iloprost and Eisenmenger-Complex

Pulmonary arterial hypertension (PAH), is a rare and progressive disease with a high morbidity and mortality. Prostanoid pulmonary vasodilators are the most effective treatment for idiopathic and connective tissue associated PAH. Nonetheless, data examining their safety and efficacy in patients with Eisenmenger syndrome the most severe form of PAH, that is, related to cyanotic congenital heart disease (CHD-PAH) remains limited.. To evaluate safety and the clinical efficacy of nebulised iloprost in patients with Eisenmenger syndrome who are on maximum background oral PAH therapy.. This pilot study was a randomised, double-blind, placebo-controlled, cross-over study. Patients were randomised to receive nebulised placebo or iloprost for 12 weeks and were then crossed over, with a 7-14-day washout. The primary endpoint was a change in 6-minute walk distance (6MWD).. Sixteen patients (11 females, aged 47.3 ± 9.8 year) were recruited, twelve completed the study. All were in WHO-FC III, with a resting oxygen saturation of 84 [81-87] % and a median 6MWD of 290 [260-300] m. There was no significant difference in the primary endpoint between nebulised iloprost (0[-4-9]m) and placebo (10 [-15-51]m), p = 0.58. There were no safety concerns with nebulised iloprost.. Our pilot study provides preliminary evidence that the addition of nebulised iloprost to maximum oral PAH therapy did not improve the primary endpoint of 6MWD. Nebulised iloprost was well tolerated with no significant safety concerns in CHD-PAH.

Topics: Adult; Cross-Over Studies; Double-Blind Method; Eisenmenger Complex; Female; Humans; Iloprost; Male; Middle Aged; Nebulizers and Vaporizers; Pilot Projects; Vasodilator Agents; Walk Test

Right ventricular (RV) function is an important prognostic factor of pulmonary arterial hypertension (PAH), but there is insufficient data regarding RV function after long-term inhaled iloprost treatment. We evaluated the effect of long-term iloprost treatment on RV function in patients with Eisenmenger syndrome (ES).. Eleven consecutive patients with ES associated with congenital heart disease underwent echocardiographic measurements at baseline and 48 weeks after iloprost therapy. In addition, we recorded World Health Organization (WHO) functional class, 6-minute walk distance (6MWD), systemic arterial oxygen saturation (SaO. After 48 weeks of iloprost therapy, mean pulmonary arterial pressure (mPAP), pulmonary arterial systolic pressure (PASP), and pulmonary vascular resistance (PVR) were significantly decreased [mPAP, 42.5 (38.5-61.0) to 36.5 (29.1-40.0)mmHg; PASP, 92.6±19.9 to 74.5±23.8mmHg; PVR, 23.4 (19.8-26.0) to 23.4 (19.8-26.0)Wood unit respectively, all p<0.05]. There was also significant improvement in RV myocardial performance index [0.68 (0.61-0.80) to 0.52 (0.51-0.62), p=0.003] and RV longitudinal strain (-15.7±1.6 to -18.1±1.5%, p<0.001). In clinical assessment, WHO functional class (p=0.006), 6MWD (310.6±44.7 to 399.7±80.8m, p<0.001), and SaO. The improvement in echocardiographic parameters of the RV function after 48 weeks of iloprost therapy may provide insight on the efficacy of long-term iloprost treatment for RV functional improvement, which is a prognostic factor in patients with ES.

Topics: Administration, Inhalation; Adult; Echocardiography; Eisenmenger Complex; Exercise Test; Female; Humans; Hypertension, Pulmonary; Iloprost; Male; Middle Aged; Oxygen; Prospective Studies; Vascular Resistance; Vasodilator Agents; Ventricular Dysfunction, Right

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

There are limited data on the effect of iloprost therapy in patients with Eisenmenger syndrome (ES). The aim of our study was to evaluate the effect of inhaled iloprost therapy on exercise capacity, quality of life (QoL), cardiac function, and hemodynamics in patients with ES. Eighteen consecutive patients with ES and exertional dyspnea according to the World Health Organization functional class III or IV were prospectively recruited. Exercise capacity was assessed by a 6-minute walk test, and QoL was measured on a 12-Item Short-Form Health Survey. Echocardiographic measurements included peak systolic and mean pulmonary arterial pressures, pulmonary vascular resistance, and myocardial performance index of the right ventricle (RV). All patients underwent comprehensive evaluation at baseline and after 24 weeks of treatment. Of the 18 patients with ES, 13 were included for analysis. After 24 weeks of iloprost therapy, 6-minute walk test distance significantly increased (289.1 ± 76.9 to 369.5 ± 93.4 m, p = 0.032) in addition to concomitant improvements in the 12-Item Short-Form Health Survey physical and mental component summaries (20.6 ± 19.3 to 52.6 ± 28.0, p <0.05; 33.9 ± 19.7 to 54.9 ± 21.3, p <0.05, respectively). RV myocardial performance index improved significantly after treatment (0.80 ± 0.31 to 0.59 ± 0.12, p = 0.042). Pulmonary arterial pressure and pulmonary vascular resistance did not improve with iloprost therapy. This study showed that 24 weeks of inhaled iloprost therapy in patients with ES led to significant improvements in exercise capacity, QoL, and RV function. These results likely explain the symptomatic relief reported by patients with ES receiving iloprost therapy.

Topics: Administration, Inhalation; Adult; Cohort Studies; Echocardiography, Doppler; Eisenmenger Complex; Exercise Test; Exercise Tolerance; Familial Primary Pulmonary Hypertension; Female; Humans; Hypertension, Pulmonary; Iloprost; Male; Middle Aged; Prospective Studies; Quality of Life; Treatment Outcome; Vascular Resistance; Vasodilator Agents; Ventricular Dysfunction, Right

Identification of the pathophysiology associated with Eisenmenger syndrome has led to the evaluation of targeted therapies. Iloprost is one such targeted therapy used for patients with Eisenmenger syndrome. This study aimed to assess the efficacy and safety of iloprost used for patients with Eisenmenger syndrome. In this study, 12 patients with Eisenmenger syndrome (mean age, 33.2 ± 12.1 years; 75% female) started receiving iloprost 10 μg/dose administered six times a day. Of the 12 patients, 9 were classified as New York Heart Association (NYHA) functional class 3, and three were categorized as functional class 4. Changes in 6-min walk distance, NYHA functional class, oxygen saturation at resting, and results after the 6-min walk test were checked, as well as changes in right ventricle diameter and pulmonary arterial pressure shown by echocardiography. The distance during a 6-min walk increased from 255.8 ± 120.4 to 349.4 ± 134.7 m (p = 0.013), and 10 patients improved their NYHA functional class by one grade (p = 0.007). The mean resting oxygen saturation (SpO(2)) increased from 80.6 ± 14.2 to 84.9 ± 13.0% (p = 0.040), and after the 6-min walk test, it increased from 63.8 ± 22.9 to 68.8 ± 21.5% (p = 0.007). The mean right ventricle diameter during the diastolic phase changed from 53.7 ± 4.8 to 51.4 ± 3.9 mm (p = 0.068), and the mean pulmonary arterial pressure changed from 62.8 ± 13.7 to 58.9 ± 11.7 mmHg (p = 0.059). Neither death nor critical adverse effects occurred for any patients. Mild headache and dyspnea were common reports during the iloprost treatments. No patients stopped the therapy due to these adverse effects. Iloprost is well tolerated and appears to be beneficial in the management of patients with Eisenmenger syndrome.

Topics: Administration, Inhalation; Adolescent; Adult; Cardiac Catheterization; Echocardiography; Eisenmenger Complex; Exercise Tolerance; Female; Humans; Iloprost; Male; Oximetry; Statistics, Nonparametric; Treatment Outcome; Vasodilator Agents

The last few years have seen significant progress in the treatment of advanced pulmonary arterial hypertension (PAH). The efficacy of new drugs has been proved mainly in idiopathic PAH or PAH associated with connective tissue diseases. As the pathophysiologic patterns are similar, it is reasonable to use these drugs also in Eisenmenger syndrome or in other congenital heart defects with PAH related to initial high pulmonary flow.. To evaluate our early experience with new drugs for PAH in patients with Eisenmenger syndrome.. A retrospective study of five patients, aged 28 to 51 years (39.6 +/- 9.94), four female, with Eisenmenger syndrome due to atrial septal defect (n = 2), patent ductus arteriosus (n = 2) or ventricular septal defect (n = 1), who began therapy with iloprost (n = 4, later associated with sildenafil in one patient) and bosentan (n = 1), between April 2001 and May 2003. The existence of severe and fixed PAH, with predominant right-to-left shunt, was confirmed by hemodynamic study in all cases. The patients were evaluated by clinical examination, Doppler echocardiography and the six-minute walk test before treatment and throughout follow-up (9 to 34 months, 19.8 +/- 9.04). Before treatment two patients were in NYHA class III and three in class III with periods in class IV. By Doppler echocardiography the right ventricle-right atrium (RV-RA) gradient was 74 to 111 mmHg (90.6 +/- 15.73) and the Tei index was 0.53 to 2.05 (1.13 +/- 0.62). In the six-minute walk test the distance was 214 to 500 meters (296.8 +/- 115.27).. All patients improved clinically, though three are still in class III. One patient is in class II and one patient died. At the latest evaluation the RV-RA gradient was 60 to 112 mmHg (84.8 +/- 19.11) and the Tei index was 0.5 to 1.33 (0.85 +/- 80.32). In the six-minute walk test a net increase in the distance covered was evident: 376 to 520 meters (420 +/- 57.89). The treatment was well tolerated in all cases, without serious adverse effects.. Though the number of patients was small, our initial experience with the new specific drugs for PAH in Eisenmenger syndrome showed promising results, with clinical and functional improvement and without adverse effects.

Topics: Adult; Antihypertensive Agents; Bosentan; Eisenmenger Complex; Female; Follow-Up Studies; Humans; Hypertension, Pulmonary; Iloprost; Male; Middle Aged; Retrospective Studies; Sulfonamides; Vasodilator Agents