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.

Pseudoaneurysm after aortopulmonary window repair and bilateral lung transplantation for eisenmenger syndrome: a case report.

BACKGROUND: Aortopulmonary window (APW) is a rare congenital cardiac anomaly characterized by communication between the main pulmonary artery and ascending aorta. There are various surgical techniques, and the short- and long-term results are excellent if the surgical repair is performed early in life. To our knowledge, there have been no reports of pseudoaneurysm after APW repair. Herein, we present a case of a 30-year-old woman with an ascending aortic pseudoaneurysm found at the site of APW repair nine months after the APW repair and bilateral lung transplantation. CASE PRESENTATIONS: A 30-year-old woman presented with APW and Eisenmenger syndrome. The patient underwent APW repair and bilateral lung transplantation. We transected the communication between the aorta and pulmonary artery and closed the aortic side directly with strips of felts. Nine months after the surgery, the patient complained of chest pain. Cardiac computed tomography revealed an ascending aortic pseudoaneurysm at the anastomotic site. Emergent graft replacement of the ascending aorta was performed and the postoperative course was uneventful. CONCLUSIONS: We have presented a case of a pseudoaneurysm at the anastomotic site after APW repair and bilateral lung transplantation. The choice of surgical technique should be based on the patient's background requiring lung transplantation, and in these cases close postoperative follow-up is required.

Characteristics of exercise intolerance in different subgroups of pulmonary arterial hypertension associated with congenital heart disease.

BACKGROUND: Exercise intolerance is a major manifestation of pulmonary arterial hypertension associated with congenital heart disease (PAH-CHD). We aimed to investigate the characteristics of exercise intolerance in different subgroups of PAH-CHD. METHODS: We retrospectively enrolled 171 adult patients with PAH-CHD and 30 age and sex-matched healthy subjects and performed cardiopulmonary exercise testing. Gas exchange parameters, including peak oxygen uptake (peak V̇o2), anaerobic threshold, and the slope of ventilatory equivalent for carbon dioxide (V̇e/V̇co2 slope), were recorded. RESULTS: The median age of patients at enrollment was 27.8 years, and 131 (76.6%) were female. Peak V̇o2 was reduced in patients compared to healthy controls (median, 14.8 ml/kg/min versus 26.9 ml/kg/min, p < 0.001). Of all 171 patients, 60 (35.1%) had Eisenmenger syndrome, 35 (20.5%) had PAH associated with systemic-to-pulmonary shunts (PAH-SP), 39 (22.8%) had PAH with small defects (PAH-SD), and 37 (21.6%) had PAH after cardiac defect correction (PAH-CD). Patients with Eisenmenger syndrome had the lowest peak V̇o2 (p = 0.003) and the highest V̇e/V̇co2 slope (p = 0.012), compared with other patients, representing the worst exercise capacity and ventilatory efficiency. Patients with PAH-SP had the best exercise capacity among the four groups, indicated by the highest peak V̇o2 (p = 0.003) compared with other patients. Peak V̇o2 was negatively correlated with pulmonary vascular resistance (r = -0.411, p < 0.001). CONCLUSIONS: Exercise capacity was severely reduced in patients with PAH-CHD. Among the four subgroups, patients with Eisenmenger syndrome had the worst exercise capacity and ventilatory efficiency.

Evolving Indications for Heart-Lung Transplant in Spain.

BACKGROUND: The outcomes of heart-lung transplant (HLT) are worse than those of heart transplant (HT) and lung transplant alone; this and the availability of mechanical assistance have meant that the indications for HLT have been changing. This study aims to analyze the evolution of indications for HLT in a country of 47 million inhabitants. METHODS: We performed a retrospective observational study of all HLTs performed in Spain (performed in 2 centers) from 1990 to 2020. The total number of patients included was 1751 (HT 1673 and HLT 78). After clinical adjustment, overall survival was compared between the 2 groups. Seven etiological subgroups were considered within the HLT group: (1) cardiomyopathy with pulmonary hypertension (CM + PH);, (2) Eisenmenger syndrome, (3) congenital heart disease without Eisenmenger syndrome, (4) idiopathic pulmonary arterial hypertension (IPAH), (5) cystic fibrosis, (6) chronic obstructive pulmonary disease (COPD) and/or emphysema), and (7) diffuse interstitial lung disease. RESULTS: There were a large number of differences between patients with HLT vs HT. HLT had a 2.69-fold increased probability of death in the first year compared with HT. The indications for HLT have changed over the years. In the recent period the indications are mainly congenital heart disease and Eisenmenger syndrome, with some cases of CM + PH. Other indications for HLT have virtually disappeared, mainly lung diseases (IPAH, COPD, cystic fibrosis). Median survival was low in CM + PH (18 days), diffuse interstitial lung disease (29 days), and ischemic heart disease (114 days); intermediate in Eisenmenger syndrome (600 days); and longer in IPAH, COPD and/or emphysema, and cystic fibrosis. CONCLUSIONS: HLT is a procedure with high mortality. This and mechanical assists mean that the indications have changed over the years. Etiological analysis is of utmost interest to take advantage of organs and improve survival.

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.

A Case of Multifocal Extramedullary and Non-Hepatosplenic Extramedullary Hematopoiesis in a 43-Year-Old Man with a History of Congenital Eisenmenger Syndrome.

BACKGROUND Extramedullary hematopoiesis in organs outside the bone marrow most commonly occurs in the liver and spleen. This report is of a case of multifocal extramedullary and non-hepatosplenic extramedullary hematopoiesis a 43-year-old man with a history of congenital Eisenmenger syndrome. CASE REPORT We present the case of a 43-year-old patient with complex heart disease and full-blown Eisenmenger syndrome associated with ventricular septal defect, bicuspid right ventricle, and pulmonary hypertension. In July 2020, the patient began to report neurological symptoms in the form of lower-limb numbness and weakness of lower-limb strength, with additional increasing lower-limb edema. A CT scan of the abdomen and pelvis revealed a 63×102×103 mm soft-tissue mass in the pelvis, located behind the urinary bladder. Due to the suspicion of proliferative disease, mainly of the lymphatic system, a diagnostic trephine biopsy was performed first, but no tumor cell infiltration was found. Then, the patient was qualified for diagnostic surgery. During the operation, tumor sections were harvested. Histopathological examination of the tissue sections showed extramedullary hematopoiesis in the tumor lining. Hydroxycarbamide was used as first-line treatment. However, it was not effective in controlling clinical symptoms. Therefore, the patient was qualified for radiotherapy as a second-line palliative treatment. CONCLUSIONS This report presents a patient with cyanotic heart disease and extramedullary and non-hepatosplenic hematopoiesis presenting as masses that mimicked malignancy. In this case, palliative radiotherapy effectively reduced the symptoms due to the size of the mass lesion.

Anaesthetic management in neurosurgery in a patient with Eisenmenger syndrome and Down syndrome. A case report.

Adults patients with congenital heart disease increasingly present for non cardiac surgery. The anesthetic management this type of patients in neurosurgery requires a meticulous surgical anesthetic planning. The need for urgent intervention, with the presence of a congenital heart disease evolved to Eisenmenger syndrome, associated to a difficult airway, is a challenge for the anesthesiologist. The use of dexmedetomidine may be a valid alternative. We present the case of a patient with Down syndrome, and Eisenmenger syndrome who underwent drainage of brain abscess from the emergency department and was subsequently scheduled for reintervention. We compare the different anesthetic techniques used in both procedures, analyzing the implications they had on the main physiopathological alterations presented by the patient.

Inflammatory markers in Eisenmenger syndrome and their association with clinical outcomes. A cross-sectional comparative study.

BACKGROUND: Inflammation may be an important factor contributing to the progression of Eisenmenger syndrome (ES). The purpose of the current study was to: characterize the inflammatory profile in ES patients and compare measures to reference values for congenital heart disease and pulmonary arterial hypertension (CHD-PAH); and investigate whether inflammatory markers are associated with other clinical markers in ES. METHODS: Twenty-seven ES patients were prospectively selected and screened for systemic inflammatory markers, including interleukin (IL)-1ß, tumor necrosis factor-alpha (TNF-α) and IL-10. Clinical data and echocardiographic parameters were obtained, with concomitant analysis of ventricular function. Functional capacity was assessed using the 6-min walk test (6MWT). Renal function and blood homeostasis were evaluated by the level of blood urea nitrogen (BUN), creatinine, and plasma electrolytes. RESULTS: Patients with ES expressed higher IL-10, IL-1ß and TNF-α compared to reference values of patients with CHD-PAH. IL-10 was negatively associated with BUN (r = -0.39,p = 0.07), creatinine (r = -0.35, p = 0.002), sodium (r = -0.45, p = 0.03), and potassium (r = -0.68, p = 0.003). IL-10 was positively associated with bicarbonate (r = 0.45, p = 0.02) and trended toward a positive association with right ventricular fractional area change (RVFAC) (r = 0.35, p = 0.059). IL-1ß was negatively associated with potassium (r = -0.5, p = 0.01). TNF-α demonstrated positive association with creatinine (r = 0.4,p = 0.006), BUN (r = 0.63,p = 0.003), sodium (r = 0.44, p = 0.04), potassium (r = 0.41, p = 0.04), and was negatively associated with RVFAC (r = -0.38,p = 0.03) and 6MWT distance (r = -0.54, p = 0.004). CONCLUSION: ES patients exhibit a more severe inflammatory profile compared to reference values for CHD-PAH. Furthermore, inflammatory markers are related to renal dysfunction, right ventricular impairment and poorer functional capacity.

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.

A Rare Case of Adult Aortopulmonary Window Combined with Anomalous Origin of the Right Pulmonary Artery from the Aorta Leading to Eisenmenger Syndrome.

Aortopulmonary window is a rare congenital heart disease that can increase pulmonary vascular resistance, exacerbate left-to-right shunt and lead to heart failure and respiratory tract infections. Most patients die during childhood. We report a 53-year-old male patient with a large aortopulmonary window combined with anomalous origin of the right pulmonary artery from the aorta, with Eisenmenger syndrome and without surgery.

Management of Eisenmenger syndrome by cardiac defect closure combined bilateral lung transplantation with intraoperative venoarterial ECMO support.

BACKGROUND: Optimal surgical treatment for Eisenmenger syndrome in adult congenital heart disease remains in debate. CASE REPORT: We report a case of a 22-year-old female with Eisenmenger syndrome secondary to ventricular septum defect (VSD), who underwent cardiac defect closure combined with bilateral lung transplantation in our center. The patient had an uncorrected peri-membranous VSD and subsequently developed severe pulmonary hypertension. We patched the defect under cardiopulmonary bypass. Then a sequential bilateral lung transplantation was performed with venoarterial extracorporeal membrane oxygenation support. The patient had a good postoperative recovery and remained well at follow-up at 1 year. To conclude, cardiac defect repair combined bilateral lung transplantation may be a feasible option for selected patients with Eisenmenger Syndrome.

Paciente con síndrome de Eisenmenger complicado por sangrado digestivo alto / Patient with Eisenmenger syndrome complicated by upper digestive bleeding

El Síndrome de Eisenmenger es un desorden multisistémico caracterizado por hipertensión pulmonar con inversión o bidireccionalidad del flujo a través de una comunicación intracardiaca o aortopulmonar. Se presenta el caso de un paciente masculino de 48 años de edad con antece- dentes de Hipertensión Pulmonar e Insuficiencia Cardíaca en tratamiento, quien acude por cuadro de melenas, decaimiento e inestabilidad hemodinámica. Al examen físico se ausculta soplo sistólico ascendente en foco pulmonar, abdomen distendido con presencia de onda ascíti- ca. En los exámenes complementarios; la radiografía convencional de tórax mostró aumento de la trama vascular pulmonar, además de encontrarse alteraciones electrocardiográficas. El paciente mostró una evolución desfavorable produciéndose falla cardíaca, que dio lugar al posterior fallecimiento debido a un paro cardiorrespiratorio.

Eisenmenger Syndrome is a multisystemic disorder identified by pulmonary hypertension with reversal or bidirectional flow through intracardiac or aortopulmonary communication. The case of a 48-year-old male patient with a history of Pulmonary Hypertension and Heart Failure in treatment is presented, who comes due to mane of mane, decay, and hemodynamic instability. The physical examination auscultated systolic murmur ascending in pulmonary focus, distended abdomen with presence of ascites wave. In the complementary exams, conventional chest x-ray, increased pulmonary vascular weft, in addition to finding electrocardiographic abnormalities. The patient seemed an unfavorable evolution, producing a heart failure, which resulted in subse- quent death due to cardiorespiratory arrest.

Focused Update on Pulmonary Hypertension in Children-Selected Topics of Interest for the Adult Cardiologist.

Pulmonary hypertensive vascular disease (PHVD), and pulmonary hypertension (PH), which is a broader term, are severe conditions associated with high morbidity and mortality at all ages. Treatment guidelines in childhood are widely adopted from adult data and experience, though big differences may exist regarding aetiology, concomitant conditions and presentation. Over the past few years, paediatric aspects have been incorporated into the common guidelines, which currently address both children and adults with pulmonary hypertension (PH). There are multiple facets of PH in the context of cardiac conditions in childhood. Apart from Eisenmenger syndrome (ES), the broad spectrum of congenital heart disease (CHD) comprises PH in failing Fontan physiology, as well as segmental PH. In this review we provide current data and novel aspects on the pathophysiological background and individual management concepts of these conditions. Moreover, we focus on paediatric left heart failure with PH and its challenging issues, including end stage treatment options, such as mechanical support and paediatric transplantation. PH in the context of rare congenital disorders, such as Scimitar Syndrome and sickle cell disease is discussed. Based on current data, we provide an overview on multiple underlying mechanisms of PH involved in these conditions, and different management strategies in children and adulthood. In addition, we summarize the paediatric aspects and the pros and cons of the recently updated definitions of PH. This review provides deeper insights into some challenging conditions of paediatric PH in order to improve current knowledge and care for children and young adults.

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.

Image diagnosis: Eisenmenger's syndrome in patients with simple congenital heart disease.

BACKGROUND: Early identification of congenital heart disease (CHD) allows detection of the pulmonary arteriopathy in an early stage, and timely shunt closure can permanently reverse pulmonary arterial hypertension (PAH). However, surgical correction is not recommended in patients with irreversible PAH. Herein we report our experience about Eisenmenger's syndrome in simple CHD. CASE PRESENTATION: From January 2017 to November 2018, a total of 8 CHD patients (3 ventricular septal defects (VSD), 2 atrial septal defects (ASD), and 3 patent ductus arteriosus (PDA), median age, 15.5 years [range, 3-18 years]) with PAH were detected by chest X-ray, electrocardiogram, transthoracic echocardiography (TTE), computed tomographic angiography (CTA) and cardiac catheterization. The median defect diameter, pulmonary artery pressure (PAP), pulmonary vascular resistance (PVR) were 16.5 mm (range, 3-30 mm), 75 mmHg (range, 60-86 mmHg), and 16 Woods units (range, 12-19 Woods units), respectively. Here, we report the representative cases of three types of simple CHD with irreversible PAH. The surgical correction was not performed in all patients who had fixed PAH and were referred to medical treatment. CONCLUSIONS: PAH in CHD can be reversed by early shunt closure, but this potential is lost beyond a certain point of no return. This article highlights the essence of enhancing the level of healthcare and services in Chinese rural areas. Failure to accurately and timely assess PAH will delay effective treatment past optimal treatment time, and even lead to death.

Sagittal mandibular osteotomy in a patient with Eisenmenger's syndrome: A case report.

The various abnormalities of occlusion cause significant discomfort to the patient suffering from them. Currently, the surgical treatment of malocclusion in healthy patients is a routine process. The situation is completely different when the patient has a serious disease of the respiratory or cardiovascular system - a condition which may contraindicate such treatment. A 30-year-old female patient, with a class III skeletal defect (open bite and progeny) and Eisenmenger's syndrome was chosen as a clinical case. The DDS-Pro software was selected to plan the operation. The bilateral sagittal split osteotomy of the mandible was selected as the method of surgery. At the time of the initial examination, the patient had been denied surgical treatment several times in several other clinics. Before the treatment began, the patient underwent intensive preparation in the cardiac surgery unit for 2.5 months. Using the software, a surgical intervention was planned with the production of a surgical template. The operation was then performed; the treatment period was unremarkable. The resulting occlusion and changes in the shape of the face fully met the patient's psychological and esthetic expectations. In conclusion, a complicated cardiovascular pathology does not always deprive patients with malocclusion of the possibility to undergo surgical treatment.