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Adults with complex congenital heart disease (CHD) are at risk for cognitive dysfunction. However, associations between cognitive dysfunction and psychosocial outcomes are poorly defined. Between June and November 2022, we prospectively recruited 39 adults with complex CHD who completed a computerized cognitive assessment (Cogstate) and validated psychosocial scales measuring psychological distress, health-related quality of life (HRQOL), and resilience. Participants had a mean age of 36.4 ± 11.2 years. Over half (62%) were women, most (79%) had complex biventricular CHD, and 21% had Fontan physiology. Prevalence of cognitive dysfunction was greatest in the domains of attention (29%), working memory (25%), and psychomotor speed (21%). Adjusting for age and sex, Pearson partial correlations between Cogstate z-scores and self-reported cognitive problems were small. Participants who lived in the most disadvantaged areas and those with a below-average annual household income had lower global cognitive z-scores (p = 0.02 and p = 0.03, respectively). Two-thirds (64%) reported elevated symptoms of depression, anxiety, and/or stress. Small correlations were observed between psychological distress and cognitive performance. Greater resilience was associated with lower psychological distress (r ≥ -0.5, p < 0.001) and higher HRQOL (r = 0.33, p = 0.02). Our findings demonstrate that adults with complex CHD have a high risk of cognitive dysfunction, though may not recognize or report their cognitive challenges. Lower socioeconomic status may be an indicator for those at risk of poorer cognitive functioning. Psychological distress is common though may not be a strong correlate of performance-based cognitive functioning. Formal cognitive evaluation in this patient population is essential. Optimizing resilience may be a protective strategy to minimize psychological distress and bolster HRQOL., (© 2024. The Author(s).)

Owing to the great advances in the care for children with congenital heart disease by paediatric cardiac surgeons and cardiologists, there are ever increasing numbers of patients with congenital heart disease who reach adult life. At some stage during the late teenage years or soon after, these patients 'transition' from paediatric cardiac care to surveillance by cardiologists who look after adults. Many such specialists, however, are more familiar with commoner acquired heart problems such as coronary disease, heart failure, and arrhythmia in structurally normal hearts and less familiar with congenital heart disease. For this reason, international guidelines have suggested that the care of young adults with congenital heart disease take place in designated specialist adult congenital heart disease centres. It remains very important, however, for general cardiologists to have a good understanding of many aspects of adult congenital heart disease, including common pitfalls to avoid and, importantly, when to refer on, to a specialist centre. To help healthcare providers across the spectrum of cardiology practice to address common themes in adult congenital heart disease, this state-of-the-art review provides a series of case vignettes to illustrate frequent diagnostic problems that we have seen in our tertiary-level adult congenital heart disease centres, which are sometimes encountered in general cardiology settings. These include commonly 'missed' diagnoses, or errors with diagnosis or management, in these often very complex patients., Competing Interests: Conflict of interest: All authors declare no conflict of interest for this contribution., (© The Author(s) 2022. Published by Oxford University Press on behalf of the European Society of Cardiology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Efficacy of therapies that target the downstream nitric oxide (NO) pathway in pulmonary arterial hypertension (PAH) depends on the bioavailability of NO. Reduced NO level in PAH is secondary to "uncoupling" of endothelial nitric oxide synthase (eNOS). Stimulation of β3 adrenergic receptors (β3 ARs) may lead to the recoupling of NOS and therefore be beneficial in PAH. We aimed to examine the efficacy of β3 AR agonism as a novel pathway in experimental PAH. In hypoxia (5 weeks) and Sugen hypoxia (hypoxia for 5 weeks + SU5416 injection) models of PAH, we examined the effects of the selective β3 AR agonist CL316243. We measured echocardiographic indices and invasive right ventricular (RV)-pulmonary arterial (PA) hemodynamics and compared CL316243 with riociguat and sildenafil. We assessed treatment effects on RV-PA remodeling, oxidative stress, and eNOS glutathionylation, an oxidative modification that uncouples eNOS. Compared with normoxic mice, RV systolic pressure was increased in the control hypoxic mice (p < 0.0001) and Sugen hypoxic mice (p < 0.0001). CL316243 reduced RV systolic pressure, to a similar degree to riociguat and sildenafil, in both hypoxia (p < 0.0001) and Sugen hypoxia models (p < 0.03). CL316243 reversed pulmonary vascular remodeling, decreased RV afterload, improved RV-PA coupling efficiency and reduced RV stiffness, hypertrophy, and fibrosis. Although all treatments decreased oxidative stress, CL316243 significantly reduced eNOS glutathionylation. β3 AR stimulation improved RV hemodynamics and led to beneficial RV-PA remodeling in experimental models of PAH. β3 AR agonists may be effective therapies in PAH., (© 2023 The Authors. Physiological Reports published by Wiley Periodicals LLC on behalf of The Physiological Society and the American Physiological Society.)

Background: This review identifies the predictors of late mortality and heart transplantation that remain relevant in the contemporary population of patients with a Fontan circulation, focusing on the potential impact of post-Fontan morbidities on the late outlook of these patients., Methods and Results: A total of 1561 patients who had survived the Fontan operation in Australia or New Zealand from 1975 to 2018 were included in this review. Over a median duration of 11.4 years, there was a total of 117 deaths (7%) and 32 heart transplantations (2%). Freedom from death and heart transplantation at 10, 20 and 35 years post Fontan surgery were 94% (95% CI 93-95%), 87% (95 %CI 85-90%) and 66% (95 %CI 57-78%) respectively. Being male, having an atriopulmonary Fontan, pre-Fontan atrioventricular valve intervention, or prolonged pleural effusions post Fontan were predictive of late death or heart transplantation. However, time-dependent variables such as the development of atrial arrhythmia, protein/losing enteropathy or late ventricular dysfunction were stronger predictors of the same outcome. Patients who developed a time-dependent risk factor had a freedom from death and heart transplantation rate of 54% (95 %CI 43-66) at 15 years and 44% (95 %CI 33-57) at 25 years post Fontan. However, 95% (95 %CI 91-99) of patients without any of the identified risk factors were free from death or heart transplantation rate at 25 years post Fontan., Conclusion: In conclusion, the occurrence of post-operative complications such as PLE, arrhythmia and ventricular dysfunction will likely precede the late demise of these patients., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Crown Copyright © 2021 Published by Elsevier B.V.)

Objectives: Long-term single-site ventricular pacing may adversely affect ventricular function, due to dyssynchronous systemic ventricular contraction. We sought to determine the incidence, predictors and outcomes of pacing-associated cardiomyopathy (PACM) in an adult congenital heart disease (ACHD) cohort., Methods: We retrospectively identified all patients in our database with a permanent pacemaker from 2000 to 2019. Patients were followed for the primary endpoint of unexplained decline in systemic ventricular function (PACM) and the secondary endpoint of heart failure admission., Results: Of 2073 patients in our database, 106 had undergone pacemaker implantation. Over a median follow-up of 9.4 years, 25 patients (24%) developed PACM, but only in those with ventricular pacing percentage (VP%) ≥70%; PACM occurred in 0% of those with VP <70% and 47% of those with VP ≥70% (p<0.001). High-burden ventricular pacing (≥70%) remained predictive of PACM in transposition of the great arteries, tetralogy of Fallot and complex biventricular repair subgroups, but not in Fontan patients. Those with PACM were more likely to be admitted with heart failure (44% vs 15%, p=0.002). Cardiac resynchronisation therapy (CRT) upgrade was performed in 11 patients, with 9 responders (82%)., Conclusions: In a cohort of patients with ACHD followed long-term post-pacing, 24% developed cardiomyopathy that was significantly associated with a higher burden of ventricular pacing (VP ≥70%). Given promising response rates to CRT, patients with ACHD expected to pace in the ventricle should be closely monitored for systemic ventricular decline., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Aims: Sudden cardiac death (SCD) accounts for up to 25% of deaths in the adult congenital heart disease (ACHD) population. Current guidelines for defibrillator implantation are either extrapolated from acquired cardiac disease or are based upon single lesion studies, predominantly Tetralogy of Fallot (TOF). Defibrillator-related morbidity appears to be substantially higher in ACHD patients., Methods: We retrospectively evaluated all patients in our ACHD database who received an implantable cardioverter-defibrillator (ICD) between 2000 and 2019, and who were ≥16 years old at time of implant. Patients were followed for appropriate shocks, inappropriate shocks, and complications., Results: Of 4748 patients in our database, 59 patients (1.2%) underwent ICD implantation. ICDs were for primary prevention in 63% and secondary prevention in 37%. Over a median follow-up of 6.6 years, 24% received an appropriate shock, 27% an inappropriate shock, and 42% suffered a device-related complication (annualized risks of 3.2%, 3.6%, and 5.7%, respectively). There were no significant predictors of appropriate shocks or inappropriate shocks. All appropriate shocks in primary prevention patients occurred in TOF or transposition of the great arteries (TGA) with atrial switch, typically in the presence of multiple SCD risk factors. The majority of inappropriate shocks were due to supraventricular arrhythmias. Device-related mortality was 1.7% (0.3% per annum)., Conclusions: Appropriate shocks were relatively common in an ACHD ICD population followed in the long term. Device-related morbidity was significant. Although risk factors have been established for TOF, and to a lesser extent TGA, risk stratification for ICD implantation in ACHD remains challenging., (© 2020 Wiley Periodicals LLC.)

Pulmonary hypertension is a progressive and often fatal disease that frequently presents with dyspnoea on exertion and results in increased right ventricular afterload and right ventricular failure. Although cardiac catheterisation is required for a formal diagnosis, transthoracic echocardiography (TTE) has a central role as a screening tool in those with symptoms and those at risk for developing pulmonary vascular disease. Echocardiographic techniques can be employed to estimate pulmonary artery pressure and resistance, right atrial pressure as well as to derive indirect information about right heart structure and function. Potential causes for pulmonary hypertension may also be identified such as congenital heart disease or left ventricular diastolic dysfunction. An increasing body of evidence has demonstrated the important prognostic utility of echocardiographic data in pulmonary hypertension and highlighted the potential for TTE to help clinicians understand whether treatment responses have been adequate or an escalation in therapy is necessary, as therapeutic options continue to expand for patients with pulmonary arterial hypertension. Although traditional echocardiographic techniques only allow surrogate measures of right ventricular systolic function due to the complex shape of the chamber, newer techniques have enabled three-dimensional assessment of the right ventricle to assess right ventricular volume and contractility. This review will discuss traditional methods as well as newer echocardiographic methods in the setting of pulmonary hypertension., (Copyright © 2019 Australian and New Zealand Society of Cardiac and Thoracic Surgeons (ANZSCTS) and the Cardiac Society of Australia and New Zealand (CSANZ). Published by Elsevier B.V. All rights reserved.)

Background: Patients with a Fontan circulation are at risk of renal dysfunction. We analyzed cross-sectional data in pediatric and adult Fontan patients in order to assess the accuracy of commonly used serum creatinine-based methods in estimating glomerular filtration rate (GFR)., Methods: A total of 124 Fontan patients (58 children, 66 adults) were enrolled across three study centers. Measurement of GFR (mGFR) using in vivo 99m Tc-DTPA clearance was performed. Various serum creatinine-based equations were used to calculate estimated GFR (eGFR)., Results: Mean mGFR was 108 ± 28 mL/min/1.73 m 2 in children and 92 ± 20 mL/min/1.73 m 2 in adults. Fourteen children (25%) and 28 adults (45%) had an mGFR <90 mL/min/1.73 m 2 . There was no significant correlation between mGFR and eGFR (Schwartz) in children (r = 0.22, P = .1), which substantially overestimated mGFR (bias 50.8, 95%CI: 41.1-60.5 mL/min/1.73 m 2 , P < .0001). The Bedside Schwartz equation also performed poorly in the children (r = 0.08, P = .5; bias 5.9, 95%CI: -2.9-14.6 mL/min/1.73 m 2 , P < .0001). There was a strong correlation between mGFR and both eGFR (CKD-EPI) and eGFR (MDRD) in adults (r = 0.67, P < .0001 in both cases), however, both methods overestimated mGFR (eGFR(CKD-EPI):bias 23.8, 95%CI: 20-27.6 mL/min/1.73 m 2 , P < .0001; eGFR (MDRD):bias 16.1, 95%CI: 11.8-20.4 mL/min/1.73 m 2 , P < .0001). None of the children with an mGFR <90 mL/min/1.73 m 2 had an eGFR (Schwartz) <90 mL/min/1.73 m 2 . Sensitivity and specificity of eGFR (CKD-EPI) and eGFR (MDRD) for mGFR <90 mL/min/1.73 m 2 in adults were 25% and 92% and 39% and 100%, respectively., Conclusions: This study identifies the unreliability of using creatinine-based equations to estimate GFR in children with a Fontan circulation. The accuracy of formulas incorporating cystatin C should be further investigated and may aid noninvasive surveillance of renal function in this population., (© 2019 Wiley Periodicals, Inc.)

Introduction: Adults with congenital heart disease (CHD) are predisposed to arrhythmias, which can often be refractory to medical therapy. Sotalol is an attractive alternative antiarrhythmic to amiodarone in this younger patient population, given the latter's toxicity profile, but it may have proarrhythmic effects. We therefore aimed to assess the efficacy and safety of sotalol in adults with CHD., Methods: We retrospectively assessed our adult CHD database for all patients ≥16 years old, with moderate to highly complex defects, who were prescribed sotalol between 2000 and 2017. Efficacy in treating the clinical arrhythmia was assessed as complete, partial or failure. Adverse effects, including proarrhythmia, were documented., Results: Sotalol was prescribed in 82 of 902 adult CHD patients reviewed (9%). The mean age at sotalol commencement was 31.8 ± 13.1 years, with a median time on sotalol of 2.8 years. The average prescribed dose was 122 ± 51 mg/daily. Sotalol was completely effective in 48% (n = 39), partially effective in 46% (n = 38) and failed to control the clinical arrhythmia in 6% (n = 5). Fifteen patients (18%) discontinued sotalol due to a side effect, most commonly fatigue or dyspnoea. No episodes of torsades de pointes or sudden cardiac death were observed. Significant bradycardia related to sotalol occurred in 13% (n = 11, with permanent pacing implemented in 4), and was associated with Fontan anatomy., Conclusions: In moderate to highly complex adult CHD, sotalol was reasonably effective and safe in low doses. Side effects limiting treatment were typically non-life-threatening, with significant bradycardia related to sotalol more likely in Fontan patients., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Background: Hepatic and renal dysfunction have been observed in survivors of the Fontan procedure, however their incidence and associated factors remain poorly defined., Methods: A total of 152 participants from a Registry of 1528 patients underwent abdominal ultrasound, transient elastography (FibroScan), serum fibrosis score (FibroTest), in vivo Tc-99m DTPA measurement of glomerular filtration rate (mGFR), and urine albumin-creatinine ratio (ACR)., Results: Mean age and time since Fontan were 19.8 ± 9.3 and 14.1 ± 7.6 years, respectively. Features suggestive of hepatic fibrosis were observed on ultrasound in 87/143 (61%) and no patient was diagnosed with hepatocellular carcinoma. FibroScan median kPa was ≥10 in 117/133 (88%), ≥15 in 75/133 (56%), and ≥20 in 41/133 (31%). Fifty-four patients (54/118, 46%) had a FibroTest score ≥0.49 (equivalent to ≥F2 fibrosis). FibroTest score correlated with FibroScan value (r = 0.24, p = 0.015) and ACR (r = 0.29, p = 0.002), and patients with ultrasound features of hepatic fibrosis had a higher FibroScan median kPa (19.5 vs 15.4, p = 0.002). Renal impairment was mild (mGFR 60-89 ml/min/1.73 m 2 ) in 46/131 (35%) and moderate (mGFR 30-59 ml/min/1.73 m 2 ) in 3/131 (2%). Microalbuminuria was detected in 52/139 participants (37%). By multivariable analysis, time since Fontan was associated with increased FibroScan median kPa (β = 0.89, 95% CI 0.54-1.25, p = 0.002) and decreased mGFR (β = -0.77, 95% CI -1.29-0.24, p = 0.005)., Conclusions: In the second decade after Fontan hepatic and renal structure and function are abnormal in a significant number of patients: close to 60% have ultrasonographic evidence of structural hepatic abnormalities, 46% have elevated serum hepatic fibrosis scores, and 57% have either reduced glomerular filtration rate or microalbuminuria. Hepatic and renal function should be monitored for potential impacts on outcomes after Fontan completion., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Objective: Amiodarone is a highly effective antiarrhythmic therapy, however its toxicity profile often limits treatment. This is particularly relevant in adults with congenital heart disease (CHD), who are often young and in whom other antiarrhythmic agents commonly fail or are contraindicated. We sought to determine incidence and predictors of adverse effects caused by amiodarone in adult CHD (ACHD)., Design: A retrospective review of patients with moderate to complex ACHD treated with amiodarone at our center between 2000 and 2017 was performed. Incidence and predictors of adverse effects were described. Efficacy of amiodarone therapy in controlling the clinical arrhythmia was assessed as complete, partial, or failed., Results: Amiodarone was prescribed in 57 patients of 902 ACHD patients reviewed (6%), for a mean duration of 2.7 ± 4.3 years. Significant adverse effects occurred in 56%, most commonly thyroid dysfunction, with amiodarone-induced thyrotoxicosis (AIT) in 30% and amiodarone-induced hypothyroidism in 14%. AIT frequently led to arrhythmia exacerbation and occurred most in those with Fontan anatomy. Severe dermatological effects were seen in 7% and bradycardia requiring pacing in 5%. Interstitial lung disease, peripheral neuropathy and alopecia were observed in single cases. Amiodarone toxicity led to discontinuation of the drug in 42%. Amiodarone was highly effective when tolerated, however, achieving complete arrhythmia control in 63%, partial control in 35%, with failure to control in only one patient., Conclusions: Amiodarone therapy is effective in moderate to complex ACHD patients, but is frequently limited by adverse effects. ACHD patients seem especially vulnerable to thyroid dysfunction, with Fontan patients in particular at increased risk of AIT., (© 2018 Wiley Periodicals, Inc.)

Objective: The life expectancy of patients with congenital heart disease (CHD) has significantly improved with advances in their paediatric medical care. Mortality patterns are changing as a result. Our study aims to describe survival and causes of death in a contemporary cohort of adult patients with CHD., Methods: We reviewed 3068 patients in our adult CHD database (age ≥16 years, seen at least once in our centre between 2000 and 2015), and documented the number and causes of death, via Australia's National Death Index. Survival and mortality patterns were analysed by complexity of CHD and by underlying congenital diagnosis., Results: Our cohort comprised 3068 adult patients (53% male). The distribution of patients (per the Bethesda classification) was 47% simple, 34% moderate and 18% complex (1% not classifiable). Over a median follow-up of 6.2 years (IQR 3.5-10.4), 341 patients (11%) died with an incidence of 0.4 deaths/100 patient years (py). Survival was significantly worse with increasing complexity of CHD (p<0.001); mortality rate in the simple group was 0.3 deaths/100 py with a median age of death 70 years, and in the complex group was 1.0 death/100 py with a median age of death 34 years. Overall, non-cardiac causes of death outnumbered cardiac causes, at 54% and 46%, respectively. The leading single cause of death was heart failure (17%), followed by malignancy (13%). Simple adult CHD patients mostly died due to non-cardiac causes such as malignancy. Perioperative mortality only accounted for 5% of deaths., Conclusions: Premature death is common in adults with CHD. Although heart failure remains the most common cause of death, in the contemporary era in a specialist CHD centre, non-cardiac related deaths outnumber cardiac deaths, particularly in those with simple CHD lesions., Competing Interests: Competing interests: None declared., (© Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.)

Objectives: This study sought to describe atrial arrhythmia mechanisms, acute outcomes, and long-term arrhythmia burdens following catheter ablation in adult atriopulmonary (AP) Fontan patients., Background: Atrial arrhythmias are a significant cause of morbidity and mortality in the AP Fontan population., Methods: Sixty consecutive atrial arrhythmia ablations were reviewed in 42 AP Fontan patients (31 ± 8 years of age), performed between 1998 and 2017. The number of induced and ablated tachycardias was recorded for each case, as well as the ability to ablate the suspected clinical tachycardia. Longer-term arrhythmia burden was assessed by using a 12-point clinical arrhythmia severity score., Results: Intra-atrial re-entrant tachycardia (IART) was induced in 93% of cases (n = 56), atrioventricular re-entrant tachycardia in 2 (3%) and atrioventricular nodal re-entrant tachycardia in a single case. The mean number of tachycardias induced per case was 2.3. The critical isthmus for IART was mapped to the lateral (n = 10), inferolateral (n = 8), posterior/posterolateral (n = 16), or septal (n = 10) systemic venous atrium, or to the pulmonary venous atrium (n = 4). Ablation of all inducible tachycardias was achieved in 62%, ablation of at least one (but not all) inducible tachycardias in 25%, with failure to ablate any tachycardias in 13%. The suspected clinical arrhythmia was ablated in 50 cases (83%). Catheter ablation resulted in a significant reduction in arrhythmia score at 3 to 6, 12, and 24 months, irrespective of whether all inducible tachycardias were ablated, or the suspected clinical arrhythmia only. Twelve patients (29%) underwent at least one repeat ablation procedure, with a mean time between ablations of 2.7 ± 3.0 years. There were no cases of periprocedural death, stroke or cardiac tamponade., Conclusions: Catheter ablation can be a safe and effective intervention that will significantly reduce arrhythmia burden in the AP Fontan patient., (Crown Copyright © 2018. Published by Elsevier Inc. All rights reserved.)

The objective of this study was to characterize late outcomes of the lateral tunnel (LT) Fontan procedure. The outcomes of all patients who underwent an LT Fontan procedure in Australia and in New Zealand were analyzed. Original files were reviewed and outcomes data were obtained through a binational registry. Between 1980 and 2014, a total of 301 patients underwent an LT Fontan procedure across 6 major centers. There were 13 hospital mortalities, 21 late deaths, 8 Fontan conversions and revisions, 8 Fontan takedowns, and 4 heart transplantations. Overall survival at 15 and 25 years was 90% (95% confidence interval [CI]: 86%-93%) and 80% (95% CI: 69%-91%), respectively. Protein-losing enteropathy or plastic bronchitis was observed in 14 patients (5%). Freedom from late failure at 15 and 25 years was 88% (95% CI: 84%-92%) and 82% (95% CI: 76%-87%), respectively. Independent predictors of late Fontan failure were prolonged pleural effusions post Fontan operations (hazard ratio [HR] 3.06, 1.05-8.95, P = 0.041), age >7 years at Fontan (vs 3-5 years, HR 9.7, 2.46-38.21, P = 0.001) and development of supraventricular tachycardia (HR 4.67, 2.07-10.58, P < 0.001). Freedom from tachy- or bradyarrhythmias at 10 and 20 years was 87% (95% CI: 83%-91%) and 72% (95% CI: 66%-79%), respectively. Thromboembolic events occurred in 45 patients (16%, 26 strokes), and freedom from symptomatic thromboembolism at 10 and 20 years was 93% (95% CI: 89%-96%) and 80% (95% CI: 74%-86%), respectively. Over a 25-year period, the LT technique has achieved excellent late survival. As this population ages, it is at an increasing risk of failure and adverse events. We are likely to see an increasing proportion requiring heart transplantation and late reintervention., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Introduction: Cyanotic congenital heart disease is associated with functional limitation and vascular events. The nature and extent of endothelial dysfunction in cyanotic adults is poorly understood. We sought to characterise endothelial function in this setting., Methods: A total of fourteen adults with cyanotic congenital heart disease (40±3 years) together with age- and sex-matched healthy controls underwent assessment of nitric oxide-dependent vascular responses, including flow-mediated dilatation of the brachial artery and dynamic vessel analysis of the retina in response to flickering light. Plasma levels of the endothelium-derived vasoconstrictor endothelin-1 and the nitric oxide antagonist, asymmetric dimethylarginine, were measured. Circulating endothelial progenitor cells were assessed by flow cytometry., Results: Flow-mediated dilatation was significantly lower in cyanosed adults than controls (4.0±0.8 versus 7.2±1.0%, p=0.019, n=11 per group). Retinal arterial and venous dilatory responses were also impaired (2.9±0.8 versus 5.0±0.6%, p=0.05 and 3.4±0.3 versus 5.2±0.7%, p=0.04, n=13). Serum levels of endothelin-1 and asymmetric dimethylarginine were higher in cyanosed adults (3.0±0.6 versus 1.1±0.1 pg/ml, p=0.004 and 0.68±0.05 versus 0.52±0.02 μmol/L, p=0.03, n=11). Endothelial progenitor cells (CD34+CD45dimCD133+KDR+) were reduced in those with chronic cyanosis (17±4 versus 40±6 per million white blood cells, p=0.005, n=11)., Conclusions: Endothelial function is impaired in the systemic arteries and retinal vessels in adults with cyanotic congenital heart disease, suggesting a widespread endotheliopathy. Diminished numbers of endothelial progenitor cells might potentially contribute to these observations.

Background: Subjects with Fontan-type circulation have no sub-pulmonary ventricle and thus depend exquisitely on the respiratory bellows and peripheral muscle pump for cardiac filling. We hypothesised that resistance training to augment the peripheral muscle pump might improve cardiac filling, reduce inspiratory-dependence of IVC return to the heart and thus improve exercise capacity and cardiac output on constant positive airway pressure (CPAP)., Methods: Eleven Fontan subjects (32+/-2 years, mean+/-SEM) had cardiac magnetic resonance imaging (MRI) and exercise testing (CPET); six underwent 20 weeks of high-intensity resistance training; others were non-exercising controls. After training, CPET was repeated. Four trainers had MRI with real-time flow measurement at rest, exercise and on CPAP in the trained state and following a 12-month detrain., Results: In the trained state, muscle strength increased by 43% (p=0.002), as did total muscle mass (by 1.94 kg, p=0.003) and peak VO2 (by 183 ml/min, p=0.02). After detraining, calf muscle mass and peak workload had fallen significantly (p<0.03 for both) as did peak VO2 (2.72 vs. 2.18 l/min, p<0.001) and oxygen pulse, a surrogate for SV (16% lower, p=0.005). Furthermore after detraining, SV on MRI decreased at rest (by 11 ml, p=0.01) and during moderate-intensity exercise (by 16 ml, p=0.04); inspiratory-dependent IVC blood return during exercise was 40% higher (p=0.02). On CPAP, cardiac output was lower in the detrained state (101 vs. 77 ml/s, p=0.03)., Conclusions: Resistance muscle training improves muscle mass, strength and is associated with improved cardiac filling, stroke volume, exercise capacity and cardiac output on CPAP, in adults with Fontan-type circulation., (Crown Copyright © 2012. Published by Elsevier Ireland Ltd. All rights reserved.)

Introduction: Cardiac arrhythmias are a significant problem in patients with congenital heart disease. Many patients with congenital heart disease have abnormal systemic venous anatomy which can complicate electrophysiologic testing, catheter ablation and pacemaker and defibrillator implantation. We reviewed the systemic venous anatomy in a cohort of patients undergoing electrophysiologic testing and catheter ablation., Methods and Results: We reviewed all electrophysiologic studies performed in patients with adult congenital heart disease (n = 80) at our institution between January 1998 and October 2009. Ten patients (13%) had a congenital systemic venous anomaly. Of these, seven (9%) had a left superior vena cava and four (5%) had infrahepatic interruption of the inferior vena cava (two had both anomalies). One patient's inferior vena cava was connected to a left-sided atrium; she had right atrial isomerism. In four patients (40%), systemic venous abnormalities were discovered at the time of electrophysiologic testing., Conclusions: Systemic venous anomalies occur frequently in the congenital heart disease population and may complicate electrophysiologic testing and catheter ablation. Pre-procedural imaging may assist in facilitating a successful procedure.

Pulmonary arterial hypertension is a major contributor to reduced functional capacity in patients with congenital heart disease. Expert care is essential. Whilst careful supportive management has traditionally been the mainstay for these patients, in recent times significant improvements in exercise capacity and even survival have been observed with the use of disease-targeted therapy, including endothelin receptor antagonists, phosphodiesterase inhibitors and prostanoids. In this review we will discuss current therapeutic options and summarise the recent literature on disease-targeted therapy.

In patients with cyanotic congenital heart disease, chronic hypoxaemia leads to important changes in blood vessel function and structure. Some of these alterations are maladaptive and probably contribute to impaired cardiopulmonary performance and an increased incidence of thrombotic and embolic events. Recent evidence suggests that deranged endothelial function, a sequel of chronic cyanosis, could be an important factor in the pathogenesis of cyanosis-associated cardiovascular risk. In this article, we discuss the physiological and mechanical consequences of compensatory erythrocytosis and possible pathophysiological mechanisms of vascular dysfunction in chronic cyanosis.