sildenafil-citrate and Eisenmenger-Complex

The efficacy of endothelin receptor antagonists (ERAs) in the management of Eisenmenger syndrome (ES) remains controversial. The aim of this study is to systemically review the safety and effects of ERAs in improving the quality of life and basic cardiac functions of these patients.. Twelve databases were searched, including PubMed, Web of Science, Scopus, Virtual Health Library, World Health Organization (WHO) Global Health Library, Google Scholar, POPLINE, Systems for Information of Grey Literature in Europe, New York Academy of Medicine, ClinicalTrials.gov, metaRegister of Controlled Trials and the WHO International Clinical Trials Registry Platform, through August 2016. We included randomized clinical trials addressing the effect of ERAs on cardiac functions in patients with ES. The quality of studies was assessed using the Cochrane Collaboration tool.. We included two trials represented by four papers, of which three papers reported the efficacy of bosentan against placebo and one paper reported the results of a combination of bosentan and sildenafil versus placebo and bosentan. One trial showed a significant effect of bosentan treatment over placebo on indexed pulmonary vascular resistance and mean pulmonary artery pressure, but a non-significant increase in 6-min walk distance and a non-significant effect on systemic pulse oximetry. The other trial reported the safe but non-significant effect of combination therapy of bosentan and sildenafil compared with bosentan and placebo.. This study demonstrated safety and improved hemodynamic effects of bosentan in ES, with a controversial effect on exercise capacity. Further randomized controlled trials with longer follow-up duration are needed to confirm these results.

Topics: Antihypertensive Agents; Blood Pressure; Bosentan; Clinical Trials as Topic; Eisenmenger Complex; Endothelin Receptor Antagonists; Humans; Quality of Life; Sildenafil Citrate; Sulfonamides; Vasodilator Agents

Pulmonary arterial hypertension (PAH) is a common complication of congenital heart disease (CHD), with most cases occurring in patients with congenital cardiac shunts. In patients with an uncorrected left-to-right shunt, increased pulmonary pressure leads to vascular remodelling and dysfunction, resulting in a progressive rise in pulmonary vascular resistance and increased pressures in the right heart. Eventually, reversal of the shunt may arise, with the development of Eisenmenger's syndrome, the most advanced form of PAH-CHD. The prevalence of PAH-CHD has fallen in developed countries over recent years and the number of patients surviving into adulthood has increased markedly. Today, the majority of PAH-CHD patients seen in clinical practice are adults, and many of these individuals have complex disease or received a late diagnosis of their defect. While there have been advances in the management and therapy in recent years, PAH-CHD is a heterogeneous condition and some subgroups, such as those with Down's syndrome, present particular challenges. This article gives an overview of the demographics, pathophysiology and treatment of PAH-CHD and focuses on individuals with Down's syndrome as an important and challenging patient group.

Topics: Antihypertensive Agents; Bosentan; Clinical Trials as Topic; Comorbidity; Down Syndrome; Eisenmenger Complex; Endothelium, Vascular; Epoprostenol; Health Behavior; Heart Defects, Congenital; Heart Transplantation; Humans; Hypertension, Pulmonary; Lung Transplantation; Oxygen Inhalation Therapy; Phosphodiesterase 5 Inhibitors; Piperazines; Practice Guidelines as Topic; Pulmonary Circulation; Purines; Sildenafil Citrate; Sulfonamides; Sulfones; Thrombosis

Eisenmenger syndrome (ES), the most advanced form of pulmonary arterial hypertension (PAH) associated with congenital heart disease, is a devastating condition that has a considerable impact on patients' lives. Patients who develop ES typically exhibit 1 or more of a range of cardiac defects, including ventricular septal defects, atrial septal defects, and patent ductus arteriosus. The nature of the congenital defect underlying ES is important because it has prognostic implications. Although ES shares similar morphological findings with idiopathic PAH, clinical differences exist between the 2 etiologies. Adults with ES exhibit increased survival and more favorable hemodynamics than those with idiopathic PAH. Treatment options for patients with ES have historically been limited; however, recent successes have been achieved with the use of therapies targeted against the pathophysiological pathways that underlie PAH. The dual endothelin receptor antagonist bosentan was demonstrated to improve hemodynamics and exercise capacity without compromising oxygen saturation, both in the short and long term. Improvements in hemodynamics also have been observed with the single endothelin receptor antagonist sitaxsentan. The phosphodiesterase type V inhibitor sildenafil may improve functional class, oxygen saturation, and hemodynamics in patients with ES, and beneficial effects of prostacyclin and prostacyclin analogs in patients with ES have been reported. The treatment of patients with PAH with the use of combinations of targeted therapies is becoming increasingly commonplace and may offer an alternative option for treatment of patients with ES. The authors of future studies may seek to investigate whether the pulmonary vascular remodeling in ES can be targeted and reversed.

Topics: Antihypertensive Agents; Bosentan; Eisenmenger Complex; Endothelin Receptor Antagonists; Epoprostenol; Humans; Hypertension, Pulmonary; Isoxazoles; Phosphodiesterase Inhibitors; Piperazines; Pulmonary Circulation; Purines; Sildenafil Citrate; Sulfonamides; Sulfones; Thiophenes

There have been remarkable advances in our understanding of the pathobiology of pulmonary hypertension. A region on chromosome 2 encoding bone morphogenetic receptor type 2 has been identified to underlie familial and many cases of sporadic primary pulmonary arterial hypertension. The vasoactive mediators, discovered and defined by vascular biologists, have been translated into promising treatments of human disease. Prostacyclin, endothelin receptor blockers, sildenafil, and nitric oxide have been applied therapeutically to limit, and occasionally reverse, the inexorable damage to the pulmonary circulation initiated by recently identified genetic and environmental triggers of pulmonary arterial hypertension.

Topics: Antihypertensive Agents; Bone Morphogenetic Protein Receptors, Type II; Bronchodilator Agents; Child; Chromosomes, Human, Pair 2; Eisenmenger Complex; Epoprostenol; Humans; Hypertension, Pulmonary; Mutation; Nitric Oxide; Piperazines; Protein Serine-Threonine Kinases; Pulmonary Artery; Purines; Receptors, Endothelin; Sildenafil Citrate; Sulfones; Transforming Growth Factor beta; Vasodilator Agents

The aim of the present study was to evaluate the safety, tolerability, clinical and haemodynamic impact of add-on sildenafil in patients with congenital heart disease (CHD)-related pulmonary arterial hypertension (PAH) and Eisenmenger physiology after failure of oral bosentan therapy.. Thirty-two patients with CHD-related PAH (14 male, mean age 37.1 ± 13.7 years) treated with oral bosentan underwent right heart catheterization (RHC) for clinical worsening. After RHC, all patients received oral sildenafil 20mg thrice daily in addition to bosentan. Clinical status, resting transcutaneous oxygen saturation (SpO(2)), 6-minute walk test (6MWT), serology and RHC were assessed at baseline (before add-on sildenafil) and after 6 months of combination therapy.. Twelve patients had ventricular septal defect, 8 atrio-ventricular canal, 6 single ventricle, and 6 atrial septal defect. Twenty-eight/32 had Eisenmenger physiology and 4 (all with atrial septal defect) did not. All patients well tolerated combination therapy. After 6 months of therapy, an improvement in clinical status (WHO functional class 2.1 ± 0.4 vs 2.9 ± 0.3; P=0.042), 6-minute walk distance (360 ± 51 vs 293 ± 68 m; P=0.005), SpO(2) at the end of the 6MWT (72 ± 10 vs 63 ± 15%; P=0.047), Borg score (2.9 ± 1.5 vs 4.4 ± 2.3; P=0.036), serology (pro-brain natriuretic peptide 303 ± 366 vs 760 ± 943 pg/ml; P=0.008) and haemodynamics (pulmonary blood flow 3.4 ± 1.0 vs 3.1 ± 1.2l/min/m(2), P=0.002; pulmonary vascular resistances index 19 ± 9 vs 24 ± 16 WU/m(2), P=0.003) was observed.. Addition of sildenafil in adult patients with CHD-related PAH and Eisenmenger syndrome after oral bosentan therapy failure is safe and well tolerated at 6-month follow-up, resulting in a significant improvement in clinical status, effort SpO(2), exercise tolerance and haemodynamics.

Topics: Administration, Oral; Adult; Bosentan; Dose-Response Relationship, Drug; Drug Therapy, Combination; Eisenmenger Complex; Exercise Test; Familial Primary Pulmonary Hypertension; Female; Follow-Up Studies; Humans; Hypertension, Pulmonary; Male; Piperazines; Prospective Studies; Pulmonary Wedge Pressure; Purines; Sildenafil Citrate; Sulfonamides; Sulfones; Time Factors; Treatment Outcome; Vascular Resistance

Patients with Eisenmenger syndrome (ES) have a decreased exercise capacity and poor quality of life (QoL). While patients may survive to middle adulthood, the burden of disease is disabling. Sildenafil seems to improve exercise tolerance and hemodynamics, but there is no data to date on its impact on QoL.. Eisenmenger patients in New York Heart Association (NYHA) class III were recruited in a prospective study of efficacy and safety of oral sildenafil. The QoL endpoint was assessed using a disease-specific questionnaire (CAMPHOR). Exercise capacity was assessed by means of six minute walk test (6MWT). All patients underwent comprehensive assessment at baseline and after 3months of treatment.. Twelve patients (mean age was 34.3±10.2, 83% female) with various cardiac anatomies were recruited. No major adverse events during the follow-up or significant drop in resting oxygen saturation were recorded. After 3months of oral sildenafil therapy, all patients improved to NYHA II with a concomitant improvement in 6MWT distance (347.3±80.7 to 392.5±82.0m, p=0.002). All components of the CAMPHOR score, relating to symptoms, activity and QoL, improved significantly resulting in substantial improvement in the total CAMPHOR score (27.6±10.5 to 15.8±10.4, p=0.002).. Three months of sildenafil therapy in adults with ES was well tolerated and associated with significant improvement in the QoL CAMPHOR questionnaire and in NYHA class and exercise capacity. Larger studies are warranted to assess long term efficacy of oral sildenafil and potential impact on survival.

Topics: Administration, Oral; Adult; Eisenmenger Complex; Exercise Tolerance; Female; Humans; Male; Piperazines; Prospective Studies; Purines; Quality of Life; Sildenafil Citrate; Sulfones; Surveys and Questionnaires; Treatment Outcome; Vasodilator Agents; Young Adult

Topics: Child; Eisenmenger Complex; Female; Follow-Up Studies; Heart Defects, Congenital; Humans; Hypoxia; Infant; Male; Oxygen; Phosphodiesterase 5 Inhibitors; Piperazines; Pulmonary Artery; Purines; Sildenafil Citrate; Sulfones

This study evaluates the efficacy and safety of sildenafil in patients with Eisenmenger's syndrome with special emphasis on haemodynamic parameters and its comparative efficacy in atrial septal defect versus ventricular septal defect patients.. Oral sildenafil was given to 22 patients with Eisenmenger's syndrome - eight with atrial septal defect and 14 with ventricular septal defect - after detailed baseline evaluation including a six-minute walk test, echocardiography, and cardiac catheterisation. Patients were followed up for a period of 6 months for functional class assessment and six-minute walk distance. Cardiac catheterisation was repeated in all patients.. A significant improvement in the World Health Organization functional class, six-minute walk distance, mean pulmonary arterial pressure, and pulmonary vascular resistance was noticed. Systemic arterial and mixed venous oxygen saturations were also significantly improved along with improvement in pulmonary blood flow. None showed any significant side effects or worsening of systemic arterial saturation. At baseline, mean pulmonary arterial pressure, pulmonary vascular resistance, and pulmonary/systemic vascular resistance ratios were significantly higher in ventricular septal defect patients than in atrial septal defect patients. Atrial septal defect patients showed better response in clinical as well as haemodynamic parameters.. Sildenafil is an effective and safe agent for patients with Eisenmenger's syndrome. It improves their functional capacity as well as haemodynamic parameters. The beneficial effects are greater in patients with Eisenmenger's syndrome secondary to atrial septal defect than ventricular septal defect.

Topics: Administration, Oral; Adolescent; Adult; Cardiac Catheterization; Eisenmenger Complex; Female; Follow-Up Studies; Heart Septal Defects, Atrial; Heart Septal Defects, Ventricular; Hemodynamics; Humans; Male; Middle Aged; Piperazines; Prospective Studies; Purines; Sildenafil Citrate; Sulfones; Treatment Outcome; Vasodilator Agents; Young Adult

Although sildenafil has been shown to be safe and effective in idiopathic pulmonary arterial hypertension (PAH) and PAH related to connective tissue disease, its effects in Eisenmenger syndrome are less clear.. To investigate whether long-term treatment (12 months) with the phosphodiesterase type 5 inhibitor sildenafil improves clinical and haemodynamic parameters in patients with Eisenmenger syndrome.. Prospective, open-label, multicentre study.. Four pulmonary hypertension centres in China.. 84 Eisenmenger syndrome functional class II-IV patients.. Oral sildenafil 20 mg orally three times a day.. 6-min walk distance (6MWD) test, resting systemic arterial blood oxygen saturation (SaO(2)) in room air, haemodynamic parameters assessed by right heart catheterisation, safety and tolerability.. The overall treatment effects at 12 months versus baseline (mean changes with 95% CIs) were 56 m increase (42 to 69, p<0.0001) in 6MWD, and 2.4% increase (1.8% to 2.9%, p<0.0001) in resting room air SaO(2). Improvements were also seen in mean pulmonary arterial pressure and pulmonary vascular resistance index (-4.7 mm Hg (-7.5 to -1.9), p=0.001; and -474 dyn×s×cm(-5)×m(2) (-634 to -314), p<0.0001, respectively). Sildenafil was well tolerated. Most adverse events were mild and transient, and occurred in the first 2 weeks of treatment.. Twelve months of oral sildenafil treatment was well tolerated and appeared to improve exercise capacity, systemic arterial oxygen saturation and haemodynamic parameters in patients with Eisenmenger syndrome.

Topics: Administration, Oral; Adolescent; Adult; China; Drug Administration Schedule; Eisenmenger Complex; Exercise Tolerance; Female; Humans; Male; Middle Aged; Piperazines; Prospective Studies; Purines; Severity of Illness Index; Sildenafil Citrate; Sulfones; Treatment Outcome; Vasodilator Agents

To evaluate the efficacy of combining the dual endothelin receptor antagonist, bosentan, and the phosfodiesterase-5-inhibitor, sildenafil, in patients with Eisenmenger syndrome.. The study was a randomized, placebo-controlled, double-blinded, cross-over design. Patients with Eisenmenger syndrome (n = 21) were treated open label with bosentan for 9 months. After 3 months, sildenafil/placebo was added for 3 months, and a cross-over was performed for the last 3 months. At baseline and after 3, 6, and 9 months, patients were examined with 6 min walk test, oxygen saturations, N-terminal pro-brain natriuretic peptide, New York Heart Association (NYHA) classification, cardiac catheterization, and magnetic resonance imaging. The primary endpoint was changed in 6 min walk distance (MWD). Bosentan improved the 6 MWD (377 vs. 414 m, P = 0.001), pulmonary vascular resistance (PVR) (28 vs. 22 wood, P = 0.01), and pulmonary blood flow (2.6 vs. 3.5 L/min, P = 0.01). Adding sildenafil to bosentan did not improve the 6 MWD significantly (21 vs. 8 m, P = 0.48), but increased saturation at rest (2.9 vs. -1.8%, P < 0.01).. In Eisenmenger syndrome, treatment with bosentan significantly improved walking distance, pulmonary blood flow, and PVR. Adding sildenafil to bosentan did not significantly improve walking distance but did increase saturation at rest. http://www.ClinicalTrial.gov: NCT00303004.

Topics: Adult; Aged; Antihypertensive Agents; Bosentan; Cross-Over Studies; Double-Blind Method; Drug Therapy, Combination; Eisenmenger Complex; Female; Humans; Male; Middle Aged; Phosphodiesterase 5 Inhibitors; Piperazines; Purines; Sildenafil Citrate; Sulfonamides; Sulfones; Treatment Outcome; Young Adult

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.. 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).. 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.. 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.

Topics: Adult; Eisenmenger Complex; Exercise Test; Female; Humans; Hypertension, Pulmonary; Lung; Male; Oxygen; Phosphodiesterase Inhibitors; Piperazines; Prospective Studies; Purines; Regional Blood Flow; Sildenafil Citrate; Sulfones; Systole; Vascular Resistance

Severe pulmonary artery hypertension (PAH) is a disorder with limited treatment options. Recently, several newer drugs have recently been introduced to treat PAH. Sildenafil is one which has shown promise in several uncontrolled studies, but controlled trials have been few. In this randomized placebo-controlled study, we evaluated the efficacy of oral sildenafil in idiopathic PAH and PAH caused by Eisenmenger syndrome.. This was a randomized, double-blind, placebo-controlled crossover study. Twenty patients, 10 of each of idiopathic PAH and Eisenmenger syndrome, were randomized to receive placebo or sildenafil in a double-blind manner for 6 weeks and, after a washout period of 2 weeks, were crossed over. The primary end point of efficacy was the improvement in distance covered in 6-minute walk test. Secondary end points were reduction in pulmonary artery pressure as measured by Doppler echocardiography after 6 weeks of treatment, improvement in clinical condition, New York Heart Association (NYHA) class, and exercise duration and metabolic equivalents (Mets) achieved on modified Bruce exercise protocol.. There was significant improvement in primary and secondary end points. The primary end point of distance covered in 6-minute walk test improved from 262 +/- 99 to 358.9 +/- 96.5 m (P < .0001) after treatment with sildenafil. Pulmonary artery pressure, the secondary end point, improved from the baseline of 98.8 +/- 20.5 to 78.3 +/- 15.3 mm Hg (P < .0001), NYHA class improved from 2.65 +/- 0.59 to 1.55 +/- 0.51 (P < .0001), exercise duration from 6.4 +/- 3.1 to 10.2 +/- 2.05 minutes (P < .0001), and Mets achieved from 3.32 +/- 1.57 to 6.04 +/- 1.87 (P < .0001) after treatment with sildenafil. There was no significant fall in blood pressure with placebo and sildenafil, and no serious side effects of drug were observed in the study.. Sildenafil significantly improved the symptomatic status, exercise capacity, NYHA class, and hemodynamic parameters of patients with severe PAH and can be safely used as a primary or adjunctive treatment of the same.

Topics: 3',5'-Cyclic-GMP Phosphodiesterases; Adolescent; Adult; Child; Child, Preschool; Cross-Over Studies; Double-Blind Method; Eisenmenger Complex; Exercise Tolerance; Female; Humans; Hypertension, Pulmonary; Male; Middle Aged; Piperazines; Purines; Sildenafil Citrate; Sulfones; Vasodilator Agents

We aimed to assess the contemporary outcome of Eisenmenger syndrome (ES), delineate the use of disease targeting therapies (DTT) in these patients and to investigate the effect of treatment on outcome in the community.. Patients with ES were systematically identified from the German National Register for Congenital Heart Defects. Data on underlying diagnosis, medical therapy, and survival were collected. The impact of DTT on survival was assessed using time-dependant Cox analysis. Overall, 153 ES patients were included (mean age 34.0 ± 13.3 years, 46% females). Of these, 88 (57.5%) were treated with at least one DTT (76.1% Bosentan, 20.5% Sildenafil) while 17.6% were on dual DTT. In addition, 24.8% of patients received digoxin, 10.5% angiotensin-converting enzyme-inhibitors/angiotensin receptor blockers, and 17.6% β-blockers. Moreover, 17.6% of patients were treated with oral anticoagulants, while 23.5% of patients received Aspirin. The survival rate at 1, 5, and 10 years of follow-up was only 92, 75, and 57% in the entire cohort, and was even worse in treatment naive ES patients (survival rate 86, 60, and 34% at 1, 5, and 10 years). Use of DTT was independently associated with a better survival (hazard ratio 0.42, P= 0.015).. This study illustrates the alarmingly poor survival prospects of Eisenmenger patients by community-based data even in the current era with advanced DTT and in a country with a wealthy health system. Treatment naive ES patients had especially high mortality rates approaching 60-70% at 10 years of follow-up. Treatment with DTT was associated with better survival.

Topics: Adult; Angiotensin-Converting Enzyme Inhibitors; Anticoagulants; Eisenmenger Complex; Female; Humans; Male; Sildenafil Citrate

This study investigated the potential value of serum high mobility group box-1 (HMGB1) level in the diagnosis, staging and treatment response of patients with pulmonary arterial hypertension secondary to congenital heart disease (PAH-CHD).. This was a single-center prospective study in 106 CHD patients. Serum HMGB1 levels were measured by enzymelinked immunosorbent assay. HMGB1 levels were significantly increased in patients with PAH compared to patients without PAH (P<0.01) and healthy controls (P<0.001). HMGB1 levels significantly correlated with pulmonary arterial pressure (P<0.001) and pulmonary vascular resistance (PVR) (P<0.001). In patients with severe PAH, HMGB1 levels were significantly higher in patients with Eisenmenger syndrome (ES) than in patients exhibiting low PVR (P<0.001). Severe PAH and ES was identified by serum HMGB1 with a cutoff value of 13.62ng/mL (P<0.001) with a specificity of 82.8% and a sensitivity of 90%, and a cutoff value of 21.62ng/mL (P=0.001) with a specificity of 85.2% and a sensitivity of 64.3%, respectively. HMGB1 levels were significantly decreased after sildenafil therapy for 6months (P<0.01).. Our study suggests that serum HMGB1 level may be used as a biomarker to identify PAH in CHD patients, assess pulmonary vascular remodeling, and evaluate the treatment response to sildenafil.

Topics: Adult; Biomarkers; Case-Control Studies; Eisenmenger Complex; Enzyme-Linked Immunosorbent Assay; Female; Heart Defects, Congenital; HMGB1 Protein; Humans; Hypertension, Pulmonary; Male; Middle Aged; Phosphodiesterase 5 Inhibitors; Prospective Studies; Sensitivity and Specificity; Severity of Illness Index; Sildenafil Citrate; Treatment Outcome; Vascular Resistance; Young Adult

Topics: Blood Transfusion; Bosentan; Diagnostic Imaging; Dobutamine; Ductus Arteriosus, Patent; Eisenmenger Complex; Epoprostenol; Female; Humans; Hypertension, Pulmonary; Magnetic Resonance Imaging; Menorrhagia; Piperazines; Purines; Sildenafil Citrate; Sulfonamides; Tomography, X-Ray Computed; Vasodilator Agents; Young Adult

Hoarseness is a common phenomenon that can be caused by uncommon pathology. One seldom cause is Ortner's syndrome, a rare cardiovocal disease that can lead to hoarseness due to left recurrent laryngeal nerve palsy induced by mechanical compression of the nerve by cardiovascular structures. This case report describes a case of a 41-year-old woman with sudden onset of hoarseness. The patient had known pulmonary hypertension and Eisenmenger's syndrome.

Topics: Adult; Antihypertensive Agents; Cardiac Catheterization; Eisenmenger Complex; Female; Hoarseness; Humans; Hypertension, Pulmonary; Laryngoscopy; Phenylpropionates; Piperazines; Pulmonary Artery; Purines; Pyridazines; Recurrent Laryngeal Nerve; Sildenafil Citrate; Sulfonamides; Syndrome; Tomography, X-Ray Computed; Vocal Cord Paralysis

In Eisenmenger syndrome (ES), oral phosphodiesterase type-5 inhibitors, which are preferential pulmonary vasodilators, reduce the elevated pulmonary artery pressure and pulmonary vascular resistance index by increasing cyclic guanosine monophosphate (cGMP). However, no information is available as to how pulmonary vasodilatation alleviates the accompanying dyspnoea and improves patient's exercising ability.. As the natural stimulus of juxtapulmonary capillary (J) receptors is an increase in interstitial pressure, the aim was to estimate their threshold level stimulation chemically by intravenous lobeline, before and after 6 weeks of sildenafil therapy in treatment-naive ES patients.. Nine Eisenmenger syndrome patients [mean age=26 (SD=1.6) years] underwent 6MWT and an exercise test before and 6 weeks after oral sildenafil (20mg 3× D). Their respiratory responses to threshold doses of intravenous lobeline were determined at both these stages.. After 6 weeks of sildenafil therapy, the 6MWD [from 453.3 (SD=50.9) m to 516.6 (SD=48.9) m; P=0.001] and the duration of exercise with the modified Bruce protocol from 7 min 53 s (SD=0.04) to 10 min 44 s (SD=0.88) (P=0.001) improved significantly. However, the improvement in oxygen saturation was not noteworthy. The lobeline dose required to produce threshold level of respiratory effects was higher in ES patients [37.5 (SD=3.4) μg/kg] and with sildenafil therapy it fell significantly [20.6 (SD=1.8) μg/kg; P=0.001].. J receptor threshold doses were elevated in ES patients and fell significantly with sildenafil therapy that was associated with improved exercise tolerance, implying thereby a role of J receptors in producing dyspnea in ES patients.

Topics: Adult; Dyspnea; Eisenmenger Complex; Exercise Test; Female; Humans; Male; Piperazines; Purines; Sensory Receptor Cells; Sildenafil Citrate; Sulfones; Vasodilator Agents

Eisenmenger syndrome (ES) occurs as the most advanced form of pulmonary arterial hypertension (PAH) in patients with congenital heart disease. In this study, we aimed to evaluate the management of ES patients, follow-up and specific PAH treatment applying and clinical outcomes during 5 years.. During the period of the month between May 2008 and 2013 ES female patients were included in the study and followed an average for 5 years. Clinical findings, brain natriuretic peptide levels, transthoracic and right heart catheterization findings, 6-min walking test distance were recorded. PAH specific treatment as bosentan, iloprost and sildenafil was given to patients according to guidelines. The patients were evaluated with 3 months intervals as requirement for hospitalization, combination treatment, and mortality.. A total of 12 patients were included in the study. All of the patients were women, the mean age was 36.5. As prognostic echocardiographic data, the patients had high pulmonary artery pressure (109.81 ± 24.94 mmHg) related with increased right ventricular wall thickness, elevated right atrial pressure, severe pulmonary regurgitation in 40%, shortened pulmonary acceleration time, diminished myocardial tissue Doppler velocities of the left and right ventricles, increased right atrium area/left atrial area ratio (1.35 ± 0.40), lower right ventricular fractional area change. During the follow-up period of 5 years, a total of 16 events occurred. Combination treatment was required in 8 patients.. Eisenmenger syndrome is a multi-system affecting disease and due to high morbidity and mortality risk patients with ES should be followed by specialized centers. PAH specific treatment improves the disease course and survival of patients.

Topics: Adult; Antihypertensive Agents; Bosentan; Echocardiography; Eisenmenger Complex; Female; Follow-Up Studies; Humans; Hypertension, Pulmonary; Iloprost; Laser-Doppler Flowmetry; Piperazines; Pulmonary Wedge Pressure; Purines; Severity of Illness Index; Sildenafil Citrate; Sulfonamides; Treatment Outcome; Turkey

A retrospective analysis of the records of all the patients of pulmonary arterial hypertension with pregnancy at AIIMS, New Delhi, India, to study maternal and perinatal outcome and to compare outcome between severe and mild pulmonary arterial hypertension.. A retrospective analysis was carried out of 30 pregnancies in women with pulmonary arterial hypertension (PAH) who delivered at ≥ 28 weeks of gestation from July 2006 through July 2012 at a tertiary care center in India. Pulmonary artery blood pressure (PABP) during the first trimester of pregnancy or before pregnancy was considered to define PABP as severe or mild, with severe cases having systolic PABP >50 mmHg on echocardiography.. Out of 30 patients, 14 patients had severe PAH and 16 patients had mild PAH. Women with severe PAH had a significantly higher incidence of preterm delivery (11 vs. 3, P < 0.05), small for gestational age infants (10 vs. 2, P < 0.05) and cardiac complications (6 vs. 1, P < 0.05) compared to women with mild PAH. There was maternal mortality in a patient with Eisenmenger syndrome. In women with severe PAH and mild PAH, PABP increased in later pregnancy from 63.14 ± 7.6 to 71.57 ± 7.9 mmHg (P < 0.05) and from 40.37 ± 3.6 to 41.69 ± 4.1 mmHg (P < 0.05), respectively.. Pregnancy in women with severe PAH is associated with higher maternal morbidity and adverse fetal outcome compared to pregnancy in women with mild PAH.

Topics: Adult; Arrhythmias, Cardiac; Arterial Pressure; Birth Weight; Cesarean Section; Echocardiography; Eisenmenger Complex; Familial Primary Pulmonary Hypertension; Female; Gestational Age; Heart Failure; Humans; Hypertension, Pulmonary; India; Infant, Newborn; Infant, Small for Gestational Age; Piperazines; Pregnancy; Pregnancy Complications, Cardiovascular; Pregnancy Outcome; Pregnancy Trimester, First; Pregnancy Trimester, Third; Premature Birth; Purines; Retrospective Studies; Severity of Illness Index; Sildenafil Citrate; Sulfones; Vasodilator Agents; Young Adult

The favorable effects of short-term use of sildenafil on patients with Eisenmenger syndrome have been reported. We further studied the impact of long-term use of sildenafil on survival of these patients. In this study, the baseline data of patients newly diagnosed as Eisenmenger syndrome in our hospital between January 2005 and December 2009 were retrospectively collected. Patients were followed-up either by telephone contacts or during visits in our out-patient clinic. A total of 121 patients (68 patients in conventional group and 53 patients in sildenafil group) were finally included and 29 patients were re-evaluated after sildenafil therapy for 3-4 months. Compared with the baseline, a 6-minute walk distance, functional classes, plasma hemoglobin level, and hemodynamics were significantly improved after sildenafil treatment. During a median follow-up period of 35.8 months, 15 patients died (11 patients in conventional group). The 1- and 3-year survival rates in sildenafil group were 97.0% and 95.2%, significantly higher than 90.6% and 82.9% in conventional group P = .025). Multivariate analysis showed that sildenafil therapy, functional class and mean pulmonary arterial pressure were independently associated with survival. Therefore, long-term sildenafil therapy improved survival in patients with Eisenmenger syndrome.

Topics: Adult; Arterial Pressure; Eisenmenger Complex; Female; Follow-Up Studies; Hemodynamics; Hemoglobins; Humans; Male; Multivariate Analysis; Piperazines; Purines; Retrospective Studies; Sildenafil Citrate; Sulfones; Survival Rate; Time Factors; Vasodilator Agents; Young Adult

The perioperative management of pulmonary hypertension in a patient with Eisenmenger syndrome, the most advanced form of associated pulmonary artery hypertension (PAH), who required a sigmoidectomy is presented. The treatment for pulmonary hypertension was switched from oral sildenafil to intravenous epoprostenol to avoid the unexpected discontinuation of vasodilation during the perioperative period. The scheduled perioperative conversion should be considered for patients with severe PAH undergoing major abdominal surgery to ensure the stabilization of pulmonary and systemic hemodynamics.

Topics: Administration, Oral; Antihypertensive Agents; Colectomy; Eisenmenger Complex; Epoprostenol; Familial Primary Pulmonary Hypertension; Humans; Hypertension, Pulmonary; Infusions, Intravenous; Male; Middle Aged; Perioperative Care; Piperazines; Purines; Sigmoid Neoplasms; Sildenafil Citrate; Sulfones; Vasodilator Agents

Topics: Adult; Combined Modality Therapy; Eisenmenger Complex; Female; Humans; Piperazines; Purines; Radiography; Sildenafil Citrate; Sulfones

To determine the effect of sildenafil for dogs with Eisenmeger's syndrome and secondary erythrocytosis.. This is a prospective, single arm, open-label study. Five clinical dogs with Eisenmeger's syndrome and secondary erythrocytosis were included. New York Heart Association functional class, packed cell volume, pulmonary artery acceleration time to ejection time ratio and serum erythropoietin concentration were evaluated before and after sildenafil therapy (0·5 mg/kg, twice a day).. New York Heart Association functional class was significantly improved after one (median 2; range 1 to 2, P=0·031) and three months (median 2; range 1 to 2, P=0·031) of sildenafil therapy, compared with the baseline (median 3, range 2 to 3). Packed cell volume was significantly decreased after three months (median 59%; range 56 to 63, P=0·031) of therapy, compared with the baseline (median 71%; range 58 to 74). Acceleration time to ejection time ratio had increased and serum erythropoietin concentration had decreased particularly after 1 month of therapy, but there was no statistical significance.. Sildenafil improved the clinical signs and secondary erythrocytosis in dogs with Eisenmeger's syndrome. Sildenafil therapy could be a useful treatment for dogs with Eisenmeger's syndrome.

Topics: Animals; Dog Diseases; Dogs; Eisenmenger Complex; Female; Male; Piperazines; Prospective Studies; Purines; Sildenafil Citrate; Sulfones; Treatment Outcome; Vasodilator Agents

Topics: Adult; Antihypertensive Agents; Bosentan; Combined Modality Therapy; Drug Therapy, Combination; Eisenmenger Complex; Exercise Tolerance; Familial Primary Pulmonary Hypertension; Female; Heart Septal Defects, Ventricular; Humans; Hypertension, Pulmonary; Iron, Dietary; Piperazines; Purines; Quality of Life; Sildenafil Citrate; Sulfonamides; Sulfones; Treatment Outcome; Vasodilator Agents

Topics: Adolescent; Antihypertensive Agents; Bosentan; Child; Eisenmenger Complex; Endothelin A Receptor Antagonists; Exercise Test; Humans; Hypertension; Piperazines; Purines; Sildenafil Citrate; Sulfonamides; Sulfones

We report a woman with atrial septal defect and severe pulmonary hypertension with 25.0 Wood unit.m(2) of indexed total pulmonary vascular resistance. She underwent successful corrective repair of atrial septal defect after 2 years of treatment with sildenafil, and has been monitored for 4 years after repair. This case supports a "treat and repair" approach using advanced pulmonary vasodilator therapy in selected patients with inoperable severe pulmonary hypertension associated with atrial septal defect.

Topics: Adult; Cardiac Catheterization; Cardiac Surgical Procedures; Echocardiography, Doppler, Color; Eisenmenger Complex; Female; Follow-Up Studies; Heart Septal Defects, Atrial; Humans; Hypertension, Pulmonary; Long-Term Care; Piperazines; Purines; Risk Assessment; Severity of Illness Index; Sildenafil Citrate; Sulfones; Time Factors; Tomography, X-Ray Computed; Treatment Outcome; Vasodilator Agents

Impaired endothelial homeostasis underlies the pathophysiology of pulmonary arterial hypertension (PAH). We speculated that PAH patients are deficient in circulating endothelial progenitor cells (EPCs), potentially contributing to endothelial dysfunction and disease progression.. We recruited 41 patients with Eisenmenger syndrome (13 with Down syndrome), 55 with idiopathic PAH, and 47 healthy control subjects. Flow cytometry and in vitro assays were used to quantify EPCs and to assess cell function. The number of circulating CD34+, CD34+/AC133+, CD34+/KDR+, and CD34+/AC133+/KDR+ progenitor cells was low in Eisenmenger patients compared with healthy control subjects, and those with Down syndrome displayed even fewer EPCs. Reductions in EPC numbers correlated with New York Heart Association functional class, 6-minute walk distance, and plasma brain-type natriuretic peptide levels. The capacity of cultured peripheral blood mononuclear cells to form colonies and incorporate into tube-like structures was impaired in Eisenmenger patients. Idiopathic PAH patients had reduced numbers of EPCs, and the number of circulating EPCs correlated with invasive hemodynamic parameters in this cohort. Levels of immune inflammatory markers, cGMP, stable nitric oxide oxidation products, and asymmetric dimethylarginine were abnormal in patients with PAH and related to numbers of EPCs. Within the idiopathic PAH population, treatment with the phosphodiesterase inhibitor sildenafil was associated with a dose-dependent rise in EPC numbers, resulting in levels consistently above those found with other therapies.. Circulating EPC numbers are reduced in 2 well-characterized forms of PAH, which also exhibit raised levels of inflammatory mediators. Sildenafil treatment may represent a pharmacological means of increasing circulating EPC numbers long-term.

Topics: AC133 Antigen; Aged; Antigens, CD; Antigens, CD34; Arginine; Cells, Cultured; Cyclic GMP; Down Syndrome; Eisenmenger Complex; Endothelium, Vascular; Exercise; Female; Flow Cytometry; Glycoproteins; Hematopoietic Stem Cells; Humans; Hypertension, Pulmonary; Inflammation Mediators; Male; Middle Aged; Natriuretic Peptide, Brain; Peptides; Piperazines; Pulmonary Artery; Purines; Sildenafil Citrate; Stem Cells; Sulfones; Vascular Endothelial Growth Factor Receptor-2; Vasodilator Agents

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.. 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.. 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.. 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.

Topics: Administration, Oral; Adolescent; Adult; Cardiac Catheterization; Chest Pain; Child; Dose-Response Relationship, Drug; Echocardiography; Eisenmenger Complex; Exercise Test; Female; Follow-Up Studies; Hemoptysis; Humans; Hypertension, Pulmonary; Male; Middle Aged; Oxygen; Phosphodiesterase Inhibitors; Piperazines; Purines; Sildenafil Citrate; Sulfones

Topics: Decision Making; Eisenmenger Complex; Humans; Hypertension, Pulmonary; Phosphodiesterase Inhibitors; Piperazines; Purines; Safety; Sildenafil Citrate; Sulfones

Pulmonary arterial hypertension carries a poor prognosis in both adult and pediatric patients. Current understanding of the mechanisms underlying pulmonary arterial hypertension has enabled the rapid development of appropriate drugs, such as endothelin receptor antagonists and 5-phosphodieste-rase inhibitors, that can be administered orally and which are generally well tolerated. The aims of the present study were to evaluate functional class and exercise capacity following long-term treatment with sildenafil or bosentan in patients with idiopathic pulmonary arterial hypertension and Eisenmenger's syndrome and to compare results in the two groups.. Seven patients were included in the pulmonary arterial hypertension study, and diagnoses of idiopathic pulmonary arterial hypertension were confirmed. Five patients were treated with sildenafil, while two received bosentan. The five patients with a non-restrictive ventricular septal defect and pulmonary arterial hypertension were treated with sildenafil. In one patient, bosentan was added to the sildenafil.. Both sildenafil and bosentan significantly improved exercise capacity in patients with idiopathic pulmonary arterial hypertension. The treatment effect was less in those with Eisenmenger physiology. Although the improvement in World Health Organization functional class was greater in patients with idiopathic pulmonary arterial hypertension, it was significant in both groups.. Long-term treatment with sildenafil and bosentan improved both exercise capacity and functional class in patients with idiopathic pulmonary arterial hypertension and in those with hypertension due to congenital heart disease. The changes were more marked in patients with idiopathic pulmonary arterial hypertension.

Topics: Adolescent; Adult; Antihypertensive Agents; Bosentan; Child; Eisenmenger Complex; Female; Humans; Hypertension, Pulmonary; Infant; Male; Piperazines; Purines; Sildenafil Citrate; Sulfonamides; Sulfones; Vasodilator Agents

Two women with Eisenmenger syndrome, aged 63 and 45 years, presented with different symptoms: the first patient had peripheral oedema, proteinuria, progressive fatigue and cyanosis and the other had increasing dyspnoea and blue lips. The first patient was successfully treated with diuretics but experienced a collum fracture that occurred after hypovolemic collapse caused by diuretic use. She was given sildenafil and underwent hip surgery with spinal anaesthesia 10 days later. In the following weeks, the patient was haemodynamically stable but then died suddenly; no autopsy was performed. The second patient was given oxygen therapy at home and bosentan. After 6 months the symptoms of dyspnoea resolved and her 6-minute walking distance increased from 453 to 512 m. The life expectancy of patients with congenital heart disorders such as Eisenmenger syndrome has improved dramatically, due in part to the efficacy of novel agents that inhibit endothelial-cell proliferation. With these advances, treatment of these patients is no longer restricted to tertiary-care centres. Therefore, community cardiologists, pulmonologists and internists should be aware of these congenital heart disorders and the available treatment options.

Topics: Bosentan; Diuretics; Eisenmenger Complex; Female; Humans; Middle Aged; Oxygen Inhalation Therapy; Piperazines; Purines; Sildenafil Citrate; Sulfonamides; Sulfones; Vasodilation; Vasodilator Agents

Topics: Adult; Antihypertensive Agents; Bosentan; Cesarean Section; Eisenmenger Complex; Female; Humans; Piperazines; Postoperative Care; Pregnancy; Pregnancy Complications, Cardiovascular; Pregnancy Outcome; Prenatal Care; Purines; Sildenafil Citrate; Sulfonamides; Sulfones; Vasodilator Agents

Topics: Eisenmenger Complex; Humans; Piperazines; Purines; Sildenafil Citrate; Sulfones; Vasodilator Agents

Eisenmenger syndrome in pregnancy may be a life-threatening disease despite recent additions to the treatment options.. We present a woman with severe pulmonary hypertension due to Eisenmenger syndrome treated during pregnancy and delivery and postpartum with L-arginine and sildenafil to enhance the nitric oxide pathway. This combination was associated with significant improvement in the mother's clinical and hemodynamic condition and fetal well-being.. The concomitant use of sildenafil and L-arginine for the management of pulmonary hypertension in pregnancy, combined with multidisciplinary care, permitted a good outcome for the mother and her infant.

Topics: 3',5'-Cyclic-GMP Phosphodiesterases; Adult; Arginine; Drug Therapy, Combination; Eisenmenger Complex; Female; Humans; Hypertension, Pulmonary; Patient Care Team; Phosphodiesterase Inhibitors; Piperazines; Pregnancy; Pregnancy Complications, Cardiovascular; Pregnancy Outcome; Purines; Sildenafil Citrate; Sulfones