Eisenmenger Syndrome in Adults: Treatment Pattern and Prognostic Factors in the Advanced Pulmonary Vasodilator Era.

Patients with Eisenmenger syndrome (ES) have a higher mortality rate than patients with simple congenital heart disease (CHD). To determine factors associated with death in the era of advanced pulmonary vasodilator treatment, we analyzed the characteristics of adult ES patients depending on underlying CHD. Simple septal defects and patent ductus arteriosus were classified as simple CHD, and other conditions were classified as complex CHD. Sixty-seven adult ES patients (50.7% women) were reviewed retrospectively. CHD was diagnosed at a median of 10.0 years of age and ES was diagnosed at 18.6 years. Thirteen patients (19.4%) died; the median age was 38.6 years (IQR 32.2-47.8). In a multivariate analysis, patients with SpO2 < 85% had a higher mortality rate than others [hazard ratio (HR) 9.7; 95% confidence interval (CI) 1.002-95.2, p = 0.05]. In simple CHD patients, those with a low platelet count (< 100 × 109/L) or low SpO2 (< 85%) were at a higher risk of death than those without (HR 16.32, 95% CI 1.25-2266.31, p = 0.032; and HR 38.91, 95% CI 3.44-5219.41, p = 0.001, respectively). Advanced pulmonary vasodilators were used more in survivors than in non-survivors (48.1% vs. 15.4%, p = 0.032). Low SpO2 and platelet count were related to mortality in adult ES, especially in those with simple CHD. Therefore, careful attention should be paid to the care of adult ES patients with this tendency; active pulmonary vasodilator treatment should be considered.

Síndrome de Eisenmenger em um gato / Eisenmenger syndrome in cat

A 6-month-old female, 1.0kg, uncastrated female Persian cat was brought to the Veterinary Hospital at State University of Ceara, with a history of dyspnea, prostration, hyporexia and progressive weight loss for a month. On physical examination, systolic cardiac murmur, cyanosis and dyspnea were detected. Unfortunately, the cat died during oxygen therapy. Necropsy examination revealed an increase in cardiac silhouette and ventricular septal defect of 2cm in diameter. Macroscopically the lungs were collapsed, with absent and diffusely reddish blackish crepitus, and the liver with blackish red coalescent multifocal areas, interspersed with lighter areas and lobular pattern with irregular brownish multifocal areas intercepted by brownish areas. Thus, the necropsy results together with the history and physical examination of the animal confirmed the diagnosis of Eisenmenger Syndrome, becoming the report of the first case, in a cat, in Brazil.(AU)

Survey of the current status and management of Eisenmenger syndrome: a Japanese nationwide survey.

BACKGROUND: The management of Eisenmenger syndrome (ES) has dramatically changed since the advent of disease-targeted therapy (DTT). However, guidelines for ES management, including DTT, have not been established. We aimed to clarify the current incidence, underlying disease, and management of ES in Japan, using a nationwide survey. METHODS: A written questionnaire was sent to members of the Japanese Society for Adult Congenital Heart Disease, through which information was obtained from 86 institutions. RESULTS: A total of 251 patients with ES (80.5% cases≥20 years of age) were followed as of February 2012; DTT was performed in 124 (49.4%) patients. Unrepaired simple anatomy was reported as an underlying condition in 165 patients (65.7%). Among patients with ES, 55 (21.9%), 128 (51%), 53 (21.1%), and 12 (4.8%) were classified into functional classes I, II, III, and IV, respectively. DTT was routinely performed at 52 (60.5%) institutions, but there were variations in the DTT therapeutic strategy at these institutions. Combined therapy was more often used than monotherapy; an endothelin receptor antagonist was the most frequently prescribed medication. There were institutional differences regarding heart failure treatment and indications for anticoagulation. Digitalis and angiotensin-converting enzyme inhibitors or angiotensin II receptor blockers were widely used, but beta-blockers were infrequently used to manage heart failure. CONCLUSIONS: This survey describes the current status, including prevalence and underlying disease, and variations in the practical management of ES in Japan. The results will help in the creation of future guidelines for ES management.

Eisenmenger syndrome: recent advances in pharmacotherapy.

Over the last decade advanced therapies for the management of pulmonary arterial hypertension have been introduced. These agents have also been effective in reducing pulmonary vascular resistance in patients with Eisenmenger syndrome. Specific guidelines focusing on modern therapies for Eisenmenger syndrome however do not exist to date. More recently, clinical trials in patients with Eisenmenger syndrome demonstrated a significant clinical improvement with favorable safety and tolerability profile. This review aims to summarize newly reported pharmacological agents used in patients with Eisenmenger syndrome.

Eisenmenger ventricular septal defect: classification, morphology, and indications for surgery.

This study aimed to examine the definition and indications for surgery, to elucidate the morphologic substrate of aortic regurgitation, and to extrapolate the pathologic mechanisms of subpulmonary stenosis in Eisenmenger ventricular septal defect (EVSD). The study enrolled 160 patients. Preoperative respiratory symptoms and poor growth were present in 41 patients (26%), and 21 patients (13%) required mechanical ventilation. Perimembranous ventricular septal defect (pVSD) had been diagnosed previously for 136 of the patients (85%) at other institutions. Of the 160 patients, 51 (32%) had muscular posteroinferior rims. Aortic regurgitation was experienced by 36 patients (23%), found to be mild in 31 cases (19%) and moderate in 5 cases (3%). None of the patients had severe regurgitation. No aortic valvuloplasty was performed. The significant risk factors for aortic regurgitation were subpulmonary stenosis (p = 0.001) and a muscular posteroinferior rim (p = 0.000). Subpulmonary stenosis was seen in 57 patients (35%), found to be mild to moderate in 42 cases (26%) and severe in 15 cases (9%). Adequacy of the stenosis band was repaired through the tricuspid valve for 57 of these patients. The definition of EVSD should identify it as a subgroup different from pVSD, and it should be closed as soon as it is identified in developing countries. Aortic regurgitation occurs rarely, and aortic valvoplasty should be performed if it exceeds a moderate level. The subpulmonary stenosis can be repaired through the tricuspid valve.

Role of oral sildenafil in severe pulmonary arterial hypertension: clinical efficacy and dose response relationship.

BACKGROUND: Sildenafil (phosphodiesterase type 5 inhibitor) has been shown to be effective in pulmonary arterial hypertension (PAH). We evaluated the efficacy and safety of oral sildenafil in patients of severe PAH with special emphasis on dose response relationship, time of onset of clinical response and its effects on different haemodynamic parameters. METHODS: Forty-four patients of severe PAH of either idiopathic pulmonary arterial hypertension [23 (51.7%)] or Eisenmenger syndrome [21 (48.3%)] were studied. All patients underwent six-minute walk test (SMWT) and echocardiography, while some also underwent cardiac catheterization. Sildenafil was started after a test dose and was gradually increased up to a target dose of 300 mg/day. Patients were followed-up 2 weekly for 10 weeks and monthly thereafter for functional class assessment and SMWT. Echocardiography and cardiac catheterization were repeated after at least 1 month of achieving maximal sildenafil dose (target dose or maximally tolerated dose). Drug safety and tolerability were assessed by monitoring patients for adverse effects including fundus examination. RESULTS: Mean follow-up duration was 18.7+/-8.8 months (range 7-30 months). Mean maximum dose achieved was 276.1+/-62.2 mg/day (range 75-300 mg/day). A significant improvement in NYHA class (2.54+/-0.5 vs. 1.31+/-0.4, p=0.0001) and in SMWT distance (247.4+/-74.7 vs. 366.3+/-93.8 m, p=0.0001) was noted. All patients reported "feeling better" within 2 weeks of starting 12.5 mg thrice a day sildenafil. Marked improvement was noticed at 150 mg/day dose. Some minor additional benefit was noticed with further increase in the dose up to 225 mg/day. No further benefit was noted in improvement of NYHA class and SMWT distance by further increasing the dose of sildenafil. Haemoptysis as well as chest pain, if present, were also improved. On follow-up cardiac catheterization, a significant reduction in mean pulmonary arterial pressure (from 67.0+/-10.2 to 56.9+/-9.5 mm Hg, p=0.001), PVRI (from 19.5+/-7.0 to 11.1+/-6.9 WU m2, p=0.0001) and PVR/SVR ratio (0.6+/-0.3 vs. 0.4+/-0.2, p=0.013) with increase in cardiac index (2.9+/-1.1 l/min vs. 3.7+/-1.1 l/min, p=0.008) was noted. Systemic as well as pulmonary arterial oxygen saturations also improved significantly. Sildenafil was generally well tolerated, except for rhinorrhoea in 2, bodyache in 1 and headache in 1 patient. No visual symptom or change in fundus examination was noted. CONCLUSIONS: Oral sildenafil improves functional capacity, haemodynamic parameters and is safe in patients with severe PAH. Benefits start as early as 2 weeks. The effects are dose related. A target dose of 150 mg/day appears to be optimal. Being very effective, widely available, relatively inexpensive, and very easy to use and very well tolerated without any major side effect, sildenafil may qualify as a first line medication for these patients.

Effects of chronic sildenafil in patients with Eisenmenger syndrome versus idiopathic pulmonary arterial hypertension.

BACKGROUND: To test the hypothesis that chronic sildenafil treatment has similar functional and hemodynamic effects in patients with severe pulmonary arterial hypertension due to Eisenmenger syndrome as those due to idiopathic pulmonary arterial hypertension without intracardiac shunts. METHODS: A prospective open-label study was carried out to compare the effects of sildenafil on the pulmonary hemodynamics between two groups of patients with severe pulmonary hypertension and similar baseline functional capacity--Eisenmenger syndrome (ES group) (n=7) versus idiopathic pulmonary arterial hypertension (IPAH group) (n=6). RESULTS: After 6 months of sildenafil, there was a significant improvement in the functional capacity, the arterial saturation and the pulmonary hemodynamics in the ES group, as shown by significant reduction in the systolic and mean pulmonary artery pressures and the pulmonary vascular resistance. CONCLUSION: Sildenafil increases pulmonary blood flow and improves cyanosis in patients with Eisenmenger syndrome. Efficacy of sildenafil as treatment for idiopathic pulmonary arterial hypertension may be extended to patients with Eisenmenger syndrome.

Long-term behavior of endothelial and coagulation markers in Eisenmenger syndrome.

The long-term behavior of endothelial markers was studied in patients with Eisenmenger syndrome who were subjected to conventional therapy (no vasodilators) and observed for 18 months. Biochemical markers were analyzed comparatively in patients with class II or III symptoms (group 1, n=10) and patients with class IV symptoms (group 2, n=7). Plasma von Willebrand factor antigen (vWF:Ag), thrombomodulin, tissue-type plasminogen activator (t-PA) and its inhibitor (PAI-1), and D-dimer were determined by immunoenzymatic assay at baseline, and at 6, 12, and 18 months. At baseline, the main clinical difference between groups was a decreased peripheral oxygen saturation in group 2 versus group 1 (77+/-5% and 86+/-4%, respectively, p=0.001). Basal vWF:Ag and t-PA were increased and thrombomodulin was decreased in both groups in comparison with controls (p<0.0001), while D-dimer was increased in group 2 only (p=0.0003). In response to treatment, there was a decrease in vWF:Ag in both groups (19% and 23%, respectively in groups 1 and 2, at 18 months vs. baseline, p<0.0001) and t-PA in group 1 (38% vs. baseline, p=0.0485). Plasma vWF:Ag tended to be higher in group 2 in comparison with group 1 during the whole follow-up. Levels of PAI-1 greater than 38.4 ng/mL (upper 90% limit for normals) and D-dimer greater than 500 ng/mL were detected in individual patients (both groups) during the follow-up period. Thrombomodulin remained decreased in both groups. Thus, severity of symptoms in the Eisenmenger syndrome appears to correlate with low oxygen saturation and higher vWF:Ag levels. Improvement of endothelial dysfunction may occur in response to treatment, although increased risk for thrombosis persists, in view of residual abnormalities.