflow tract reconstruction long after the successful repair of conotruncal anomalies were reviewed. Ten adult patients with conotruncal anomalies (6 females, 22.9 ± 5.5 years old) underwent the reoperative double ventricular outflow tract reconstruction. Primary diagnosis was pulmonary atresia with ventricular septal defect in 6 patients, truncus arteriosus in 3, and double-outlet right ventricle in 1. The indication for the left ventricular outflow tract reconstruction was the left ventricular dilatation and dysfunction derived from moderate or greater systemic semilunar valve insufficiency. The indication for the right ventricular outflow tract reconstruction was severe pulmonary insufficiency in all patients, and concomitant right ventricular outflow tract obstruction in 7. The systemic semilunar valve replacement was performed in all patients. The right ventricular outflow tract patching was performed in 4 patients, and the revision of extra-cardiac conduit in 6. Within a mean follow-up of 9.0 ± 7.0 years, there was no mortality. The left ventricular end-diastolic volume index improved from 147 ± 37 to 108 ± 19 ml/m2 (p = 0.005), and the peak pressure gradient across right ventricular outflow tract improved from 43 ± 17 mmHg to 9 ± 2 at 1 year after (p = 0.02). The plasma brain natriuretic peptide level improved from 83 ± 57 to 34 ± 32 pg/ml (p = 0.03). Reoperative double ventricular outflow tract reconstruction long after the repair of conotruncal anomalies was safely performed, and provided the ventricular reverse remodeling and improvement of serum BNP level.

Background Cardiac resynchronization therapy (CRT) can result in functional improvement and reduced mortality in patients with medically refractory heart failure. Although CRT is reportedly effective in patients with congenital heart disease (CHD), it is still controversial in patients who have systemic right ventricle. METHODS AND RESULTS: Twenty CHD patients treated with CRT since 2006 were divided into 3 groups based on systemic ventricular (sysV) morphology (7 with left ventricle [sLV], 7 with right ventricle [sRV], and 6 with unbalanced 2 ventricles as a single-ventricular physiology [sBV]). The acute effects of CRT on hemodynamics and sysV function before device implantation was retrospectively evaluated and the chronic (≥6 months) effects of CRT on late outcomes was assessed. In our CHD populations, sysV volume index was reduced from 139±41 to 118±33 ml/m(2)(P=0.04) after CRT, and there was significant improvement in B-type natriuretic peptide levels (from 341±384 to 160±152 pg/ml, P=0.01) and New York Heart Association (NYHA) functional class (from 2.1±0.6 to 1.8±0.7, P=0.02) on a late outcome. The sRV group did not show a late sysV volume reduction despite significant QRS shortening, and an increase of sysV peak dP/dt in the acute study differed from that of other groups. Conclusions CRT improves late hemodynamic and functional status in sLV and sBV CHD patients with a dyssynchronized sysV. However, an acute CRT effect cannot guarantee long-term benefit in sRV patients.

BACKGROUND There are no definitive diagnostic criteria or follow-up strategies for long QT syndrome (LQTS) in children with a borderline long QT interval (b-LQT).Methods and Results:We retrospectively evaluated the clinical course, genetic testing results, corrected QT interval (QTc), and LQTS score of 59 school-aged children (5-18 years old) with a b-LQT (400≤QTc

The pathophysiology of congenital heart disease includes aortic dilation and increased stiffness. However, the clinical determinants and significance remain unclear in patients after the Fontan operation.Size and stiffness index (SI) of the ascending and descending aorta (aAO and dAO, respectively) were assessed using angiography in 130 consecutive Fontan patients and 30 age-matched controls. Compared with controls, Fontan patients showed a dilated aAO and smaller dAO (P < 0.0001) with greater SI (3.2 ± 0.7 versus 2.2 ± 0.3 for aAO and 2.7 ± 0.6 versus 2.2 ± 0.3 for dAO, P < 0.0001 for both). aAO was stiffer than dAO (P < 0.0001) and the greater aAO size was independently determined by the presence of pulmonary atresia, older age at Fontan operation, and low arterial oxygen saturation (P < 0.05-0.01). High plasma levels of brain natriuretic peptide (BNP) and glucose were independently associated with aAO SI (P < 0.05-0.01) and the SI ratio of aAO to dAO SI, whereas body mass index, plasma levels of highsensitivity C-reactive protein, and dAO size were independently associated with dAO SI (P < 0.05-0.01). A greater aAO and aAO/dAO ratio predicted an impaired exercise blood pressure response (P < 0.0001). Furthermore, in addition to age at Fontan operation and BNP level, the aAO SI independently predicted a lower peak oxygen uptake (P < 0.05).Fontan patients have a stiffer dilated aAO with rapidly tapering smaller dAO that predicts exercise pathophysiology. In addition to intrinsic aortic structural abnormalities, heart failure severities as well as traditional cardiovascular risk factors are also involved in the aortic structural and functional abnormalities.

The number of adults with congenital heart disease (ACHD), especially those with complex CHD, is increasing substantially. The major clinical characteristics include (1) a high prevalence of right-sided heart failure (HF) due to systolic and/or diastolic dysfunction of the right ventricle (RV), which is frequently seen in repaired patients with tetralogy of Fallot (TF); (2) pressure and/or volume overload to the ventricles due to intra- and/or extracardiac shunting, atrioventricular or semilunar valve stenosis, and/or regurgitation; and (3) a morphologic RV as a systemic ventricle seen in those with congenitally corrected transposition of the great arteries or in those after an atrial switch operation. In addition, some CHD-specific conditions are also included in these pathophysiologic conditions, such as cyanosis (hypoxia) in unrepaired patients with complex CHD, Eisenmenger syndrome, and single ventricular physiology, i.e., Fontan circulation. The impaired function of the noncardiac organs may also be involved in some ACHD patients. Furthermore, surgery-related issues, including perioperative myocardial damage and electrical pathophysiology, can modify and make the ACHD HF pathophysiology more complex. The application of an established anti-HF strategy used in non-ACHD patients with left-sided HF to ACHD patients is questionable and possibly limited efficacy. Although most of the ACHD HF pathophysiology appears progressive, and determining the optimal timing for surgical interventions, such as pulmonary valve replacement, is often difficult because some of those procedures are prophylactic. Thus, a comprehensive understanding of ACHD HF, including noncardiac issues, is required to manage ACHD CHF and anticipate a better long-term outcome in these patients. In this review, the common ACHD HF pathophysiology and major specific ACHD conditions are discussed.

Aortopathy has been recognized as one of the major pathophysiologic features in patients with congenital heart disease (CHD) that includes dilatation and/or increased stiffness of the aorta. A body of evidence of “aortopathy” has been also reported in patients after the Fontan operation and most of studies had focused on the dilated stiffened ascending aorta (aAO). In general, Fontan patients have dilated aAO with smaller descending aorta (dAO) and the other peripheral arteries, including carotid artery, indicating vascular remodeling. However, these features of aAO and dAO may be different from those in Fontan patients with hypoplastic left heart syndrome (HLHS) who have dilated dAO. In non-HLHS Fontan patients, stiffened aAO itself is considered as one of the causes for progressive dilatation of the aorta. In addition to aging, body size, and late first Fontan operation, impaired glucose tolerance, diminished nitric oxide bioavailability, and inflammation are also thought to be additional risk factors for the stiffened aorta, and most of those factors are determinants of endothelial function. An increased pulse pressure due to the stiffened aorta leads to ventricular pressure overload as well as low perfusion for the coronary circulation and ultimately may result in systemic ventricular dysfunction, especially in Fontan patients with the non-left ventricular morphologic ventricle as a systemic ventricle. Furthermore, the dilated stiffened aorta is detrimental to cardiovascular response and exercise capacity in these patients. Thus, prospective study to establish therapeutic strategy for “aortopathy” may be needed to improve long-term outcome of these vulnerable patients.

Background The prognostic value of cardiopulmonary exercise testing (CPX) for mortality risk remains controversial in Fontan patients. Purpose Our goal of the present study was to clarify the prognostic value of major CPX variables and the factors determining exercise capacity in a large cohort of Fontan patients. Methods Since 1990, heart rate (HR), oxygen uptake (VO2), and ventilatory equivalent for carbon dioxide production (VE/VCO2) at peak exercise were determined in 335 Fontan patients (18 ± 5 years old), and the CPX variables were compared with the clinical profile and events. Results When compared with 209 controls, peak HR (148 ± 24 bpm), VO2 (27 ± 7 mL/kg/minute, [61 ± 15%]), and VE/VCO2 (40 ± 8 [117 ± 24%]) were markedly impaired in the Fontan patients (P

We treated four postoperative adults with congenital heart disease with severe restrictive hemodynamics (RH), and performed decortication (DC) with the anticipation of some relief of the RH. The catheterizations before DC showed high central venous, and right and left ventricular end-diastolic pressures with "dip-and-plateau" pressure waveforms in the right and left ventricles. Upon myocardial histopathologic examination, moderate myocardial fibrotic change was demonstrated in two of three cases. DC led to decrease in type B natriuretic peptide levels in all cases, resulting in a decline in the central venous, right and left ventricular end-diastolic pressures in three cases. Successful DC-related relief of RH, dilatation of the ventricles with decline in central and end-diastolic pressures, was observed in only one case. Our limited DC-related hemodynamic improvement indicates a complexity of the severe RH, which may represent a unique intractable heart failure pathophysiology in intractable postoperative adult congenital heart disease.

We present a case of a high-risk 19-year-old female with long-QT syndrome (LQTS) with compound mutations. She had a history of aborted cardiac arrest and syncope and had received treatment with propranolol for 15 years. However, because she developed adult-onset asthma we tried to switch propranolol, a nonselective beta-blocker, to beta-1-cardioselective agents, bisoprolol and metoprolol. These resulted in both a markedly prolonged corrected QT interval and the development of LQTS-associated arrhythmias. Eventually, propranolol was reinitiated at a higher dose with the addition of verapamil, and she has had no further cardiac or asthmatic events for 5 years.

Background The management of Eisenmenger syndrome (ES) has dramatically changed since the advent of disease-targeted therapy (DTT). However, guidelines for ES management, including DTT, have not been established. We aimed to clarify the current incidence, underlying disease, and management of ES in Japan, using a nationwide survey. Methods A written questionnaire was sent to members of the Japanese Society for Adult Congenital Heart Disease, through which information was obtained from 86 institutions. Results A total of 251 patients with ES (80.5% cases ≥ 20 years of age) were followed as of February 2012; DTT was performed in 124 (49.4%) patients. Unrepaired simple anatomy was reported as an underlying condition in 165 patients (65.7%). Among patients with ES, 55 (21.9%), 128 (51%), 53 (21.1%), and 12 (4.8%) were classified into functional classes I, II, III, and IV, respectively. DTT was routinely performed at 52 (60.5%) institutions, but there were variations in the DTT therapeutic strategy at these institutions. Combined therapy was more often used than monotherapy; an endothelin receptor antagonist was the most frequently prescribed medication. There were institutional differences regarding heart failure treatment and indications for anticoagulation. Digitalis and angiotensin-converting enzyme inhibitors or angiotensin II receptor blockers were widely used, but beta-blockers were infrequently used to manage heart failure. Conclusions This survey describes the current status, including prevalence and underlying disease, and variations in the practical management of ES in Japan. The results will help in the creation of future guidelines for ES management.

Most adults with congenital heart disease show high levels of natriuretic peptide (NP) when compared with normal controls. Levels of norepinephrine and NP were strongly related to outcome in studies that included many symptomatic patients, especially those with unrepaired congenital heart disease, Eisenmenger syndrome, and pulmonary hypertension. Limited data are available regarding serial assessment of biomarkers; such information could provide additional important information to help identify patients at risk, as demonstrated during patient follow-up and pregnancy.

Objectives Pregnancy can be well tolerated after the repair of aortic coarctation. However, a higher incidence of hypertensive disorders during these pregnancies was reported. We analyzed the perinatal changes in echocardiographic parameters in women with aortic coarctation and investigated the risk factors of gestational hypertension (GH). Methods We retrospectively identified 15 pregnancies in nine Japanese women with aortic coarctation between 1982 and 2015. We categorized the patients according to the presence/absence of GH as the group with GH(n=3) and that without GH(n=12). The echocardiographic parameters were compared between groups. Results Our analysis revealed that a pre-pregnancy Doppler-measured pressure gradient≥20mmHg and a left ventricular mass index≥95g/m 2 were significant risk factors for GH. The left ventricular end-diastolic diameters at the first and the third trimesters, the left ventricular end-systolic diameters at the first trimester, and the left ventricular ejection fraction at the third trimester were also significantly higher in the pregnancies with GH. All of these findings had been obtained before the patients' GH occurred. Conclusions Hypertrophy of the left ventricle with a lower ejection fraction and a high pressure gradient across the coarctation were risk factors for GH in the patients with aortic coarctation. Thus, serial measurements using echocardiography are important for predicting GH in women with aortic coarctation. However, further research investigating this finding with a larger sample size is needed.

The Fontan procedure is an open heart procedure performed in pediatric patients with a particular congenital cardiac anomaly known as a univentricular heart. The procedure is used to reroute the systemic venous blood from the inferior vena cava directly to the pulmonary artery. It improves patients' prognoses, but various late-phase extracardiac complications that manifest when patients reach adolescence have been recognized. These complications, pulmonary arteriovenous fistula and protein losing gastroenteropathy, for example, present significant challenges in the management of adults with Fontan circulation. Liver fibrosis is another possible late-phase complication and one of the most serious. Development of a neoplasm, usually a hepatocellular carcinoma, is sometimes reported. We encountered a young patient in whom Fontan circulation led to the development of a histologically unusual liver cancer that resembled the poorly differentiated hepatocellular carcinoma or the combined hepatocellular-cholangiocarcinoma with stem-cell features described in the latest WHO classification.

OBJECTIVES: Determinant risk factors for developing protein losing enteropathy (PLE), including haemodynamics, remain unclear in patients after the Fontan operation. METHODS: Our purpose was to characterize the serial PLE haemodynamics before and after the onset and to determine the risk factors based on the cardiac catheterization-based analysis. RESULTS: Of 354 Fontan survivors who had undergone postoperative cardiac catheterizations, we experienced 26 PLE patients during the follow-up. Non-left ventricular morphology systemic ventricle, functional one-lung pulmonary circulation and an early postoperative high central venous pressure (CVP) were associated with the PLE onset and the high CVP (odds ratio (OR) = 1.19 per 1 mmHg, 95% confidence interval (CI) 1.04–1.37, especially ≥12 mmHg, OR = 3.09, 95% CI 1.25–7.64, P< 0.05 for both) and one-lung pulmonary circulation (OR = 10.0–10.5, P< 0.001) independently predicted the onset. At the time of the PLE onset, a Fontan route stenosis/obstruction, arrhythmias, ventricular dysfunction/heart failure and pulmonary arterio-venous fistulae were demonstrated in 10 (38%), 8 (31%), 4 (15%) and 3 (12%) patients, respectively. When compared with 56 excellent Fontan survivors, the high CVP, ventricular end-diastolic pressure, and pulmonary artery resistance, and the low arterial oxygen saturation, systemic artery pressure, and ventricular ejection fraction characterized the pre-PLE Fontan haemodynamics (P< 0.05–0.0001). However, the following intensive treatments reduced the CVP, systemic artery pressure and cardiac output (P< 0.05–0.01), resulting in haemodynamics no different from those of the excellent survivors, except for the low systemic pressure (P< 0.0001). CONCLUSIONS: The pre-PLE haemodynamics was characterized by several impaired haemodynamics, while those after PLE only by a low systemic pressure. A high early postoperative CVP was the only haemodynamic predictor for a new onset of PLE. Strict selective criteria for the operation and strategies to eliminate CVP-raising factors are mandatory to prevent a new onset of PLE.

BACKGROUND Although the survival rate for repaired Tetralogy of Fallot (TOF) is dramatically improving, anatomical and functional residua and sequelae followed by arrhythmias and sudden death are still challenging issues to be resolved. Reoperation can reduce the incidence of arrhythmias and sudden death, but there is no consensus on the indications of reoperation for patients with TOF, especially in Japan. METHODS AND RESULTS A cross-sectional questionnaire survey of reoperation indications in patients with TOF was performed through a Japanese multicenter study. The questionnaire, which focused on the number of repaired TOF patients aged >15 years old, reoperation indications and management, was sent to the institutions belonging to Japanese Society for Adult Congenital Heart Disease. In total, 41.5% (78/188) of the institutions replied. The total number of repaired TOF patients was 4,010, and sudden cardiac death was observed in 45.236/4,010 (5.9%) experienced reoperation. Pulmonary stenosis (32%) and pulmonary regurgitation (29%) were the most common reasons for reoperation. There were only 2 implantable cardioverter defibrillator or resynchronization therapy defibrillator implantations. The physiological/anatomical indications of reoperation differed among the hospitals. CONCLUSIONS Approximately 1.1% of patients suffered sudden death and 6% of repaired TOF patients had reoperation. The indications of reoperation, however, varied among the institutions. Therefore, detailed information for each case of sudden death or reoperation should be collected and analyzed in order to establish guidelines for reoperation.

Systemic right ventricular (RV) failure in patients with congenitally corrected transposition of the great arteries (ccTGA), a major cause of mortality in the long-term follow-up, is usually induced by concomitant severe morphologically tricuspid regurgitation (TR) with/without Ebstein's anomaly or progressive conduction tissue disturbances. However, whether or not myocardial fibrosis is a common cause of systemic RV failure in patients with ccTGA remains unclear. Here, we describe an 82-year-old man who had been diagnosed previously as having uncomplicated ccTGA and situs inversus and recently developed systemic RV failure, which was neither associated with severe TR nor advanced conduction tissue abnormalities. Cardiovascular magnetic resonance (CMR) with delayed-enhancement imaging clearly detected extensive myocardial scars (presumably fibrosis) in the RV wall as well as prominent dilatation, hypertrophy, and systolic dysfunction of the systemic RV. These findings suggest that myocardial fibrosis can cause systemic RV failure in elderly patients with uncomplicated ccTGA despite the absence of severe TR or advanced conduction tissue abnormalities and that CMR may be a useful examination to accurately detect systemic RV failure associated with myocardial fibrosis and to subsequently clarify the prognosis in these patients.

We describe of a unique pattern of cardiac dyssynchrony in a patient with a biventricular physiology and systemic right ventricle (RV): the interventricular dyssynchrony due to a contraction delay between the left ventricle and RV. In the present case, the cineangiography and intracardiac electrocardiography of the RV did not reveal intraventricular dyssynchrony of the RV, but revealed interventricular dyssynchrony. In addition, the pressure curves of the ventricles exhibited time phase differences between the two ventricles. The cardiac resynchronization therapy determining the pacing lead positions based on the idea of interventricular dyssynchrony induced reverse cardiac remodeling in this patient with systemic RV dysfunction.

Background Some patients with congenital complete atrioventricular block (CCAVB) develop dilated cardiomyopathy (DCM) after pacemaker implantation (PMI). We evaluated the relationship between pacing site and DCM incidence. Methods and results We retrospectively evaluated 38 patients with CCAVB; 8 (25%) of 32 patients who had PMI developed DCM/heart failure death (HFD) after PMI, although none of the 6 patients without PMI showed DCM/HFD. All DCM/HFD occurred within 50 months of PMI. Among the 32 patients with PMI, the DCM/HFD incidence was 55% (6/11) for right ventricular inlet (RVI), 18% (2/11) for RV apex (RVA), and 0% for left ventricle (LV) (P=0.013). At the endpoint, the LV ejection fraction and septal-to-posterior wall motion delay of patients with LV pacing were better than those for patients with other pacing sites. Among the 8 DCM/HFD patients, 2 in whom the pacing site was changed from RVI to LV apex or in whom therapy was upgraded to cardiac resynchronization remained alive with no heart failure symptoms, whereas the other 6 died of heart failure. Conclusions A total of 25% of the patients who underwent PMI because of CCAVB, but none in the non-PMI group, developed DCM/HFD. DCM/HFD incidence was higher in patients with RVI pacing. Ventricular dyssynchrony related to pacing site may be one cause of DCM in patients with CCAVB. (Circ J 2016; 80: 1251-1258).

Background Cardiorenal interactions adversely impact the prognosis in heart failure patients an effect which crucially involves increased central venous pressure (CVP). However, it is unclear whether the same pathophysiology operates in adults with congenital heart disease (CHD). Purpose The present study was designed to assess cardiorenal interactions in adults with CHD after biventricular repair. Methods and Results We measured the kidney length (KL, cm/m) and renal resistive index (RI) in 77 consecutive patients and 30 controls. We also measured hemodynamics, plasma B-type natriuretic peptide level, 24-hour creatinine clearance, and peak oxygen uptake in each patient. The CVP correlated with the KL (r = 0.44, P

Background: Supraventricular and ventricular tachyarrhythmias (SVT, VT) are major concerns after repair of tetralogy of Fallot (TOF). This study evaluated the impact of comprehensive treatment, including hemodynamic interventions such as surgery, catheter-based intervention and pacemaker implantation (PMI), on tachyarrhythmia in repaired TOF patients. Methods and Results: Of 66 repaired TOF patients with tachyarrhythmia (age at onset, 23±11 years), 29 patients had sustained SVT, 21 had sustained or non-sustained VT, and 16 had both (SVT+VT). Successful treatment with catheter-directed ablation and/or anti-arrhythmic drugs (AADs) alone was achieved in 31 (69%) and partially achieved in 6 (13%) of 45 patients. Surgery, catheter-based intervention, and/or PMI were performed in 21 (32%) of 66 patients and resulted in complete control of the arrhythmia in 8 (38%) and partial control in 7 (33%) of these 21 patients, 20 (95%) of whom were receiving AADs. Patients with successfully controlled tachyarrhythmia in response to catheter ablation and/or AADs without hemodynamic intervention had a significantly higher probability of absence of sinus node dysfunction (odds ratio [OR], 23.2; 95% confidence interval [CI], 1.8–845.2; P=0.02) and lone intra-atrial reentrant tachycardia (OR, 12.4; 95% CI: 1.3–278.7; P=0.03). Conclusions: Hemodynamic interventions resulted in an improvement in outcomes in repaired TOF patients with tachyarrhythmia. To effectively manage intractable tachyarrhythmia with hemodynamic abnormalities, it is essential to understand hemodynamics and consider hemodynamic intervention. (Circ J 2012; 76: 2855–2862)

Background Abnormal cardiac autonomic nervous activity (CANA) is not uncommon in postoperative patients with congenital heart disease (CHD). Methods and results We attempted to clarify the prognostic value of the CANA variables in postoperative CHD patients and prospectively evaluated the CANA variables in 292 consecutive biventricular and 91 Fontan repair patients. The CANA variables included the heart rate variability, arterial baroreflex sensitivity (BRS), washout ratio of the myocardial metaiodobenzylguanidine scintigraphy, and plasma norepinephrine level. With a follow-up of 10 ± 2 years, 98 total events that required hospitalization, including 13 deaths and 48 unscheduled cardiac events (UCEs), occurred. In all the CHD patients, all the CANA indices predicted the total events and UCEs. Of those, the NE level (p = 0.0004) and BRS (p = 0.0373) predicted the mortality. In a multivariate analysis, the BRS was an independent CANA-predictor for the total events (p = 0.007). In the biventricular patients, the plasma NE level, heart rate variability, and BRS predicted the total events and UCEs and the BRS was the only independent CANA-predictor for the total events (p = 0.0329). In the Fontan patients, the plasma NE level was the only predictor for the UCEs (p = 0.0242) and no other CANA variables were independent predictors of the total events or UCEs. Conclusions All CANA variables, especially the BRS, were useful predictors for future clinical events in biventricular CHD patients, whereas no CANA variables, except for the plasma NE level, predicted future clinical events in the Fontan patients.

gradually increasing the number of medications and doses. Oral amiodarone was administered for atrial arrhythmia. Subsequently, her cardiothoracic ratio improved from 70% to 65%. We performed cardiac catheterization and an electrophysiology study (EPS) to evaluate hemodynamics and arrhythmogenic substrates before surgical treatment. In cardiac catheterization, right ventricular (RV) end-diastolic volume index improved, from 255 to 128 ml/m 2 after optimal medical treatment. EPS 1 An EPS was performed with the patient under general anesthesia. For this intervention, a 4-mm-tip 7-F quadripolar catheter (Navistar, Biosense-Webster, Diamond Bar, California) was used for mapping and ablation. A steerable multipolar circular mapping catheter (Lasso, BiosenseWebster) was placed at the junction between the left superior caval veins and the left side of the atrium to serve as a reference for mapping. First, we mapped the area around the common AV ring to determine the location of the AV node during continuous atrial pacing. Two separate His bundle electrograms were recorded at the dorsal and inferior portions of the common AV ring (Figure 1). We detected an anterior AV node based on recording at the dorsal site of the AV ring, while a posterior AV node was recorded at the inferior site of the AV ring. During atrial pacing, 2 different QRS complexes were observed dependent on the pacing rate (Figure 2A). These QRS complexes did not show preexcitation, but QRS duration was prolonged dependent on the pacing rate. Figure 2A indicates 3 types of QRS complexes: (a) was recorded at rest and with lead I positive; (b) was recorded during atrial pacing, which was relatively rapid as compared with that at rest; and (c) was recorded during transient mechanical conduction block of the anterior AV node via catheter manipulation. Thus, QRS complexes at rest represented a fusion beat between the anterior and posterior AV nodes. No ventriculoatrial conduction was seen during ventricular pacing, even with isoproterenol infusion. Next, we initiated AT using atrial burst stimulation. The QRS complexes during AT (atrial tachycardia) (AT cycle length 450

Background. Hyponatremia (HN) is relatively common in adults with congenital heart disease and is a powerful predictor of mortality. However, the precise relationship of HN to the Fontan pathophysiology remains unknown. Purpose. Our study aimed to clarify the association of HN to the Fontan pathophysiology. Methods and Results. We measured the plasma sodium (Na) level in 169 consecutive Fontan patients (78 children) and HN (≤137 mEq/L) was observed in 50 patients (30% of the total patients, 31% of the children). The HN patients showed a lower peak oxygen uptake (VO2) with a greater New York Heart Association class (P < .0001). The plasma level of norepinephrine (NE), rennin activity (PRA), arginine vasopressin, central venous pressure (CVP) and medications were associated with the Na levels and the NE, PRA, and diuretic use were the independent determinants (P < .01−.0001). The plasma B-type natriuretic peptide was not correlated with the Na levels. In the children, diuretic use and the PRA independently determined the Na levels without any association to the CVP or peak VO2. During a median follow-up of 2.1 years, the HN in addition to the CVP and peak VO2 independently predicted the unscheduled hospitalizations in all patients, while the HN was the only independent predictor of the hospitalizations in the adult patients (hazard ratio: 3.1, 95% confidence interval 1.2–8.0, P= .021). Conclusions. Child and adult Fontan patients exhibited a high prevalence for HN that closely reflected some neurohumoral activation and predicted adverse clinical events, especially in adult Fontan patients.

The influence of volume overload on ventricular performance has been previously investigated but primarily with respect to the duration of overload. The aim of the present study was to elucidate whether the magnitude of the preoperative volume overload, represented by the ventricular volume, has any effect on ventricular performance long after the Fontan operation in patients with tricuspid atresia. We evaluated consecutive changes in hemodynamic catheterization data obtained at 1, 5, and 10 years after primary Fontan repair. The variables were compared between patients with larger (n = 20) and smaller (n = 21) ventricles (preoperative end-diastolic volume [percentage of predicted] 262 ± 33%, maximum 320% vs 182 ± 22%, minimum 133%, respectively). In a subgroup of patients (n = 33) who underwent symptom-limited exercise at 10.7 ± 3.0 postoperative years, the peak oxygen uptake was measured, and the potential predictors were interrogated. The difference in ventricular contractility between the groups tended to increase with time, with those with a larger ventricle showing poorer contraction, irrespective of whether it was assessed in a load-dependent (ejection fraction) or load-independent (end-systolic elastance) manner. The differences in these variables reached statistical significance at 10 years (p = 0.028 and p = 0.032). Multivariate analysis indicated a larger ventricle was an independent risk factor of poorer aerobic capacity (p = 0.047). In conclusion, ventricular performance was less preserved in those with a larger ventricle, which might result in suboptimal aerobic capacity. Our findings suggest not only early unloading, but also avoidance of excessive volume overload is of importance to minimize the deleterious effect of volume overload on an inherently susceptible ventricle.

Background: The extra-cardiac conduit Fontan (EC) has a lower incidence of tachyarrhythmias than other types of Fontan. However, some intrinsic arrhythmogenic conditions, such as atrial isomerism, have been associated with a high incidence of arrhythmias. Methods and Results: We retrospectively reviewed the clinical course of the supraventricular tachyarrhythmias (SVTs) in 212 patients after an EC, compared the results according to the atrial situs and investigated the substrate of the SVTs. The atrial situs was a solitus or inversus (SS/SI) in 152 patients, right isomerism (RI) in 45 and left isomerism (LI) in 15. Twenty-four SVTs occurred in 22 (11%) patients ≥3 months after the EC. The freedom from SVT after the EC was 95%, 76% and 77% in the SS/SI, RI and LI patients at 5 years, respectively (P

Background: Focal atrial tachycardias (ATs) arising from the atrial appendages (AAT) are uncommon in adults. On the other hand, we frequently encounter AATs during childhood. However, the topographic distribution and clinical characteristics of focal ATs during childhood have not yet been clearly revealed. The aim of this study was to investigate the clinical characteristics of AATs in childhood. Methods: The study population consisted of 16 consecutive pediatric patients with focal AT enrolled between March 1991 and June 2009. A retrospective analysis was performed. The patients with focal AT were divided into two groups: the AAT group and other AT (OAT) group, in which the foci arose from other atrial sites. Results: Fifty percent had AAT. The AAT patients consisted of more males (88% vs 25%; P < 0.05), were more often asymptomatic at the initial visit (75% vs 25%; P < 0.05), and more often presented with an incessant form of the AT (88% vs 25%; P < 0.05) than the OAT patients. Second-degree atrioventricular block during slow ATs of

The atrioventricular (AV) conduction system in AV discordance remains unclear, especially in cases with complex cardiac anomaly. We report a case of accessory pathway reciprocating tachycardia in atrioventricular discordance (AVD) and mitral atresia with twin AV nodes. In this case, the anterior AV node was located along the atretic mitral valve. The anterior AV node was involved in tachycardia and the posterior AV node acted as a bystander during tachycardia. The anterior AV node in AVD can be located along the atretic mitral valve, and one of twin AV nodes might act as a bystander during AV reciprocating tachycardia.

To evaluate the impact of systemic ventricular (SV) morphology on mechano-electrical interaction (MEI) and compare the results with clinical profiles in Fontan patients.Abnormal ventricular MEI causes systolic dysfunction of the right and left ventricles (RV, LV).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.Preoperative QRS-d was wider in the Fontan patients (86+/-14 vs. 64+/-9, p0.001) and steadily increased for the next 15 years (107+/-25 vs. 85+/-9, p0.001). QRS-d was wider in non-LV type SV patients than those with LV morphology (p0.05) with a positive association with age at repair (p0.001). SV contractility (Ees) improved in the RV and LV groups (p0.05), 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 (p0.01), 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)) (p0.001) and QRS-d was one of the main determinants of peak VO(2) (r=-0.48, p0.001).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.

Background Sotalol is a class III antiarrhythmic agent that is highly effective for tachyarrhythmias in adults, but its efficacy in patients with congenital heart disease (CHD) remains unclear. The purpose of this study was to assess the efficacy and safety of sotalol for refractory tachyarrhythmias in patients with CHD. Methods and Results Forty four-patients with CHD and refractory tachyarrhythmias (age, 23±12 years; follow-up period, 13±12 months) were administered sotalol orally during the period December 2002 to May 2007, resulting in complete control of tachyarrhythmias in 18 patients (41%), partial control in 15 patients (34%), and no control in 11 patients (25%). Non-pharmacological intervention (eg, surgery, pacemaker implantation, catheter ablation) was performed in 9 patients and resulted in an augmented response to sotalol in 6 patients. Tachyarrhythmia combined with atrial fibrillation was a risk factor for treatment failure with sotalol (odds ratio, 18.3; 95% confidence interval, 1.8-189.6; p=0.0053). Conclusion Sotalol is partially or completely effective for refractory tachyarrhythmias in patients with CHD, and non-pharmacological interventions improve the efficacy of sotalol. This multimodal approach should be considered in patients with refractory tachyarrhythmias and CHD. (Circ J 2008; 72: 1998 - 2003)

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)) (p0.05-0.001). 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) (p0.01-0.001). Among cardiac autonomic and neurohumoral activities, only the higher plasma norepinephrine concentration was associated with higher Chemo in Fontan patients (r=0.40, p0.01) 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.

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.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.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.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.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.

Supraventricular tachycardia (SVT) is becoming of great concern for patients long after the Fontan operation and arterial blood pressure (BP) decreases during SVT may be associated with their morbidity and mortality.We investigated the BP during supraventricular pacing (SVP) to simulate SVT in these patients. We measured femoral venous pressure (FVP) and plasma norepinephrine (NE) during SVP at 150 and 180 per minute in 20 Fontan patients and recorded the initial BP fall, its recovery and steady-state BP.Wide QRS duration had a significant impact on a greater BP decline and increases in steady-state FVP and NE at 150 SVP. Changes in BP, FVP and NE were greater at 180 SVP and in adult patients. In addition to a greater impact of baseline BP and age on the initial BP drop and steady-state BP (p0.01); older age at Fontan repair, lower ventricular ejection fraction and heart rate variability were major determinants of greater BP fluctuation during 180 SVP (p0.05). Patients with a history of SVT (n=5) exhibited a greater initial BP drop and increase in FVP during 180 SVP (p0.01). The type of Fontan procedure had no influence on BP dynamics during SVP.In Fontan patients, wide QRS duration causes a greater hemodynamic fluctuation at slower SVT. Higher baseline BP and age, impaired ventricular function, late Fontan repair and a history of SVT were major determinants of hemodynamic deterioration during faster SVT.

Background: Fontan circulation may be, in part, characterized by portal hypertension that can be estimated by hepatic vein wedge pressure (HWP). Purpose: To evaluate associations of HWP in cosecutive 318 Fontan patients (18±7 years old) during catheterization and compared the results with the hemodynamics, liver function and the related plasma biomarkers. HWP significantly correlated positively with inferior vena cava pressure (IVCP), pulmonary artery resistance (Rp), ration of Rp to systemic artery resistance (Rs) (Rp/Rs), and cardiac index and negatively with Rs and arterial and mixed venous oxgen saturations. Of those, high IVCP, low Rp and high Rp/Rs were independently correlated with high HWP (p Conclusion: High HWP associates with a significant reduction of Rp and Rs with preserved cardiac output. This unique Fontan circulation with Rs-dominant reduction may be due to both portal hypertension and overproduction of nitric oxide secondary to liver dysfunction.

Background Tolvaptan, a vasopressin V2-receptor antagonist, has been reported to improve congestion in adult patients with heart failure. However, it has not been fully clarified whether tolvaptan is also effective and safe for pediatric patients as well as adult. Methods This trial was a multicenter, retrospective, observational study, and was led by the Japanese Society of PEdiatric Circulation and Hemodynamics (J-SPECH). Thirty-four pediatric patients who received tolvaptan to treat congestive heart failure were enrolled in this study. Results An increment in the urinary volume and decrease in the body weight from baseline were significant at day 1 (+106.7±241.5%, p=0.008 and −2.30±4.17%, p=0.01), day 3 (+113.5±261.9%, p=0.02 and −2.30±4.17%, p=0.01), week 1 (+56.3±163.5%, p=0.01 and −1.55±4.09%, p=0.03) and month 1 (+91.1±171.6%, p=0.01 and −2.95±5.98, p=0.03). The significant predictive factors in responders, who was defined as patients who achieved an increase in the urinary volume at day 1, were older age (p=0.03), larger body weight before exacerbation (p=0.04), higher weight at one day before the first administration of tolvaptan (p=0.03), higher aspartate aminotransferase levels (p=0.03) and higher urinary osmolality levels (p=0.03). A logistic regression analysis showed that the urinary osmolality was the only significant predictive factor for responders to tolvaptan. Adverse drug reactions were observed in 7 patients (20.6%). Six patients had thirst and a dry month, and 1 had a mild increase in the alanine aminotransferase and aspartate aminotransferase. Conclusion Tolvaptan can be effectively and safely administered in pediatric patients. Because the kidneys in neonates and infants are resistant to arginine vasopressin, the efficacy of tolvaptan may be less effective compared to older children.

BackgroundThe peri-operative mortality of the arterial switch operation in neonates with transposition of the great arteries is considerably low; however, long-term outcomes of translocated coronary arteries still remain one of the most crucial issues.Methods and resultsA total of 110 neonates with transposition of the great arteries after arterial switch operation were evaluated; three (2.7%) late deaths occurred. The remaining 107 patients except for one underwent follow-up angiography. Angiography showed coronary artery stenosis in nine (8.4%), with right coronary artery lesions in two and left main trunk lesions in seven. In two patients, right coronary artery stenosis regressed during follow-up. In left main trunk lesions, the severity of stenosis improved in four, did not change in one, and progressed to total occlusion in two patients. In children with coronary artery stenosis, myocardial scintigraphy showed perfusion defects in five out of six (83%) with left main trunk with ⩾75% stenosis and in four out of four with left main trunk stenosis ⩾90%. In contrast, patients whose coronary artery stenosis disappeared during follow-up had no perfusion defects on scintigraphy.ConclusionsRegression of ostial stenosis of the transplanted coronary artery on angiogram was observed. The stenosis regressed over time in six patients; two coronary arteries with 99% stenosis and delayed angiographic enhancement of the distal coronary artery resulted in total occlusion within 1 year after the arterial switch operation. Combination of angiography and myocardial scintigraphy could be useful to differentiate deceptive stenosis from progressive stenosis.

This study aimed to clarify whether there is an association between ventricular sympathetic nervous activity (SNA) and clinically relevant ventricular arrhythmia (a run of ≥ 3 consecutive ventricular beats, RVA) in postoperative patients with tetralogy of Fallot (TOF). We performed a retrospective study in a national referral center of pediatric cardiology in Japan. Twenty-four postoperative TOF patients (13 males, median age 17 years) undergoing myocardial (123)I metaiodobenzylguanidine (MIBG) scintigraphy were included. We measured the heart-to-mediastinum ratio (HMR) and washout ratio (WR) from planar MIBG myocardial scintigraphy. Tomographic images and polar maps were generated with 20 segments. The standard deviation of percentage uptake of 20 segments (SD-uptake) as an index of heterogeneous MIBG uptake to the ventricular myocardium was calculated. We compared these MIBG-derived variables with the patients' clinical profiles, including ECG findings and hemodynamics. Eight of 24 patients had RVA (RVA group), and the other 16 did not have RVA (non-RVA group). There were no significant differences in the HMR (1.9 ± 0.5 vs. 2.2 ± 0.4) and WR (50 ± 5 vs. 42 ± 10) between the two groups. SD-uptake was significantly higher in the RVA group than in the non-RVA group (15 ± 3 vs. 12 ± 3, p = 0.03). QT dispersion (ms) was also higher in the RVA group than in the non-RVA group (53 ± 23 vs. 44 ± 18, p = 0.04). Multivariate logistic regression showed that SD-uptake and QT dispersion were independent predictors in the RVA group (p = 0.02, p = 0.03). In addition to greater QT dispersion, heterogeneous SNA is associated with RVA in TOF patients postoperatively.

We evaluated exercise tolerance and cardiorespiratory responses to exercise in patients with atrioventricular discordance (AVD) and abnormal ventriculoarterial connection after anatomic repair. Cardiopulmonary treadmill exercise testing with gas measurement was done 62 times in 19 patients with AVD who had undergone anatomic repair at the National Cardiovascular Center. Exercise duration, oxygen uptake ( $ {\dot {\rm V}} $ O2) and heart rate at anaerobic threshold and peak, and oxygen pulse during exercise were significantly lower in patients with AVD after anatomic repair than in controls. Carbon dioxide ventilatory equivalent during exercise was worse in patients with AVD after anatomic repair than in controls. Percentage peak $ {\dot {\rm V}} $ O2 significantly correlated positively with percentage peak oxygen pulse and tended to correlate positively with the heart rate increments. Patients with AVD after anatomic repair exhibit impaired responses of heart rate and oxygen pulse with lower exercise capacity. Careful attention should be paid to patients with AVD after anatomic repair in terms of their functional capacity as well as other postoperative complications.

The Fontan circuit is characterized by a pulmonary circulation dependent on central venous pressure in the absence of a subpulmonary ventricle. Patients with this circulation usually exhibit a low cardiac output. In addition to their abnormal cardiac state, recent studies have demonstrated impaired cardiac autonomic nervous activity, elevated neurohormonal factors, and impaired endothelial function, findings also encountered in adults with chronic heart failure. One major component of these impairments is the abnormal cardiorespiratory response during exercise. Despite some pathophysiologic similarities to adults with cardiac disease, those with the Fontan circulation usually have a congenitally malformed heart underscoring abnormal haemodynamics, with further compromise from multiple surgical procedures. It differs in many aspects from the situation in the adults with impaired systolic ventricular function in the setting of chronic cardiac failure. In this review, I will focus on the cardiorespiratory response during exercise, seeking to clarify the characteristics in these particular patients with the Fontan circulation.

Background Post-exercise heart rate (HR) and oxygen uptake (V˙O 2 ) recover more slowly in patients with the Fontan circulation, but little is known about the determinants of the delayed recovery. Purpose To evaluate the post-exercise cardiovascular dynamics and clinical profiles in these patients. Methods and results We studied 51 Fontan patients (14±4 years) (atriopulmonary connection, APC=18 and total cavopulmonary connection, TCPC=33) and compared the results with 34 patients after right ventricular outflow tract reconstruction (RVOTR) with identical exercise capacity and arterial baroreflex sensitivity (BRS) (15±4 years) and with 26 controls (14±4 years). There were no differences in post-exercise HR or V˙O 2 declines between the Fontan and RVOTR groups. Although the systolic blood pressure (SBP) decline was delayed in the RVOTR group ( p p 2 decline was determined by peak V˙O 2 , age and cardiac index ( p p p Conclusions In the Fontan group, post-exercise HR and V˙O 2 declines are markedly delayed and are determined by cardiac vagal nervous activity, exercise capacity and age, respectively. Despite identical impaired hemodynamics and exercise capacity, post-exercise SBP decline is greater in the Fontan group, especially after APC, than in the RVOTR patients.

Background: The aim of this study was to evaluate the clinical features of patients with congenital complete heart block (CCHB) who developed dilated cardiomyopathy (DCM) after pacemaker implantation (PMI) and to determine factors predicting DCM development. Method: A total of 15 patients were reviewed retrospectively. They were classified into two groups, one consisted of four patients who were diagnosed as having CCHB in utero or at birth and who developed DCM after PMI (DCM group) and the other consisted of 11 patients who did not (non-DCM group). Results: Maternal autoantibodies were found in two of the DCM group and in five of the non-DCM group. Perfusion defects in myocardial imaging were detected in all DCM patients and in five non-DCM patients. DCM developed 2 to 43 months after PMI and three DCM patients died of heart failure 7 to 48 months after PMI. In pathological studies, endocardial or interstitial fibrosis was present in all DCM patients and in one of two in the non-DCM group. No significant differences between the two groups were found in age at PMI, atrial or ventricular rate, end-diastolic dimension and ejection fraction of the left ventricle before PMI, and width of QRS after PMI. Conclusion: Although it was suspected that the patients with CCHB had myocardial involvement before PMI, there was no significant factor predicting the risk of DCM after PMI. In addition to cardiac rhythm abnormalities, careful attention should be paid to cardiac function in CCHB patients after PMI.

To investigate the negative chronotropic response (NCR) to low-dose atropine in postoperative patients with congenital heart disease (CHD).Low-dose atropine causes a NCR through the central nervous system muscarinic receptor and is attenuated in adult heart failure patients. It has never been evaluated in CHD patients.NCR corrected for basal heart rate (HR) (minimal HR/basal HR=cNCR) was determined after low-dose atropine (3 microg/kg) administration in 124 postoperative CHD patients (97 biventricular repair and 27 Fontan patients) and 11 controls and was compared with the cardiac autonomic nervous and functional status.The cNCR in simple CHD (post atrial or ventricular septal defect closure), complex biventricular CHD, and Fontan patients were 0.92+/-0.04, 0.94+/-0.04 and 0.96+/-0.04, respectively, and higher than in controls (0.87+/-0.03, p0.001). In the complex CHD patients, higher cNCR was mainly associated with the lower pharmacologically determined cardiac parasympathetic nervous tone (PST), HR variability, high atrial natriuretic peptide, and lower right ventricular ejection fraction (p0.0001). In Fontan patients, the lower beta sensitivity of the sinus node and the PST mainly determined the higher cNCR (p0.01) and the cNCR did not correlate with either hemodynamics or exercise capacity.NCR is attenuated in proportion to the impaired cardiac parasympathetic nervous system and hemodynamics in postoperative complex biventricular CHD patients. In addition to PST, beta sensitivity of the sinus node significantly influences the NCR in Fontan patients.