Beneficial effect of high dose statins on the vascular wall in patients with repaired aortic coarctation?

BACKGROUND: Carotid intima-media thickness (CIMT) is a marker for atherosclerosis. Adult post-coarctectomy patients (CoA) demonstrate an increased cardiovascular risk and increased CIMT compared to controls. This study evaluates the effect of high dose statins on the change in CIMT and cardiovascular risk. METHODS: We designed a multicenter, prospective, randomized, open label trial with blinded endpoint (PROBE design) to evaluate the effect of three year treatment with atorvastatin 80 mg on CIMT and cardiovascular risk. Primary endpoint was CIMT measured by B mode ultrasonography. Secondary endpoints were mortality and morbidity due to cardiovascular disease and serum lipids. RESULTS: 155 patients (36.3 ± 11.8 years, 96 (62%) male) were randomized (atorvastatin=80, no treatment=75). There was no significant effect of atorvastatin on the change in CIMT (treatment effect -0.005, 95% CI, -0.039-0.029; P=0.76). A significant effect on serum cholesterol and LDL levels was found (- 0.71, 95% CI, - 1.16 to - 0.26; P = 0.002 vs - 0.66, 95% CI - 1.06 to - 0.26; P = 0.001). There was no difference in secondary outcome measures. Baseline CIMT was higher in hypertensive compared to normotensive CoA. (0.69 ± 0.16 mm vs 0.61 ± 0.98 mm; P=0.002). Hypertension (ß=0.043, P=0.031) was the strongest determinant CIMT. CONCLUSION: Three year treatment with atorvastatin does not lead to a reduction of CIMT and secondary outcome measures, despite a decrease in total cholesterol and LDL levels. Hypertensive CoA demonstrate the highest CIMT and the largest CIMT progression. Blood pressure control should be the main focus in CoA to decrease cardiovascular risk.

Pulmonary arterial hypertension in congenital heart disease: an epidemiologic perspective from a Dutch registry.

BACKGROUND: Pulmonary arterial hypertension (PAH) associated with congenital heart disease is usually the result of a large systemic-to-pulmonary shunt, and often leads to right ventricular failure and early death. The purpose of this study was to determine the prevalence of PAH among adult patients included in a national registry of congenital heart disease and to assess the relation between patient characteristics and PAH. METHODS: Patients with PAH associated with a septal defect were identified from the registry. Gender, age, underlying diagnosis, previous closure, age at repair and NYHA classification were recorded. PAH was defined as a systolic pulmonary arterial pressure (sPAP) greater than 40 mm Hg, estimated by means of echocardiographical evaluation. RESULTS: The prevalence of PAH among all 5970 registered adult patients with congenital heart disease was 4.2%. Of 1824 patients with a septal defect in the registry, 112 patients (6.1%) had PAH. Median age of these patients was 38 years (range 18-81 years) and 40% were male. Of these patients, 58% had the Eisenmenger syndrome. Among the patients with a previously closed septal defect, 30 had PAH (3%). Ventricular septal defect (VSD) was the most frequent underlying defect (42%) among patients with PAH and a septal defect. Female sex (Odds ratio=1.5, p=0.001) and sPAP (Odds ratio=0.04, p<0.001) were independently associated with a decreased functional class. CONCLUSION: PAH is common in adult patients with congenital heart disease. In our registry the prevalence of PAH in septal defects is around 6%. More than half of these patients have the Eisenmenger syndrome, which accounts for 1% of the total population in the CONCOR registry. Whether the prevalence of PAH will decrease in the future as a result of early detection and intervention remains to be awaited.

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

INTRODUCTION: Survival of patients with congenital heart disease has dramatically improved after surgical repair became available 40 years ago. Instead of a mortality of 85% during childhood following the natural course, over 85% of these infants are now expected to reach adulthood. However, data on long-term outcome is scarce due to the lack of large, national registries. Moreover, little is known about the genetic basis of congenital heart defects. In 2000, the Interuniversity Cardiology Institute of the Netherlands and the Netherlands Heart Foundation have taken the initiative to develop a national registry and DNA-bank of patients with congenital heart disease in the Netherlands named CONCOR. OBJECTIVES: The aims of the CONCOR project are to facilitate investigation of the prevalence and long-term outcome of specific congenital heart defects and their treatment, to develop an efficient organisational structure for the improvement of healthcare for patients with congenital heart disease, and to allow investigation of the molecular basis of congenital heart defects. METHODS: After informed consent, research nurses enter data of participating patients into the CONCOR database using a web application. Data is transferred over the Internet via a secure connection. About 20 ml blood is withdrawn from the patient, and the DNA is isolated and stored. From each participating patient family history on congenital heart disease is obtained. RESULTS: Within two and a half years more than 4200 patients have agreed to participate. More than 99% of the patients that were asked have given their consent to participate in CONCOR. From 60% of these patients DNA has already been obtained. Mean age of the patients included is 34 years; more than 85% of the patients are younger than 45 years. Late complications occur frequently and the incidence increases with advancing age. 18% of the patients are known with supraventricular or ventricular arrhythmias. 2% of the included patients suffered a cerebrovascular accident, 139 (3%) had endocarditis. 6% of the patients has pulmonary hypertension or Eisenmenger syndrome. More than 15% of the patients reported an affected family member with congenital heart disease in the first, second, or third degree. 6% has an affected first-degree relative, and 4% a second-degree relative. Already 10 research projects have started using the CONCOR data and DNA. CONCLUSION: The population of patients with congenital heart disease is young and rapidly growing. Late complications occur frequently and the incidence increases with advances age. The CONCOR registry and DNA-bank facilitates research on prevalence and long-term outcome and allows investigation of the molecular basis of congenital heart disease.

[National registry and DNA-bank of patients with congenital heart disease: the CONCOR-project]. / Landelijke registratie en DNA-bank van patiënten met aangeboren hartafwijkingen, het CONCOR-project.

Although survival of patients with congenital heart disease has dramatically improved since surgical repair has become available, cure is seldom achieved. Exact data on long-term outcome are not available, however, because a national registry is lacking. Furthermore, little is known about the role of genetic defects in the development of congenital heart disease. The CONCOR-project (CONgenital CORvitia) has been set up to facilitate the investigation of the long-term outcome and molecular basis of specific congenital heart defects and their treatment. It will also facilitate the development of an efficient organisational structure for the improvement of healthcare for patients with congenital heart disease.

Aortic coarctation: the need for lifelong surveillance.

Survival of patients with aortic coarctation improved dramatically after surgical repair became available and the number of patients who undergo surgery and reach adulthood is steadily increasing. However, life expectancy is still not as normal as in unaffected peers. Cardiovascular complications are frequent and require indefinite follow-up. Concern falls chiefly into five categories: recoarctation, endocarditis, stenotic and/or incompetent coexisting bicuspid aortic valve, aortic aneurysm formation and systemic hypertension. In this review, these complications, with particular reference to late hypertension, are discussed and strategies for the clinical management of postcoarctectomy patients are described.