B-type natriuretic peptide levels predict long-term mortality in a large cohort of adults with congenital heart disease.

BACKGROUND AND AIMS: Many adult patients with congenital heart disease (ACHD) are still afflicted by premature death. Previous reports suggested natriuretic peptides may identify ACHD patients with adverse outcome. The study investigated prognostic power of B-type natriuretic peptide (BNP) across the spectrum of ACHD in a large contemporary cohort. METHODS: The cohort included 3392 consecutive ACHD patients under long-term follow-up at a tertiary ACHD centre between 2006 and 2019. The primary study endpoint was all-cause mortality. RESULTS: A total of 11 974 BNP measurements were analysed. The median BNP at baseline was 47 (24-107) ng/L. During a median follow-up of 8.6 years (29 115 patient-years), 615 (18.1%) patients died. On univariable and multivariable analysis, baseline BNP [hazard ratio (HR) 1.16, 95% confidence interval (CI) 1.15-1.18 and HR 1.13, 95% CI 1.08-1.18, respectively] and temporal changes in BNP levels (HR 1.22, 95% CI 1.19-1.26 and HR 1.19, 95% CI 1.12-1.26, respectively) were predictive of mortality (P < .001 for both) independently of congenital heart disease diagnosis, complexity, anatomic/haemodynamic features, and/or systolic systemic ventricular function. Patients within the highest quartile of baseline BNP (>107 ng/L) and those within the highest quartile of temporal BNP change (>35 ng/L) had significantly increased risk of death (HR 5.8, 95% CI 4.91-6.79, P < .001, and HR 3.6, 95% CI 2.93-4.40, P < .001, respectively). CONCLUSIONS: Baseline BNP and temporal BNP changes are both significantly associated with all-cause mortality in ACHD independent of congenital heart disease diagnosis, complexity, anatomic/haemodynamic features, and/or systolic systemic ventricular function. B-type natriuretic peptide levels represent an easy to obtain and inexpensive marker conveying prognostic information and should be used for the routine surveillance of patients with ACHD.

Occurrence and Outcome of Infective Endocarditis after Surgical Compared to Transcatheter Pulmonary Valve Implantation in Congenital Heart Disease.

Background: Conflicting data exist on the occurrence and outcome of infective endocarditis (IE) after pulmonary valve implantation. Objectives: This study sought to assess the differences between transcatheter pulmonary valve implantation (TPVI) and surgical pulmonary valve replacement (SPVR). Methods: All patients ≥ 4 years who underwent isolated pulmonary valve replacement between 2005 and 2018 were analyzed based on the data of a major German health insurer (≈9.2 million insured subjects representative of the German population). The primary endpoint was a composite of IE occurrence and all-cause death. Results: Of 461 interventions (cases) in 413 patients (58.4% male, median age 18.9 years [IQR 12.3-33.4]), 34.4% underwent TPVI and 65.5% SPVR. IE was diagnosed in 8.0% of cases during a median follow-up of 3.5 years. Risk for IE and all-cause death was increased in patients with prior IE (p < 0.001), but not associated with age (p = 0.50), sex (p = 0.67) or complexity of disease (p = 0.59). While there was no difference in events over the entire observational time period (p = 0.22), the time dynamics varied between TPVI and SPVR: Within the first year, the risk for IE and all-cause death was lower after TPVI (Hazard Ratio (HR) 95% CI 0.19 (0.06-0.63; p = 0.006) but increased over time and exceeded that of SPVR in the long term (HR 10.07 (95% CI 3.41-29.76; p < 0.001). Conclusions: Patients with TPVI appear to be at lower risk for early but higher risk for late IE, resulting in no significant difference in the overall event rate compared to SPVR. The results highlight the importance of long-term specialized care and preventive measures after both interventions.

Clinical Risk Assessment and Prediction in Congenital Heart Disease Across the Lifespan: JACC Scientific Statement.

Congenital heart disease (CHD) comprises a range of structural anomalies, each with a unique natural history, evolving treatment strategies, and distinct long-term consequences. Current prediction models are challenged by generalizability, limited validation, and questionable application to extended follow-up periods. In this JACC Scientific Statement, we tackle the difficulty of risk measurement across the lifespan. We appraise current and future risk measurement frameworks and describe domains of risk specific to CHD. Risk of adverse outcomes varies with age, sex, genetics, era, socioeconomic status, behavior, and comorbidities as they evolve through the lifespan and across care settings. Emerging technologies and approaches promise to improve risk assessment, but there is also need for large, longitudinal, representative, prospective CHD cohorts with multidimensional data and consensus-driven methodologies to provide insight into time-varying risk. Communication of risk, particularly with patients and their families, poses a separate and equally important challenge, and best practices are reviewed.

[Pulmonary hypertension in adults with congenital heart disease in light of the 2022-ESC-PAH guidelines - Part II: Supportive therapy, special situations (pregnancy, contraception, non-cardiac surgery), targeted pharmacotherapy, organ transplantation, special management (shunt lesions, left ventricular disorders, univentricular hearts), interventions, intensive care, follow-up, future perspectives]. / Pulmonale Hypertonie bei Erwachsenen mit angeborenen Herzfehlern im Lichte der 2022-ESC-PAH-Leitlinien.

The number of adults with congenital heart defects (CHD) is steadily rising and amounts to approximately 360,000 in Germany. CHD is often associated with pulmonary hypertension (PH), which may develop early in untreated CHD. Despite timely treatment of CHD, PH not infrequently persists or recurs in older age and is associated with significant morbidity and mortality.The revised European Society of Cardiology/European Respiratory Society 2022 guidelines for the diagnosis and treatment of PH represent a significant contribution to the optimized care of those affected. However, the topic of "adults with congenital heart disease" is addressed only relatively superficial in these guidelines. Therefore, in the present article, this topic is commented in detail from the perspective of congenital cardiology.

Impact of COVID-19 Infections among Unvaccinated Patients with Congenital Heart Disease: Results of a Nationwide Analysis in the First Phase of the Pandemic.

Background: The outcome data and predictors for mortality among patients with congenital heart disease (CHD) affected by COVID-19 are limited. A more detailed understanding may aid in implementing targeted prevention measures in potential future pandemic events. Methods: Based on nationwide administrative health insurance data, all the recorded in-hospital cases of patients with CHD with COVID-19 in 2020 were analyzed. The demographics, treatment details, as well as 30-day mortality rate were assessed. The associations of the patients' characteristics with death were assessed using multivariable logistic regression analysis. Results: Overall, 403 patients with CHD were treated in- hospital for COVID-19 in 2020. Of these, 338 patients presented with virus detection but no pneumonia whilst, 65 patients suffered from associated pneumonia. The cohort of patients with pneumonia was older (p = 0.04) and presented with more cardiovascular comorbidities such as diabetes mellitus (p = 0.08), although this parameter did not reach a statistically significant difference. The 30-day mortality rate was associated with highly complex CHD (odds ratio (OR) 7.81, p = 0.04) and advanced age (OR 2.99 per 10 years, p = 0.03). No child died of COVID-related pneumonia in our dataset. Conclusions: COVID-19 infection with associated pneumonia chiefly affected the older patients with CHD. Age and the complexity of CHD were identified as additional predictors of mortality. These aspects might be helpful to retrospectively audit the recommendations and guide health politics during future pandemic events.

Surveillance of adults with congenital heart disease: Current guidelines and actual clinical practice.

BACKGROUND AND AIM: Congenital heart disease (CHD) is the most common birth defect with prevalence of 0.8%. Thanks to tremendous progress in medical and surgical practice, nowadays, >90% of children survive into adulthood. Recently European Society of Cardiology (ESC), American College of Cardiology (ACC)/ American Heart Association (AHA) issued guidelines which offer diagnostic and therapeutic recommendations for the different defect categories. However, the type of technical exams and their frequency of follow-up may vary largely between clinicians and centres. We aimed to present an overview of available diagnostic modalities and describe current surveillance practices by cardiologists taking care of adults with CHD (ACHD). METHODS AND RESULTS: A questionnaire was used to assess the frequency cardiologists treating ACHD for at least one year administrated the most common diagnostic tests for ACHD. The most frequently employed diagnostic modalities were ECG and echocardiography for both mild and moderate/severe CHD. Sixty-seven percent of respondents reported that they routinely address psychosocial well-being. CONCLUSION: Differences exist between reported current clinical practice and published guidelines. This is particularly true for the care of patients with mild lesions. In addition, some differences exist between ESC and American guidelines, with more frequent surveillance suggested by the Americans.

Utility of Coronary Computed Tomography Angiography in Patients Undergoing Transcatheter Aortic Valve Implantation: A Meta-Analysis and Meta-Regression Based on Published Data from 7458 Patients.

BACKGROUND: Coronary CT angiography (CCTA) may detect coronary artery disease (CAD) in transcatheter aortic valve implantation (TAVI) patients and may obviate invasive coronary angiography (ICA) in selected patients. We assessed the diagnostic accuracy of CCTA for detecting CAD in TAVI patients based on published data. METHODS: Meta-analysis and meta-regression were performed based on a comprehensive electronic search, including relevant studies assessing the diagnostic accuracy of CCTA in the setting of TAVI patients compared to ICA. The sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV), were calculated on a patient and per segment level. RESULTS: Overall, 27 studies (total of 7458 patients) were included. On the patient level, the CCTA's pooled sensitivity and NPV were 95% (95% CI: 93-97%) and 97% (95% CI: 95-98%), respectively, while the specificity and PPV were at 73% (95% CI: 62-82%) and 64% (95% CI: 57-71%), respectively. On the segmental coronary vessel level, the sensitivity and NPV were 90% (95% CI: 79-96%) and 98% (95% CI: 97-99%). CONCLUSIONS: This meta-analysis highlights CCTA's potential as a first-line diagnostic tool although its limited PPV and specificity may pose challenges when interpreting heavily calcified arteries. This study underscores the need for further research and protocol standardization in this area.

[Pulmonary arterial hypertension in congenital heart disease - Part I]. / Pulmonale arterielle Hypertonie bei Erwachsenen mit angeborenen Herzfehlern ­ Teil I.

The number of adults with congenital heart disease (CHD) is steadily rising and amounts to approximately 360,000 in Germany. CHD is often associated with pulmonary arterial hypertension (PAH), which may develop early in untreated CHD. Despite timely treatment of CHD, PAH often persists or recurs in older age and is associated with significant morbidity and mortality.The revised European Society of Cardiology/European Respiratory Society 2022 guidelines for the diagnosis and treatment of PH represent a significant contribution to the optimized care of those affected. However, the topic of "adults with congenital heart defects" is addressed only relatively superficially in these guidelines. Therefore, this article addresses the perspective of congenital cardiology in greater depth.

Acquired cardiovascular disease in adults with congenital heart disease.

Rates of successful surgical repair and life expectancy for patients with congenital heart disease have increased dramatically in recent decades. Thanks to advances in diagnosis, treatment, and follow-up care, an ever-increasing number of individuals with congenital heart disease are reaching advanced age. The exposure to cardiovascular risk factors during their lifetime is modifying the outlook and late clinical trajectory of adult congenital heart disease (ACHD). Their disease burden is shifting from congenital to acquired, primarily atherosclerotic cardiovascular disease (ASCVD) with worrisome consequences. In addition, the complex background of ACHD often curbs appropriate preventive strategies by general practitioners or adult cardiologists. Comprehensive guidance for the prevention and management of acquired heart disease in ACHD patients is currently not available, as this topic has not been covered by the European Society of Cardiology (ESC) guidelines on cardiovascular disease prevention or the ESC guidelines for the management of ACHD. In this document, a state-of-the-art overview of acquired heart disease in ACHD patients and guidance on ASCVD prevention for both ACHD specialists and non-ACHD cardiologists are provided. The aim is to provide a clinical consensus statement to foster the development of a sustainable strategy for the prevention of ASCVD in a practical and simple-to-follow way in this ever-growing cardiovascular cohort, thus reducing their cardiovascular burden.

The Right Heart in Congenital Heart Disease.

PURPOSE OF REVIEW: To analyze the pathophysiologic importance of the right heart in different types of congenital heart disease (CHD), summarize current diagnostic modalities, and discuss treatment options. RECENT FINDINGS: The right ventricle (RV) plays a key role in disease progression and prognosis, either as the subpulmonary or as the systemic ventricle. Volume and/or pressure overload as well as intrinsic myocardial disease are the main factors for RV remodeling. Echocardiography and cardiac magnetic resonance imaging are important noninvasive modalities for assessing anatomy, size, and function of the right heart. Timely repair of related lesions is essential for preventing RV dysfunction. Few inconclusive data exist on conventional pharmacotherapy in CHD-related RV dysfunction. Cardiac resynchronization therapy and ventricular assist devices are an option in patients with advanced systemic RV failure. Right heart disease is highly related with adverse clinical outcomes in CHD. Research should focus on early identification of patients at risk and development of medical and interventional treatments that improve RV function.

Prognostic Value of Transthoracic Echocardiography in Children With Pulmonary Arterial Hypertension.

Background Transthoracic echocardiography is part of the regular follow-up protocol at most pediatric pulmonary arterial hypertension (PAH) centers. We aimed to develop a comprehensive and simple echocardiographic risk stratification for children with PAH. Methods and Results We included 63 children with PAH and a biventricular cardiac anatomy without relevant shunt lesions (60% female patients; mean age, 9.0 years; 42 idiopathic PAH and 21 associated PAH) undergoing a standardized transthoracic echocardiographic assessment. The prognostic value of echocardiographic parameters was assessed using Cox proportional hazards survival analysis and recursive partitioning for classification tree methods. Over a median follow-up period of 4.0 years, 17 patients died and 4 underwent lung transplantation. Various echocardiographic parameters were associated with the combined endpoint of death and transplantation on univariate analysis. On further analysis, right atrial area (z score) and left ventricular diastolic eccentricity index (LVEId) emerged as robust and independent predictors of transplant-free survival. Considering mortality alone as an end point, a combination of right atrial area, left ventricular diastolic eccentricity index, and tricuspid annular plane systolic excursion were identified as independent predictors of outcome. Based on these parameters, we propose simple risk scores that can be applied at the bedside without computer assistance. CONCLUSIONS Echocardiographic parameters predict prognosis in children with pulmonary hypertension. A combination of widely available parameters including right atrial area, left ventricular eccentricity index, and tricuspid annular plane systolic excursion emerged as risk stratifiers that await external validation but may assist clinicians determining the prognosis of children with PAH.

Immunodeficiency is prevalent in congenital heart disease and associated with increased risk of emergency admissions and death.

AIMS: To provide population-based data on the prevalence and clinical significance of immune deficiency syndromes (IDS) associated with congenital heart disease (CHD). METHODS AND RESULTS: Utilizing administrative German Health System data the prevalence of increased susceptibility to infection (ISI) or confirmed IDS was assessed in CHD patients and compared with an age-matched non-congenital control group. Furthermore, the prognostic significance of IDS was assessed using all-cause mortality and freedom from emergency hospital admission. A total of 54 449 CHD patients were included. Of these 14 998 (27.5%) had ISI and 3034 (5.6%) had a documented IDS (compared with 2.9% of the age-matched general population). During an observation period of 394 289 patient-years, 3824 CHD patients died, and 31 017 patients experienced a combined event of all-cause mortality or emergency admission. On multivariable Cox proportional-hazard analysis, the presence of ISI [hazard ratio (HR): 2.14, P < 0.001] or documented IDS (HR: 1.77, P = 0.035) emerged as independent predictors of all-cause mortality. In addition, ISI and confirmed IDS were associated with a significantly higher risk of emergency hospital admission (P = 0.01 for both on competing risk analysis) during follow-up. CONCLUSION: Limited immune competence is common in CHD patients and associated with an increased risk of morbidity and mortality. This highlights the need for structured IDS screening and collaboration with immunology specialists as immunodeficiency may be amenable to specific therapy. Furthermore, studies are required to assess whether IDS patients might benefit from intensified antibiotic shielding or tailored prophylaxis.

Infective endocarditis in adults with congenital heart disease: Contemporary management and related outcomes in Central and South-Eastern European region.

BACKGROUND: Infective endocarditis (IE) remains major cause of morbidity and mortality in adult congenital heart disease (ACHD). Limited data exists on ACHD with IE in Central and South-Eastern European (CESEE) countries. The aim of this study is to characterize contemporary management and assess outcomes of ACHD with IE in CESEE region. METHODS: Data on ACHD patients with IE from 9 tertiary centres in 9 different CESEE countries between 2015 and 2020 was included. Baseline demographics, clinical presentation, indication for surgery, outcomes, hospital and all-cause-1-year mortality were studied. RESULTS: A total of 295 ACHD patients (mean age 40 ± 14 years) with IE were included. Median time from symptoms onset to establishing diagnosis was 25 (11-59) days. The majority of patients (203, 68.8%) received previous empiric oral antibiotic therapy. The highest incidence of IE was observed on native and left sided valves, 194(65.8%) and 204(69.2%), respectively. More than half had a vegetation size ≥10 mm (164, 55.6%); overall 138 (46.8%) had valve complications and 119 (40.3%) had heart failure. In-hospital mortality was 26 (8.8%). CONCLUSION: There is clear delay in establishing IE diagnosis amongst ACHD patients in CESEE countries. Adequate diagnosis is hampered by common prescription of empiric antibiotics before establishing formal diagnosis. Hence, patients commonly present with associated complications requiring surgery. Hospital treatment and survival are, nevertheless, comparable to other Western European countries. Improved awareness and education of patients and medical profession regarding IE preventive measures, risks, signs, and symptoms are urgently needed. Empiric antibiotic prescription before blood cultures are taken must be omitted.

Changing epidemiology of congenital heart disease: effect on outcomes and quality of care in adults.

The epidemiology of congenital heart disease (CHD) has changed in the past 50 years as a result of an increase in the prevalence and survival rate of CHD. In particular, mortality in patients with CHD has changed dramatically since the latter half of the twentieth century as a result of more timely diagnosis and the development of interventions for CHD that have prolonged life. As patients with CHD age, the disease burden shifts away from the heart and towards acquired cardiovascular and systemic complications. The societal costs of CHD are high, not just in terms of health-care utilization but also with regards to quality of life. Lifespan disease trajectories for populations with a high disease burden that is measured over prolonged time periods are becoming increasingly important to define long-term outcomes that can be improved. Quality improvement initiatives, including advanced physician training for adult CHD in the past 10 years, have begun to improve disease outcomes. As we seek to transform lifespan into healthspan, research efforts need to incorporate big data to allow high-value, patient-centred and artificial intelligence-enabled delivery of care. Such efforts will facilitate improved access to health care in remote areas and inform the horizontal integration of services needed to manage CHD for the prolonged duration of survival among adult patients.

Treatment of advanced heart failure in adults with congenital heart disease: a narrative review and clinical cases.

Background and Objective: The number of adults with congenital heart disease (ACHD) is increasing worldwide. Almost all congenital cardiac lesions can be successfully treated due to the progress in neonatal surgery and pediatric cardiology with a high likelihood of surviving until adulthood. However, ACHD frequently develop sequelae related to the initial cardiac anomaly. Heart failure (HF) is one of the most common complications associated with a high morbidity and mortality. Methods: The authors did search the PubMed database regarding relevant content covering publications up to March 2022. Relevant manuscripts were classified according to the impact factor of the journal, being a guideline manuscript, a position paper by a society or a comprehensive review of the current literature. Key Content and Findings: Optimal HF treatment remains an unmet need in ACHD. In particular, advanced HF therapy with cardiac resynchronization therapy, ventricular assist devices or organ transplantation is still very different and more specific in ACHD compared to non-ACHD. This review aims to compile international views and evidence from the literatures on the treatment of advanced HF in ACHD. Current challenges, but also the success of different treatment strategies in ACHD are illustrated by clinical cases. Conclusions: The main finding of the review is that data is still scarce regarding ACHD with advanced HF and international efforts to collect data regarding these patients needed to improve the current standard of care.

A framework of deep learning networks provides expert-level accuracy for the detection and prognostication of pulmonary arterial hypertension.

AIMS: To test the hypothesis that deep learning (DL) networks reliably detect pulmonary arterial hypertension (PAH) and provide prognostic information. METHODS AND RESULTS: Consecutive patients with PAH, right ventricular (RV) dilation (without PAH), and normal controls were included. An ensemble of deep convolutional networks incorporating echocardiographic views and estimated RV systolic pressure (RVSP) was trained to detect (invasively confirmed) PAH. In addition, DL-networks were trained to segment cardiac chambers and extracted geometric information throughout the cardiac cycle. The ability of DL parameters to predict all-cause mortality was assessed using Cox-proportional hazard analyses. Overall, 450 PAH patients, 308 patients with RV dilatation (201 with tetralogy of Fallot and 107 with atrial septal defects) and 67 normal controls were included. The DL algorithm achieved an accuracy and sensitivity of detecting PAH on a per patient basis of 97.6 and 100%, respectively. On univariable analysis, automatically determined right atrial area, RV area, RV fractional area change, RV inflow diameter and left ventricular eccentricity index (P < 0.001 for all) were significantly related to mortality. On multivariable analysis DL-based RV fractional area change (P < 0.001) and right atrial area (P = 0.003) emerged as independent predictors of outcome. Statistically, DL parameters were non-inferior to measures obtained manually by expert echocardiographers in predicting prognosis. CONCLUSION: The study highlights the utility of DL algorithms in detecting PAH on routine echocardiograms irrespective of RV dilatation. The algorithms outperform conventional echocardiographic evaluation and provide prognostic information at expert-level. Therefore, DL methods may allow for improved screening and optimized management of PAH.

Development of a Semiautomated Database for Patients With Adult Congenital Heart Disease.

BACKGROUND: Databases for Congenital Heart Disease (CHD) are effective in delivering accessible datasets ready for statistical inference. Data collection hitherto has, however, been labour and time intensive and has required substantial financial support to ensure sustainability. We propose here creation and piloting of a semiautomated technique for data extraction from clinic letters to populate a clinical database. METHODS: PDF formatted clinic letters stored in a local folder, through a series of algorithms, underwent data extraction, preprocessing, and analysis. Specific patient information (diagnoses, diagnostic complexity, interventions, arrhythmia, medications, and demographic data) was processed into text files and structured data tables, used to populate a database. A specific data validation schema was predefined to verify and accommodate the information populating the database. Unsupervised learning in the form of a dimensionality reduction technique was used to project data into 2 dimensions and visualize their intrinsic structure in relation to the diagnosis, medication, intervention, and European Society of Cardiology classification lists of disease complexity. Ninety-three randomly selected letters were reviewed manually for accuracy. RESULTS: There were 1409 consecutive outpatient clinic letters used to populate the Scottish Adult Congenital Cardiac Database. Mean patient age was 35.4 years; 47.6% female; with 698 (49.5%) having moderately complex, 369 (26.1%) greatly complex, and 284 (20.1%) mildly complex lesions. Individual diagnoses were successfully extracted in 96.95%, and demographic data were extracted in 100% of letters. Data extraction, database upload, data analysis and visualization took 571 seconds (9.51 minutes). Manual data extraction in the categories of diagnoses, intervention, and medications yielded accuracy of the computer algorithm in 94%, 93%, and 93%, respectively. CONCLUSIONS: Semiautomated data extraction from clinic letters into a database can be achieved successfully with a high degree of accuracy and efficiency.