Cyanotic Nephropathy in an Adult Patient with Eisenmenger Syndrome: A Case Report and Literature Review.

INTRODUCTION: Cyanotic nephropathy, a rare disease characterized by proteinuria, decreased estimated glomerular filtration rate, thrombocytopenia, polycythemia, and hyperuricemia, may occasionally be secondary to cyanotic congenital heart disease (CHD). There are currently no detailed diagnostic criteria or treatments for cyanotic nephropathy, owing to its extremely low incidence. Eisenmenger syndrome (ES) was initially defined by Paul Wood in pathophysiologic terms as "pulmonary hypertension (PH) at the systemic level, caused by a high pulmonary vascular resistance, with a reversed or bidirectional shunt at the aorto-pulmonary, ventricular, or atrial level." It typically develops in the presence of large, unrepaired atrial or ventricular septal defects, arterial shunts, or complex forms of CHD and is the most severe hemodynamic phenotype of pulmonary arterial hypertension associated with CHD. This study aimed to outline the case of an ES patient who developed cyanotic nephropathy and successfully achieved clinical remission through primary disease treatment and symptomatic management. Overall, this case expands our understanding of cyanotic nephropathy and lays a theoretical reference for the treatment of ES. CASE PRESENTATION: A 33-year-old Chinese female attended the outpatient department with abnormal urine test results over the past two and a half years. Following a comprehensive medical history collection, she underwent the necessary tests. Cardiac color ultrasound displayed a significant widening of the pulmonary artery and PH (severe), as well as mild tricuspid regurgitation and patent ductus arteriosus. The results of the kidney biopsy, combined with clinical findings, suggested a high risk of polycythemia-related kidney disease. She was eventually diagnosed with cyanotic nephropathy and ES. Her symptoms were relieved following symptomatic treatment, such as the administration of ambrisentan, febuxostat, and home oxygen therapy. Her follow-up visit at 6 months demonstrated improvements in hyperuricemia and a significant increase in physical strength. CONCLUSION: Cyanotic nephropathy is a rare condition in adults. Kidney biopsy remains the gold standard of diagnosis for various nephropathies. Active treatment of CHD and alleviating hypoxia may be pivotal for the treatment of cyanotic nephropathy.

Lung infarction secondary to infected pulmonary arterial thrombosis in a patient with Eisenmenger's syndrome.

A case is presented where a patient with Eisenmenger's syndrome is successfully treated for infection of chronic pulmonary arterial thrombosis with good effect. The evidence for antibiotic and anticoagulant therapy in this patient group is discussed.

Eisenmenger Syndrome: A Revisit of a Hidden but Catastrophic Disease.

BACKGROUND: Eisenmenger syndrome (ES) is a rare condition seen in children with congenital heart disease (CHD). It is characterized by raised pulmonary vascular resistance (PVR) arising from a shunt reversal with the presence of desaturated blood in the systemic circulation. Proper timing and early intervention in children with congenital heart disease have made the syndrome a rare occurrence. However, this cannot be said in developing countries where facilities for the diagnosis and management of children with congenital heart disease are not optimal. OBJECTIVES: The aim of this narrative review is to highlight the importance of early diagnosis and to review the new techniques in the evaluation of children with ES. It also highlights in a snapshot the state of management of ES in a developing country. METHODS: A search for published data on ES was done through several search engines such as Pubmed, google scholar citation, systematic reviews, and meta-analysis. This involves research done over the past 30 years. Keywords such as Eisenmenger'syndrome, 'congenital heart defect', 'Pulmonary hypertension', 'catherterization', 'echocardiography', and children' were used. RESULTS: This review shows the new technique in the diagnosis, aetio-pathogenesis, management and treatment of children with ES in-depth descriptive analysis and new advances in the management of children with ES. CONCLUSION: Eisenmenger syndrome is a preventable disease that can be curbed by early diagnosis and treatment of children with congenital heart disease, especially in the developing world.

CONTEXTE: Le syndrome d'Eisenmenger (SE) est une affection rare observée chez les enfants atteints de cardiopathie congénitale. Il se caractérise par une augmentation de la résistance vasculaire pulmonaire (RVP) due à l'inversion d'un shunt et à la présence de sang désaturé dans la circulation systémique. Le syndrome est devenu rare chez les enfants atteints de cardiopathie congénitale grâce à un choix judicieux du moment et à une intervention précoce. Toutefois, il n'en va pas de même dans les pays en développement où les moyens de diagnostic et de prise en charge des enfants atteints de cardiopathies congénitales ne sont pas optimaux. OBJECTIFS: L'objectif de cette revue narrative est de souligner l'importance d'un diagnostic précoce et de passer en revue les nouvelles techniques d'évaluation des enfants atteints de SE. Elle met également en lumière, sous forme d'un instantané, l'état de la prise en charge de l'ES dans un pays en développement. MÉTHODES: Une recherche de données publiées sur l'ES a été effectuée à l'aide de plusieurs moteurs de recherche tels que Pubmed, google scholar citation, revues systématiques et méta-analyses. Il s'agit de recherches effectuées au cours des 30 dernières années. Des mots clés tels que "syndrome d'Eisenmenger", "malformation cardiaque congénitale", "hypertension pulmonaire", "cathétérisme", "échocardiographie" et "enfants" ont été utilisés. RÉSULTATS: Cette revue présente les nouvelles techniques de diagnostic, d'étio-pathogénie, de prise en charge et de traitement des enfants atteints de SE, ainsi qu'une analyse descriptive approfondie et les nouvelles avancées dans la prise en charge des enfants atteints de SE. CONCLUSION: Le syndrome d'Eisenmenger est une maladie évitable qui peut être enrayée par un diagnostic et un traitement précoces des enfants atteints de cardiopathies congénitales, en particulier dans les pays en développement. Mots-clés: Syndrome d'Eisenmenger; Enfants; Cardiopathie congénitale; Hhypertension pulmonaire; Prise en charge.

Management and outcomes of pulmonary artery hypertension and Eisenmenger syndrome during pregnancy: a prospective observational cohort study.

OBJECTIVES: Maternal-fetal morbidity and mortality among pregnant women with pulmonary artery hypertension (PAH) and Eisenmenger syndrome are unacceptable, and management decision-making in these clinical scenarios remains debatable. This study aimed to compare and analyse clinical characteristics, management and pregnancy outcomes in PAH and Eisenmenger syndrome. DESIGN: Prospective observational cohort study. SETTINGS: A large tertiary care university hospital. PATIENTS: Thirty patients with pulmonary artery hypertension and 20 patients with Eisenmenger syndrome. METHODS: Data pertaining to clinical characteristics, anaesthetic, medical and obstetric management, and outcomes in pregnancy complicated by PAH and Eisenmenger syndrome were collected between July 2020 and June 2022. Each treating unit followed its management protocol in consultation with the multidisciplinary team. MAIN OUTCOME MEASURES: Maternal mortality and morbidity. RESULTS: Maternal mortality was lower in the PAH group (6.6% versus 15%; p = 0.33). All mortalities were in the postpartum period. The incidence of new-onset or exacerbation of heart failure (23.3% versus 60%; p = 0.009) and hypoxaemia (13.3% versus 50%; p = 0.005) were significantly lower in the PAH group. In the Eisenmenger syndrome group, a significantly higher number of women received pulmonary hypertension and heart failure medications. Prematurity and neonatal intensive care unit admission were frequently noticed in Eisenmenger syndrome, whereas perinatal mortality, birthweight and APGAR score were comparable. CONCLUSIONS: Fetomaternal outcomes are inferior in Eisenmenger syndrome compared with PAH and are either lower or comparable to those reported from contemporary cohorts of developed nations.

Characteristics, treatments and survival of pulmonary arterial hypertension associated with congenital heart disease in China: Insights from a national multicenter prospective registry.

BACKGROUND: The purpose of this registry was to provide insights into the characteristics, treatments and survival of patients with PAH-CHD in China. METHODS: Patients diagnosed with PAH-CHD were enrolled in this national multicenter prospective registry. Baseline and follow-up data on clinical characteristics, PAH-targeted treatments and survival were collected. RESULTS: A total of 1060 PAH-CHD patients (mean age 31 years; 67.9% females) were included, with Eisenmenger syndrome (51.5%) being the most common form and atrial septal defects (37.3%) comprising the most frequent underlying defect. Approximately 33.0% of the patients were in World Health Organization functional class III to IV. The overall mean pulmonary arterial pressure and pulmonary vascular resistance were 67.1 (20.1) mm Hg and 1112.4 (705.9) dyn/s/cm5, respectively. PAH-targeted therapy was utilized in 826 patients (77.9%), and 203 patients (19.1%) received combination therapy. The estimated 1-, 3-, 5-, and 10-year survival rates of the overall cohort were 96.9%, 92.9%, 87.6% and 73.0%, respectively. Patients received combination therapy had significantly better survival than those with monotherapy (p = 0.016). NT-proBNP >1400 pg/ml, SvO2 ≤ 65% and Borg dyspnea index ≥ 3 and PAH-targeted therapy were independent predictors of mortality. Hemoglobin > 160g/L was a unique predictor for mortality in Eisenmenger syndrome. CONCLUSIONS: Chinese PAH-CHD patients predominantly exhibit Eisenmenger syndrome and have significantly impaired exercise tolerance and right ventricular function at diagnosis, which are closely associated with long-term survival. PAH-targeted therapy including combination therapy showed a favorable effect on survival in PAH-CHD. The long-term survival of Chinese CHD-PAH patients remains to be improved.

Multidisciplinary approach for the management of term pregnancy complicated by Eisenmenger syndrome.

Pregnancy in patients with Eisenmenger syndrome (ES) is associated with high maternal mortality rates of 30%‒50%, or even up to 65% in the case of a cesarean section (Yuan, 2016). Here, we report a case of term pregnancy complicated with ES and severe pulmonary artery hypertension (PAH), which was managed by a multidisciplinary team (MDT) and resulted in an uncomplicated delivery via elective cesarean section. The goal of this study is to emphasize the importance of multidisciplinary approach in the management of pregnancy with ES, which can profoundly improve maternal and infant outcomes.

Multidisciplinary approach for the management of term pregnancy complicated by Eisenmenger syndrome / 浙江大学学报（英文版）（B辑：生物医学和生物技术）

Pregnancy in patients with Eisenmenger syndrome (ES) is associated with high maternal mortality rates of 30%‒50%, or even up to 65% in the case of a cesarean section (Yuan, 2016). Here, we report a case of term pregnancy complicated with ES and severe pulmonary artery hypertension (PAH), which was managed by a multidisciplinary team (MDT) and resulted in an uncomplicated delivery via elective cesarean section. The goal of this study is to emphasize the importance of multidisciplinary approach in the management of pregnancy with ES, which can profoundly improve maternal and infant outcomes.

Successful Bronchial Artery Embolization after Stabilization with Nitric Oxide for the Treatment of Haemoptysis in a Patient with Eisenmenger Syndrome.

Hemoptysis, accompanying various chronic lung diseases, some systemic diseases, infections, structural heart diseases, or syndromes is a clinical condition that is quite mortal when it is massive. Hemoptysis is a common complication of Eisenmenger syndrome. Its frequency increases with age. It is an important cause of mortality in patients with Eisenmenger syndrome. Embolization of systemic-pulmonary collateral arteries is an effective method in the treatment of hemoptysis in eligible patients with Eisenmenger syndrome. In this case report, a patient with Eisenmenger syndrome, developed due to large patent ductus arteriosus, received dual pulmonary arterial hypertension-specific treatment, after the development of hemoptysis, medical stabilization was provided with initial inhaled nitric oxide therapy and then treated with bronchial artery embolization without complications is presented.

Challenges in managing a critically ill patient with decompensated Eisenmenger syndrome.

Eisenmenger syndrome (ES) is the most severe form of pulmonary arterial hypertension and is associated with congenital heart disease. ES itself is a challenging condition to manage, further compounded if the patient is critically ill and acutely decompensated. We share our experience of managing a critically ill adult patient with ES who presented with acute decompensation due to sepsis.

Eisenmenger Syndrome: JACC State-of-the-Art Review.

Although major breakthroughs in the field of pediatric cardiology, cardiac surgery, intervention, and overall care improved the outlook of congenital heart disease, Eisenmenger syndrome (ES) is still encountered and remains a complex clinical entity with multisystem involvement, including secondary erythrocytosis, increased thrombotic and bleeding diathesis, high arrhythmogenic risk, progressive heart failure, and premature death. Clearly, care for ES is best delivered in multidisciplinary expert centers. In this review, we discuss the considerable recent progress in understanding the complex pathophysiology of ES, means of prognostication, and improvement in clinical outcomes achieved with pulmonary arterial hypertension-targeted therapies. Additionally, we delineate areas of uncertainty in various aspects of care, discuss gaps in current evidence, and review current status in less privileged countries and propose initiatives to reduce disease burden. Finally, we propose the application of emerging technologies to enhance the delivery and quality of health care related to ES and beyond.

Pulmonary Hypertension in Adults with Congenital Heart Disease.

Pulmonary arterial hypertension related to congenital heart disease (PAH-CHD) affects 5% to 10% of adults with CHD and is associated with significant morbidity and mortality. PAH-CHD develops as a consequence of intracardiac or extracardiac systemic-to-pulmonary shunts that lead to pulmonary vascular remodeling through a pathologic process that is similar to other causes of PAH. Eisenmenger syndrome is the most severe phenotype of PAH-CHD and is characterized by severe elevation in pulmonary vascular resistance, with shunt reversal causing hypoxemia and central cyanosis. The primary management strategy for most patients with PAH-CHD is medical therapy, although defect closure is considered in select cases.

Evaluation and Management of Pulmonary Arterial Hypertension in Congenital Heart Disease.

Pulmonary arterial hypertension is a common complication in patients with congenital heart disease (CHD), aggravating the natural course of the underlying defect. Pulmonary arterial hypertension (PAH) has a multifactorial etiology depending on the size and nature of the cardiac defect as well as environmental factors. Although progress has been made in disease-targeting therapy using pulmonary vasodilators to treat Eisenmenger syndrome, important gaps still exist in the evaluation and management of adult patients with CHD-associated PAH (PAH-CHD) who have systemic-to-pulmonary shunts. The choice of interventional, medical, or both types of therapy is an ongoing dilemma that requires further data. This review focuses on the evaluation and management of PAH-CHD in the contemporary era.

Preventing disease progression in Eisenmenger syndrome.

Introduction: Eisenmenger syndrome describes a condition in which a congenital heart defect has caused severe pulmonary vascular disease, resulting in reversed (right-left) or bidirectional shunting and chronic cyanosis.Areas covered: In this paper, the progression of congenital heart defects to Eisenmenger syndrome, including early screening, diagnosis and operability are covered. The mechanisms of disease progression in Eisenmenger syndrome and management strategies to combat this, including the role of pulmonary arterial hypertension therapies, are also discussed.Expert opinion/commentary: Patients with congenital heart disease (CHD) are at increased risk of developing pulmonary arterial hypertension with Eisenmenger syndrome being its extreme manifestation. All CHD patients should be regularly assessed for pulmonary hypertension. Once Eisenmenger syndrome develops, shunt closure should be avoided. The clinical manifestations of Eisenmenger syndrome are driven by the systemic effects of the pulmonary hypertension, congenital defect and long-standing cyanosis. Expert care is essential for avoiding pitfalls and preventing disease progression in this severe chronic condition, which is associated with significant morbidity and mortality. Pulmonary arterial hypertension therapies have been used alongside supportive care to improve the quality of life, exercise tolerance and the outcome of these patients, although the optimal timing for their introduction and escalation remains uncertain.

Síndrome de Eisenmenger y embarazo - reporte de 2 casos / Eisenmenger's and pregnancy syndrome - 2 case report

RESUMEN El síndrome de Eisenmenger es una patología del sistema vascular pulmonar, que se caracteriza por un incremento de las resistencias en los vasos sanguíneos pulmonares, en pacientes con antecedentes de cardiopatía con comunicación entre la circulación pulmonar y circulación sistémica. Este síndrome en la mujer embarazada representa un alto índice de morbilidad y mortalidad tanto para la madre como para el feto; los síntomas que presentan surgen como consecuencia de los cambios fisiológicos en el sistema cardiovascular y hematopoyético. Es un desafío para el obstetra el manejo de estas pacientes idealmente debe ofrecerse asesoría preconcepcional, y valoración por cardiología; si no es posible, se realizará evaluación del riesgo desde el primer control prenatal. El mejor tratamiento consiste en oxigenoterapia, medicamentos vasodilatadores, y anticoagulantes, logrando disminuir el porcentaje de pobres desenlaces materno-fetales. Es de vital importancia definir el momento del nacimiento con el fin de tomar las medidas terapéuticas necesarias para evitar complicaciones, además se requiere de un manejo multidisciplinario, incluido el apoyo por una unidad de cuidado intensivo dado la alta probabilidad de complicaciones asociadas a esta patología.

ABSTRACT Eisenmenger syndrome is a pathology of the pulmonary vascular system, which is characterized by an increase in resistance of the pulmonary blood vessels in patients with a history of heart disease with communication between the pulmonary circulation and the systemic circulation. This syndrome in pregnant women represents a high morbidity and mortality rate for both the mother and the fetus. The symptoms that arise are a consequence of the physiological changes in the cardiovascular and hematopoietic system. The management of these patients is a challenge for the obstetrician; ideally, preconception counseling and cardiology assessment should be offered and if this is not possible, risk assessment should be carried out from the first prenatal control. The best treatment consists of oxygen therapy, vasodilating agents, and anticoagulant medications with the goal of reducing the percentage of poor maternal-fetal outcomes. It is vitally important to define the time of birth in order to take the necessary therapeutic measures to avoid complications. In addition, multidisciplinary management and an intensive care unit are required due to the high probability of complications associated with this pathology.

Simple equations to predict the effects of veno-venous ECMO in decompensated Eisenmenger syndrome.

Adult patients with uncorrected congenital heart diseases and chronic intracardiac shunt may develop Eisenmenger syndrome (ES) due to progressive increase of pulmonary vascular resistance, with significant morbidity and mortality. Acute decompensation of ES in conditions promoting a further increase of pulmonary vascular resistance, such as pulmonary embolism or pneumonia, can precipitate major arterial hypoxia and death. In such conditions, increasing systemic oxygenation with veno-venous extracorporeal membrane oxygenation (VV-ECMO) could be life-saving, serving as a bridge to treat a potential reversible cause for the decompensation, or to urgent lung transplantation. Anticipating the effects of VV-ECMO in this setting could ease the clinical decision to initiate such therapeutic strategy. Here, we present a series of equations to accurately predict the effects of VV-ECMO on arterial oxygenation in ES and illustrate this point by a case of ES decompensation with refractory hypoxaemia consecutive to an acute respiratory failure due to viral pneumonia.

Transcatheter closure for patent ductus arteriosus in patients with Eisenmenger syndrome: to do or not?

BACKGROUND: Patent ductus arteriosus (PDA) complicated by Eisenmenger syndrome (ES) remains to be a major cause of morbidity and mortality worldwide. Giving increasing evidences of benefit from targeted therapies, ES patients once thought to be inoperable may have increasing options for management. This study aims to explore whether PDA in patients with ES can be treated with transcatheter closure (TCC). METHODS: Between August 2014 and July 2016, four of fifteen PDA-ES patients whose Qp/Qs improved significantly and Qp/Qs > 1.5 after acute vasodilator testing with 100% oxygen were selected to receive TCC and pulmonary vasodilator therapy. PAH-targeted drugs were prescribed before and after occlusion for all. Trial occlusion was performed before permanent closure. RESULTS: The first TCC failed after initiation of PAH-targeted drugs for 6 months in four patients. After the medication was adjusted and extended to 12 months, TCC was performed for all without hemodynamic intolerances during perioperative period. Pulmonary artery systolic pressure (PASP) was significantly decreased (≥ 40%) immediately after TCC. During a mean follow-up of 48 ± 14.70 months, there were a further decrease of PASPs in two patients, the other two showed improved pulmonary vascular resistance, WHO functional class and six-minute walking distance despite deteriorated PASP. CONCLUSION: Some selected PDA-ES patients might benefit from TCC and combined PAH-targeted drugs play a crucial role.

Reversing Inoperability in Eisenmenger Syndrome: The "Drug-and-Banding" Approach.

Eisenmenger syndrome (ES) has been considered a cause of inoperability in patients with congenital heart disease (CHD). Even if long-standing vasodilators are efficient to reduce pulmonary vascular resistance (PVR), the best approach to grant stable repair of these patients is still unknown. We describe the case of a 28-year-old man with a diagnosis of untreated large ventricular septal defect and established ES. After few years of vasodilator therapy, the patient underwent pulmonary banding with significant reduction of his PVR. His CHD was then repaired, with clinical and functional improvement at 2-year follow-up.

Eisenmenger syndrome: diagnosis, prognosis and clinical management.

Eisenmenger syndrome (ES) represents the most severe phenotype of pulmonary arterial hypertension (PAH) associated with congenital heart disease (CHD) and occurs in patients with large unrepaired shunts. Despite early detection of CHD and major advances in paediatric cardiac surgery, ES is still prevalent and requires a multidisciplinary approach by adult CHD experts in tertiary centres. Central cyanosis is the primary clinical manifestation leading to secondary erythrocytosis and various multiorgan complications that increase morbidity and affect quality of life. Close follow-up is needed to early diagnose and timely manage these complications. The primary goal of care is to maintain patients' fragile stability. Although the recent use of advanced PAH therapies has substantially improved functional capacity and increased life expectancy, long-term survival remains poor. Progressive heart failure, infectious diseases and sudden cardiac death comprise the main causes of death in patients with ES. Impaired exercise tolerance, decreased arterial oxygen saturation, iron deficiency, pre-tricuspid shunts, arrhythmias, increased brain natriuretic peptide, echocardiographic indices of right ventricular dysfunction and hospitalisation for heart failure predict mortality. Endothelin receptor antagonists are used as first-line treatment in symptomatic patients, while phosphodiesterase-5 inhibitors may be added. Due to the lack of evidence, current guidelines do not provide a clear therapeutic strategy regarding treatment escalation. Additional well-designed trials are required to assess the comparative efficacy of various PAH agents and the benefit of combination therapy. Finally, the development of a risk score is of utmost importance to guide clinical therapy.

Pulmonary arterial hypertension: closing the gap in congenital heart disease.

PURPOSE OF REVIEW: Pulmonary arterial hypertension associated with congenital heart disease (PAH-CHD) is a common association adversely affecting quality of life and survival in these patients. We provide herewith recent advances in the understanding and management of PAH-CHD. RECENT FINDINGS: Significant progress has been made in disease-targeting therapy with pulmonary vasodilators for the treatment of Eisenmenger syndrome, the most severe form of PAH-CHD. Important gaps, however, still exist in the assessment and management of patients with PAH-CHD with systemic to pulmonary shunts. The choice of therapy, either interventional, medical, or both is an on-going dilemma that requires more long-term data. PAH after defect closure represents the most concerning subgroup of patients with the worst prognosis, requiring close follow-up and proactive disease-targeting therapy treatment. Small defects are not considered responsible for patients who have severe PAH and therefore, present different subgroup of patients similar to idiopathic PAH. SUMMARY: Even with advances in diagnosis and treatment PAH-CHD remains a challenging field requiring lifelong follow-up and meticulous treatment in centres specialized in both CHD and PAH.