Down patients with Eisenmenger syndrome: Is bosentan treatment an option?

Duffels, Marielle G.; Vis, Jeroen C.; Loon, Rosa L. E. van; Berger, Rudolphus; Hoendermis, Elke S.; Dijk, Arie P.J. van; Bouma, Berto J.; Mulder, Barbara J.M.

doi:10.1016/j.ijcard.2008.02.025

Cited by 62 publications

(53 citation statements)

References 25 publications

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“…Importantly, there have been no randomised controlled trials in Down syndrome with PAH examining response to vasodilator therapy [64,65]. The available data suggest that persons with Down syndrome are equally as responsive as PAH patients without Down syndrome to endothelin receptor antagonists such as bosentan [64][65][66][67][68], although the 6-min walk test may not be an effective end-point [69]. Despite the high incidence of CHD in individuals with trisomy 21, pulmonary thrombosis does not appear to be a cause of morbidity or mortality in Down syndrome [70][71][72][73][74].…”

Section: Respiratory Disease In Down Syndromementioning

confidence: 99%

What people with Down Syndrome can teach us about cardiopulmonary disease

Colvin

Yeager

2017

Eur Respir Rev

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Down syndrome is the most common chromosomal abnormality among live-born infants. Through full or partial trisomy of chromosome 21, Down syndrome is associated with cognitive impairment, congenital malformations ( particularly cardiovascular) and dysmorphic features. Immune disturbances in Down syndrome account for an enormous disease burden ranging from quality-of-life issues (autoimmune alopecia) to more serious health issues (autoimmune thyroiditis) and life-threatening issues (leukaemia, respiratory tract infections and pulmonary hypertension). Cardiovascular and pulmonary diseases account for ∼75% of the mortality seen in persons with Down syndrome. This review summarises the cardiovascular, respiratory and immune challenges faced by individuals with Down syndrome, and the genetic underpinnings of their pathobiology. We strongly advocate increased comparative studies of cardiopulmonary disease in persons with and without Down syndrome, as we believe these will lead to new strategies to prevent and treat diseases affecting millions of people worldwide.

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Section: Respiratory Disease In Down Syndromementioning

confidence: 99%

What people with Down Syndrome can teach us about cardiopulmonary disease

Colvin

Yeager

2017

Eur Respir Rev

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“…This apparent change in outcome may be attributable to the availability of new, targeted treatments for PAH and their use in combination therapy, which has improved prognoses for patients with IPAH. More recently, studies on the use of targeted PAH therapies in PAH-CHD, which have included patients with Eisenmenger's syndrome, have suggested that such targeted therapies may also improve the natural history of the disease in patients with PAH-CHD [15][16][17][18][19].…”

Section: Clinical Presentation Of Pah-chdmentioning

confidence: 99%

“…They were also less likely to be receiving advanced PAH therapy. Bosentan has been investigated for its effects in patients with both Eisenmenger's syndrome and Down's syndrome [18]: median 6-min walk distance (6MWD) significantly increased among bosentan-treated patients over 12 weeks, but not over 52 weeks. The results were consistent with those observed in Eisenmenger's syndrome patients without Down's syndrome, and it appears that bosentan may be of some benefit in dual Down's-Eisenmenger's syndrome patients, especially in the short term.…”

Section: Review: Pah In Chd Bjm Muldermentioning

confidence: 99%

Changing demographics of pulmonary arterial hypertension in congenital heart disease

Mulder¹

2010

European Respiratory Review

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Pulmonary arterial hypertension (PAH) is a serious complication of congenital heart disease (CHD). Without early surgical repair, around one-third of paediatric CHD patients develop significant PAH. Recent data from the Netherlands suggest that .4% of adult CHD patients have PAH, with higher rates in those with septal defects. A spectrum of cardiac defects is associated with PAH-CHD, although most cases develop as a consequence of large systemic-to-pulmonary shunts. Eisenmenger's syndrome, characterised by reversed pulmonary-to-systemic (right-to-left) shunt, represents the most advanced form of PAH-CHD and affects as many as 50% of those with PAH and left-to-right shunts. It is associated with the poorest outcome among patients with PAH-CHD. 40 yrs ago, ,50% of children with CHD requiring intervention died within the first year, and ,15% survived to adulthood. Subsequent advances in paediatric cardiology have seen most patients with CHD survive to adulthood, with resulting shifts in the demographics of CHD and PAH-CHD. The number of adults presenting with CHD is increasing and, although mortality is decreasing, morbidity is increasing as older patients are at increased risk of arrhythmia, heart failure, valve regurgitation and PAH. Data show that probability of PAH increases with age in patients with cardiac defects.KEYWORDS: Congenital heart disease, pulmonary arterial hypertension P ulmonary arterial hypertension (PAH), a disease of the pulmonary vasculature characterised by an elevated mean pulmonary arterial pressure (P pa) at rest of o25 mmHg [1], is one of the most serious complications of congenital heart disease (CHD). After idiopathic PAH (IPAH) and PAH associated with connective tissue diseases (PAH-CTD), it is the third most common form of PAH [2].A diagnosis of PAH has ramifications for both paediatric and adult CHD patients. In children, the course of CHD is complicated by the presence of PAH: estimates suggest that approximately one-third of paediatric CHD patients develop significant PAH without early surgical repair [3]. Increasing numbers of adults are presenting with CHD, illustrated by the fact that there are 1.2 million adult CHD patients in Europe alone, all of whom are at risk of developing PAH. The prevalence of PAH associated with CHD (PAH-CHD) was calculated as 4.2% among a population of 5,970 CHD patients included in the Dutch CONCOR registry, rising to 6.2% among 1,824 patients with septal defects [4]. In a separate Dutch study, 9.9% of 1,148 patients with CTD were found to have PAH [5].PAH can occur in association with a number of conditions other than CHD, although the underlying pathophysiology is similar in each case. Previous studies have suggested that PAH-CHD has a better prognosis than PAH of other aetiologies. Research has demonstrated an actuarial 3-yr survival rate for PAH-CHD of 77%, compared with only 35% at 3 yrs for untreated IPAH [6], 37% for PAH-CTD and 21% for PAH associated with HIV infection [3].Although progression of PAH appears slower in patients with ...

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“…7 An important subgroup in this Eisenmenger population is patients with Down syndrome. 8 Once developed Eisenmenger syndrome patients tend to remain stable for many years, although highly symptomatic, requiring major lifestyle adjustments due to limited functional capacity. 9 Exercise capacity and quality of life (QoL) are diminished, pregnancy is strongly contraindicated in female patients 10 and associated life-threatening complications are numerous.…”

Section: Introduction To the Management Of Pulmonary Arterial Hypertementioning

confidence: 99%

Adult patients with pulmonary arterial hypertension due to congenital heart disease: a review on advanced medical treatment with bosentan

Schuuring

Vis²,

Duffels³

et al. 2010

TCRM

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Pulmonary arterial hypertension (PAH) is a progressive disease with poor survival outcome. PAH is classified by the 2009 updated clinical classification of pulmonary hypertension and a major subgroup is PAH due to congenital heart disease (CHD) with systemic-to-pulmonary shunt. CHD-PAH is a result of systemic-to-pulmonary shunting and chronic increased flow that ultimately results in adaptations of pulmonary vasculature and endothelial dysfunction. The advanced stage is called Eisenmenger syndrome which forms a small percentage (1%) of all CHD patients. Therapies targeted on PAH symptoms are called primary therapy for PAH, but most CHD-PAH patients progress to advanced therapy which is directed at the PAH itself. In CHD-PAH, advanced therapies are extensively investigated for all three major pathways: endothelin-1 receptor antagonists such as bosentan, prostanoids such as epoprostenol and phosphodiesterase 5 inhibitors such as sildenafil. Endpoints in most trials were catheterization hemodynamics, World Health Organization functional class, six-minute walking distance and patient-focused outcomes, based on quality of life questionnaires and Borg dyspnea index. The BREATHE-5 and EARLY study were two important randomized controlled trials showing efficacy of bosentan at short follow-up. Moreover in patients with Eisenmenger syndrome, one recent survival retrospective study with majority of patients on bosentan showed strong survival benefit over conservative therapy. A diversity of prospective cohort and retrospective studies were performed but all with limited data, due to small numbers and heterogeneity of underlying CHD diagnoses. Further larger studies are needed to determine optimal treatment for adults with CHD-PAH. This review focuses on bosentan in CHD-PAH. In particular, we discuss outcome of various clinical trials and compare efficacy and safety of bosentan to other advanced therapies.

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Down patients with Eisenmenger syndrome: Is bosentan treatment an option?

Cited by 62 publications

References 25 publications

What people with Down Syndrome can teach us about cardiopulmonary disease

What people with Down Syndrome can teach us about cardiopulmonary disease

Changing demographics of pulmonary arterial hypertension in congenital heart disease

Adult patients with pulmonary arterial hypertension due to congenital heart disease: a review on advanced medical treatment with bosentan

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