lu-208075 and Eisenmenger-Complex

It is commonly reported a limitation of therapeutic strategy in Eisenmenger syndrome (ES) historically. This qualitative systematic review is conducted to evaluate the safety and efficacy of pulmonary arterial hypertension-specific drug therapy (PAH-SDT) for ES patients for a clinical therapeutic strategy based on evidence.. PubMed, EMBASE, and the Cochrane Library databases have been systematically reviewed up to January 2019. Two reviewers independently conducted a literature search, quality evaluation, and data extraction. The occurrence of death, deterioration, and adverse events (AEs) has respectively been described as a count or percentage. Meta-analysis was conducted by Stata 15.1, and weighted mean differences (WMD) with 95% confidence intervals (CI) were recorded for continuous data. Randomized-effect model or fixed-effect model was applied according to the heterogeneity test.. Fifteen citations recruiting 456 patients associated with ES were eventually pooled, which involved 4 RCTs, 6 prospective studies, and 5 retrospective studies. Within the first year, it indicated PAH-SDT significantly ameliorated exercise capacity in 6-minute walk distance (6MWD) (I = 60.5%; WMD: 53.86 m, 95% CI [36.59, 71.13], P < .001), functional class (FC) (WMD = -0.71, 95% CI [-0.98, -0.44], P < .001) and Borg dyspnea index (WMD = -1.28, 95% CI [-1.86, -0.70], P < .001), in addition to hemodynamics, especially mean pulmonary arterial pressure by 5.70 mmHg (WMD = -5.70 mmHg, 95% CI [-8.19, -3.22], P < .001) and pulmonary vascular resistance by 4.20 wood U (WMD: -4.20, 95% CI [-7.32, -1.09], P = .008), but unsatisfactory effects in oxygen saturation at exercise (P = .747). In a prolonged medication, bosentan, a dual ERA, has been proved acting an important role in improving exercise tolerance of patients with ES (6MWD: I = 47.5%; WMD: 88.68 m, 95% CI [54.05, 123.3], P < .001; FC: I = 0.0%; WMD = -0.65, 95% CI [-1.10, -0.19], P = .006). While a nonsignificant change of 6MWD was noted in a long-term therapy of ambrisentan (P = .385). There existed rare evidence about the efficacy and safety of macitentan, phosphodiesterase-5 inhibitors (PDE5i), and prostanoids in a prolonged medication. Most AEs were recorded as mild to moderate with PAH-SDT, but about 4.3% individuals treated with endothelin receptor antagonists (ERAs) suffered from serious ones, and 3.9% suffered from death.. This systematic review and meta-analysis proved PAH-SDT as a safe and effective role in ES in an early stage. However, in a long-term treatment, bosentan has been supported for a lasting effect on exercise tolerance. A further multicenter research with a large sample about pharmacotherapy of ES is necessary.

Topics: Antihypertensive Agents; Bosentan; Eisenmenger Complex; Endothelin Receptor Antagonists; Exercise Tolerance; Hemodynamics; Humans; Hypertension, Pulmonary; Oxygen; Phenylpropionates; Phosphodiesterase 5 Inhibitors; Prostaglandins; Pyridazines; Pyrimidines; Sulfonamides

Previous studies examining the use of pulmonary arterial hypertension (PAH) drugs in patients with Eisenmenger syndrome (ES) have shown that it may have beneficial effects in some patients with ES; however, experience with additional cases is necessary to confirm its efficacy and appropriate clinical use. We herein report our experience of an adult patient with ES who benefitted from treatment with PAH drugs. A 32-year-old Japanese man with severe ES induced by a ventricular septal defect associated with Down syndrome began treatment with bosentan at 62.5 mg. Eleven months later, he was admitted for tadalafil (40 mg) add-on therapy because his 6-minute walking distance and brain natriuretic peptide (BNP) level had not improved and his hepatic enzyme levels had increased. However, marked hypotension developed, and the tadalafil dose was decreased. His BNP level subsequently increased, so the bosentan dose was increased to 125 mg. The bosentan was then abruptly stopped because of a low platelet count and high liver enzyme levels. Ambrisentan was then administered for these side effects, but because severe dyspnea developed, the bosentan was started again at 62.5 mg. This resulted in immediate clinical improvement. The patient was finally switched to ambrisentan (5 mg), which was well tolerated. The findings in this particular case show that although it should be used with caution, bosentan may be beneficial in select patients with ES. In addition, ambrisentan may be considered as first-line treatment in some patients as long as liver enzymes and platelets are carefully monitored.

Topics: Adult; Antihypertensive Agents; Bosentan; Down Syndrome; Eisenmenger Complex; Endothelin Receptor Antagonists; Heart Septal Defects, Ventricular; Humans; Hypertension, Pulmonary; Male; Phenylpropionates; Pyridazines; Sulfonamides

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

Eisenmenger syndrome (ES) is a known complication of congenital heart disease associated with unrepaired systemic to pulmonary shunts. Evidence for use of targeted pulmonary arterial hypertension therapy in ES is limited. The early experience using ambrisentan was evaluated in a cohort of consecutive patients with ES who initiated ambrisentan at Columbia University's Pulmonary Hypertension Center from January 1, 2007, to August 1, 2008. Effects of ambrisentan on rest and exercise systemic arterial oxygen saturation (S(a)O(2)), exercise capacity, functional status, hemoglobin levels, and hemodynamics were evaluated and compared using paired Student's t tests. Seventeen patients were evaluated at short-term (mean 163 ± 57 days) and longer term (mean 2.5 ± 0.5 years) follow-up. At short-term follow-up, there was an improvement in exercise capacity (6-minute walking distance 389 ± 74 vs 417 ± 77 m, p=0.03, n=11) and maintenance of rest S(a)O(2) (89 ± 7% vs 89% ± 6%, p=0.75, n=15), exercise S(a)O(2) (75 ± 15% vs 77% ± 15%, p=0.33, n=11), functional class (improvement in 2 patients, no change in 13), and hemoglobin (16.5 ± 2.8 vs 15.8 ± 1.8 g/dl, p=0.11, n=14). At longer term follow-up compared to baseline and short-term follow-up, there was stability of exercise capacity, S(a)O(2), functional class, and hemoglobin. In conclusion, in this single-center cohort of patients with ES, ambrisentan was safe and was associated with increasing exercise capacity at short-term follow-up, with patients maintaining S(a)O(2), functional class, and hemoglobin, and with no significant evidence of clinical deterioration at longer term follow-up. Additional studies are required to further assess the efficacy of ambrisentan in patients with ES.

Topics: Adult; Eisenmenger Complex; Familial Primary Pulmonary Hypertension; Female; Heart Defects, Congenital; Humans; Hypertension, Pulmonary; Male; Phenylpropionates; Pyridazines; Retrospective Studies; Treatment Outcome