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.

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.

[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.

Three-dimensional printing, holograms, computational modelling, and artificial intelligence for adult congenital heart disease care: an exciting future.

Congenital heart disease (CHD) is often comprised of complex three-dimensional (3D) anatomy that must be well understood to assess the pathophysiological consequences and guide therapy. Thus, detailed cardiac imaging for early detection and planning of interventional and/or surgical treatment is paramount. Advanced technologies have revolutionized diagnostic and therapeutic practice in CHD, thus playing an increasing role in its management. Traditional reliance on standard imaging modalities including echocardiography, cardiac computed tomography (CT) and magnetic resonance imaging (MRI) has been augmented by the use of recent technologies such as 3D printing, virtual reality, augmented reality, computational modelling, and artificial intelligence because of insufficient information available with these standard imaging techniques. This has created potential opportunities of incorporating these technologies into routine clinical practice to achieve the best outcomes through delivery of personalized medicine. In this review, we provide an overview of these evolving technologies and a new approach enabling physicians to better understand their real-world application in adult CHD as a prelude to clinical workflow implementation.

[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.

Coronavirus disease 2019 in adults with congenital heart disease: a position paper from the ESC working group of adult congenital heart disease, and the International Society for Adult Congenital Heart Disease.

We are witnessing an unparalleled pandemic caused by the novel Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) associated with coronavirus disease 2019 (COVID-19). Current data show that SARS-CoV-2 results in mild flu-like symptoms in the majority of healthy and young patients affected. Nevertheless, the severity of COVID-19 respiratory syndrome and the risk of adverse or catastrophic outcomes are increased in patients with pre-existing cardiovascular disease. Patients with adult congenital heart disease (ACHD)-by definition-have underlying cardiovascular disease. Many patients with ACHD are also afflicted with residual haemodynamic lesions such as valve dysfunction, diminished ventricular function, arrhythmias or cyanosis, have extracardiac comorbidities, and face additional challenges regarding pregnancy. Currently, there are emerging data of the effect of COVID-19 on ACHD patients, but many aspects, especially risk stratification and treatment considerations, remain unclear. In this article, we aim to discuss the broad impact of COVID-19 on ACHD patients, focusing specifically on pathophysiology, risk stratification for work, self-isolation, hospitalization, impact on pregnancy, psychosocial health, and longer-term implications for the provision of ACHD care.

Maternal and neonatal complications in women with congenital heart disease: a nationwide analysis.

AIMS: The aim of this study was to provide population-based data on maternal and neonatal complications and outcome in the pregnancies of women with congenital heart disease (CHD). METHODS AND RESULTS: Based on administrative data from one of the largest German Health Insurance Companies (BARMER GEK, ∼9 million members representative for Germany), all pregnancies in women with CHD between 2005 and 2018 were analysed. In addition, an age-matched non-CHD control group was included for comparison and the association between adult CHD (ACHD) and maternal or neonatal outcomes investigated. Overall, 7512 pregnancies occurred in 4015 women with CHD. The matched non-CHD control group included 6502 women with 11 225 pregnancies. Caesarean deliveries were more common in CHD patients (40.5% vs. 31.5% in the control group; P < 0.001). There was no excess mortality. Although the maternal complication rate was low in absolute terms, women with CHD had a significantly higher rate of stroke, heart failure and cardiac arrhythmias during pregnancy (P < 0.001 for all). Neonatal mortality was low but also significantly higher in the ACHD group (0.83% vs. 0.22%; P = 0.001) and neonates to CHD mothers had low/extremely low birth weight or extreme immaturity (<0.001) or required resuscitation and mechanical ventilation more often compared to non-CHD offspring (P < 0.001 for both). On multivariate logistic regression maternal defect complexity, arterial hypertension, heart failure, prior fertility treatment, and anticoagulation with vitamin K antagonists emerged as significant predictors of adverse neonatal outcome (P < 0.05 for all). Recurrence of CHD was 6.1 times higher in infants to ACHD mothers compared to controls (P < 0.0001). CONCLUSIONS: This population-based study illustrates a reassuringly low maternal mortality rate in a highly developed healthcare system. Nevertheless, maternal morbidity and neonatal morbidity/mortality were significantly increased in women with ACHD and their offspring compared to non-ACHD controls highlighting the need of specialized care and pre-pregnancy counselling.

Lack of specialist care is associated with increased morbidity and mortality in adult congenital heart disease: a population-based study.

AIMS: The aim of this study was to provide population-based data on the healthcare provision for adults with congenital heart disease (ACHD) and the impact of cardiology care on morbidity and mortality in this vulnerable population. METHODS AND RESULTS: Based on administrative data from one of the largest German Health Insurance Companies, all insured ACHD patients (<70 years of age) were included. Patients were stratified into those followed exclusively by primary care physicians (PCPs) and those with additional cardiology follow-up between 2014 and 2016. Associations between level of care and outcome were assessed by multivariable/propensity score Cox analyses. Overall, 24 139 patients (median age 43 years, 54.8% female) were included. Of these, only 49.7% had cardiology follow-up during the 3-year period, with 49.2% of patients only being cared for by PCPs and 1.1% having no contact with either. After comprehensive multivariable and propensity score adjustment, ACHD patients under cardiology follow-up had a significantly lower risk of death [hazard ratio (HR) 0.81, 95% confidence interval (CI) 0.67-0.98; P = 0.03) or major events (HR 0.85, 95% CI 0.78-0.92; P < 0.001) compared to those only followed by PCPs. At 3-year follow-up, the absolute risk difference for mortality was 0.9% higher in ACHD patients with moderate/severe complexity lesions cared by PCPs compared to those under cardiology follow-up. CONCLUSION: Cardiology care compared with primary care is associated with superior survival and lower rates of major complications in ACHD. It is alarming that even in a high resource setting with well-established specialist ACHD care approximately 50% of contemporary ACHD patients are still not linked to regular cardiac care. Almost all patients had at least one contact with a PCP during the study period, suggesting that opportunities to refer patients to cardiac specialists were missed at PCP level. More efforts are required to alert PCPs and patients to appropriate ACHD care.

Emergency department management of patients with adult congenital heart disease: a consensus paper from the ESC Working Group on Adult Congenital Heart Disease, the European Society for Emergency Medicine (EUSEM), the European Association for Cardio-Thoracic Surgery (EACTS), and the Association for Acute Cardiovascular Care (ACVC).

Adult congenital heart disease (ACHD) patients represent a growing population with increasing use of acute emergency department (ED) care. Providing comprehensive ED care necessitates an understanding of the most common clinical scenarios to improve morbidity and mortality in this population. The aim of this position document is to provide a consensus regarding the management of the most common clinical scenarios of ACHD patients presenting to the ED.

Late outcome, therapy and systemic ventricular function in patients with a systemic right ventricle: data of the German National Register for Congenital Heart Defects.

BACKGROUND: Adults with systemic right ventricle have a significant risk for long-term complications such as arrhythmias or heart failure. METHODS: A nationwide retrospective study based on the German National Register for Congenital Heart Disease was performed. Patients with transposition of the great arteries after atrial switch operation or congenitally corrected TGA were included. RESULTS: Two hundred and eight-five patients with transposition of the great arteries after atrial switch operation and 95 patients with congenitally corrected transposition of the great arteries were included (mean age 33 years). Systolic function of the systemic ventricle was moderately or severely reduced in 25.5 % after atrial switch operation and in 35.1% in patients with congenitally corrected transposition. Regurgitation of the systemic atrioventricular valve was present in 39.5% and 43.2% of the cases, respectively. A significant percentage of patients also had a history for supraventricular or ventricular arrhythmias. However, polypharmacy of cardiovascular drugs was rare (4.5%) and 38.5 % of the patients did not take any cardiovascular medication. The amount of cardiovascular drugs taken was associated with NYHA class as well as systemic right ventricular dysfunction. Patients with congenitally corrected transposition were more likely to receive pharmacological treatment than patients after atrial switch operation. CONCLUSION: A significant portion of patients with systemic right ventricle suffer from a relevant systemic ventricular dysfunction, systemic atrioventricular valve regurgitation, and arrhythmias. Despite this, medication for heart failure treatment is not universally used in this cohort. This emphasises the need for randomised trials in patient with systemic right ventricle.

Heart Failure Results in Inspiratory Muscle Dysfunction Irrespective of Left Ventricular Ejection Fraction.

BACKGROUND: Exercise intolerance in heart failure with reduced ejection fraction (HFrEF) or heart failure with preserved ejection fraction (HFpEF) results from both cardiac dysfunction and skeletal muscle weakness. Respiratory muscle dysfunction with restrictive ventilation disorder may be present irrespective of left ventricular ejection fraction and might be mediated by circulating pro-inflammatory cytokines. OBJECTIVE: To determine lung and respiratory muscle function in patients with HFrEF/HFpEF and to determine its associations with exercise intolerance and markers of systemic inflammation. METHODS: Adult patients with HFrEF (n = 22, 19 male, 61 ± 14 years) and HFpEF (n = 8, 7 male, 68 ± 8 years) and 19 matched healthy control subjects underwent spirometry, measurement of maximum mouth occlusion pressures, diaphragm ultrasound, and recording of transdiaphragmatic and gastric pressures following magnetic stimulation of the phrenic nerves and the lower thoracic nerve roots. New York Heart Association (NYHA) class and 6-min walking distance (6MWD) were used to quantify exercise intolerance. Levels of circulating interleukin 6 (IL-6) and tumor necrosis factor-α (TNF-α) were measured using ELISAs. RESULTS: Compared with controls, both patient groups showed lower forced vital capacity (FVC) (p < 0.05), maximum inspiratory pressure (PImax), maximum expiratory pressure (PEmax) (p < 0.05), diaphragm thickening ratio (p = 0.01), and diaphragm strength (twitch transdiaphragmatic pressure in response to supramaximal cervical magnetic phrenic nerve stimulation) (p = 0.01). In patients with HFrEF, NYHA class and 6MWD were both inversely correlated with FVC, PImax, and PEmax. In those with HFpEF, there was an inverse correlation between amino terminal pro B-type natriuretic peptide levels and FVC (r = -0.77, p = 0.04). In all HF patients, IL-6 and TNF-α were statistically related to FVC. CONCLUSIONS: Irrespective of left ventricular ejection fraction, HF is associated with respiratory muscle dysfunction, which is associated with increased levels of circulating IL-6 and TNF-α.

Current use and safety of novel oral anticoagulants in adults with congenital heart disease: results of a nationwide analysis including more than 44 000 patients.

AIMS: To evaluate the use of novel oral anticoagulants (NOACs) compared with vitamin K antagonists (VKAs) in adult congenital heart disease (ACHD) and assess outcome in a nationwide analysis. METHODS AND RESULTS: Using data from one of Germany's largest Health Insurers, all ACHD patients treated with VKAs or NOACs were identified and changes in prescription patterns were assessed. Furthermore, the association between anticoagulation regimen and complications including mortality was studied. Between 2005 and 2018, the use of oral anticoagulants in ACHD increased from 6.3% to 12.4%. Since NOACs became available their utilization increased constantly, accounting for 45% of prescribed anticoagulants in ACHD in 2018. Adult congenital heart disease patients on NOACs had higher thromboembolic (3.8% vs. 2.8%), MACE (7.8% vs. 6.0%), bleeding rates (11.7% vs. 9.0%), and all-cause mortality (4.0% vs. 2.8%; all P < 0.05) after 1 year of therapy compared with VKAs. After comprehensive adjustment for patient characteristics, NOACs were still associated with increased risk of MACE (hazard rate-HR 1.22; 95% CI 1.09-1.36) and increased all-cause mortality (HR 1.43; 95% CI 1.24-1.65; both P < 0.001), but also bleeding (HR 1.16; 95% CI 1.04-1.29; P = 0.007) during long-term follow-up. CONCLUSION: Despite the lack of prospective studies in ACHD, NOACs are increasingly replacing VKAs and now account for almost half of all oral anticoagulant prescriptions. Particularly, NOACs were associated with excess long-term risk of MACE, and mortality in this nationwide analysis, emphasizing the need for prospective studies before solid recommendations for their use in ACHD can be provided.

Utility of deep learning networks for the generation of artificial cardiac magnetic resonance images in congenital heart disease.

BACKGROUND: Deep learning algorithms are increasingly used for automatic medical imaging analysis and cardiac chamber segmentation. Especially in congenital heart disease, obtaining a sufficient number of training images and data anonymity issues remain of concern. METHODS: Progressive generative adversarial networks (PG-GAN) were trained on cardiac magnetic resonance imaging (MRI) frames from a nationwide prospective study to generate synthetic MRI frames. These synthetic frames were subsequently used to train segmentation networks (U-Net) and the quality of the synthetic training images, as well as the performance of the segmentation network was compared to U-Net-based solutions trained entirely on patient data. RESULTS: Cardiac MRI data from 303 patients with Tetralogy of Fallot were used for PG-GAN training. Using this model, we generated 100,000 synthetic images with a resolution of 256 × 256 pixels in 4-chamber and 2-chamber views. All synthetic samples were classified as anatomically plausible by human observers. The segmentation performance of the U-Net trained on data from 42 separate patients was statistically significantly better compared to the PG-GAN based training in an external dataset of 50 patients, however, the actual difference in segmentation quality was negligible (< 1% in absolute terms for all models). CONCLUSION: We demonstrate the utility of PG-GANs for generating large amounts of realistically looking cardiac MRI images even in rare cardiac conditions. The generated images are not subject to data anonymity and privacy concerns and can be shared freely between institutions. Training supervised deep learning segmentation networks on this synthetic data yielded similar results compared to direct training on original patient data.

Pharmacological therapy in adult congenital heart disease: growing need, yet limited evidence.

Congenital heart disease (CHD) is the most common inborn defect. Due to advances in paediatric care, surgical, and catheter procedures the number of adults with CHD has grown remarkably in recent years. Most of these patients, however, have residua from their original operation/s and require life-long care, many of them are subjected to further haemodynamic and electrophysiological interventions during adulthood. While such re-do surgical or catheter interventions together with device therapy and transplantation play a key therapeutic role, increasingly, adults with CHD require drug therapy for late complications namely heart failure (HF), arrhythmias, pulmonary and systemic hypertension, thromboembolic events, etc. Unlike other cardiovascular areas, drug therapy in adult CHD is based on scarce clinical data and remains largely empiric. Consequently, pharmacological therapies are individualized to ameliorate patients' symptoms and/or degree of haemodynamic impairment. Thus far, recommendations have been difficult to make and formalized guidelines on drug therapy are lacking. We review herewith the rationale, limited evidence and knowledge gaps regarding drug therapy in this growing cardiovascular field and discuss pharmacotherapy options in specific conditions namely HF, arrhythmias, thrombosis, pulmonary arterial hypertension, contraception, and pregnancy.

Machine learning algorithms estimating prognosis and guiding therapy in adult congenital heart disease: data from a single tertiary centre including 10 019 patients.

AIMS: To assess the utility of machine learning algorithms on estimating prognosis and guiding therapy in a large cohort of patients with adult congenital heart disease (ACHD) or pulmonary hypertension at a single, tertiary centre. METHODS AND RESULTS: We included 10 019 adult patients (age 36.3 ± 17.3 years) under follow-up at our institution between 2000 and 2018. Clinical and demographic data, ECG parameters, cardiopulmonary exercise testing, and selected laboratory markers where collected and included in deep learning (DL) algorithms. Specific DL-models were built based on raw data to categorize diagnostic group, disease complexity, and New York Heart Association (NYHA) class. In addition, models were developed to estimate need for discussion at multidisciplinary team (MDT) meetings and to gauge prognosis of individual patients. Overall, the DL-algorithms-based on over 44 000 medical records-categorized diagnosis, disease complexity, and NYHA class with an accuracy of 91.1%, 97.0%, and 90.6%, respectively in the test sample. Similarly, patient presentation at MDT-meetings was predicted with a test sample accuracy of 90.2%. During a median follow-up time of 8 years, 785 patients died. The automatically derived disease severity-score derived from clinical information was related to survival on Cox analysis independently of demographic, exercise, laboratory, and ECG parameters. CONCLUSION: We present herewith the utility of machine learning algorithms trained on large datasets to estimate prognosis and potentially to guide therapy in ACHD. Due to the largely automated process involved, these DL-algorithms can easily be scaled to multi-institutional datasets to further improve accuracy and ultimately serve as online based decision-making tools.

Systemic Right Ventricle in Adults With Congenital Heart Disease: Anatomic and Phenotypic Spectrum and Current Approach to Management.

The systemic right ventricle (SRV) is commonly encountered in congenital heart disease representing a distinctly different model in terms of its anatomic spectrum, adaptation, clinical phenotype, and variable, but overall guarded prognosis. The most common clinical scenarios where an SRV is encountered are complete transposition of the great arteries with previous atrial switch repair, congenitally corrected transposition of the great arteries, double inlet right ventricle mostly with previous Fontan palliation, and hypoplastic left heart syndrome palliated with the Norwood-Fontan protocol. The reasons for the guarded prognosis of the SRV in comparison with the systemic left ventricle are multifactorial, including distinct fibromuscular architecture, shape and function, coronary artery supply mismatch, intrinsic abnormalities of the tricuspid valve, intrinsic or acquired conduction abnormalities, and varied SRV adaptation to pressure or volume overload. Management of the SRV remains an ongoing challenge because SRV dysfunction has implications on short- and long-term outcomes for all patients irrespective of underlying cardiac morphology. SRV dysfunction can be subclinical, underscoring the need for tertiary follow-up and timely management of target hemodynamic lesions. Catheter interventions and surgery have an established role in selected patients. Cardiac resynchronization therapy is increasingly used, whereas pharmacological therapy is largely empirical. Mechanical assist device and heart transplantation remain options in end-stage heart failure when other management strategies have been exhausted. The present report focuses on the SRV with its pathological subtypes, pathophysiology, clinical features, current management strategies, and long-term sequelae. Although our article touches on issues applicable to neonates and children, its main focus is on adults with SRV.

Impact of Simulated Hyperventilation and Periodic Breathing on Sympatho-Vagal Balance and Hemodynamics in Patients with and without Heart Failure.

BACKGROUND: The effects of hyperventilation and hyperventilation in the context of periodic breathing (PB) on sympatho-vagal balance (SVB) and hemodynamics in conditions of decreased cardiac output and feedback resetting, such as heart failure (HF) or pulmonary arterial hypertension (PAH), are not completely understood. OBJECTIVES: To investigate the effects of voluntary hyperventilation and simulated PB on hemodynamics and SVB in healthy subjects, in patients with systolic HF and reduced or mid-range ejection fraction (HFrEF and HFmrEF) and in patients with PAH. METHODS: Study participants (n = 20 per group) underwent non-invasive recording of diastolic blood pressure, heart rate variability (HRV), baroreceptor-reflex sensitivity (BRS), total peripheral resistance index (TPRI) and cardiac index (CI). All measurements were performed at baseline, during voluntary hyperventilation and during simulated PB with different length of the hyperventilation phase. RESULTS: In healthy subjects, voluntary hyperventilation led to a 50% decrease in the mean BRS slope and a 29% increase in CI compared to baseline values (p < 0.01 and p < 0.05). Simulated PB did not alter TPRI or CI and showed heterogeneous effects on BRS, but analysis of dPBV revealed decreased sympathetic drive in healthy volunteers depending on PB cycle length (p < 0.05). In HF patients, hyperventilation did not affect BRS and TPRI but increased the CI by 10% (p < 0.05). In HF patients, simulated PB left all of these parameters unaffected. In PAH patients, voluntary hyperventilation led to a 15% decrease in the high-frequency component of HRV (p < 0.05) and a 5% increase in CI (p < 0.05). Simulated PB exerted neutral effects on both SVB and hemodynamic parameters. CONCLUSIONS: Voluntary hyperventilation was associated with sympathetic predominance and CI increase in healthy volunteers, but only with minor hemodynamic and SVB effects in patients with HF and PAH. Simulated PB had positive effects on SVB in healthy volunteers but neutral effects on SVB and hemodynamics in patients with HF or PAH.

Immediate and Midterm Cardiac Remodeling After Surgical Pulmonary Valve Replacement in Adults With Repaired Tetralogy of Fallot: A Prospective Cardiovascular Magnetic Resonance and Clinical Study.

BACKGROUND: Pulmonary valve replacement (PVR) in patients with repaired tetralogy of Fallot provides symptomatic benefit and right ventricular (RV) volume reduction. However, data on the rate of ventricular structural and functional adaptation are scarce. We aimed to assess immediate and midterm post-PVR changes and predictors of reverse remoeling. METHODS: Fifty-seven patients with repaired tetralogy of Fallot (age ≥16 y; mean age, 35.8±10.1 y; 38 male) undergoing PVR were prospectively recruited for cardiovascular magnetic resonance performed before PVR (pPVR), immediately after PVR (median, 6 d), and midterm after PVR (mPVR; median, 3 y). RESULTS: There were immediate and midterm reductions in indexed RV end-diastolic volumes and RV end-systolic volumes (RVESVi) (indexed RV end-diastolic volume pPVR versus immediately after PVR versus mPVR, 156.1±41.9 versus 104.9±28.4 versus 104.2±34.4 mL/m2; RVESVi pPVR versus immediately after PVR versus mPVR, 74.9±26.2 versus 57.4±22.7 versus 50.5±21.7 mL/m2; P<0.01). Normal postoperative diastolic and systolic RV volumes (the primary end point) achieved in 70% of patients were predicted by a preoperative indexed RV end-diastolic volume ≤158 mL/m2 and RVESVi ≤82 mL/m2. RVESVi showed a progressive decrease from baseline to immediate to midterm follow-up, indicating ongoing intrinsic RV functional improvement after PVR. Left ventricular ejection fraction improved (pPVR versus mPVR, 59.4±7.6% versus 61.9±6.8%; P<0.01), and right atrial reverse remodeling occurred (pPVR versus mPVR, 15.2±3.4 versus 13.8±3.6 cm2/m2; P<0.01). Larger preoperative RV outflow tract scar was associated with a smaller improvement in post-PVR RV/left ventricular ejection fraction. RV ejection fraction and peak oxygen uptake predicted mortality (P=0.03) over a median of 9.5 years of follow-up. CONCLUSIONS: Significant right heart structural reverse remodeling takes place immediately after PVR, followed by a continuing process of further biological remodeling manifested by further reduction in RVESVi. PVR before RVESVi reaches 82 mL/m2 confers optimal chances of normalization of RV function.

Predictors of Death in Contemporary Adult Patients With Eisenmenger Syndrome: A Multicenter Study.

BACKGROUND: Eisenmenger syndrome is associated with substantial morbidity and mortality. There is no consensus, however, on mortality risk stratification. We aimed to investigate survival and predictors of death in a large, contemporary cohort of Eisenmenger syndrome patients. METHODS: In a multicenter approach, we identified adults with Eisenmenger syndrome under follow-up between 2000 and 2015. We examined survival and its association with clinical, electrocardiographic, echocardiographic, and laboratory parameters. RESULTS: We studied 1098 patients (median age, 34.4 years; range, 16.1-84.4 years; 65.1% female; 31.9% with Down syndrome). The majority had a posttricuspid defect (n=643, 58.6%), followed by patients with a complex (n=315, 28.7%) and pretricuspid lesion (n=140, 12.7%). Over a median follow-up of 3.1 years (interquartile range, 1.4-5.9), allowing for 4361.6 patient-years observation, 278 patients died and 6 underwent transplantation. Twelve parameters emerged as significant predictors of death on univariable analysis. On multivariable Cox regression analysis, only age (hazard ratio [HR], 1.41/10 years; 95% confidence interval [CI], 1.24-1.59; P<0.001), pretricuspid shunt (HR, 1.56; 95% CI, 1.02-2.39; P=0.041), oxygen saturation at rest (HR, 0.53/10%; 95% CI, 0.43-0.65; P<0.001), presence of sinus rhythm (HR, 0.53; 95% CI, 0.32-0.88; P=0.013), and presence of pericardial effusion (HR, 2.41; 95% CI, 1.59-3.66; P<0.001) remained significant predictors of death. CONCLUSIONS: There is significant premature mortality among contemporary adults with Eisenmenger syndrome. We report, herewith, a multivariable mortality risk stratification model based on 5 simple, noninvasive predictors of death in this population.

Past and current cause-specific mortality in Eisenmenger syndrome.

AIMS: Eisenmenger syndrome (ES) is associated with considerable morbidity and mortality. Therapeutic strategies have changed during the 2000s in conjunction with an emphasis on specialist follow-up. The aim of this study was to determine the cause-specific mortality in ES and evaluate any relevant changes between 1977 and 2015. METHODS AND RESULTS: This is a retrospective, descriptive multicentre study. A total of 1546 patients (mean age 38.7 ± 15.4 years; 36% male) from 13 countries were included. Cause-specific mortality was examined before and after July 2006, 'early' and 'late', respectively. Over a median follow-up of 6.1 years (interquartile range 2.1-21.5 years) 558 deaths were recorded; cause-specific mortality was identified in 411 (74%) cases. Leading causes of death were heart failure (34%), infection (26%), sudden cardiac death (10%), thromboembolism (8%), haemorrhage (7%), and peri-procedural (7%). Heart failure deaths increased in the 'late' relative to the 'early' era (P = 0.032), whereas death from thromboembolic events and death in relation to cardiac and non-cardiac procedures decreased (P = 0.014, P = 0.014, P = 0.004, respectively). There was an increase in longevity in the 'late' vs. 'early' era (median survival 52.3 vs. 35.2 years, P < 0.001). CONCLUSION: The study shows that despite changes in therapy, care, and follow-up of ES in tertiary care centres, all-cause mortality including cardiac remains high. Patients from the 'late' era, however, die later and from chronic rather than acute cardiac causes, primarily heart failure, whereas peri-procedural and deaths due to haemoptysis have become less common. Lifelong vigilance in tertiary centres and further research for ES are clearly needed.