Right ventricular function (RVF) is often selectively declined after coronary artery bypass graft surgery. In adult patients with congenital heart disease (CHD) the incidence and persistence of... Show moreRight ventricular function (RVF) is often selectively declined after coronary artery bypass graft surgery. In adult patients with congenital heart disease (CHD) the incidence and persistence of declined RVF after cardiac surgery is unknown. The current study aimed to describe RVF after cardiac surgery in these patients. Adult CHD patients operated between January 2008 and December 2009 in the Academic Medical Centre in Amsterdam were studied. Clinical characteristics, laboratory tests, surgical data and intensive care unit outcome were obtained from medical records. RVF was measured by trans-thoracic echocardiography (TTE) and expressed by tricuspid annular plane systolic excursion (TAPSE), tissue Doppler imaging (RV S') and myocardial performance index (MPI) pre-operatively and direct, at intermediate and late follow up. Of a total of 185 operated, 86 patients (mean age 39 ± 13 years, 54% male) had echo data available. There was a significant fall in RVF after cardiac surgery. TAPSE and RV S' were significantly higher and MPI was significantly lower pre-operatively compared to direct post-operative values (TAPSE 22 ± 5 versus 13 ± 3 mm (P < 0.01), RV S' 11 ± 4 versus 8 ± 2 cm/s (P < 0.01) and MPI 0.36 ± 0.14 vs 0.62 ± 0.25; P < 0.01). There were no significant differences in left ventricular function pre-operatively compared to post-operative values. Right-sided surgery was performed in 33, left-sided surgery in 37 and both sided surgery in 16 patients. Decline in RVF was equal for those groups. Patients with severe decline in RVF, were patients who underwent tricuspid valve surgery. Decline in RVF was associated with post-operative myocardial creatine kinase level and maximal troponin T level. There was no association between decline in RVF and clinical outcome on the intensive care unit. 18 months post-operatively, most RVF parameters had recovered to pre-operative values, but TAPSE which remained still lower (P < 0.01). CHD patients have a decline in RVF directly after cardiac surgery, regardless the side of surgery. Although a gradual improvement was observed, complete recovery was not seen 18 months post-operatively. Show less
Engelen, K. van; Postma, A.V.; Meerakker, J.B.A. van de; Roos-Hesselink, J.W.; Helderman-van den Enden, A.T.J.M.; Vliegen, H.W.; ... ; Mulder, B.J.M. 2011
Ebstein's anomaly is a rare congenital heart malformation characterised by adherence of the septal and posterior leaflets of the tricuspid valve to the underlying myocardium. Associated... Show moreEbstein's anomaly is a rare congenital heart malformation characterised by adherence of the septal and posterior leaflets of the tricuspid valve to the underlying myocardium. Associated abnormalities of left ventricular morphology and function including left ventricular noncompaction (LVNC) have been observed. An association between Ebstein's anomaly with LVNC and mutations in the sarcomeric protein gene MYH7, encoding β-myosin heavy chain, has been shown by recent studies. This might represent a specific subtype of Ebstein's anomaly with a Mendelian inheritance pattern. In this review we discuss the association of MYH7 mutations with Ebstein's anomaly and LVNC and its implications for the clinical care for patients and their family members. Show less
Joziasse, I.C.; Smith, K.A.; Chocron, S.; Dinther, M. van; Guryev, V.; Smagt, J.J. van de; ... ; Bakkers, J. 2011
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... Show moreDown'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. European Journal of Human Genetics (2011) 19, 389-393; doi:10.1038/ejhg.2010.224; published online 19 January 2011 Show less
BACKGROUND Previous research has shown that women with congenital heart disease (CHD) are more susceptible to cardiovascular, obstetric, and offspring events. The causative pathophysiologic... Show moreBACKGROUND 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. Show less
Down syndrome is the most common chromosomal abnormality among liveborn infants and is the most frequent chromosomal cause of intellectual disability (Frid, Drott, Lundell, Rasmussen, & Anneren... Show moreDown syndrome is the most common chromosomal abnormality among liveborn infants and is the most frequent chromosomal cause of intellectual disability (Frid, Drott, Lundell, Rasmussen, & Anneren, 1999). It is a multisystem disorder, characterized by various congenital defects, organic disorders, dysmorphic features, and other health-related problems (Roizen & Patterson, 2003). The heart is affected frequently and the association between Down syndrome and congenital heart disease was already recognized by Garrod in 1894 (Richards, 1965). Although a critical region on chromosome 21 as well as several candidate genes has been proposed, the genetic basis and pathogenesis of congenital heart defects in Down syndrome remain largely unknown. Cardiovascular disorders related to Down syndrome are numerous. Here, we review prenatal screening, intrauterine interventions, and management of congenital heart defects in early childhood. Moreover, we discuss cardiovascular manifestations in adulthood, in particular pulmonary arterial hypertension and cardiac surgery in adults with Down syndrome. Show less
Background Previous studies demonstrated that ventricular response to stress cardiovascular magnetic resonance (CMR) is frequently abnormal in patients with a systemic right ventricle (RV). However... Show moreBackground Previous studies demonstrated that ventricular response to stress cardiovascular magnetic resonance (CMR) is frequently abnormal in patients with a systemic right ventricle (RV). However, the clinical implications of these findings remained unknown. We sought to evaluate whether abnormal response to stress CMR predicts adverse outcome in patients with a systemic RV. Methods Thirty-nine adult patients (54% male;mean age 26, range 18-65 years) with a systemic RV underwent stress CMR to determine the response of RV volumes and ejection fraction (EF). During follow-up, cardiac events, defined as hospitalization for heart failure, cardiac surgery, aborted cardiac arrest, or death, were recorded. The prognostic value of an abnormal response to stress, defined as lack of a decrease in RV end-systolic volume (ESV) or lack of an increase in RV EF, was assessed. Results We frequently observed an abnormal response to stress, as RV ESV did not decrease in 17 patients (44%), and RV EF did not increase in 15 patients (38%). After a mean follow-up period of 8.1 years, 8 (21%) patients had reached the composite end point. The inability to decrease RV ESV during stress was predictive for cardiac events with a hazard ratio of 2.3 (95% CI 1.19-88.72, P=.034), as was the inability to increase RV EF with a hazard ratio of 2.3 (95% CI 1.31-81.59, P=.027). Conclusions Stress CMR potentially has important prognostic value in patients with a systemic RV. Patients with a systemic RV who show abnormal cardiac response to stress have a substantially higher risk of adverse outcome. (Am Heart J 2010;160:870-6.) Show less
Bom, T. van der; Winter, M.M.; Bouma, B.J.; Groenink, M.; Vliegen, H.W.; Pieper, P.G.; ... ; Mulder, B.J.M. 2010
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... Show moreBackground 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. (Am Heart J 2010;160:812-8.) Show less
Scherptong, R.W.C.; Hazekamp, M.G.; Mulder, B.J.M.; Wijers, O.; Swenne, C.A.; Wall, E.E. van der; ... ; Vliegen, H.W. 2010
OBJECTIVES The aim of this study was to analyze whether QRS duration, before and after pulmonary valve replacement (PVR), is related to long-term outcome in patients with tetralogy of Fallot (TOF).... Show moreOBJECTIVES The aim of this study was to analyze whether QRS duration, before and after pulmonary valve replacement (PVR), is related to long-term outcome in patients with tetralogy of Fallot (TOF). BACKGROUND Key factors that determine outcome after PVR in adult TOF patients are largely unknown. Recognition of such factors assists the identification of patients at increased risk of adverse events. METHODS Adults who previously underwent total correction for TOF (n=90; age 31.4±10.3 years) and required PVR for pulmonary regurgitation were included. The QRS duration was measured pre-operatively and 6 months after PVR. The post-operative changes in QRS duration were calculated. Adverse events (death, re-PVR, ventricular tachycardia, and symptomatic heart failure) were noted during follow-up. RESULTS During 5.5±3.5 years of follow-up, 13 adverse events occurred. The 5-year event-free survival rate was 76% for patients with a pre-operative QRS duration>180 ms and 90% in patients with a QRS duration≤180 ms (p=0.037). For patients with a post-operative QRS duration>180 ms, 5-year event-free survival was 71%, whereas it was 91% for patients with a post-operative QRS duration≤180 ms (p=0.004). After multivariate correction, a post-operative QRS duration>180 ms (hazard ratio: 3.685, 95% confidence interval: 1.104 to 12.304, p<0.05) and the absence of a reduction in QRS duration post-PVR (hazard ratio: 6.767, 95% confidence interval: 1.704 to 26.878, p<0.01), was significantly associated with adverse outcome. CONCLUSIONS Severe QRS prolongation, before or after PVR, and the absence of a reduction in QRS duration after PVR, are major determinants of adverse outcome during long-term follow-up of patients with TOF. Show less
Scherptong, R.W.C.; Hazekamp, M.G.; Mulder, B.J.M.; Wijers, O.; Swenne, C.A.; Wall, E.E. van der; ... ; Vliegen, H.W. 2010
Objectives The aim of this study was to analyze whether QRS duration, before and after pulmonary valve replacement (PVR), is related to long-term outcome in patients with tetralogy of Fallot (TOF).... Show moreObjectives The aim of this study was to analyze whether QRS duration, before and after pulmonary valve replacement (PVR), is related to long-term outcome in patients with tetralogy of Fallot (TOF). Background Key factors that determine outcome after PVR in adult TOF patients are largely unknown. Recognition of such factors assists the identification of patients at increased risk of adverse events. Methods Adults who previously underwent total correction for TOF (n = 90; age 31.4 +/- 10.3 years) and required PVR for pulmonary regurgitation were included. The QRS duration was measured pre-operatively and 6 months after PVR. The post-operative changes in QRS duration were calculated. Adverse events (death, re-PVR, ventricular tachycardia, and symptomatic heart failure) were noted during follow-up. Results During 5.5 +/- 3.5 years of follow-up, 13 adverse events occurred. The 5-year event-free survival rate was 76% for patients with a pre-operative QRS duration >180 ms and 90% in patients with a QRS duration <= 180 ms (p = 0.037). For patients with a post-operative QRS duration >180 ms, 5-year event-free survival was 71%, whereas it was 91% for patients with a post-operative QRS duration <= 180 ms (p = 0.004). After multivariate correction, a post-operative QRS duration >180 ms (hazard ratio: 3.685, 95% confidence interval: 1.104 to 12.304, p < 0.05) and the absence of a reduction in QRS duration post-PVR (hazard ratio: 6.767, 95% confidence interval: 1.704 to 26.878, p < 0.01), was significantly associated with adverse outcome. Conclusions Severe QRS prolongation, before or after PVR, and the absence of a reduction in QRS duration after PVR, are major determinants of adverse outcome during long-term follow-up of patients with TOF. (J Am Coll Cardiol 2010;56:1486-92) (C) 2010 by the American College of Cardiology Foundation Show less
Data on relational and sexuality issues in adult patients with congenital heart disease (CHD) are scarce. The present study aimed to evaluate relational and sexual behaviors, satisfaction, and... Show moreData on relational and sexuality issues in adult patients with congenital heart disease (CHD) are scarce. The present study aimed to evaluate relational and sexual behaviors, satisfaction, and functioning in a representative sample of patients with CHD and their partners. In addition, we aimed to evaluate the relation between sexuality parameters and quality of life. Relational and sexuality issues were assessed using a sexuality questionnaire in 133 patients (52% men, 37 13 years old) with CHD (43 with coarctation of the aorta, 42 with transposition of great arteries, 36 with Marfan syndrome, and 12 with Eisenmenger syndrome), and 74 partners. Quality of life was assessed using the Dutch translation of the Medical Outcomes Study Short Form 36-Item Health Survey. Data were compared to an age- and gender-matched control group (n = 3,642). Seventy-one percent of patients with CHD were involved in a relationship, which was significantly less compared to controls (79%, p <0.05). Nonetheless, patients perceived their relationship as more satisfactory compared to controls (p <0.05). Overall, sexual satisfaction was equal in patients compared to controls, although they perceived lower body esteem (p <0.001), decreased sexual esteem (p <0.05), and more distress during sex (p <0.001). Patients reported no more erectile and lubrication problems compared to partners and to controls. We found significant associations between most relational and sexual parameters and quality of life. In conclusion, many aspects of sexuality are affected in adult patients with CHD, whereas their partners remain relatively unaffected. Moreover, sexuality is an important aspect of quality of life in these patients. We advise physicians to be receptive to discuss sexuality issues and provide patients with adequate therapy. (C) 2010 Elsevier Inc. All rights reserved. (Am J Cardiol 2010;106:1163-1168) Show less
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... Show moreAims 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. Show less
Objective To assess the extent and the characteristics of hospital admissions in registered adult patients with congenital heart disease. Design Observational cohort study. Setting The Netherlands.... Show moreObjective To assess the extent and the characteristics of hospital admissions in registered adult patients with congenital heart disease. Design Observational cohort study. Setting The Netherlands. Patients 5798 adult patients with congenital heart disease from the Dutch CONCOR national registry linked to the Dutch National Medical Registration (Prismant). Main outcome measures All hospital admissions from the years 2001 up until 2006. Results During 28 990 patient-years, 2908 patients (50%) were admitted to hospital. Median age at admission was 39 years (range 18-86 years); 46% were male. Admission rate in CONCOR patients was high among all ages (range 11-68%) and exceeded that of the general Dutch population two to three times; this difference was most pronounced in the older age groups. Altogether there were 8916 admissions, 5411 (61%) of which were for cardiovascular indications. Among cardiovascular admissions, referrals for arrhythmias were most common (31%). Of 4926 interventions, 2459 (50%) were cardiovascular, most often reparative interventions or cardioversion (53%). Most non-cardiovascular admissions were obstetric. Among defects, univentricular heart and tricuspid atresia had the highest incidence and duration of admission. Conclusions Healthcare utilisation in registered and medically supervised adult patients with congenital heart disease is high and increases with age. Admission rates are at least two times higher than in the general population, and most marked in the older age groups. With the ageing of this population, a major increase in healthcare utilisation is imminent in the near future. Timely preparation of healthcare resources is crucial to sustain optimal care. Show less
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... Show moreObjective 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. Show less
Mortality in adults with congenital heart disease is known to be increased, yet its extent and the major mortality risks are unclear. The Dutch CONCOR national registry for adult congenital heart... Show moreMortality in adults with congenital heart disease is known to be increased, yet its extent and the major mortality risks are unclear. The Dutch CONCOR national registry for adult congenital heart disease was linked to the national mortality registry. Cox's regression was used to assess mortality predictors. Of 6933 patients, 197 (2.8%) died during a follow-up of 24 865 patient-years. Compared with the general national population, there was excess mortality, particularly in the young. Median age at death was 48.8 years. Of all deaths, 77% had a cardiovascular origin; 45% were due to chronic heart failure (26%, age 51.0 years) or sudden death (19%, age 39.1 years). Age predicted mortality, as did gender, severity of defect, number of interventions, and number of complications [hazard ratio (HR) range 1.1-5.9, P < 0.05]. Several complications predicted all-cause mortality beyond the effects of age, gender, and congenital heart disease severity, i.e. endocarditis, supraventricular arrhythmias, ventricular arrhythmias, conduction disturbances, myocardial infarction, and pulmonary hypertension (HR range 1.4-3.1, P < 0.05). These risks were similar in patients above and below 40 years of age. Almost all complications predicted death due to heart failure (HR range 2.0-5.1, P < 0.05); conduction disturbances and pulmonary hypertension predicted sudden death (HR range 2.0-4.7, P < 0.05). Mortality is increased in adults with congenital heart disease, particularly in the young. The vast majority die from cardiovascular causes. Mortality risk, particularly by heart failure, is increased by virtually all complications. Complications are equally hazardous in younger as in older patients. Show less
Engelen, K. van; Topf, A.; Keavney, B.D.; Goodship, J.A.; Velde, E.T. van der; Baars, M.J.H.; ... ; Mulder, B.J.M. 2010
Background Three quarters of patients with 22q11.2 Deletion Syndrome (22q11.2DS) have congenital heart disease (CHD), typically conotruncal heart defects. Although it is currently common practice... Show moreBackground Three quarters of patients with 22q11.2 Deletion Syndrome (22q11.2DS) have congenital heart disease (CHD), typically conotruncal heart defects. Although it is currently common practice to test all children with typical CHD for 22q11.2DS, many adult patients have not been tested in the past and therefore 22q11.2DS might be under-recognised in adults. Objectives To determine the prevalence of 22q11.2DS in adults with tetralogy of Fallot (TOF) and pulmonary atresia (PA)/ventricular septal defect (VSD) and to assess the level of recognition of the syndrome in adult patients. Methods Patients were identified from CONCOR, a nationwide registry for adult patients with CHD. Inclusion criteria were diagnosis of TOF or PA/VSD and the availability of DNA. Patients with syndromes other than 22q11.2DS were excluded. Multiplex ligation-dependent probe amplification was used to detect 22q11.2 microdeletions. Results 479 patients with TOF and 79 patients with PA/VSD (56% male, median age 34.7 years) were included and analysed. Twenty patients were already known to have 22q11.2DS. A 22q11.2 microdeletion was detected in a further 24 patients. Thirty-one patients with TOF (6.5%) had 22q11.2DS, whereas 13 patients with PA/VSD had 22q11.2DS (16.5%). Of all 22q11.2 microdeletions, 54% (24/44) were unknown before this study. Conclusion This study shows that although the prevalence of 22q11.2DS in adults with TOF and PA/VSD is substantial, it is unrecognised in more than half of patients. As the syndrome has important clinical and reproductive implications, a diagnostic test should be considered in all adult patients with TOF and PA/VSD. Show less
Winter, M.M.; Mulder, B.J.M.; Velde, E.T. van der 2010
