Adult Congenital Heart Disease Research Articles

The Unique Challenge of Coronary Artery Disease in Adult Patients with Congenital Heart Disease

Advances in medical and surgical interventions have resulted in a steady increase in the number of patients with congenital heart disease (CHD) reaching adult age. Unfortunately, this ever-growing population faces an added challenge: an increased risk of acquiring coronary artery disease. This review provides insight into the complex interactions between coronary artery disease and CHD in adults. We describe the peculiar features of cardiac anatomy in these patients, the possible role cardiac sequelae may play in an increased risk of myocardial ischemia, and the diagnostic challenges in this patient group. Furthermore, this review outlines the risk factors and potential mechanisms of accelerated atherosclerosis in adults with CHD by pointing out areas where current knowledge is incomplete and highlighting areas for further research. The review concludes by examining potential management strategies for this particular population, emphasizing the necessity for a multidisciplinary approach. Understanding the unique coronary risks that adults with CHD experience can enhance patient care and improve long-term results.

Paraganglioma and phaeochromocytoma in adult Fontan patients.

The purpose of this study was to address the gap in knowledge in the incidence, presentation and imaging features of PPGL in Fontan patients. It has been hypothesised in the literature that Fontan circulation patients have an increased incidence of these tumours. This study is the largest cohort of adult Fontan patients in North America. The Fontan procedure is a palliative procedure for single ventricle congenital heart disease where the systemic venous return is directed into the pulmonary circulation. Fontan patients are at increased risk of developing several extracardiac complications including phaeochromocytoma and paraganglioma (PPGL). This retrospective single-centre study includes all adult patients who were treated between 1 September 2015 and 1 September 2022 in a tertiary referral centre for adult congenital heart disease. Imaging and electronic medical records were retrospectively searched for the presence of PPGL. Five hundred and forty-seven Fontan patients were included in the study. Three patients had PPGL with an incidence of 0.5%. Two patients were diagnosed with paraganglioma and one with phaeochromocytoma. All patients were female. Median age of Fontan procedure was 1.8 years (range: 1.75-27 years). Median age of PPGL diagnosis was 19 years (range: 12-39 years). Median time from Fontan operation to diagnosis of PPGL was 12 years (range: 10.3-17.2 years). Fontan patients are at increased risk of PPGL. Clinically, the diagnosis of PPGL is challenging as symptoms and serum markers can be confounding in this population; however, the imaging features of PPGL remain typical making the role of the radiologist crucial.

Post-traumatic Distress in Adults with Congenital Heart Disease: Protective Factors and Clinical Implications.

Due to various reasons explored in previous studies, adults with congenital heart disease (ACHD) are at risk of developing post-traumatic stress symptoms (PTSS). The aim of this study is to explore multiple potential psychosocial protective factors in ACHD and to understand their role in different complexities of congenital heart disease (CHD) and PTSS. This study was part of the "ABS-AHF" study, where 234 ACHD were recruited from November 2021 to August 2022 at a tertiary CHD care center. Data were collected on PTSS (PDS), resilience (RS-13), sense of coherence (SOC-L9), and social support (F-SozU K-14). The mean scores were 70.55 + / - 12.31 [21-91] for resilience, 35.83 + / - 4.81 [15-60] for sense of coherence (SOC), and 4.30 + / - 0.79 [0.93-5] for social support. SOC (OR, .91; p = .024 [.84; 9.98]) and social support (OR, .48; p = .001 [.29; 7.96]) were shown to reduce the likelihood of PTSS. Low resilience (OR, 2.40, p = .0248 [1.18; 5.18]) seems to increase this likelihood. Integrating parents and relatives early on seems to be an important protective resource. Parental support in childhood affects the development of SOC which is in line with social support related to lower PTSS. With regard to resilience and SOC, a brief and manageable screening option for personal resources is available to refer potentially vulnerable patients to specialized psychosocial care. Care offers should address coping styles and life with CHD. Offering multidisciplinary care, integrating the patient's social network, and education for patients to increase resilience and SOC might provide a way to enhance psychosocial outcomes, quality of life, and adherence in ACHD.

Abstract 4138620: Assessment of the Accuracy of the Perioperative Mortality Risk in Adults with Congenital Heart Disease (PEACH) Score

INTRODUCTION: Previous mortality risk scores for adult cardiac surgery patients did not include adult congenital heart disease (ACHD) patients. Development of ACHD specific mortality risk scores include the procedure-specific ACHS score and recently derived PEACH score. While validated in Europe, further evaluation of the PEACH score in additional settings is necessary. RESEARCH QUESTION: We assessed the efficacy of the PEACH score to predict mortality in ACHD patients undergoing congenital cardiac surgery at our institution. We compared the PEACH score to the ACHS and STS scores and assessed for additional risk factors which may further augment the PEACH score. Methods: A retrospective cohort study was conducted of patients who underwent congenital cardiac surgery at the University of Colorado Hospital and Children’s Hospital Colorado between 2010-2022. Patients were identified by the institutional STS congenital cardiac surgery database and were eligible if 18 years or older and underwent congenital cardiac surgery. Components of the PEACH score and additional postulated risk factors were evaluated by univariate analysis. A receiver operating characteristic (ROC) curve was used to compare the PEACH score to existing risk models. Logistic regression analysis determined additional risk factors to augment the PEACH score. Results: A total of 516 patients were included with a median age of 30 (IQR 23-42) and 51% were male. There were nine deaths overall. The PEACH score was predictive of mortality (OR: 2.09, p<0.001) with a score of 0: 0 deaths/240 patients (0%); 1-2: 6 deaths/229 patients (2.6%); 3+: 3 deaths/41 patients (7.3%). Of additional risk factors tested, platelets less than 184,000 per mcL (OR: 8.36, p=0.01) was significantly associated with mortality. Comparison of the models revealed PEACH score AUC 0.832 (95% CI: 0.740,0.924), ACHS score AUC 0.869 (95% CI: 0.806, 0.932), and STAT AUC 0.769 (95% CI: 0.616, 0.922, Figure 1). The addition of platelet level improved the predictive ability of the PEACH score (AUC 0.881). Conclusion: In this single-center analysis, the PEACH score provided strong predictive ability for peri-operative mortality. The addition of platelet levels may further augment this score.

Abstract 4147614: Prevalence and Impact of Stroke In Young (18-44 Years) ACHD-Related Admissions by Median Household Income Quartiles: A 2019 National Inpatient Sample Analysis

Background: The risk of stroke in Adult Congenital Heart Disease (ACHD) is well established. However, the prevalence and impact of stroke in young ACHD-related admissions stratified by median household income remain underexplored. Methods: The National Inpatient Sample (2019) was utilized to identify the rate of stroke admissions among young (18-44 years) ACHD patients. We also evaluated comorbidities and outcomes (all-cause mortality [ACM], length of stay [LOS], disposition,&charges) based on the median household income quartiles and compared two cohorts of lowest (0-25th percentile) and highest (75-100thpercentile) median household income (LMHI vs HMHI). Results: Of 41950 young (18-44 years) ACHD patients, 5360 patients had stroke (12.8%). Patients in the LMHI group were relatively older (median age 36 years vs 35 years) and had a greater proportion of males (53.8% vs 46.0%) when compared to patients in the HMHI group. Patients admitted with stroke were of greater proportion in the LMHI group (13.2% vs 12.1%) compared to the HMHI group. Comorbidities like alcohol abuse (4.7% vs. 2.3%), depression (9.8% vs. 7.0%), hypertension (13.0% vs. 5.6%), obesity (21.2% vs. 18%), drug abuse (12.3% vs 4.2%), and tobacco use disorder (30.4% vs 11.2%) were higher for LMHI when compared to HMHI. Regarding in-hospital outcomes, ACM (3.7 vs. 1.9%) and discharge to home (71.6 vs. 66.5) were higher with HMHI, whereas the LMHI cohort demonstrated fewer routine discharges, higher transfers to other facilities, and prolonged LOS (5 vs. 3 days, p<0.001). When adjusted for confounders, there were statistically higher odds of AIS in ACHD patients from the LMHI group vs. the HMHI group [aOR 1.33; 1.02-1.74; p=0.045]. However, no association of income quartile with overall stroke risk was observed. Conclusion: The prevalence of stroke is significantly higher in the LMHI group. When controlled for confounders, there was a higher risk of AIS without any impact on overall stroke. Furthermore, the lowermost income quartile was associated with fewer routine dispositions, and frequent transfers can further adversely increase healthcare inequalities and healthcare costs.

Safety and Efficacy of GLP-1 Agonists in a Cohort of Patients with Fontan Circulation.

There are a growing number of adult patients palliated to a Fontan circulation. As these patients age, many develop symptomatic heart failure (d'Udekem et al in Circulation 130:S32-S38, 2014) that is exacerbated by acquired comorbidities such as obesity and hypertension. Increased body mass index (BMI) and adiposity have been associated with worse hemodynamics and clinical outcomes in these patients (Yogeswaran et al in J Am Hear Assoc: Cardiovasc Cerebrovasc Dis 12:e026732, 2023). Recently, glucagon-like peptide-1 (GLP-1) agonists, originally developed to treat diabetes mellitus, received FDA approval for weight loss and have been shown to reduce the risk of cardiovascular events in the general population (Vilsbøll et al in BMJ 344:d7771, 2012). There are limited data on these medications in patients with a Fontan circulation. We conducted a retrospective review of adults with Fontan circulation followed in our adult congenital heart disease (ACHD) clinic between 2009 and 2023 and identified 8 patients prescribed GLP-1 agonists. We found that GLP-1 agonists were well-tolerated and led to modest reduction in weight and blood pressure. Further study of the use of these medications in this population is warranted.

Atrial arrhythmia and heart failure in adult patients with congenital heart disease: a retrospective cohort study

BackgroundAtrial arrhythmias (AA) and heart failure (HF) are major causes of hospitalisation in adult congenital heart disease (ACHD). This study aimed to evaluate the temporal relationship between AA and HF...

Interventional Management of a Rare Case of Complex Congenital Heart Disease in an Adult Patient: A Case Report

Congenital heart disease (CHD), which accounts for about one-third of all congenital defects and affects approximately 1% of all live births worldwide, has maintained a stable incidence rate while experiencing a decrease in mortality rates since 1990. Despite advancements in fetal cardiac ultrasound examinations and routine pulse oximetry screening of newborns, a significant proportion of CHD patients may still be undiagnosed until adulthood. This oversight can lead to considerable morbidity and mortality due to physical limitations and reduced quality of life. In this case report, we describe a 29-year-old woman who was initially misdiagnosed as having an inoperable case of CHD and was referred to our center with symptoms of palpitations and exertional dyspnea. During her evaluation, she was diagnosed with severe pulmonary hypertension associated with patent ductus arteriosus (PDA), pre-ductal aortic coarctation, ventricular septal defect (VSD), and bicuspid aortic valve, all of which had been overlooked since infancy. Following initial medical treatment for pulmonary hypertension, a simultaneous transcatheter approach was employed, during which the PDA was closed using an occluder device, and the coarctation was repaired concurrently with a self-expanding stent. Eight months later, her VSD was successfully closed using a muscular VSD occluder device through an interventional technique. This case underscores the importance of adult CHD fellowship training, which enables cardiologists specializing in this field to accurately diagnose and treat complex cases of CHD that may have been missed during infancy and early childhood. This timely intervention ultimately led to the complete relief of her symptoms and prevented progression to Eisenmenger syndrome.

Heart Transplantation for Adult Congenital Heart Disease: Where We Are Now, and What Comes Next?

Heart Transplantation for Adult Congenital Heart Disease: Where We Are Now, and What Comes Next?

The relation between atrial arrhythmias and heart failure in adult patients with congenital heart disease

Abstract Background Advances in care have significantly improved survival in patients with adult congenital heart disease (ACHD). This growing population is now confronted with new challenges due to their structural malformations, surgical scars, cyanosis and/or longstanding abnormal pressure and volume load that lead to progressive atrial fibrosis. Atrial arrhythmias (AA) and heart failure (HF) have become the leading causes of hospitalisation in patients with ACHD and pose specific challenges in management. Purpose To assess the relationship between a first AA diagnosis and development of HF in patients with ACHD and investigate the impact of HF on the treatment success of radiofrequency ablation (RFA) for AA. Methods This single-centre, retrospective study included 3995 patients with ACHD. AA was defined as: (I) Atrial fibrillation (AF); (II) Intra-atrial re-entrant tachycardia (IART); (III) Atrial flutter (AFL); or (IV) Focal atrial tachycardia (AT). HF was defined as clinical signs and/or symptoms of HF necessitating medical intervention, along with one of the following: (I) impaired ventricular function with elevated intracardiac pressures; (II) elevated N-terminal B-type natriuretic peptide; (III) peak oxygen consumption in the lowest quartile as per specific ACHD subtype; or (IV) distinctive HF manifestations in patients with a Fontan circulation. Both AA and HF were collected with corresponding dates of first presentation. Details on RFA procedures were collected and acute and long-term success rates were calculated using Kaplan-Meier analysis. Results The mean age of the ACHD cohort at last follow-up was 35.4 ± 13.2 y. As per Bethesda complexity classification, 28.0% of ACHD patients had mild defects, 59.4% moderate and 12.6% severe defects. AA was documented in 348 (8.7%) patients with mean age at first presentation of 37.3 ± 19.6 y (Figure 1). Patients with Fontan circulation (38.5%), cyanotic ACHD (21.0%), and systemic right ventricle (24.2%) were more likely to present with AA. Furthermore, patients with a Fontan circulation (18.8 ± 12.4 y) or a systemic right ventricle (29.7 ± 16.1 y) presented with AA at younger age. The overall prevalence of HF was 6.4%. A total of 130 (3.3%) patients were diagnosed with AA as well as HF. Of these, 103 (79.2%) patients were diagnosed with AA 8.2 ± 7.4 y before HF diagnosis. RFA procedures were performed in 119 patients (34.2%), of which 45 (21.0%) were performed in patients with HF. Overall, 72% of patients undergoing RFA remained free from AA at 2 years after RFA (Figure 2.A). Acute success rates were higher and recurrence rates lower in those without HF (Figure 2.B, p=0.0001). Conclusions In patients with ACHD AA and HF are prevalent, especially in complex ACHD, and a first AA occurs on average 8 years prior to HF diagnosis. The main outcome is driven by HF and not AA. RFA can be an effective treatment for AA with 72% being recurrence free 2 years after RFA, but outcome is affected by coinciding HF.Overview of relation between AA and HFKaplan-meier analysis of AA RFA.

Short-term mechanical circulatory support in adults with congenital heart disease: indications and outcomes

Abstract Background An increasing number of adults with congenital heart disease (ACHD) present with heart failure (HF), which may require short- or long-term mechanical circulatory support (MCS), often around cardiac surgery or other interventions. Even though MCS has entered ACHD practice over the last few years, little is known on its indications and outcomes in this population. Purpose To assess the use and outcomes of short-term MCS in ACHD patients in a specialist centre, and assess the predictive power of the Survival After Veno-Arterial Extracorporeal Membrane Oxygenation (SAVE) score in this population. Methods Data on all ACHD patients who received MCS since 2008 in a single tertiary centre were collected. Immediate, short and longer-term outcomes were also collected, including death, complications, and weaning success. Logistic regression and ROC analysis were performed to identify predictors of in-hospital mortality. Result There were 65 episodes of MCS in 63 patients during the study period: age 36.9+-13.6 years, 61.5% male. Most patients had CHD of moderate or severe complexity (49.2% moderate and 10.8% severe according to ESC guidelines). The most common anatomical diagnoses were left outflow tract obstruction in 35.4%, Marfan syndrome in 20.0% and tetralogy of Fallot or pulmonary atresia in 10.8%. The most common indications for ECMO were perioperative support (not endocarditis) in 55.6%, HF in 14.3%, pneumonia in 12.7% and endocarditis-related surgery in 7.9%. A critical preoperative status was present in 26.8%; median PEACH score (a validated ACHD peri-operative risk score) was 1.0[1.0-3.0] and ACHS score was 0.6[0.6-1.0]. Median SAVE score was -4.0[-9.0–2.0], with 21(43.8%) in SAVE class 4 or 5. VA-ECMO was used in 69.2%, VV-ECMO in 21.5%, BiVAD-ECMO in 4.6% and RVAD support in 4.6% of patients. The median duration of ECMO support was 198.6[133.0-354.2] hours. Complications included ischemic stroke (15.4%), intracerebral bleeding (9.2%), and other thromboembolism (23.8%). Successful weaning was achieved in 56.2%, whereas 4.6% were switched to more definitive MCS. In-hospital mortality was 47.7%, and this was higher in patients receiving VA support (OR 4.92, 95%CI:1.32-23.93, p=0.03). For patients on VA-ECMO or BiVAD support, the presence of Marfan syndrome (OR 4.92, 95%CI:1.32-23.93, p=0.03) and a lower (worse) SAVE score (OR 1.3 per point reduction, 95%CI:1.11-1.59, p=0.004) were associated with in-hospital mortality. An adjusted SAVE score that accounted for the presence of heritable thoracic aortic diseases (HTAD, -3 points) performed well at predicting in-hospital mortality (AUC increasing from 0.73 to 0.8, Figure). Conclusions Short-term MCS is a useful temporary rescue intervention in patients with ACHD, as a bridge to recovery or durable support, with 1 in 2 patients surviving to hospital discharge. The SAVE score adjusted for HTAD can reliably predict outcomes in patients with VA-ECMO and requires external validation.Figure

Pregnancy in women with congenital heart disease : new insights into neonatal risk predictioc

Abstract Background Advances in managing adult congenital heart disease (ACHD) have led to an increased number of women with CHD reaching childbearing age. This demographic shift underscores the need for improved understanding and prediction of complications during pregnancy in this specific ACHD population. Despite progress in maternal cardiac risk assessment, the prediction of neonatal outcomes for ACHD pregnancies remains underdeveloped. Therefore, the aims of this study are (1) to assess neonatal outcomes in a CHD women population, (2) to identify their predictive factors and (3) to propose a new risk score for predicting neonatal complications. Methods This registry study included all women born between 1975 and 1996 diagnosed with ACHD who underwent at least one cardiology consultation for ACHD in Cliniques Universitaires Saint-Luc. A multivariate analysis was performed to identify predictors of neonatal complications and these were incorporated into a new risk index. Its validity was assessed using bootstrap method. This score was then compared with scores adapted from the ZAHARA and CARPREG studies for offspring events prediction. Results Analysis of 491 pregnancies revealed 31.4% of neonatal complications. Four significant predictors of adverse neonatal outcomes were identified: cardiac treatment during pregnancy (OR 14.9, 95%CI [4.6-64.3]), hypertensive disorders of pregnancy (OR 10.4, 95%CI [3.4-39.5]), smoking during pregnancy (OR 10.3, 95% CI [3.0-44.9]), and pre-pregnancy BMI < 18.5 kg/m² (OR 6.2, 95% CI [2.6-16.5]). The risk model demonstrated an AUC of 0.70 (95% CI [0.65-0.75), which remained stable after bootstrap validation. This model significantly outperformed the scores adapted from ZAHARA and CARPREG data. Based on the regression coefficients, a risk score was subsequently developed comprising 5 risk categories. Conclusion One third of ACHD pregnancies are complicated by poor neonatal outcome. These complications are determined by 4 independent factors relating to the cardiac and non-cardiac status of the patients, which have been incorporated into a risk score. Our study is one of the first to propose a predictive risk score of neonatal outcomes in ACHD pregancies, and paves the way for other validation and confirmation studies.Offspring scores: performance comparisonNew risk score for neonatal outcome

Cardiac resynchronization therapy in adult congenital heart disease: single center cohort study

Abstract Introduction Cardiac resynchronization therapy (CRT) is a recommended therapeutic measure for patients with heart failure. Heart failure is a major morbidity amongst patients with adult congenital heart disease (ACHD). However, the data on the efficacy and safety of CRT amongst ACHD is limited. Methods Data was analyzed from a retrospective cohort of patients with a known diagnosis of ACHD and implantation of CRT between 2015-2022. The primary outcome was echocardiographic response to CRT. This was defined as either:1) an increase in systemic ventricular ejection fraction (EF) of ≥5% in patients with EF <50% (therapeutic) or 2) maintenance of EF in patients with EF≥50% (preventative). Secondary outcomes included change in QRS duration, heart failure admissions, death and CIED (cardiovascular implantable electronic devices) infection during follow up. The outcomes were also assessed by subgroup of systemic left or right ventricle systemic ventricle. Results Our cohort included 46 patients, 96% male and average age was 54±14 years. 26 patients had a systemic left ventricle (56.6%) and 20 patients had a systemic right ventricle (44.4%). The indication for CRT implantation was 1) Reduced EF with wide QRS (n=10, 22%), 2) Reduced EF and RV (right ventricular) pacing (n=22, 49%), and 3) Normal EF with RV pacing (n=14, 33%). 25 patients (55%) had an implanted defibrillator at baseline. Primary outcome amongst patients with preserved EF at baseline was achieved in 22/32 patients (68.7%) and was achieved in 12/14 patients (85.7%) amongst patients with reduced EF at baseline. During follow up, QRS duration was shortened in 68.7%, 13 patients had heart failure admissions (30%), 4 patients underwent heart transplants/mechanical support device implantation (8.6%), death occurred in 11 patients (24%) and 3 had CIED infection (7%). There was no significant difference in complication or efficacy rates between the left systemic and right systemic group. Conclusion CRT is effective in patients with ACHD both as a therapeutic and as a preventative measure for heart failure. There was no difference in clinical response to CRT between patients with SRV compared to SLV. The percentage of patients with a safety outcome was relatively high in this subpopulation due to advanced ACHD.

Risk factors of 30-day mortality following cardiac surgery in adults with congenital heart disease: analysis from the Japanese registry

Abstract Background With advancements in pediatric therapies, the adult congenital heart disease (ACHD) population has grown consistently. ACHD patients often face complications necessitating cardiac surgery, and understanding surgical risk factors is essential. Purpose This study aims to assess ACHD surgical risk factors using big data, addressing evidence gaps in previous research limited to univariate analysis due to few perioperative adverse events. Methods We analyzed the Japanese Registry of All Cardiac and Vascular Diseases-Diagnosis Procedure Combination (JROAD-DPC) database from April 2013 to March 2020. The JROAD-DPC database covers nearly all teaching hospitals with cardiovascular beds participation in JROAD. Our study included ACHD patients (>15 years) undergoing open-heart surgery. Our primary outcome was 30-day mortality. We assessed clinical backgrounds, admission status, treatment, and length of hospital stay. Results Out of 13,677 ACHD patients (mean age: 53 years, females 47%) undergoing cardiac surgery assessed for 30-day mortality, 13,516 (98.8%) patients were categorized into the survival group and 161 (1.2%) into the death group. Mortality rates varied by complexity of congenital heart disease (CHD): 0.8% for simple, 1.8% for moderate, and 0.9% for great. The figure shows that a significant increase in 30-day mortality rates with age was demonstrated in simple and moderate complexity (p<0.001 for trend analysis in both categories). In contrast, for cases of great complexity, the increase in 30-day mortality rates with aging was not statistically significant (p=0.443). The death group was significantly older and had higher rates of ambulance admissions, renal disease, and peripheral vascular disease. Intra-aortic balloon pumps (IABP), veno-arterial extracorporeal membrane oxygenation (VA-ECMO), and dialysis during hospitalization were significantly higher among deceased patients. Length of ICU stay was significantly longer in the death group (median [IQR]; 3 [2-4] vs. 6 [3-11], p<0.001). Cox proportional-hazards model showed that age, moderate complexity, emergency admission, hospital bed counts, renal disease, and use of IABP and VA-ECMO were independently associated with 30-day mortality (Table). Conclusions The present study, which utilizes the nationwide administrative DPC database, demonstrates that surgical outcomes for patients with ACHD, as measured by 30-day mortality rates, are generally favorable. These outcomes significantly depend on factors such as age, complexity of CHD, emergency admissions, hospital capacity, renal disease, and use of mechanical circulatory support.

Engagement of adults with congenital heart disease in research: overcoming barriers relating to social deprivation

Abstract Background In adult congenital heart disease (ACHD), social deprivation is associated with adverse health outcomes, such as increased inpatient admissions and major adverse cardiovascular events (1). Research studies on this topic often rely on patients engaging with surveys, and the characteristics of non-respondents in relation to social deprivation remain unknown. Purpose We assessed the association between social deprivation and response to a research survey in the ACHD population. Methods We included all individuals in the UK who were invited to participate in the APPROACH-IS II study (2), which assessed patient-reported outcomes in ACHD. A validated index of relative deprivation was derived from household postcodes, based on the 2019 Index of Multiple Deprivation (IMD) scores for geographic units in England (3). A lower IMD decile indicates a greater degree of deprivation. We compared patient engagement rates between 2 centres utilising different recruitment approaches: a Southern centre (South) relying on recruitment during mainly telephone or video consultations, and a Northern centre (North) recruiting patients during face-to-face clinic appointment, with the help of an ACHD clinical and research nurse specialist. Results In total, 593 patients were asked to take part in APPROACH-IS II in the UK: 324 patients from the Southern centre and 269 patients from the Northern centre, of whom 130(40.1%) and 209(77.7%) responded, respectively (p<0.0001). In the South, patients approached were homogeneously spread amongst IMD deciles (6.0[4.0-9.0]) and respondents were significantly less deprived (higher IMD decile) than non-respondents (7.0[5.0-9.0] vs 6.0[4.0-8.0], p=0.02). Indeed, the response rate in areas of higher deprivation (IMD decile<=4) was significantly lower than in the least deprived areas (IMD >=8) (31.3% vs 47.0%, p=0.03). In the North, the distribution of deprivation in patients was skewed towards lower IMD deciles, with a significantly higher proportion of patients from areas of higher deprivation (Figure A, 26 vs 99(30.6%) in the South, p<0.0001). There was no difference in IMD decile between respondents and non-respondents in the North (Figure B, 5.0[2.0-7.0] vs 4.0[2.0-7.0], p=0.26). When comparing patients living in the most deprived areas (IMD <=4), there was a large and significant difference in response rate between centres (p<0.0001). Conclusions In our population, deprivation appears to have a significant impact on the likelihood of patients engaging with clinical research. An enhanced approach, involving face-to-face contact and the involvement of a dedicated clinical nurse specialist, can improve recruitment to research studies and abolish the effect of socioeconomic status on patient engagement.Figure 1A and B

Cardio-pulmonary exercise testing in adult congenital heart patients: a new data-focused approach to predict mortality

Abstract Background/Introduction The cardio-pulmonary exercise test (CPET) has been a pivotal tool for functional and prognostic evaluation in adults with congenital heart disease (ACHD). During a routine CPET test, a myriad of variables are collected reflecting the cardiovascular, pulmonary, and skeletal muscle systems. However, clinicians typically use only a few easily and accessible variables to establish prognosis, which can come at an accuracy cost. Machine learning algorithms have undergone significant development in recent years and have found applications in the medical field. One of their main advantages is the ability to handle a large number of variables and extract information from their various combinations, while excluding redundant data, thus offering a higher level of prediction accuracy. Purpose Our objective was to develop a machine learning model to predict death during follow-up in a large population of ACHD patients who have undergone routine CPET in a large-volume single specialist centre. Methods All available CPET studies for adult ACHD patients (age > 15 years) performed from December 1999 to December 2021 at our centre were included, and all standard available variables were extracted. The primary outcome was all-cause mortality since the CPET, collected up to November 2023. Data exploration, data cleaning, and feature engineering steps were conducted using Python (v3.8). Continuous variables were standardised. The supervised machine learning algorithm XGBoost was used for classification (all-cause mortality), with the best hyperparameters selected through cross-validation. For the final model, a feature importance analysis based on permutation techniques was used to explore the variables with more impact on model accuracy. Results A total of 6361 studies were included, with median age of 31 years (IQR 23-43), 56% male. During follow-up, a total of 491 deaths were recorded. Of available demographic, clinical and exercise parameters (n=129 variables), 21 were deemed sufficient in terms of completeness, absence of significant correlation and clinically relevant for the subsequent analysis. These included demographic variables (age and sex) and CPET variables (peak VO2, FEV1, peak heart rate, exercise time, etc.) and were used to train the model. The accuracy of the model in predicting death after CPET in the test set had an accuracy of 93.5% and an area under the ROC curve (AUC) of 85.0% (Figure1). The parameters with the highest relative feature importance were FEV1, body mass index and percent predicted peak VO2 (Figure 2). Conclusions Machine learning models can be effectively employed in specialised cardiac populations, such as ACHD, potentially providing a high level of prediction accuracy by efficiently harnessing the potential of available data. However, its applicability to mortality prediction for ACHD patients requires further external validation.ROC curve AUC for the model predictionsFeature importance using permutation

A meta-analysis of the effects of sacubitril-valsartan on surrogate markers of systemic right ventricular dysfunction in congenital heart disease

Abstract Introduction Dysfunction of systemic right ventricle (sRV) in adult congenital heart disease (ACHD) patients is expectable and often associated with heart failure and other dismal cardiovascular events. Despite limited evidence, several neurohormonal modulators approved for heart failure with reduced ejection fraction (HFrEF) have been used off-label in patients with RV dysfunction1. Sacubitril-valsartan (ARNI) effects on sRV remains poorly studied, with current evidence being limited to small cohorts. Purpose Review and summarize current evidence about the effects of ARNI in ACHD patients with sRV. Methods We performed a systematic review on MEDLINE, EMBASE, COCHRANE, and SCOPUS for articles that included "systemic right ventricle" and "sacubitril valsartan" until January 2024. Two investigators screened the literature and extracted data. Treatment effects were measured by Cohen's d effect-size (EZ) pre and post-ARNI, with a 95% confidence interval (CI), using a restricted maximum likelihood model. Results From 197 publications screened, five studies fulfilled our criteria, comprising a total of 135 patients. Follow-up after ARNI therapy ranged from 12 to 27 months. No randomized clinical trials were found, and only two studies had a prospective design. Dextro-transposition of the great arteries (D-TGA) after atrial switch operation was the most common type of congenital heart disease with sRV (n=95; 70%). Meta-analysis demonstrates that ARNI reduced NT-proBNP levels during follow-up (EZ= -0.34, CI -0.59 to 0.08; p=0.01; I2=4.0%). Regarding RV function, ARNI improved RV fractional area change (RVFAC) (EZ= 0.75, CI 0.01 to 1.50; p= 0.048; I2=85.0%). A trend for RV global longitudinal strain improvement was also observed with ARNI (EZ= 1.74, CI -0.05 to 3.54; p=0.06; I2=95.9%) but not for tricuspid annular plane systolic excursion (EZ= -0.07, CI -0.33 to 0.20; p=0.62; I2=0.0%). RV diastolic diameter did not change significantly with ARNI (EZ= 0.07, CI -0.43 to 0.56; p=0.79; I2=68.2%). A trend for improvement on the 6-minute walk test was observed (EZ= 1.89, CI -0.13 to 3.91; p=0.07; I2=96.3%), but no effect on exercise oxygen consumption (VO2) (EZ= -0.09, CI -1.32 to 1.15; p=0.89; I2=91.4%). During follow-up ARNI did not change significantly systolic blood pressure (EZ= -0.32, CI -0.74 to 0.11; p=0.15; I2=58.4%) or serum creatinine (EZ= 0.23, CI -0.04 to 0.49; p=0.09; I2=0.0%). Conclusions Despite heterogeneity among these studies, this meta-analysis demonstrates that ARNI might improve NT-proBNP levels and RV function. ARNI seems safe and well tolerated, with no significant effect on blood pressure and renal function. More well-powered studies are needed to confirm the beneficial effects of ARNI in ACHD with sRV.

Heart failure burden among adults with congenital heart disease

Abstract Background Adult congenital heart disease (ACHD) is associated with high rates of healthcare utilization and mortality. Data on Heart failure (HF) burden among ACHD patients are limited. Purpose To study the association between HF and healthcare utilization and mortality among ACHD patients in the community. Methods The retrospective cohort study comprised 11,653≥ 18 year old ACHD patients insured by two large Israeli healthcare providers between January 2007 and December 2011. We used multivariable Cox proportional hazard and negative binomial models to study the associations of HF with mortality and healthcare utilization, respectively. Inverse treatment probability weighting accounted for drug indication. Results ACHD-HF patients (N=908; 7.8%) were older (median: 69 vs. 45 years), more likely men (53% vs. 45%), with complex congenital heart disease (14% vs. 4%), and higher comorbidity rates than ACHD patients without HF. HF was associated with higher healthcare utilization. Compared to patients without HF, ACHD-HF patients had higher adjusted relative rates (RR) of primary care (1.26, 95% confidence interval [CI]: 1.17-1.3), and cardiology clinic visits (1.9, 95% CI: 1.7-2.0), higher hospitalization rates (RR=2.0, 95% CI: 1.7-2.1), and higher risk of death (mortality hazard ratio [HR]: 1.9, 95% CI: 1.5-20.) over the study period. Among ACHD-HF patients, Angiotensin-converting enzyme inhibitors or angiotensin receptor blockers, beta-blockers, and diuretics were associated with a lower mortality risk (treated vs. untreated HR=0.56, 95% CI: 0.48-0.65; HR=0.7, 95% CI: 0.6-0.8; HR=0.84, 95% CI: 0.73-0.97; respectively). Conclusions HF presents a major burden on ACHD patients and health care systems. Drugs recommended to the general HF patient population are also associated with lower risk of hospitalization and mortality in ACHD patients. Clinical trials are needed to establish the benefit of HF pharmacotherapy in ACHD patients.Age adjusted ACHD patient survival by HF

Remodeling of adult rat heart subjected to pressure overload from the neonatal period is dependent on the sex

Abstract Background Congenital heart diseases (CHD) represents the most common birth defect. Despite progress in their treatment improving acute survival, there is a paucity of data concerning the long-term consequences of CHD in adults. Purpose Here, we investigate the remodeling in adult rat hearts subjected to pressure overload from the early postnatal period. Methods We used the neonatal abdominal aortic constriction (AAC) model to analyze morphological, functional (by echocardiography), and electrophysiological long-term outcomes. Given the known differences in cardiac pathologies between males (M) and females (F), we focused on the role of sex in cardiac remodeling. Results Our data showed that both sexes exhibited a similar left ventricular weight/body weight ratio at the age of 12 weeks, indicating comparable left ventricle (LV) enlargement as a response to AAC (increase by 103 ± 9 % in M AAC and 99 ± 10 % in F AAC vs. sham-operated animals). However, the right ventricular weight/body weight and lung/ body weight ratios, indicative of LV failing, differed significantly between sexes with better values in F AAC. The favorable cardiac remodeling in F AAC was corroborated by significantly smaller LV systolic and diastolic diameters, along with a lower amount of myocardial fibrosis. Using optical mapping, we revealed preserved longitudinal and transversal conduction velocities (CVL; CVT) in females (CVL 104 ± 8 vs. 109 ± 8 cm/s and CVT 66 ± 7 vs. 59 ± 6 cm/s in F AAC and F Sham, respectively). However, compared to M Sham, the conduction velocities in M AAC showed a significant decrease (CVL 80 ± 3 vs. 92 ± 3 cm/s and CVT 35 ± 2 vs. 54 ± 3 cm/s). Similarly, the amount of connexion 43 (Cx43) and its phosphorylated state (Cx43Ser368) was preserved in F AAC while exhibiting a decrease in M AAC compared to the sham-operated controls. Thus, electrophysiological findings implicate that while the adult M AAC underwent pro-arrhythmogenic remodeling due to the elevated workload, the adult F AAC preserved physiological conduction properties. Conclusion Our data showed different consequences of the increased pressure load exposed from early after birth to the adult M and F heart. These findings highlighted the involvement of both sexes in cardiac studies.

High prevalence of coronary artery calcium and aortic calcification in adults with repaired coarctation of the aorta and interrupted aortic arch

Abstract Background There is a high rate of late cardiovascular mortality in patients with repaired coarctation of the aorta (CoA) and interrupted aortic arch (IAA). Coronary artery calcium (CAC) is a marker of cardiovascular disease and there is growing evidence for aortic calcification as a predictor. Recent research in the general population suggests any CAC in males <35 years old and females ≤45 years places them at ≥90th percentile. Aims We aimed (1) to determine the prevalence of CAC, thoracic aorta calcification (TAC), and abdominal aorta calcification (AAC) in patients with CoA or IAA repair, and (2) to compare patients to a control group of Tetralogy of Fallot (TOF) patients, a condition with no known increased risk of atherosclerotic cardiovascular disease. Methods Retrospective cohort study of adult survivors of CoA/IAA repair followed up at an adult congenital heart disease (ACHD) clinic. Patients with at least 1 chest, abdomen, or pelvis computerised tomography (CT) scan for any indication were included. The presence/absence of calcification in the coronary arteries or aorta was assessed qualitatively. Patients on antihypertensive and statin therapy were considered hypertensive and hypercholesterolaemic, respectively. Patients were compared to adult survivors of TOF repair with CT scans for any indication (controls). Results Ninety-three CoA/IAA patients (87% CoA/13% IAA, median age at latest follow-up 34 years) had a total of 169 chest and 37 abdomen/pelvis CTs; 82, 93, and 37 patients had at least 1 CT suitable for CAC, TAC, and AAC review, respectively. CAC was present in 22% (18/82), TAC in 33% (31/93), and AAC in 23% (5/22) of CoA/IAA patients. CAC was present in 12% (18/153) and TAC in 11% (18/158) of TOF patients. CoA/IAA patients were more likely to have CAC and TAC than TOF patients (p=0.04 and p<0.0001; respectively) and be younger at the time of diagnosis (CAC p=0.03, TAC p=0.0001) despite TOF patients being older at time of latest CT scan (p=0.0003) (Table 1). Males aged <35 years and females ≤45 years represented 44% (8/18) of CoA/IAA patients with CAC. CoA/IAA patients with CAC were more likely to be hypertensive and hypercholesterolaemic than those without (78% [14/18] vs 48% [31/64], p=0.03; and 28% [5/18] vs 0% [0/64], p<0.0001; respectively) and was similar for TAC (hypertension p=0.005, hypercholesterolaemia p=0.04) but not AAC. After a mean follow-up of 11±7 years from first ACHD clinic, of the 93 patients, 2 patients died, 5 had coronary artery disease (at least mild stenosis on invasive angiography), 3 had a stroke, and 70% (65/93) were considered hypertensive at latest follow-up. Conclusions There is a high prevalence of CAC, aortic calcification, and hypertension in young adults with repaired CoA/IAA. Coronary and thoracic aortic calcification occurs at a younger age compared to controls. Further studies are warranted to assess the impact of aggressive cardiovascular risk reduction in this high-risk group.