http://repub.eur.nl/res/aut/4092/ List of Publications en http://repub.eur.nl/static-eur/img/logo.png http://repub.eur.nl http://repub.eur.nl/res/pub/40107/ 2013-05-01T00:00:00Z Thoracic aortic aneurysms and dissections (TAAD) is a serious condition with high morbidity and mortality. It is estimated that 20% of non-syndromic TAAD cases are inherited in an autosomal-dominant pattern with variable expression and reduced penetrance. Mutations in myosin heavy chain 11 (MYH11), one of several identified TAAD genes, were shown to simultaneously cause TAAD and patent ductus arteriosus (PDA). We identified two large Dutch families with TAAD/PDA and detected two different novel heterozygote MYH11 variants in the probands. These variants, a heterozygote missense variant and a heterozygote in-frame deletion, were predicted to have damaging effects on protein structure and function. However, these novel alterations did not segregate with the TAAD/PDA in 3 out of 11 cases in family TAAD01 and in 2 out of 6 cases of family TAAD02. No mutation was detected in other known TAAD genes. Thus, it is expected that within these families other genetic factors contribute to the disease either by themselves or by interacting with the MYH11 variants. Such an oligogenic model for TAAD would explain the variable onset and progression of the disorder and its reduced penetrance in general. We conclude that in familial TAAD/PDA with an MYH11 variant in the index case caution should be exercised upon counseling family members. Specialized surveillance should still be offered to the non-carriers to prevent catastrophic aortic dissections or ruptures. Furthermore, our study underscores that segregation analysis remains very important in clinical genetics. Prediction programs and mutation evaluation algorithms need to be interpreted with caution. http://repub.eur.nl/res/pub/39472/ 2013-03-19T00:00:00Z Aims: The twisting motion of the heart has an important role in the function of the left ventricle. Speckle tracking echocardiography is able to quantify left ventricular (LV) rotation and twist. So far this new technique has not been used in congenital heart disease patients. The aim of our study was to investigate the feasibility and the intra- and inter-observer reproducibility of LV rotation parameters in adult patients with congenital heart disease. Methods and Results: The study population consisted of 66 consecutive patients seen in the outpatient clinic (67% male, mean age 31 ± 7.7 years, NYHA class 1 ± 0.3) with a variety of congenital heart disease. First, feasibility was assessed in all patients. Intra- and inter-observer reproducibility was assessed for the patients in which speckle tracking echocardiography was feasible. Adequate image quality, for performing speckle echocardiography, was found in 80% of patients. The bias for the intra-observer reproducibility of the LV twist was 0.0°, with 95% limits of agreement of -2.5° and 2.5° and for interobserver reproducibility the bias was 0.0°, with 95% limits of agreement of -3.0° and 3.0°. Intra- and inter-observer measurements showed a strong correlation (0.86 and 0.79, respectively). Also a good repeatability was seen. The mean time to complete full analysis per subject for the first and second measurement was 9 and 5 minutes, respectively. Conclusion: Speckle tracking echocardiography is feasible in 80% of adult patients with congenital heart disease and shows excellent intra- and inter-observer reproducibility. http://repub.eur.nl/res/pub/39706/ 2013-03-19T00:00:00Z Background: Discrete subaortic stenosis is notable for its unpredictable hemodynamic progression in childhood and high reoperation rate; however, data about adulthood are scarce. Methods and Results: Adult patients who previously underwent surgery for discrete subaortic stenosis were included in this retrospective multicenter cohort study. Mixed-effects and joint models were used to assess the postoperative progression of discrete subaortic stenosis and aortic regurgitation, as well as reoperation. A total of 313 patients at 4 centers were included (age at baseline, 20.2 years [25th-75th percentile, 18.4-31.0 years]; 52% male). Median follow-up duration was 12.9 years (25th-75th percentile, 6.2-20.1 years), yielding 5617 patient-years. The peak instantaneous left ventricular outflow tract gradient decreased from 75.7±28.0 mm Hg preoperatively to 15.1±14.1 mm Hg postoperatively (P<0.001) and thereafter increased over time at a rate of 1.31±0.16 mm Hg/y (P=0.001). Mild aortic regurgitation was present in 68% but generally did not progress over time (P=0.76). A preoperative left ventricular outflow tract gradient ≥80 mm Hg was a predictor for progression to moderate aortic regurgitation postoperatively. Eighty patients required at least 1 reoperation (1.8% per patient-year). Predictors for reoperation included female sex (hazard ratio, 1.53; 95% confidence interval, 1.02-2.30) and left ventricular outflow tract gradient progression (hazard ratio, 1.45; 95% confidence interval, 1.31-1.62). Additional myectomy did not reduce the risk for reoperation (P=0.92) but significantly increased the risk of a complete heart block requiring pacemaker implantation (8.1% versus 1.7%; P=0.005). Conclusions: Survival is excellent after surgery for discrete subaortic stenosis; however, reoperation for recurrent discrete subaortic stenosis is not uncommon. Over time, the left ventricular outflow tract gradient slowly increases and mild aortic regurgitation is common, although generally nonprogressive over time. Myectomy does not show additional advantages, and because it is associated with an increased risk of complete heart block, it should not be performed routinely. http://repub.eur.nl/res/pub/38672/ 2012-09-26T00:00:00Z Background: The aim of this study was to evaluate the natural progression of aortic dilatation and its association with aortic valve stenosis (AoS) in patients with bicuspid aortic valve (BAV). Methods: Prospective study of aorta dilatation in patients with BAV and AoS using cardiac magnetic resonance (CMR). Aortic root, ascending aorta, aortic peak velocity, left ventricular systolic and diastolic function and mass were assessed at baseline and at 3-year follow-up. Results: Of the 33 enrolled patients, 5 needed surgery, while 28 patients (17 male; mean age: 31 ± 8 years) completed the study. Aortic diameters significantly increased at the aortic annulus, sinus of Valsalva and tubular ascending aorta levels (P < 0.050). The number of patients with dilated tubular ascending aortas increased from 32 % to 43 %. No significant increase in sino-tubular junction diameter was observed. Aortic peak velocity, ejection fraction and myocardial mass significantly increased while the early/late filling ratio significantly decreased at follow-up (P < 0.050). The progression rate of the ascending aorta diameter correlated weakly with the aortic peak velocity at baseline (R2= 0.16, P = 0.040). Conclusion: BAV patients with AoS showed a progressive increase of aortic diameters with maximal expression at the level of the tubular ascending aorta. The progression of aortic dilatation correlated weakly with the severity of AoS. Key Points: • Bicuspid aortic valve (BAV) is the most common congenital heart defect. • BAV patients have an increased risk of developing aortic valve stenosis (AoS). • BAV patients have an increased risk of developing thoracic aorta dilatation. • The severity of aortic stenosis is correlated to the progression of aortic dilatation. • Cardiac magnetic resonance can rapidly assess patients with a bicuspid aortic valve. http://repub.eur.nl/res/pub/37728/ 2012-09-01T00:00:00Z The objective of the present study was to report our ongoing prospective cohort of autograft recipients with up to 21 years of follow-up. All consecutive patients (n = 161), operated between 1988 and 2010, were analysed. Mixed-effects models were used to assess changes in echocardiographic measurements (n = 1023) over time in both the autograft and the pulmonary allograft. The mean patient age was 20.9 years (range 0.05-52.7)-66.5% were male. Early mortality was 2.5% (n = 4), and eight additional patients died during a mean follow-up of 11.6 ± 5.7 years (range 0-21.5). Patient survival was 90% [95% confidence interval (CI), 78-95] up to 18 years. During the follow-up, 57 patients required a re-intervention related to the Ross operation. Freedom from autograft reoperation and allograft re-intervention was 51% (95% CI 38-63) and 82% (95% CI 71-89) after 18 years, respectively. No major changes were observed over time in autograft gradient, and allograft gradient and regurgitation. An initial increase of sinotubular junction and aortic anulus diameter was observed in the first 5 years after surgery. The only factor associated with an increased autograft reoperation rate was pre-operative pure aortic regurgitation (AR) (hazard ratio 1.88; 95% CI 1.04-3.39; P= 0.037). We observed good late survival in patients undergoing autograft procedure without reinforcement techniques. However, over half of the autografts failed prior to the end of the second decade. The reoperation rate and the results of echocardiographic measurements over time underline the importance of careful monitoring especially in the second decade after the initial autograft operation and in particular in patients with pre-operative AR. http://repub.eur.nl/res/pub/35039/ 2012-01-01T00:00:00Z Background: Aneurysmseosteoarthritis syndrome (AOS) is a new autosomal dominant syndromic form of thoracic aortic aneurysms and dissections characterised by the presence of arterial aneurysms and tortuosity, mild craniofacial, skeletal and cutaneous anomalies, and early-onset osteoarthritis. AOS is caused by mutations in the SMAD3 gene. Methods: A cohort of 393 patients with aneurysms without mutation in FBN1, TGFBR1 and TGFBR2 was screened for mutations in SMAD3. The patients originated from The Netherlands, Belgium, Switzerland and USA. The clinical phenotype in a total of 45 patients from eight different AOS families with eight different SMAD3 mutations is described. In all patients with a SMAD3 mutation, clinical records were reviewed and extensive genetic, cardiovascular and orthopaedic examinations were performed. Results Five novel SMAD3 mutations (one nonsense, two missense and two frame-shift mutations) were identified in five new AOS families. A follow-up description of the three families with a SMAD3 mutation previously described by the authors was included. In the majority of patients, early-onset joint abnormalities, including osteoarthritis and osteochondritis dissecans, were the initial symptom for which medical advice was sought. Cardiovascular abnormalities were present in almost 90% of patients, and involved mainly aortic aneurysms and dissections. Aneurysms and tortuosity were found in the aorta and other arteries throughout the body, including intracranial arteries. Of the patients who first presented with joint abnormalities, 20% died suddenly from aortic dissection. The presence of mild craniofacial abnormalities including hypertelorism and abnormal uvula may aid the recognition of this syndrome. Conclusion: The authors provide further insight into the phenotype of AOS with SMAD3 mutations, and present recommendations for a clinical work-up. http://repub.eur.nl/res/pub/34420/ 2011-12-14T00:00:00Z http://repub.eur.nl/res/pub/33897/ 2011-11-15T00:00:00Z Congenital heart disease (CHD) accounts for nearly one-third of all major congenital anomalies. CHD birth prevalence worldwide and over time is suggested to vary; however, a complete overview is missing. This systematic review included 114 papers, comprising a total study population of 24,091,867 live births with CHD identified in 164,396 individuals. Birth prevalence of total CHD and the 8 most common subtypes were pooled in 5-year time periods since 1930 and in continent and income groups since 1970 using the inverse variance method. Reported total CHD birth prevalence increased substantially over time, from 0.6 per 1,000 live births (95% confidence interval [CI]: 0.4 to 0.8) in 1930 to 1934 to 9.1 per 1,000 live births (95% CI: 9.0 to 9.2) after 1995. Over the last 15 years, stabilization occurred, corresponding to 1.35 million newborns with CHD every year. Significant geographical differences were found. Asia reported the highest CHD birth prevalence, with 9.3 per 1,000 live births (95% CI: 8.9 to 9.7), with relatively more pulmonary outflow obstructions and fewer left ventricular outflow tract obstructions. Reported total CHD birth prevalence in Europe was significantly higher than in North America (8.2 per 1,000 live births [95% CI: 8.1 to 8.3] vs. 6.9 per 1,000 live births [95% CI: 6.7 to 7.1]; p < 0.001). Access to health care is still limited in many parts of the world, as are diagnostic facilities, probably accounting for differences in reported birth prevalence between high- and low-income countries. Observed differences may also be of genetic, environmental, socioeconomical, or ethnic origin, and there needs to be further investigation to tailor the management of this global health problem. http://repub.eur.nl/res/pub/30703/ 2011-10-11T00:00:00Z There are physiological reasons for the effects of positioning on hemodynamic variables and cardiac dimensions related to altered intra-abdominal and intra-thoracic pressures. This problem is especially evident in pregnant women due to the additional aorto-caval compression by the enlarged uterus. The purpose of this study was to investigate the effect of postural changes on cardiac dimensions and function during mid and late pregnancy using cardiovascular magnetic resonance (CMR). Healthy non-pregnant women, pregnant women at 20th week of gestation and at 32nd week of gestation without history of cardiac disease were recruited to the study and underwent CMR in supine and left lateral positions. Cardiac hemodynamic parameters and dimensions were measured and compared between both positions. Five non-pregnant women, 6 healthy pregnant women at mid pregnancy and 8 healthy pregnant women at late pregnancy were enrolled in the study. In the group of non-pregnant women left ventricular (LV) cardiac output (CO) significantly decreased by 9% (p=0.043) and right ventricular (RV) end-diastolic volume (EDV) significantly increased by 5% (p=0.043) from the supine to the left lateral position. During mid pregnancy LV ejection fraction (EF), stroke volume (SV), left atrium lateral diameter and left atrial supero-inferior diameter increased significantly from the supine position to the left lateral position: 8%, 27%, 5% and 11%, respectively (p<0.05). RV EDV, SV and right atrium supero-inferior diameter significantly increased from the supine to the left lateral position: 25%, 31% and 13% (p<0.05), respectively. During late pregnancy a significant increment of LV EF, EDV, SV and CO was observed in the left lateral position: 11%, 21%, 35% and 24% (p<0.05), respectively. Left atrial diameters were significantly larger in the left lateral position compared to the supine position (p<0.05). RV CO was significantly increased in the left lateral position compared to the supine position (p<0.05). During pregnancy positional changes affect significantly cardiac hemodynamic parameters and dimensions. Pregnant women who need serial studies by CMR should be imaged in a consistent position. From as early as 20 weeks the left lateral position should be preferred on the supine position because it positively affects venous return, SV and CO. http://repub.eur.nl/res/pub/33365/ 2011-07-15T00:00:00Z Recent trials have failed to show that statin therapy halts the progression of calcific aortic stenosis (AS). We hypothesized that statin therapy in younger patients with congenital AS would be more beneficial, because the valve is less calcified. In the present double-blind, placebo-controlled trial, 63 patients with congenital AS (age 18 to 45 years) were randomly assigned to receive either 10 mg of rosuvastatin daily (n = 30) or matched placebo (n = 33). The primary end point was the progression of peak aortic valve velocity. The secondary end points were temporal changes in the left ventricular mass, ascending aortic diameter, and N-terminal pro-brain natriuretic peptide (NT-proBNP). The median follow-up was 2.4 years (interquartile range 1.9 to 3.0). The mean increase in peak velocity was 0.05 ± 0.21 m/s annually in the rosuvastatin group and 0.09 ± 0.24 m/s annually in the placebo group (p = 0.435). The annualized change in the ascending aorta diameter (0.4 ± 1.7 mm with rosuvastatin vs 0.5 ± 1.6 mm with placebo; p = 0.826) and left ventricular mass (1.1 ± 15.8 g with rosuvastatin vs -3.7 ± 30.9 g with placebo; p = 0.476) were not significantly different between the 2 groups. Within the statin group, the NT-proBNP level was 50 pg/ml (range 19 to 98) at baseline and 21 pg/ml (interquartile range 12 to 65) at follow-up (p = 0.638). NT-proBNP increased from 40 pg/ml (interquartile range 20 to 92) to 56 pg/ml (range 26 to 130) within the placebo group (p = 0.008). In conclusion, lipid-lowering therapy with rosuvastatin 10 mg did not reduce the progression of congenital AS in asymptomatic young adult patients. Interestingly, statins halted the increase in NT-proBNP, suggesting a potential positive effect of statins on cardiac function in young patients with congenital AS. http://repub.eur.nl/res/pub/33654/ 2011-07-01T00:00:00Z Thoracic aortic aneurysms (TAAs) are a potential life-threatening disease with limited pharmacological treatment options. Current treatment options are aimed at lowering aortic hemodynamic stress, predominantly with β-adrenoceptor blockers. Increasing evidence supports a role for the renin-angiotensin system (RAS) in aneurysm development. RAS blockade would not only lower blood pressure, but might also target the molecular pathways involved in aneurysm formation, in particular the transforming growth factor-β and extracellular signal-regulated kinase 1/2 pathways. Indeed, the angiotensin II type 1 (AT1) receptor blocker losartan was effective in lowering aortic root growth in mice and patients with Marfan's syndrome. RAS inhibition (currently possible at 3 levels, i.e. renin, ACE and the AT1receptor) is always accompanied by a rise in renin due to interference with the negative feedback loop between renin and angiotensin II. Only during AT1receptor blockade will this result in stimulation of the non-blocked angiotensin II type 2 (AT2) receptor. This review summarizes the clinical aspects of TAAs, provides an overview of the current mouse models for TAAs, and focuses on the RAS as a new target for TAA treatment, discussing in particular the possibility that AT2receptor stimulation might be crucial in this regard. If true, this would imply that AT1receptor blockers (and not ACE inhibitors or renin inhibitors) should be the preferred treatment option for TAAs. http://repub.eur.nl/res/pub/26303/ 2011-06-01T00:00:00Z Background: Substantial variability in sequential echocardiographic right ventricular (RV) quantification may exist. Interobserver and intraobserver values are well known, but acquisition (test-retest) variability has been rarely assessed. The objective of this study was to determine the test-retest variability of sequential RV volume and ejection fraction (EF) measurements by real-time three-dimensional echocardiography in patients with congenital heart disease and healthy controls. Methods: Twenty-eight participants (21 patients with congenital heart disease, seven healthy controls; mean age, 30 ± 14 years; 43% men) underwent a series of three echocardiographic studies. To obtain interobserver and intraobserver test-retest variability, two sonographers acquired sequential RV data sets in each participant during one outpatient visit. RV volumetric quantification was done using semiautomated three-dimensional border detection. The variability data were analyzed using correlation coefficients, Bland-Altman analysis, and coefficients of variation. Results: Absolute mean differences for sequential intraobserver acquisitions were 12 ± 12 mL for end-diastolic volume, 7 ± 6 mL for end-systolic volume, and 4 ± 3% for EF. Interobserver and intraobserver test-retest variability, respectively, were 7% and 7% for RV end-diastolic volume, 14% and 7% for end-systolic volume, and 8% and 6% for EF. Conclusions: Good test-retest variability, besides the practical nature of real-time three-dimensional echocardiography for RV volume and EF assessment, makes it a valuable technique for serial follow-up. Although it may be challenging to diminish all factors that can influence echocardiographic examination for serial follow-up, standardization of RV size and functional measurements should be a goal to produce more interchangeable data. Copyright 2011 by the American Society of Echocardiography. http://repub.eur.nl/res/pub/33702/ 2011-03-03T00:00:00Z Background: In patients with complex congenital heart disease (CHD) abnormal ventricular stress responses have been reported with dobutamine stress cardiovascular magnetic resonance (DCMR). These abnormal stress responses are potential indicators of long-term outcome. However, safety and reproducibility of this technique has not been reported in a larger study. The aim of this study was to report our experiences regarding safety and intra-observer and inter-observer variability of low-dose DCMR in complex CHD. Methods: In 91 patients, 110 low-dose DCMR studies were performed with acquisition of a short axis set at rest, and during dobutamine administration (7.5 μg/kg/min maximum). We assessed biventricular end-diastolic volumes, end-systolic volumes, stroke volumes, ejection fraction and ventricular mass. Intra- and inter-observer variability for all variables was assessed by calculating the coefficient of variation (%), i.e. the standard deviation of the difference divided by the mean of 2 measurements multiplied by 100%. Results: In 3 patients minor side effects occurred (vertigo, headache, and bigeminy). Ten patients experienced an increase in heart rate of > 150% from baseline, although well tolerated. For all variables, intra-observer variability was < 10% at rest and during stress. At rest, inter-observer variability was 10.5% maximal. With stress-testing, only the variability of biventricular end-systolic volumes (ESV) exceeded 10%. Conclusions: In patients with complex CHD low-dose DCMR is feasible, and safe. Intra-observer variability is low for rest and stress measurements. Inter-observer variability of biventricular ESV is high with stress-testing. Whether this limits the potential usefulness of DCMR for risk assessment during follow-up has to be assessed. http://repub.eur.nl/res/pub/22768/ 2011-03-01T00:00:00Z While nifedipine is commonly used for tocolysis, the controversy on its safety remains. So far, the haemodynamic effects on maternal and fetal circulations have not been well documented. Fifteen normotensive women who received 20 mg nifedipine were included in this prospective observational study. The maternal and fetal haemodynamic effects were analysed using maternal echocardiography and fetal Doppler ultrasonography. Nifedipine induced a significant afterload reduction in all women. It triggered a compensatory increase in cardiac output, which maintained blood pressure. These maternal changes had no influence on the uteroplacental and fetal circulations. http://repub.eur.nl/res/pub/22905/ 2011-02-01T00:00:00Z Background: Previous research has shown that women with congenital heart disease (CHD) are more susceptible to cardiovascular, obstetric, and offspring events. The causative pathophysiologic mechanisms are incompletely understood. Inadequate uteroplacental circulation is an important denominator in adverse obstetric events and offspring outcome. The relation between cardiac function and uteroplacental perfusion has not been investigated in women with CHD. Moreover, the effects of physiologic changes on pregnancy-related events are unknown. In addition, long-term effects of pregnancy on cardiac function and exercise capacity are scarce. Methods: Zwangerschap bij Aangeboren Hartafwijking (ZAHARA) II, a prospective multicenter cohort study, investigates changes in and relations between cardiovascular parameters and uteroplacental Doppler flow patterns during pregnancy in women with CHD compared to matched healthy controls. The relation between cardiovascular parameters and uteroplacental Doppler flow patterns and the occurrence of cardiac, obstetric, and offspring events will be investigated. At 20 and 32 weeks of gestation, clinical, neurohumoral, and echocardiographic evaluation and fetal growth together with Doppler flow measurements in fetal and maternal circulation are performed. Maternal evaluation is repeated 1 year postpartum. Implications: By identifying the factors responsible for pregnancy-related events in women with CHD, risk stratification can be refined, which may lead to better pre-pregnancy counseling and eventually improve treatment of these women. http://repub.eur.nl/res/pub/23490/ 2011-02-01T00:00:00Z Background: In women with corrected tetralogy of Fallot (ToF), pregnancy is associated with maternal cardiac, obstetric, and offspring complications. Our aim is to investigate the magnitude and determinants of pregnancy outcome in women with corrected ToF. Methods: In this retrospective international multicenter study using 2 congenital heart disease registries, 204 women with corrected ToF were identified. Within this group, 74 women had 157 pregnancies, including 30 miscarriages and 4 terminations of pregnancy. Detailed information on each completed pregnancy (n = 123) was obtained using medical records and supplementary interviews. Results: Cardiovascular events occurred during 10 (8.1%) pregnancies, mainly (supra)ventricular arrhythmias. Obstetric and offspring events occurred in 73 (58.9%) and 42 (33.9%) pregnancies, respectively, including offspring mortality in 8 (6.4%). The most important predictor was use of cardiac medication before pregnancy (odds ratio for cardiac events 11.7, 95% CI 2.2-62.7; odds ratio for offspring events 8.4, 95% CI 1.4-48.6). In pregnancies with cardiovascular events, significantly more small-for-gestational-age children were born (P value < .01). Conclusions: Cardiovascular, obstetric, and offspring events occur frequently during pregnancies in women with ToF. Maternal use of cardiovascular medication is associated with pregnancy outcome, and maternal cardiovascular events during pregnancy are highly associated with offspring events. http://repub.eur.nl/res/pub/31637/ 2011-02-01T00:00:00Z Thoracic aortic aneurysms and dissections are a main feature of connective tissue disorders, such as Marfan syndrome and Loeys-Dietz syndrome. We delineated a new syndrome presenting with aneurysms, dissections and tortuosity throughout the arterial tree in association with mild craniofacial features and skeletal and cutaneous anomalies. In contrast with other aneurysm syndromes, most of these affected individuals presented with early-onset osteoarthritis. We mapped the genetic locus to chromosome 15q22.2-24.2 and show that the disease is caused by mutations in SMAD3. This gene encodes a member of the TGF-β pathway that is essential for TGF-β signal transmission. SMAD3 mutations lead to increased aortic expression of several key players in the TGF-β pathway, including SMAD3. Molecular diagnosis will allow early and reliable identification of cases and relatives at risk for major cardiovascular complications. Our findings endorse the TGF-β pathway as the primary pharmacological target for the development of new treatments for aortic aneurysms and osteoarthritis. http://repub.eur.nl/res/pub/23161/ 2011-01-01T00:00:00Z While nifedipine is commonly used for tocolysis, the controversy on its safety remains. So far, the haemodynamic effects on maternal and fetal circulations have not been well documented. Fifteen normotensive women who received 20 mg nifedipine were included in this prospective observational study. The maternal and fetal haemodynamic effects were analysed using maternal echocardiography and fetal Doppler ultrasonography. Nifedipine induced a significant afterload reduction in all women. It triggered a compensatory increase in cardiac output, which maintained blood pressure. These maternal changes had no influence on the uteroplacental and fetal circulations. http://repub.eur.nl/res/pub/28247/ 2010-12-06T00:00:00Z Objective: Allograft conduits are used for reconstruction of the right ventricular outflow tract in congenital heart malformations (biventricular repair) and autograft procedures. A retrospective evaluation of allograft reconstruction of the right-ventricular-outflow-tract reconstruction was conducted and a cross-sectional quality of life study was performed. Methods: Between August 1986 and March 2009, 509 allografts (435 pulmonary and 74 aortic) were implanted in 463 pediatric and adult patients (308 right-sided congenital heart malformations and 155 autograft procedures). Perioperative and follow-up data were collected and analyzed. Kaplan-Meier analyses were done for survival, valve-related re-operation, and valve-related events. Cox regression analysis was used for evaluation of potential risk factors. In addition, the Short Form-36 was presented to patients to assess the perceived quality of life. The results of the Short Form-36 were compared to age-adjusted Dutch population norms. Results: The mean age at allograft implantation was 19 years (1 week-66 years). Mean follow-up was 9 years (2 days-22 years). Forty-eight patients died during follow-up. Patient survival was 93% at 10 years and 88% at 15 years. A total of 63 re-operations were required for allograft dysfunction in 58 patients. Freedom from valve-related re-operation was 89% at 10 years and 81% at 15 years. Freedom from valve-related events was 86% at 10 years and 74% at 15 years. Younger patient age (p = 0.007) and the use of an aortic allograft (p < 0.001) were identified as independent risk factors for allograft re-operation. Patients between 14 and 40 years scored significantly lower on 'physical functioning' and 'general health' subscales than the general Dutch population, but scored better on the subscales 'emotional role functioning' and 'bodily pain'. Except for the subscale 'general health', on which patients within our study population scored lower, patients between 41 and 60 years had comparable average scores as the general Dutch population. The older patient group (61 years or older) had a better average score on the subscale 'bodily pain' and similar scores on other subscales with respect to the general Dutch population. Conclusions: Right-ventricular-outflow-tract reconstruction with an allograft conduit can be performed with good patient survival, acceptable long-term allograft durability, and good perceived quality of life. http://repub.eur.nl/res/pub/22054/ 2010-11-01T00:00:00Z Background: Angiotensin II receptor blockers have been proven to be beneficial in left ventricular failure. In patients with a morphologic right ventricle supporting the systemic circulation, its efficacy has not yet been established. Methods: We designed a multicenter, prospective, randomized, double-blind, placebo-controlled trial studying the effect of valsartan in patients with a systemic right ventricle due to a congenitally or surgically corrected transposition of the great arteries. The primary end point is the change in right ventricular ejection fraction as measured by cardiovascular magnetic resonance or multidetector row cardiac computed tomography in case of pacemaker patients. Conclusion: This large prospective, double-blind, randomized, placebo-controlled trial will establish the role of angiotensin II receptor blockers (valsartan) in the treatment of patients with a systemic right ventricle. http://repub.eur.nl/res/pub/27586/ 2010-09-15T00:00:00Z Because right ventricular (RV) dysfunction predicts a poor outcome in patients with congenital heart disease (CHD), regular monitoring of RV function is indicated. To date, cardiac magnetic resonance (CMR) imaging has been the reference method. A more practical, more accessible, and accurate tool would be preferred. We defined normality regarding RV systolic function using healthy controls and tested the ability of real-time 3-dimensional echocardiographic (RT3DE) findings to identify patients with CHD with RV dysfunction. The cutoff values for the RV volumes and ejection fraction (EF) were derived from the CMR imaging findings from 41 healthy controls (mean age 27 ± 8 years, 56% men). In 100 patients with varying CHDs (mean age 27 ± 11 years, 65% men), both RT3DE data sets (iE33) and short-axis CMR imaging (1.5 T) were obtained within 2 hours. The RT3DE and CMR RV volumes and EF were calculated using commercially available software. Receiver operating characteristic curves were created to obtain the sensitivity and specificity of the RT3DE data to identify RV dysfunction. Applying the cutoff values derived from the healthy controls using the CMR data of patients with CHD, we identified 23 patients with an enlarged indexed end-diastolic volume, 29 patients with an enlarged indexed end-systolic volume, and 21 patients with an impaired RVEF. The best cutoff values predicting RV dysfunction using the RT3DE findings were identified (indexed end-diastolic volume >105 ml/m2, indexed end-systolic volume >54 ml/m2, and EF <43%). The RT3DE findings revealed 23 patients with impaired RVEF, with 95% sensitivity, 89% specificity, and a negative predictive value of 99%. In conclusion, real-time 3-dimensional echocardiography is a very sensitive tool to identify RV dysfunction in patients with CHD and could be applied clinically to rule out RV dysfunction or to indicate additional quantitative analysis of RV function. http://repub.eur.nl/res/pub/27764/ 2010-09-01T00:00:00Z Aims:Data regarding pregnancy outcome in women with congenital heart disease (CHD) are limited.Methods and results: In 1802 women with CHD, 1302 completed pregnancies were observed. Independent predictors of cardiac, obstetric, and neonatal complications were calculated using logistic regression. The most prevalent cardiac complications during pregnancy were arrhythmias (4.7) and heart failure (1.6). Factors independently associated with maternal cardiac complications were the presence of cyanotic heart disease (corrected/uncorrected) (P < 0.0001), the use of cardiac medication before pregnancy (P < 0.0001), and left heart obstruction (P < 0.0001). New characteristics were mechanical valve replacement (P = 0.0014), and systemic (P = 0.04) or pulmonary atrioventricular valve regurgitation related with the underlying (moderately) complex CHD (P = 0.03). A new risk score for cardiac complications is proposed. The most prevalent obstetric complications were hypertensive complications (12.2). No correlation of maternal characteristics with adverse obstetric outcome was found. The most prevalent neonatal complications were premature birth (12), small for gestational age (14), and mortality (4). Cyanotic heart disease (corrected/uncorrected) (P = 0.0003), mechanical valve replacement (P = 0.03), maternal smoking (P = 0.007), multiple gestation (P = 0.0014), and the use of cardiac medication (P = 0.0009) correlated with adverse neonatal outcome.Conclusion: In our tertiary CHD cohort, cardiac, obstetric, and neonatal complications were frequently encountered, and (new) correlations of maternal baseline data with adverse outcome are reported. A new risk score for adverse cardiac complications is proposed, although prospective validation remains necessary. http://repub.eur.nl/res/pub/28442/ 2010-05-01T00:00:00Z Objective To compare the risks of pregnancy complications in women with repaired and unrepaired isolated ventricular septal defect (VSD). Design A retrospective multicentre study. Setting Tertiary centres in the Netherlands and Belgium. Methods Women were identified using two congenital heart disease registries. Eighty-eight women were identified who had experienced 202 pregnancies, including 46 miscarriages and nine terminations of pregnancy. Information on each completed pregnancy (n = 147; unrepaired VSD, n = 104; repaired VSD, n = 43) was obtained using medical records and telephone interviews. Data from the Generation R database (prospective cohort study; n = 9667) were used to determine the background risk (controls). Odds ratios and 95% CI were estimated using general estimation equation analysis adjusted for multiple pregnancies per woman, maternal age and parity status. Main outcome measures Adjusted odds ratios (AORs) for developing pregnancy complications in relation to corrective status. Results Pregnancies in women with an unrepaired VSD were associated with a higher risk of pre-eclampsia (AOR 4.59, 95% CI 2.01-10.5, P < 0.001) compared with controls. No differences were observed when comparing women with repaired VSD and controls. Pregnancies in women with repaired VSD were associated with a higher risk of premature labour (AOR 4.02, 95% CI 1.12-14.4, P = 0.03) and small-for-gestational-age (SGA) births (AOR 4.09, 95% CI 1.27-13.2, P = 0.02) compared with women with unrepaired VSD. Conclusions Women with unrepaired VSD are at increased risk of pre-eclampsia, which suggests that it is not a benign condition. In addition, women with repaired VSD are at increased risk of premature labour and SGA births compared with women with unrepaired VSD. http://repub.eur.nl/res/pub/27959/ 2010-04-01T00:00:00Z Background: Cannabis is commonly used among pregnant women. It is unclear whether cannabis exposure causes hemodynamic modifications in the fetus, like tobacco does. Aims: This study aims to ascertain fetal blood redistribution due to intrauterine cannabis exposure. Methods: This study was embedded in the Generation R Focus Study, a population-based cohort of parents and children followed from pregnancy onwards. In late pregnancy, fetal hemodynamics was assessed with ultrasound measurements in cannabis-exposed and non-exposed fetuses. Pregnant women reported about substance use during pregnancy. A distinction was made between continued cannabis use (n=9), cannabis use only in early pregnancy (n=14), continued tobacco use (n=85), tobacco use only in early pregnancy (n=92), and no tobacco or cannabis use during pregnancy (n=85). Results: Continued cannabis use was associated with an increased pulsatility and resistance index of the uterine artery, while discontinued cannabis use was associated with a decreased pulsatility, and resistance index, as compared to controls. Additionally, continued cannabis exposure resulted in a significantly higher uterine pulsatility index and uterine resistance index compared to tobacco exposure. Continued cannabis use was found to be associated with a smaller aortic diameter, as well. No association between intrauterine cannabis exposure and the fetal cerebral vascular system was found. Conclusions: Our findings suggest that intrauterine cannabis exposure was associated with changes in hemodynamic programming of the vascular system of the fetus in late pregnancy mainly due to tobacco exposure, but intrauterine cannabis exposure did demonstrate a specific effect on the uterine blood flow. http://repub.eur.nl/res/pub/28048/ 2010-02-01T00:00:00Z Background: The objective of this study was to test the feasibility, accuracy, and reproducibility of the assessment of right ventricular (RV) volumes and ejection fraction (EF) using real-time three-dimensional echocardiographic (RT3DE) imaging in patients with congenital heart disease (CHD), using cardiac magnetic resonance (CMR) as a reference. Methods: RT3DE data sets and short-axis cine CMR images were obtained in 62 consecutive patients (mean age, 26.9 ± 10.4 years; 65% men) with various CHDs. RV volumetric quantification was done using semiautomated 3-dimensional border detection for RT3DE images and manual tracing of contours in multiple slices for CMR images. Results: Adequate RV RT3DE data sets could be analyzed in 50 of 62 patients (81%). The time needed for RV acquisition and analysis was less for RT3DE imaging than for CMR (P < .001). Compared with CMR, RT3DE imaging underestimated RV end-diastolic and end-systolic volumes and EF by 34 ± 65 mL, 11 ± 55 mL, and 4 ± 13% (P < .05) with 95% limits of agreement of ±131 mL, ±109 mL, and ±27%, as shown by Bland-Altman analyses, with highly significant correlations (r = 0.93, r = 0.91, and r = 0.74, respectively, P < .001). Interobserver variability was 1 ± 15%, 6 ± 17%, and 8 ± 13% for end-diastolic and end-systolic volumes and EF, respectively. Conclusion: In the majority of unselected patients with complex CHD, RT3DE imaging provides a fast and reproducible assessment of RV volumes and EF with fair to good accuracy compared with CMR reference data when using current commercially available hardware and software. Further studies are warranted to confirm our data in similar and other patient populations to establish its use in clinical practice. http://repub.eur.nl/res/pub/27704/ 2010-01-21T00:00:00Z http://repub.eur.nl/res/pub/27470/ 2010-01-15T00:00:00Z Even after successful repair, hypertension is one of the main determinants of cardiovascular morbidity and mortality in patients with aortic coarctation (CoA). We compared the effect of candesartan (angiotensin II receptor blockade) and metoprolol (β-adrenergic receptor blockade) on blood pressure, large artery stiffness, and neurohormonal status in hypertensive patients after repair of CoA. In the present open-label, crossover study, hypertensive patients after CoA repair were first randomly assigned to treatment with candesartan 8 mg or metoprolol 100 mg once per day. After 8 weeks of treatment with one of the drugs, the other treatment was given for 8 weeks. The treatment effects were assessed with 24-hour ambulatory blood pressure monitoring, measurement of large artery stiffness, and neurohormonal plasma levels at baseline and after 8 weeks of either treatment. Sixteen patients (mean age 37 ± 12 years, 26 ± 15 years after repair, 63% men) completed the study. The 24-hour mean arterial pressure at baseline was 97.7 ± 6.2 mm Hg. Metoprolol (mean dose 163 ± 50 mg/day) decreased the mean arterial pressure (7.0 ± 4.2 and 4.1 ± 3.6 mm Hg, respectively) more than did candesartan (mean dose 13 ± 4 mg/day; p = 0.018, 95% confidence interval 0.6 to 5.5). Large artery stiffness did not change with either treatment. With metoprolol, plasma B-type natriuretic peptide increased and plasma renin decreased. With candesartan, the plasma renin and noradrenaline levels increased and aldosterone levels decreased. In conclusion, in adult hypertensive patients after CoA repair, metoprolol had more of an antihypertensive effect than did candesartan. Moreover, the neurohormonal outcome did not support a significant role for the renin-angiotensin system in the causative mechanism of hypertension after CoA. http://repub.eur.nl/res/pub/20926/ 2010-01-01T00:00:00Z Background: Cardiac defects can be the presenting symptom in patients with mutations in the X-linked gene FLNA. Dysfunction of this gene is associated with cardiac abnormalities, especially in the left ventricular outflow tract, but can also cause a congenital malformation of the cerebral cortex. We noticed that some patients diagnosed at the neurogenetics clinic had first presented to a cardiologist, suggesting that earlier recognition may be possible if the diagnosis is suspected. Methods and results: From the Erasmus MC cerebral malformations database 24 patients were identified with cerebral bilateral periventricular nodular heterotopia (PNH) without other cerebral cortical malformations. In six of these patients, a pathogenic mutation in FLNA was present. In five a cardiac defect was also found in the outflow tract. Four had presented to a cardiologist before the cerebral abnormalities were diagnosed. Conclusions: The cardiological phenotype typically consists of aortic or mitral regurgitation, coarctation of the aorta or other left-sided cardiac malformations. Most patients in this category will not have a FLNA mutation, but the presence of neurological complaints, hyperlaxity of the skin or joints and/or a family history with similar cardiac or neurological problems in a possibly X-linked pattern may alert the clinician to the possibility of a FLNA mutation. http://repub.eur.nl/res/pub/24283/ 2009-12-01T00:00:00Z Background: Surgical intervention for persistent active native aortic valve endocarditis (NVE) remains challenging. We analyzed our combined experience with allografts and mechanical prostheses (MP) in NVE operations. Methods: Between 1980 and 2002, 138 patients (81% males) underwent aortic valve replacement for NVE in 2 centers (106 allografts; 32 MPs). Perioperative characteristics and early and late morbidity and mortality were analyzed. Results: Mean age was 47 years (range, 14 to 76 years), and 34% required emergency surgery. Abscess rate was 38% for allografts vs 18% for MPs. Concomitant mitral valve replacement was required in 38% MP patients and in 5% allograft patients. Hospital mortality was 8% (n = 11; p = 0.25): 10 allograft patients (9%) and 1 MP patient (3%). During a mean 8-year follow-up (range, 0 to 25 years) 33 patients died: 22 allograft (24%) and 11 MP patients (21%; p = 0.14). Survival at 15 years was 59% ± 6% for allograft patients and 66% ± 9% for MP patients (p = 0.68). Late recurrent endocarditis developed in 6 allograft patients and 1 MP patient (p = 0.29). Overall 15-year freedom from reoperation was 76% ± 9% for allografts and 93% ± 6% for MPs (p = 0.02). Conclusions: Mechanical prostheses have comparable rates of midterm survival and freedom from recurrent infection. However, this is in combination with extensive excision of destructive tissue in a specific patient subset. Allograft reoperation rates increase with time. The importance of the mechanical prosthesis in NVE might be established in the coming years. http://repub.eur.nl/res/pub/26901/ 2009-12-01T00:00:00Z http://repub.eur.nl/res/pub/24385/ 2009-11-01T00:00:00Z http://repub.eur.nl/res/pub/24823/ 2009-11-01T00:00:00Z Objective To compare the risks of complications during pregnancy in women with repaired andunrepaired atrial septal defects (ASDs) without associated complex cardiac lesions. Design A retrospective multicentre study. Setting Tertiary centres in the Netherlands and Belgium. Population Women with ASD without associated complex cardiac lesions. Methods Women were identified using two congenital heart disease registries. One hundred women were identified who had 243 pregnancies, including 49 miscarriages and six terminations of pregnancy. Detailed information on each completed pregnancy (n = 188; unrepaired ASD, n = 133; repaired ASD, n = 55) was obtained using medical records and telephone interviews. In addition, data from the Generation R database (a prospective cohort study; n = 9667) were used to determine the background risk (control group). Main outcome measures Adjusted odds ratios (AORs) for cardiac, obstetric and neonatal events controlled for multiple pregnancies per woman using general estimating equation analysis. Results Women with an unrepaired ASD had a higher risk of neonatal events (AOR = 2.99, 95% confidence interval [CI] 1.14-7.89, P = 0.027) than women with a repaired ASD. The risk of cardiac and obstetric complications was comparable between women with unrepaired and repaired ASDs. Compared with the general population, women with an unrepaired ASD had higher risks of pre-eclampsia (AOR = 3.54, 95% CI 1.26-9.98, P = 0.017), small-for-gestational-age births (AOR = 1.95, 95% CI 1.15-3.30, P = 0.013) and fetal mortality (AOR = 5.55, 95% CI 1.77-17.4, P = 0.003). By contrast, no differences were observed when comparing women with a repaired ASD versus controls. Conclusions Women with an unrepaired ASD are at increased risk of neonatal events in comparison with women with a repaired ASD. Compared with the general population, women with an unrepaired ASD are at increased risk of pre-eclampsia, small-for-gestational-age births and fetal mortality. http://repub.eur.nl/res/pub/24345/ 2009-07-01T00:00:00Z Objective: With a growing number of children with congenital heart disease (CHD) reaching adulthood, an extensive experience with cardiac surgery in adults with CHD is accumulating. To increase insight in this patient category we report our 17-year single centre experience including predictors for adverse outcome and EuroSCORE performance. Methods: Patients and operative characteristics of all consecutive adult CHD patients operated upon between January 1990 and January 2007 were collected. Categorisation was done according to the EACTS/STS congenital database. Early and late morbidity and mortality were assessed with follow-up extending up to 17 years. EuroSCORE performance was assessed. Results: Nine hundred and sixty-three procedures were performed in 830 patients (mean age 39.3 years, 50.3% male). A total of 49% were re-do procedures, frequent procedures were for left heart lesions (37%), right heart lesions (31%) and septal defects (8%). The 51% primary procedures largely consisted of less complex procedures but also included 1.4% of tetralogy of Fallot repairs, 4.1% of aortic coarctation repairs and 2.7% of Ebstein's disease repairs. Thirty-day mortality was 1.5% (n = 14); predicted mortality by logistic EuroSCORE was 4.6%. c-index was 0.61 (95% CI 0.46-0.75). Major complications such as tamponade requiring intervention occurred in 3.2%, postoperative bleeding requiring re-exploration in 7.1% and renal insufficiency requiring dialysis in 4 (0.4%). Pulmonary hypertension was a strong predictor for short-term mortality; impaired ventricular function and cyanosis for long-term mortality. Overall 17-year survival was 71% (95% CI 61%-82%). Eighty percent of patients were in NYHA class I at last follow-up, 17% in II, 3% in III, 0% in IV. Conclusions: Surgery in adult CHD patients can be performed with low operative mortality and good clinical outcome. EuroSCORE is not a good model for risk assessment in this group of patients. http://repub.eur.nl/res/pub/27212/ 2009-04-01T00:00:00Z http://repub.eur.nl/res/pub/18519/ 2009-02-01T00:00:00Z Only a limited number of families with clear monogenic inheritance of nonsyndromic forms of congenital valve defects have been described. We describe two multiplex pedigrees with a similar nonsyndromic form of heart valve anomalies that segregate as an autosomal dominant condition. The first family is a three-generation pedigree with 10 family members affected with congenital defects of the cardiac valves, including six patients with aortic stenosis and/or aortic regurgitation. Pulmonary and/or tricuspid valve abnormalities were present in three patients, and ventricular septal defect (VSD) was present in two patients. The second family consists of 11 patients in three generations with aortic valve stenosis in seven patients, defects of the pulmonary valves in two patients, and atrial septal defect (ASD) in two patients. Incomplete penetrance was observed in both families. Although left-ventricular outflow tract obstruction was present in most family members, the co-occurrence with pulmonary valve abnormalities and septal defects in both families is uncommon. These families provide evidence that left-sided obstructive defects and thoracic aortic aneurysm may be accompanied by right-sided defects, and even septal defects. These families might be instrumental in identifying genes involved in cardiac valve morphogenesis and malformation. http://repub.eur.nl/res/pub/19343/ 2009-01-20T00:00:00Z Background - Reports on outcome after the Ross procedure are limited by small study size and show variable durability results. A systematic review of evidence on outcome after the Ross procedure may improve insight into outcome and potential determinants. Methods and Results - A systematic review of reports published from January 2000 to January 2008 on outcome after the Ross procedure was undertaken. Thirty-nine articles meeting the inclusion criteria were allocated to 3 categories: (1) consecutive series, (2) adult patient series, and (3) pediatric patient series. With the use of an inverse variance approach, pooled morbidity and mortality rates were obtained. Pooled early mortality for consecutive, adult, and pediatric patients series was 3.0% (95% confidence interval [CI], 1.8 to 4.9), 3.2% (95% CI, 1.5 to 6.6), and 4.2% (95% CI, 1.4 to 11.5). Autograft deterioration rates were 1.15% (95% CI, 1.06 to 2.06), 0.78% (95% CI, 0.43 to 1.40), and 1.38%/patient-year (95% CI, 0.68 to 2.80), respectively, and for right ventricular outflow tract conduit were 0.91% (95% CI, 0.56 to 1.47), 0.55% (95% CI, 0.26 to 1.17), and 1.60%/patient-year (95% CI, 0.84 to 3.05), respectively. For studies with mean patient age >18 years versus mean patient age ≤ 18 years, pooled autograft and right ventricular outflow tract deterioration rates were 1.14% (95% CI, 0.83 to 1.57) versus 1.69% (95% CI, 1.02 to 2.79) and 0.65% (95% CI, 0.41 to 1.02) versus 1.66%/patient-year (95% CI, 0.98 to 2.82), respectively. Conclusions - The Ross procedure provides satisfactory results for both children and young adults. Durability limitations become apparent by the end of the first postoperative decade, in particular in younger patients. http://repub.eur.nl/res/pub/17069/ 2009-01-01T00:00:00Z http://repub.eur.nl/res/pub/29368/ 2008-08-29T00:00:00Z Background: Abnormalities of the aortic root are common in patients with a bicuspid aortic valve. Our aim was to investigate the elastic properties of the aortic root in patients with congenital aortic valvular stenosis (AS) in comparison with age- and gender-matched controls, and to investigate the influence of stenosis severity and aortic size on aortic root elasticity. Methods: Thirty-two adults (mean age 30.4 ± 7.5 years, 22 men) with congenital AS without previous cardiovascular surgery were prospectively studied. Aortic root elasticity indices such as aortic stiffness index (ASI), aortic root distensibility (ARD), and aortic strain were calculated with the use of M-mode echocardiography. Results: ASI was significantly higher in patients compared to controls, 8.5 ± 8.4 versus 4.0 ± 1.4, respectively (P < 0.01). Other indices of aortic root elasticity were similar between patients and controls: ARD was 4.2 ± 3.6 versus 4.3 ± 1.9 × 10- 6cm2/dynes, respectively, and aortic strain was 12.4 ± 9.6 versus 13.5 ± 5.0%, respectively (P = NS for all). Correlations were found between aortic size and indices of aortic elasticity (i.e., aortic strain and ARD), denoting that an increased aortic dimension is associated with a stiffer aorta. Interestingly, no correlations were found between indices of severity of AS and aortic elasticity, suggesting that an abnormal aortic elasticity is independent of stenosis severity. Conclusions: Congenital AS results in abnormal aortic elastic properties, independent of stenosis severity. Furthermore, there seems to be a relationship between aortic dimensions and aortic stiffness. http://repub.eur.nl/res/pub/29281/ 2008-05-23T00:00:00Z Background: Pregnancy in women with congenital aortic stenosis (AS) is associated with increased cardiac complications. Data on non-cardiac complications are limited, and this information is crucial for prenatal counselling and perinatal care. The aim of this study was to present the maternal and perinatal outcome of pregnancy in women with congenital AS. Methods: By review of the Dutch CONCOR national registry and a local Belgian tertiary care centre database, 35 women with congenital AS with a history of completed pregnancy before aortic valve replacement were enrolled in this study. Medical history and maternal and perinatal outcome were determined. Results: Thirty-five women had 58 pregnancies resulting in 53 successful pregnancies, three miscarriages, and two abortions. The most serious cardiac complications were heart failure (n = 2, 3.8%) and atrial arrhythmia (n = 3, 5.7%). Although cardiac complications were present (9.4%), obstetric (22.6%) and perinatal (24.5%) complications were observed more often. A total of six pregnancies (11.3%) were complicated by hypertension-related disorders, including one case of eclampsia. Furthermore, 7 premature births (13.2%) and 7 small-for-gestational-age births (13.2%) were encountered. Pregnancy in women with severe AS was characterized by an increased incidence of heart failure and premature labour, and shorter pregnancy duration. Older women (> 30 years) were at increased risk of perinatal events (odds ratio 4.38, 95% confidence interval 1.02 to 18.81). Conclusions: Pregnancy is generally well tolerated in women with congenital AS. Importantly, an excess of obstetric and perinatal complications was found, requiring more meticulous attention. http://repub.eur.nl/res/pub/29312/ 2008-05-07T00:00:00Z Discussion exists whether discrete subaortic stenosis (DSS) is a congenital or acquired cardiac defect. Currently, it is regarded an "acquired" cardiac defect presumably secondary to altered flow patterns due to morphological abnormalities in the left ventricular outflow tract, as have been shown by some studies in the pediatric population. In this report, we demonstrated a steepened aortoseptal angle in adults with DSS without previous cardiac surgery in comparison to controls. Our results strengthen the hypothesis that altered flow patterns due to a steepened aortoseptal angle are a substrate for development of DSS in adults. http://repub.eur.nl/res/pub/29860/ 2008-03-01T00:00:00Z Background: Patients with severe aortic stenosis (AS) require valve replacement before development of irreversible left ventricular (LV) dysfunction. It has been postulated that Doppler tissue imaging (DTI) parameters are more sensitive to detect subtle LV dysfunction compared with conventional echocardiographic parameters. Objective: We sought to assess early LV dysfunction with DTI-derived echocardiographic parameters and N-terminal pro-B-type natriuretic peptide (NT-proBNP) in patients with severe AS and normal LV ejection fraction. Methods: A total of 29 patients (mean age 65 ± 12 years, 15 male) with symptomatic severe AS and 17 control subjects were included in the study. DTI was performed at the level of the mitral lateral (mlat) and septal (msep) annulus. Systolic (Sm), early (Em), and late (Am) diastolic velocities were measured, and E/Em ratio was calculated. NT-proBNP was determined by an electrochemiluminescence immunoassay. Results: Baseline characteristics between patients and control subjects were similar regarding LV ejection fraction and mitral inflow E/A ratio. However, patients with AS had significantly lower DTI values (Sm, Em, Am) compared with control subjects. Moreover, LV filling pressures, expressed by the E/Em ratio, were significantly higher in patients. Correlation analysis showed a relationship between the natural logarithm of NT-proBNP and aortic valve area, Smlat, and E/Emsepratio. Using stepwise multiple linear regression, Smlatwas found to be independently related to NT-proBNP. Conclusions: In patients with severe AS and normal LV ejection fraction, DTI showed LV systolic and diastolic dysfunction compared with control subjects. DTI-derived variables, and especially Smlat, were correlated with NT-proBNP levels. http://repub.eur.nl/res/pub/30431/ 2008-03-01T00:00:00Z Aims: To evaluate the accuracy of real-time three-dimensional echocardiography (RT3DE) using a biplane and multiplane method in determining left ventricular (LV) mass compared to cardiac magnetic resonance imaging (CMR). Methods and results: LV mass was measured in 18 adult patients with congenital aortic stenosis using CMR and echocardiography (M-mode, two-dimensional echocardiography (2DE), and RT3DE). RT3DE data were analysed using a biplane and multiplane method. No geometric assumptions were necessary using the multiplane RT3DE method.With regard to biplane or multiplane RT3DE, no tendency of over- or underestimation of LV mass was observed. Pearson's correlation coefficients for RT3DE versus CMR were 0.84 and 0.90 for the biplane and multiplane method, respectively. In addition, the accuracy of both RT3DE methods were comparable (Fisher's R-to-Z transformation: Z = 0.69, P = NS). Finally, off-line analysis using biplane RT3DE was significantly faster than multiplane RT3DE (3.8 ± 1.2 vs. 7.8 ± 1.7 minutes, P < 0.001). Conclusions: Biplane RT3DE provided an accurate estimate of LV mass in patients with concentric left ventricular hypertrophy, which was not improved by multiplane RT3DE. The accuracy and speed of analysis renders biplane RT3DE an attractive tool in daily clinical practice for assessing the degree of LV hypertrophy. http://repub.eur.nl/res/pub/29358/ 2008-02-01T00:00:00Z The survival of patients with congenital heart disease (CHD) has increased immensely and nowadays, most children reach adulthood. The long-term outcome is hampered by the occurrence of late complications such as arrhythmias. Supraventricular and ventricular arrhythmias have an impact notably not only on morbidity but also on mortality in patients with congenital heart disease. Therefore, life-long follow-up in most of these patients is required. http://repub.eur.nl/res/pub/28740/ 2008-01-01T00:00:00Z Objectives: To investigate outcome of pregnancy and fertility in women with double outlet right ventricle (DORV). Methods: Using 2 congenital heart disease registries, 21 female patients with DORV (aged 18-39 years) were retrospectively identified. Detailed recordings of each patient and their completed (>20 weeks gestation) pregnancies were recorded. Results: Overall, 10 patients had 19 pregnancies, including 3 spontaneous miscarriages (16%). During the 16 live birth pregnancies, primarily (serious) noncardiac complications were observed, e.g. premature labor/delivery (n = 7 and n = 3, respectively), small for gestational age (n = 4), preeclampsia (n = 2) and recurrence of congenital heart disease (n = 2). Except for postpartum endocarditis and deterioration of subpulmonary obstruction, only mild cardiac complication pregnancies were recorded. Two women with children reported secondary female infertility. Several menstrual cycle disorders were reported: secondary amenorrhea (n = 4), primary amenorrhea (n = 3) and oligomenorrhea (n = 2). Conclusion: Successful pregnancy in women with DORV is possible. Primarily noncardiac complications were observed and only few (minor) cardiac complications. Infertility and menstrual cycle disorders appear to be more prevalent. Copyright http://repub.eur.nl/res/pub/28935/ 2008-01-01T00:00:00Z Objective: The aim of the study was to assess the long-term results of a selective policy toward pulmonary valve replacement in adult patients with repaired tetralogy of Fallot and severe pulmonary regurgitation. Methods: Sixty-seven patients with tetralogy of Fallot were followed up from 15 ± 3 years until 27 ± 3 years after surgery. Results: Twenty-two patients had mild-to-moderate pulmonary regurgitation. No significant changes occurred in the follow-up period. Of 45 patients with severe pulmonary regurgitation and severe right ventricular dilatation, 28 (62%) remained free of symptoms and did not undergo pulmonary valve replacement. No changes in right ventricular size or exercise capacity were found. In 3 (11%) of 28 patients, QRS duration increased to more than 180 ms. Seventeen patients had symptoms and underwent pulmonary valve replacement: 9 (54%) of 17 patients improved clinically and echocardiographically, and QRS duration shortened postoperatively. Right ventricular dimensions did not regress despite pulmonary valve replacement in 8 patients. Conclusion: Refraining from pulmonary valve replacement in asymptomatic patients led to no measurable deterioration in 25 (89%) of 28 patients. Referring symptomatic patients for pulmonary valve replacement led to an improvement in 9 (53%) of 17 patients. In 11 (24%) of 45, a selective approach led to questionable or unsatisfactory results. http://repub.eur.nl/res/pub/35694/ 2007-11-30T00:00:00Z Background: Little data are available on the natural history of young adults with congenital valvular aortic stenosis (AS). The aim of the present study was to determine the progression rate of AS in young adults, and to identify predictors of stenosis progression and outcome. Methods: Retrospective study of all patients seen at a single centre diagnosed with congenital AS (≥ 2.5 m/s) between 1992 and 2005, excluding patients with severe aortic regurgitation. The slope of the regression of the aortic jet velocity on the time elapsed since the baseline study was used to define the rate of progression of stenosis. Results: A total of 84 adults (mean age, 23.5 ± 7.9 years) were studied who had at least two echocardiograms > 1 year (5.6 ± 2.6 years) apart. The annual progression of aortic jet velocity was 0.09 ± 0.15 m/s per year. Multivariable linear regression analysis identified older age (p < 0.001) as an independent predictor of faster haemodynamic progression. During the follow-up period of 7.7 ± 2.7 years, no patient died and 35 patients (42%) underwent aortic valve intervention. By multivariable Cox regression analysis, severe AS (≥ 4.0 m/s) and rapid progression of aortic jet velocity (≥ 0.2 m/s/year) were independent predictors of intervention. Cumulative intervention-free survival for patients with severe AS was 78 ± 8% at 3 years and 48 ± 10% at 5 years versus respectively 98 ± 2% and 96 ± 3% for patients with mild-to-moderate AS (log-rank: p < 0.001). Conclusions: Progression of congenital AS was relatively low in young adults compared to elderly with degenerative AS. Older age was associated with more rapid progression. http://repub.eur.nl/res/pub/36874/ 2007-09-01T00:00:00Z Increasing numbers of women with complex congenital heart disease are reaching childbearing age. Pregnancy is a major issue in the management of adult congenital heart disease. Cardiac disease is one of the most common causes of maternal morbidity and mortality. Complications, such as growth retardation, preterm and premature birth and even fetal and neonatal mortality, are more frequent among children of women with congenital heart disease. The risk of complications is determined by the severity of the cardiac lesion, the presence of cyanosis, the maternal functional class and the use of anticoagulation. However, the pathophysiology of these complications is not completely understood and may be related to a diminished increase in cardiac output and/or endothelial dysfunction. The management of pregnant cardiac patients is based on limited clinical information. This article reviews prepregnancy counseling and management during pregnancy in patients with congenital heart disease. http://repub.eur.nl/res/pub/36878/ 2007-09-01T00:00:00Z The prevalence of coronary artery disease in female patients is increasing due to changing lifestyle patterns including cigarette smoking, diabetes and stress. Since women are delaying childbearing until older age, acute coronary syndrome will more frequently occur during pregnancy. Although rare, acute coronary-syndrome during pregnancy often has devastating consequences. It is associated with increased maternal and neonatal mortality and morbidity compared with the nonpregnant situation. Furthermore, it constitutes an important problem for the patient and the treating physician, because the selection of diagnostic and therapeutic approaches is greatly influenced not only by maternal, but also by fetal safety. http://repub.eur.nl/res/pub/35749/ 2007-08-01T00:00:00Z Aims: The Ross operation is the operation of choice for children who require aortic valve replacement (AVR) and may also provide a good option in selected adult patients. Although the autograft does not require anticoagulation and has a superior haemodynamic profile, concern regarding autograft and allograft longevity has risen. In this light, we report the 13-year results of our prospective autograft cohort study. Methods and results: Between 1988 and 2005, 146 consecutive patients underwent AVR with a pulmonary autograft at Erasmus Medical Center Rotterdam. Mean age was 22 years (SD 13; range 4 months-52 years), 66% were male. Hospital mortality was 2.7% (N = 4); during follow-up four more patients died. Thirteen-year survival was 94 ± 2%. Over time, 22 patients required autograft reoperation for progressive neo-aortic root dilatation. In addition, eight patients required allograft reoperation. Freedom from autograft reoperation at 13 years was 69 ± 7%. Freedom from allograft reoperation for structural failure at 13 years was 87 ± 5%. Risk factors for autograft reoperation were previous AVR and adult patient age. Conclusion: Although survival of the Rotterdam autograft cohort is excellent, over time a worrisome increase in reoperation rate is observed. Given the progressive autograft dilatation, careful follow-up of these patients is warranted in the second decade after operation. http://repub.eur.nl/res/pub/36199/ 2007-06-19T00:00:00Z A search of peer-reviewed literature was conducted to identify reports that provide data on complications associated with pregnancy in women with structural congenital heart disease (CHD). This review describes the outcome of 2,491 pregnancies, including 377 miscarriages (15%) and 114 elective abortions (5%). Important cardiac complications were seen in 11% of the pregnancies. Obstetric complications do not appear to be more prevalent. In complex CHD, premature delivery rates are high, and more children are small for gestational age. The offspring mortality was high throughout the spectrum and was related to the relatively high rate of premature delivery and recurrence of CHD. http://repub.eur.nl/res/pub/13445/ 2004-07-01T00:00:00Z BACKGROUND: Great concern exists about the ability of the anatomic right ventricle to sustain the systemic circulation in patients with transposition of the great arteries who have undergone a Mustard procedure. A prospective study was made to examine long-term survival, clinical outcome, and right ventricular function 25 years after surgery. METHODS: Ninety-one consecutive patients underwent the Mustard procedure between 1973 and 1980. After 14 years and again after 25 years (range 22-29 years), patients were studied with ECG, echocardiography, exercise testing, and Holter monitoring. RESULTS: The cumulative survival and event-free survival were 77% and 36%, respectively, after 25 years. Reoperation was necessary in 46%. No major loss of sinus rhythm was found. While all patients had good right ventricular function 14 years after repair, 61% of patients showed moderate-to-severe dysfunction after 25 years, when studied by echocardiography. Furthermore, the QRS complex widened and exercise capacity decreased. CONCLUSION: The anatomic right ventricle appears to be unable to sustain the systemic circulation at long-term follow-up and the clinical condition of patients late after Mustard repair is declining. We can expect more deaths or need for heart transplantation in the next decade. http://repub.eur.nl/res/pub/13419/ 2004-06-01T00:00:00Z BACKGROUND: Long-term survival and clinical outcome after surgical closure of a VSD is poorly documented. Such data are important for the future perspectives, medical care, employability, and insurability of these patients. METHODS: 176 consecutive patients underwent surgical closure of an isolated VSD between 1968 and 1980 in our hospital. A systematic follow-up study was performed in 1990 and again in 2001. FINDINGS: Late survival was poorer than in the general population. Pulmonary hypertension and right ventricular hypertrophy were present in the 4 patients who died suddenly, late after operation. During follow-up no new pulmonary hypertension became manifest. Re-operations were necessary in 6%. Some patients (4%) developed sinus node disease late after repair, requiring pacemaker implantation. At last follow-up (91 survivors) 92% of the patients were in NYHA class I. Pulmonary hypertension was found in 4%, and aorta insufficiency in 16%. Patients experienced difficulties when applying for insurance. CONCLUSION: Among patients with surgically repaired VSDs, late results were good, although some late sudden deaths occurred in the patients with pulmonary hypertension. Furthermore, some patients developed sinus node disease late after repair, requiring pacemaker implantation. Employability is good, but pregnancy and insurance matters need further attention. http://repub.eur.nl/res/pub/10117/ 2003-04-01T00:00:00Z AIMS: Since knowledge about the psychosocial function of adult patients with congenital heart disease is limited, we compared biographical characteristics, and emotional and social functioning of these patients with that of the reference groups. METHODS AND RESULTS: Patients with congenital heart disease (N=362, aged 20-46 years), belonging to five diagnostic groups, were subjected to extensive medical and psychological examination, 20-33 years after their first open heart surgery. All the patients were seen by the same psychologist, who examined their psychosocial functioning using a structured interview and questionnaires. The majority (78%)was living independently and showed favourable outcome regarding the marital status. Among married/cohabitant patients, 25-39-year-olds showed normal offspring rates. None of the 20-24-year-old patients had any children. The offspring rate dropped after the age of 40. The proportion of adult patients with a history of special education was high (27%). Accordingly, patients showed lower educational and occupational levels compared to reference groups. As regard to the emotional and social functioning (leisure-time activities), the sample showed favourable results. CONCLUSIONS: Overall, this sample of patients with congenital heart disease seemed capable of leading normal lives and seemed motivated to make good use of their abilities. http://repub.eur.nl/res/pub/10094/ 2003-01-01T00:00:00Z AIMS: Although studies have suggested good long-term results, arrhythmias, pulmonary hypertension and left ventricular dysfunction are mentioned as sequelae long-term after surgical atrial septal defect closure at young age. Most studies were performed only by questionnaire and in a retrospective manner. The long-term outcome is very important with regard to future employment and acceptance on insurance schemes. METHODS AND RESULTS: One hundred and thirty-five consecutive ASD-patients, operated on in childhood, were studied longitudinally with ECG, echocardiography, exercise testing and Holter-recording 15 (10-22) and 26 (21-33) years after surgery. During follow-up no cardiovascular mortality, stroke, heart failure and no pulmonary hypertension occurred. Symptomatic supraventricular tachyarrhythmias were present in 6% after 15 years, and an additional 2% occurred in the last decade; 5% needed pacemaker implantation. No relation was found between arrhythmias and type of ASD, baseline data, right ventricular dimensions, or age at operation. Left and right ventricular function and dimension remained unchanged. Slightly more patients had right atrial dilatation at last follow-up. Exercise capacity was comparable with the normal Dutch population. CONCLUSIONS: The long-term outcome after ASD closure at young age shows excellent survival and low morbidity. The incidence of supraventricular arrhythmias is lower than in natural history studies of ASD patients and also lower than after surgical correction at adult age. http://repub.eur.nl/res/pub/8335/ 2003-01-01T00:00:00Z OBJECTIVE: To investigate the incidence of clinical problems related to a bicuspid valve (aortic stenosis and regurgitation) and the incidence of ascending aorta and aortic arch pathology in combination with coarctation repair. PATIENTS: 124 adult patients after surgical correction of aortic coarctation were studied. The incidence of aortic valve, ascending aorta, and aortic arch pathology was determined using echocardiography and magnetic resonance imaging. The median age at coarctation repair was 9 years and at last follow up 28 years. RESULTS: Three patients died from aorta pathology. Aortic valve disease was found in 63% of the patients, requiring an intervention in 22%, at a median of 13 years after coarctation repair. Ascending aorta dilatation was observed in 28% and aortic arch abnormalities in 23%, among whom kinking of the aortic arch was found in 12%. Antihypertensive medication was used in 24%. In the patients with hypertension the age at operation and age at follow up were significantly higher (p = 0.0001 and p < 0.0001, respectively). CONCLUSION: In addition to the well known problems of hypertension and recoarctation, aortic valve and aortic arch pathology are commonly encountered in patients with previous coarctation repair. Aortic abnormalities may predispose to dilatation and dissection, thus necessitating careful lifelong attention in all patients with coarctation. http://repub.eur.nl/res/pub/5608/ 1999-12-01T00:00:00Z Although it is well known that smoking is strongly associated with coronary heart disease, many patients continue or resume smoking after being diag- nosed with coronary heart disease and even after an important event such as a myocardial infarction, angio- plasty or coronary bypass surgery. The evidence that smoking causes cardiovascular disease and new events in patients with coronary heart disease, among other serious disorders such as lung cancer and emphysema, justifies the promotion of smoking cessation. All rec- ommendations on the prevention of coronary heart dis- ease emphasize the importance of smoking cessation in the reduction of the risk of coronary death and non-fatal coronary events[3,4]. The recent EUROASPIRE study on the status of secondary prevention of coronary heart disease in nine European countries has shown, however, that success in smoking cessation among coronary heart disease patients is far from satisfactory[5]. In this era of evidence-based medicine, information from systematic reviews of published studies should guide physicians and other health professionals advising patients in smoking cessation. With this in mind, we have carried out a systematic review of published observational studies on the impact of smoking cessation on the prognosis and on smoking intervention trials in patients with coronary heart disease.