CONCOR, an initiative towards a national registry and DNA-bank of patients with congenital heart disease in the Netherlands: Rationale, design, and first results

Velde, Enno T. van der; Vriend, Joris W.J.; Mannens, Marcel M.A.M.; Uiterwaal, Cuno S.P.M.; Brand, Ronald; Mulder, Barbara J.M.

doi:10.1007/s10654-005-4264-9

Cited by 234 publications

(138 citation statements)

References 16 publications

(21 reference statements)

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“…In fact, there was an 85% increase in adult prevalence between 1985 and 2000, with the largest increase occurring in adolescents and young adults. This pattern is consistent with data on the age distribution of CHD from the Mayo Clinic, USA, which followed adult patients transferred from an existing paediatric programme [23], and from the CONCOR registry in the Netherlands [24]. In both cases, prevalence of CHD was highest in patients aged 20-30 yrs, reflecting improvements in diagnosis, surgery and postoperative care, while 75% of cases occurred in patients aged ,50 yrs [23,24].…”

Section: Changing Demographics Of Chdsupporting

confidence: 86%

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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Section: Changing Demographics Of Chdsupporting

confidence: 86%

Changing demographics of pulmonary arterial hypertension in congenital heart disease

Mulder¹

2010

European Respiratory Review

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“…Moreover, prospective documentation of cases in preferably large registries is necessary to increase knowledge about the clinical course of this population and the effect of treatment strategies. Especially in the field of GUCH, such registries have proven to be very useful for evaluation of outcome and best practice [26,27]. At present, we conclude that improvement in pulmonary flow and clinical functioning can be achieved in selected patients with complex CHD-PH through combination of tailored invasive and medical treatment.…”

Section: Discussionmentioning

confidence: 71%

Tailored circulatory intervention in adults with pulmonary hypertension due to congenital heart disease

et al. 2016

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Background Adults with pulmonary hypertension associated with congenital heart disease (PH-CHD) often have residual shunts. Invasive interventions aim to optimise pulmonary flow and prevent right ventricular failure. However, eligibility for procedures strongly depends on the adaptation potential of the pulmonary vasculature and right ventricle to resultant circulatory changes. Current guidelines are not sufficiently applicable to individual patients, who exhibit great diversity and complexity in cardiac anomalies. Methods and ResultsWe present four complex adult PH-CHD patients with impaired pulmonary flow, including detailed graphics of the cardiopulmonary circulation. All these patients had an ambiguous indication for shunt intervention. Our local multidisciplinary Grown-Ups with Congenital Heart Disease team reached consensus regarding a patient-tailored invasive treatment strategy, adjacent to relevant guidelines. Interventions improved pulmonary haemodynamics and short-term clinical functioning in all cases. Conclusions Individual evaluation of disease characteristics is mandatory for tailored interventional treatment in PH-CHD patients, adjacent to relevant guidelines. Both strict

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“…Patient material was acquired from the CONCOR (CONgenital CORvitia) database. 15 DNA material was obtained from the patient and first-degree relatives by buccal swabs. Family members were clinically evaluated and individuals testing positive for the ALK2, ERBB3 and ALK3 variant were examined by echocardiography.…”

Section: Genetic Materials and Clinical Evaluationmentioning

confidence: 99%

ALK2 mutation in a patient with Down's syndrome and a congenital heart defect

et al. 2011

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Down's syndrome (DS), resulting from an additional copy of chromosome 21 (trisomy 21), is frequently associated with congenital heart defects (CHDs). Although the increased dosage of chromosome 21 sequences is likely to be part of the etiology of cardiac defects, only a proportion of DS patients exhibit a congenital heart defect (birth prevalence 40-60%). Through a large-candidate gene-sequencing screen in patients with atrioventricular septal defects, substitutions were identified in bone morphogenetic protein (BMP ) type I receptor ALK2 and two other genes in a patient with DS and a primum-type atrial septal defect. Structural modeling of the cytoplasmic domain of the ALK2 receptor suggests that H286 is in close proximity to the nucleotide-binding site of the kinase domain. We investigated whether this p.His286Asp substitution altered ALK2 function by using both in vitro as well as in vivo assays. The p.His286Asp variant demonstrated impaired functional activity as measured by BMP-specific transcriptional response assays. Furthermore, mild dominant-interfering activity was observed in vivo compared with wild-type ALK2 as determined by RNA injection into zebrafish embryos. These data indicate that in the context of a DS background, ALK2-mediated reduction of BMP signaling may contribute to CHDs.

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CONCOR, an initiative towards a national registry and DNA-bank of patients with congenital heart disease in the Netherlands: Rationale, design, and first results

Cited by 234 publications

References 16 publications

Changing demographics of pulmonary arterial hypertension in congenital heart disease

Changing demographics of pulmonary arterial hypertension in congenital heart disease

Tailored circulatory intervention in adults with pulmonary hypertension due to congenital heart disease

ALK2 mutation in a patient with Down's syndrome and a congenital heart defect

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