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Contains fulltext : 283508.pdf (Publisher’s version ) (Open Access) Marfan syndrome (MFS) is a connective tissue disorder affecting the cardiovascular, ocular, and skeletal system, which may be accompanied by psychological features. This study aimed to determine the prevalence of fatigue, anxiety, and symptoms of depression in MFS patients, and to assess the degree to which sociodemographic and clinical variables are associated with fatigue and psychological aspects. The prevalence of fatigue, anxiety, and symptoms of depression were assessed in two cohorts of MFS patients and compared with healthy controls. The checklist individual strength (CIS), and hospital anxiety and depression scale (HADS) questionnaires were utilized. Medical status was assessed (family history of MFS, aortic root dilatation >40 mm, previous aortic surgery, aortic dissection, chronic pain, skeletal involvement, and scoliosis). Severe fatigue was experienced by 37% of the total MFS cohort (n = 155). MFS patients scored significantly higher on the CIS questionnaire, concerning severe fatigue, as compared with the general Dutch population (p

Patients with a Fontan circulation for single-ventricle physiology are at increased risk of developing thromboembolic events. Thromboembolic events can lead to failure of the Fontan circulation, chronic sequelae in case of stroke, and early mortality. Controversies exist regarding the substrates, risk factors, and optimal detection methods for thromboembolic events. Despite the major clinical implications, there is currently no consensus regarding the optimal antithrombotic therapy to prevent or treat thromboembolic events after the Fontan procedure. In this review we aimed to untangle the available literature regarding antithrombotic prophylaxis and treatment for pediatric and adult Fontan patients. A decision-tree algorithm for thromboprophylaxis in Fontan patients is proposed. Additionally, the current state of knowledge is reviewed with respect to the epidemiology, pathophysiology, and detection of thromboembolic events in Fontan patients, and important evidence gaps are highlighted.

ObjectiveThe clinical and prognostic implications of a hypertensive response to exercise after repair of coarctation of the aorta (CoA) remain controversial. We aimed to determine the prevalence of a hypertensive response to exercise, identify factors associated with peak exercise systolic blood pressure (SBP) and explore the association of peak exercise SBP with resting blood pressure and cardiovascular events during follow-up.MethodsFrom the Dutch national CONgenital CORvitia (CONCOR) registry, adults with repaired CoA who underwent exercise stress testing were included. A hypertensive response to exercise was defined as a peak exercise SBP ≥210 mm Hg in men and ≥190 mm Hg in women. Cardiovascular events consisted of coronary artery disease, stroke, aortic complications and cardiovascular death.ResultsOf the original cohort of 920 adults with repaired CoA, 675 patients (median age 24 years (range 16–72 years)) underwent exercise stress testing. Of these, 299 patients (44%) had a hypertensive response to exercise. Mean follow-up duration was 10.1 years. Male sex, absence of a bicuspid aortic valve and elevated resting SBP were independently associated with increased peak exercise SBP. Peak exercise SBP was positively predictive of office SBP (β=0.11, pConclusionsA hypertensive response to exercise was present in nearly half of the patients in this large, prospective cohort of adults with repaired CoA. Risk factors for increased peak exercise SBP were male sex, absence of a bicuspid aortic valve and elevated resting SBP. Increased peak exercise SBP independently predicted hypertension at follow-up. These results support close follow-up of patients with a hypertensive response to exercise to ensure timely diagnosis and treatment of future hypertension.

Background Marfan syndrome (MFS) is a connective tissue disorder caused by mutations in the Fibrillin-1 gene (FBN1). Here, we undertook the first epigenome-wide association study (EWAS) in patients with MFS aiming at identifying DNA methylation loci associated with MFS phenotypes that may shed light on the disease process. Methods The Illumina 450 k DNA-methylation array was used on stored peripheral whole-blood samples of 190 patients with MFS originally included in the COMPARE trial. An unbiased genome-wide approach was used, and methylation of CpG-sites across the entire genome was evaluated. Additionally, we investigated CpG-sites across the FBN1-locus (15q21.1) more closely, since this is the gene defective in MFS. Differentially Methylated Positions (DMPs) and Differentially Methylated Regions (DMRs) were identified through regression analysis. Associations between methylation levels and aortic diameters and presence or absence of 21 clinical features of MFS at baseline were analyzed. Moreover, associations between aortic diameter change, and the occurrence of clinical events (death any cause, type-A or -B dissection/rupture, or aortic surgery) and methylation levels were analyzed. Results We identified 28 DMPs that are significantly associated with aortic diameters in patients with MFS. Seven of these DMPs (25%) could be allocated to a gene that was previously associated with cardiovascular diseases (HDAC4, IGF2BP3, CASZ1, SDK1, PCDHGA1, DIO3, PTPRN2). Moreover, we identified seven DMPs that were significantly associated with aortic diameter change and five DMP’s that associated with clinical events. No significant associations at p –8 or p –6 were found with any of the non-cardiovascular phenotypic MFS features. Investigating DMRs, clusters were seen mostly on X- and Y, and chromosome 18–22. The remaining DMRs indicated involvement of a large family of protocadherins on chromosome 5, which were not reported in MFS before. Conclusion This EWAS in patients with MFS has identified a number of methylation loci significantly associated with aortic diameters, aortic dilatation rate and aortic events. Our findings add to the slowly growing literature on the regulation of gene expression in MFS patients.

Although major breakthroughs in the field of pediatric cardiology, cardiac surgery, intervention, and overall care improved the outlook of congenital heart disease, Eisenmenger syndrome (ES) is still encountered and remains a complex clinical entity with multisystem involvement, including secondary erythrocytosis, increased thrombotic and bleeding diathesis, high arrhythmogenic risk, progressive heart failure, and premature death. Clearly, care for ES is best delivered in multidisciplinary expert centers. In this review, we discuss the considerable recent progress in understanding the complex pathophysiology of ES, means of prognostication, and improvement in clinical outcomes achieved with pulmonary arterial hypertension-targeted therapies. Additionally, we delineate areas of uncertainty in various aspects of care, discuss gaps in current evidence, and review current status in less privileged countries and propose initiatives to reduce disease burden. Finally, we propose the application of emerging technologies to enhance the delivery and quality of health care related to ES and beyond.

Background Marfan syndrome (MFS) is a connective tissue disorder characterized by mutations in the fibrillin-1 (FBN1) gene. The most important manifestation is progressive enlargement of the aorta, ultimately leading to aortic dissection or rupture. Present day pharmacological treatment is based on drugs that decrease repetitive stress on the aorta and improve elastic properties and transport function of the aorta. Unfortunately, this is not sufficient for most patients and surgical resection and reconstruction of the enlarged part of the aorta is still necessary. We have shown earlier that the food supplement Resveratrol inhibits aortic growth and promotes aortic repair in a murine MFS model. Resveratrol is a natural polyphenol commonly found in the skin of berries and in nuts. Here, we hypothesize that Resveratrol treatment will also be protective against aortic dilatation and functional deterioration in humans with MFS. Methods/Design The RESVcue Marfan study is an investigator-initiated, prospective, pre-post observational, multicenter trial. Four specialized academic centers in the Netherlands will recruit 100 patients with genetically confirmed MFS. Patients will use Resveratrol for one year, on top of their ongoing medicinal regime. The primary endpoints consist of the following two main parameters; 1) aortic aneurysm expansion rate and 2) improvement of aortic functional indices. All indices will be measured before and after treatment by echocardiography and (4D flow) MRI. The 4D flow MRI allows for analysis of blood flow patterns and quantification of stresses on the aortic wall, distensibility and pulse wave velocity. Blood and skin samples will be taken to assess the effect of Resveratrol on potential biomarkers associated with Resveratrol metabolism and changes in the primary endpoints. Three psychological tests (The Well-being questionnaire (SF-12), the Hospital Depression and Anxiety Scales (HADS) questionnaire and the Checklist Individual Strength (CIS)) will be taken by the MFS patients to assess the effect of Resveratrol on their well-being. Discussion The RESVcue Marfan trial may provide sufficient data on beneficial effects of Resveratrol on aortic aneurysm expansion rate, aortic functional properties, and biomarkers in patients with MFS to justify a future randomized trial in a larger cohort for a longer study period.Trial registration NL66127.018.18, approved on 24 September 2018. https://www.toetsingonline.nl/ Resveratrol as potential aortic growth inhibitor in patients with Marfan syndrome.

Heritable thoracic aortic disease (H-TAD) comprises a heterogeneous group of disorders with as a common denominator aortic aneurysm or dissection. Depending on the presence or absence of manifestations in other organ systems, H-TAD can be further subdivided into syndromic and nonsyndromic H-TAD. Pathogenic variants have been identified in numerous genes involved in structure and in maintenance of tissue homeostasis in the aortic wall. Identification of the underlying genetic defect is not only important for confirmation of the diagnosis but may also help in risk stratification and guidance of management—which will ultimately lead to more personalized medicine. A substantial proportion of (mainly nonsyndromic) families with H-TAD remains in whom the underlying gene defect has not been identified yet, and in these cases, clinical imaging of patients and relatives is the mainstay of follow-up.

Objective Adult congenital heart disease (ACHD) patients are at risk of sudden cardiac death (SCD). However, methods for risk stratification are not yet well‐defined. The Tpeak‐Tend (TpTe) interval, a measure of dispersion of ventricular repolarization, is a risk factor for SCD in non‐ACHD patients. We aim to evaluate whether TpTe can be used in risk stratification for SCD in ACHD patients. Design From an international multicenter cohort of 25 790 ACHD patients, we identified all SCD cases. Cases were matched to controls by age, gender, congenital defect, and (surgical) intervention. Outcome Measures TpTe was measured on a standard 12‐lead ECG. The maximum TpTe of all ECG leads (TpTe‐max), mean (TpTe‐mean), and TpTe dispersion (maximum minus minimum) were obtained. Odds ratios (OR) for SCD cases vs controls were calculated using conditional logistic regression analysis. Results ECGs were available for 147 cases (median age at death 33.5 years (quartiles 26.2, 48.7), 66% male) and 267 controls. The mean TpTe‐max was 97 ± 24 ms in cases vs 84 ± 17 ms in controls (P

Patients with grown-up congenital heart disease (GUCH) constitute an expanding population. This population presents in such a way that is different from children with congenital heart disease and from adults with acquired heart disease and therefore requires a specialized multidisciplinary care. In addition to a specialized GUCH cardiologist, imaging specialists, interventional cardiologists, and GUCH surgeons constitute the backbone of the GUCH Heart Team. The aim of this integrative care is to secure a good quality of social, practical, and private life of the patient and, at the same time, minimize the number of interventions in a lifetime.

Patients with grown-up congenital heart disease (GUCH) constitute an expanding population. This population presents in such a way that is different from children with congenital heart disease and from adults with acquired heart disease and therefore requires a specialized multidisciplinary care. In addition to a specialized GUCH cardiologist, imaging specialists, interventional cardiologists, and GUCH surgeons constitute the backbone of the GUCH Heart Team. The aim of this integrative care is to secure a good quality of social, practical, and private life of the patient and, at the same time, minimize the number of interventions in a lifetime.

Congenital heart disease (CHD) is a prevalent but heterogeneous substrate for infective endocarditis (IE). Risk depends on CHD type, repair status, and the presence of prosthetics. Overall, clinical presentation, diagnosis, microbiology, and treatment of CHD-associated IE do not differ from IE in general. However, right-sided infections are more frequent, and echocardiographic sensitivity may be reduced. IE should be suspected in all patients with CHD with ongoing fever or other suggestive symptoms. Care is best provided in specialized CHD centres. While treatment remains challenging, overall outcome of CHD-associated IE is relatively good. Primary prevention is important in this population, and the value of proper dental health and hygiene should be stressed in patient education.

Heritable thoracic aortic disease (H-TAD) comprises a heterogeneous group of disorders with as a common denominator aortic aneurysm or dissection on one or several levels from the aortic annulus till the diaphragm. Depending on the presence or absence of manifestations in other organ systems, H-TAD can be further subdivided into syndromic and nonsyndromic H-TAD (NS H-TAD). For both clinical entities, multiple underlying gene defects have been identified, although we must recognize that in a substantial number of patients and families no causal mutation has been identified, defining them as “Heritable” but strictly speaking not (yet) as “Genetic.”

Congenital heart disease (CHD) is a substrate for infective endocarditis (IE). With advancements in surgical care, the CHD population has expanded over the past decades, while use of prosthetic material provides additional IE targets. Studies on CHD-associated IE in the era of commonplace cardiac prosthetics are scarce. Right-sided IE is relatively common in CHD. Streptococcus and Staphylococcus species are the predominant causative agents. The threshold for suspecting IE should be low. Reduced sensitivity of echocardiography, especially in the setting of complex anatomy or prosthetics, may warrant use of alternative imaging modalities. While treatment remains challenging, the outcome of CHD-associated IE is relatively good. Prevention of IE in this population should focus on good dental health and hygiene.

With recent advances in medical and surgical management, most patients with congenital heart disease (CHD) survive to reproductive age. Current guidelines recommend counseling about inheritance and transmission of CHD to offspring. We evaluated whether adult CHD patients recalled having received information about the inheritance of their CHD, patients' knowledge about inheritance and their concerns in this regard. A questionnaire was sent to 486 non-syndromic CHD patients aged 20-45 years. We received 332 useful questionnaires (response rate 68%). One-third (33%) of patients recalled receiving information about inheritance of CHD from their cardiologist, and 13% had consulted a clinical geneticist. Eight percent of patients who were considering having children estimated the recurrence risk for their own offspring to be 1% or lower, whereas one-fourth (25%) estimated it to be higher than 10%. According to our classification, 44% estimated the recurrence risk in a correct range of magnitude. Additional information about inheritance of CHD was desired by 41% of patients. Forty-two percent of patients considering having children reported concerns about transmitting CHD to offspring. We conclude that a substantial proportion of adult CHD patients lacks knowledge and desires more information about inheritance, indicating a need for better patient education. Current guidelines and/or their implementation do not seem to meet the needs of these patients. A dedicated program of counseling for adults with CHD has to be developed to optimize knowledge and satisfaction with information provision and to reduce or manage concerns regarding inheritance of CHD.

Congenital heart defects (CHDs) occur mostly sporadic, but familial CHD cases have been reported. Mutations in several genes, including NKX2.5, GATA4 and NOTCH1, were identified in families and patients with CHD, but the mechanisms underlying CHD are largely unknown. We performed genome-wide linkage analysis in a large four-generation family with autosomal dominant CHD (including atrial septal defect type I and II, tetralogy of Fallot and persistent left superior vena cava) and low atrial rhythm, a unique phenotype that has not been described before. We obtained phenotypic information including electrocardiography, echocardiography and DNA of 23 family members. Genome-wide linkage analysis on 12 affected, 5 unaffected individuals and 1 obligate carrier demonstrated significant linkage only to chromosome 9q21-33 with a multipoint maximum LOD score of 4.1 at marker D9S1690, between markers D9S167 and D9S1682. This 48-cM critical interval corresponds to 39 Mb and contains 402 genes. Sequence analysis of nine candidate genes in this region (INVS, TMOD1, TGFBR1, KLF4, IPPK, BARX1, PTCH1, MEGF9 and S1PR3) revealed no mutations, nor were genomic imbalances detected using array comparative genomic hybridization. In conclusion, we describe a large family with CHD and low atrial rhythm with a significant LOD score to chromosome 9q. The phenotype is representative of a mild form of left atrial isomerism or a developmental defect of the sinus node and surrounding tissue. Because the mechanisms underlying CHD are largely unknown, this study represents an important step towards the discovery of genes implied in cardiogenesis.

Item does not contain fulltext OBJECTIVE: A high prevalence of migraine has been described in various forms of congenital heart disease, with and without shunt. In this study we investigated the prevalence of migraine in patients with Marfan syndrome (MFS). METHODS: All 457 adult patients with MFS from the participating centres and 194 controls received a validated questionnaire about headache. Migraine was diagnosed according to the International Headache Society criteria, by three independent neurologists, blinded to patient files. RESULTS: Response rate was 68% and 56% in Marfan patients and controls, respectively. Forty percent of the 309 responding MFS patients (mean age 40+/-14 years; 51% females) and 28% of the 102 controls (mean age 43+/-15 years; 58% females), suffered from migraine (p=0.03). The prevalence of migraine with aura (MA) was 22% in MFS patients and 14% in controls (p=0.06). We found MFS to be an independent risk factor for having overall migraine (OR 1.7; 95%CI 1.1-2.8), also after adjustment for age and gender (OR 1.9; 95%CI 1.1-3.1; p=0.02) and for MA after adjustment for gender (OR 2.0; 95%CI 1.1-3.7; p=0.04). In patient with MFS, previous aortic root surgery appeared to be an independent risk factor for having MA (OR 2.2; 95%CI; 1.2.-4.0, p=0.01) adjusted for gender. CONCLUSION: MFS is an independent risk factor for having overall migraine and MA. Moreover, we found that a history of aortic root surgery seems to be associated with an increased risk of MA.

This review focuses on the heart and vascular system in patients with Down syndrome. A clear knowledge on the wide spectrum of various abnormalities associated with this syndrome is essential for skillful management of cardiac problems in patients with Down syndrome. Epidemiology of congenital heart defects, cardiovascular aspects and thyroid-related cardiac impairment in patients with Down syndrome will be discussed.

Vis JC, Thoonsen H, Duffels MG, de Bruin-Bon RA, Huisman SA, van Dijk AP, Hoendermis ES, Berger RM, Bouma BJ, Mulder BJ. Six-minute walk test in patients with Down syndrome: validity and reproducibility. Arch Phys Med Rehabil 2009;90:1423-7. Objectives: To examine the validity of the six-minute walk test (6MWT) as a tool to evaluate functional exercise performance in patients with Down syndrome (DS). Design: Comparison of the six-minute walk distance (6MWD) in 2 distinct groups of DS patients: with and without severe cardiac disease. To test reproducibility, a group of patients with DS performed the 6MWT twice. Setting: Tertiary referral centers for patients with congenital heart defects and outpatient clinics for people with intellectual disabilities. Participants: Adult patients with DS with (n=29) and without (n=52) severe cardiac disease categorized by cardiac echocardiography. Interventions: Not applicable. Main Outcome Measure: Distance walked on the 6MWT. Results: The mean 6MWD in the group with severe cardiac disease was 289 +/- 104m and in the group without severe cardiac disease 280 +/- 104m (P=.70). Older age, female sex, and severe level of intellectual disability were all found to be independently and significantly correlated with a lower 6MWD (r=.67, P

Background: In the large and expanding population of adults with congenital heart disease, little is known about their long-term outcome. By means of a systematic literature search, we aimed to assess the quantity and quality of data on long-term survival and morbidity in adults with common congenital heart defects. Methods: All literature on MEDLINE from January 1980 to January 2007 was searched, using a broad range of keywords for atrial septal defect, ventricular septal defect, pulmonary stenosis, tetralogy of Fallot, aortic coarctation, and transposition of the great arteries. After study selection using pre-specified criteria and quality assessment, data were extracted and weighed according to number of patients. Pooled estimates were obtained. Results: We identified 322 articles. Selection yielded 35 articles comprising 7894 patients. Data on survival were mainly available up until 40 years of age. In this young population, survival varied from 87.4% in aortic coarctation to 99.6% in atrial septal defect. Data on morbidity were sparse. Based on these data, morbidity was substantial. Conclusions: Until the age of 40 years, survival is decreased in patients with congenital heart defects, albeit most pronounced among patients with complex heart defects. Moreover, morbidity is considerable in all defects. Sufficient data on long-term survival and morbidity beyond the age of 40 years are lacking, yet crucial for optimal clinical care. (C) 2008 Elsevier Ireland Ltd. All rights reserved

Contains fulltext : 51420.pdf (Publisher’s version ) (Closed access) AIMS: To investigate outcome and complications of implantable cardioverter defibrillators (ICDs) in adults with congenital heart disease (CHD) and to identify predictors of (in-) appropriate shocks. METHODS AND RESULTS: Sixty-four CHD patients >/= 18 years at first ICD implantation [63% tetralogy of Fallot (TOF) and age at implantation 37 +/- 13 years] were identified using the Dutch adult CHD registry and a Belgian tertiary care centre database. Median follow-up duration was 3.7 years. Early complications included pocket haematoma (n = 3), lead failure (n = 2), and pneumothorax (n = 2). Late complications occurred in 11 (17%) patients, including lead failure (n = 6) and and electrical storm (n = 3). Overall, 30 device-related re-interventions were performed in 20 patients (31%), including four premature generator changes and seven lead replacements. Half of the patients received one or more shocks, and 46 shocks in 15 patients (23%) were classified as appropriate. One hundred and sixty shocks in 26 patients (41%) were classified as inappropriate. No predictors of (in-)appropriate shocks were identified, except TOF being associated with less appropriate shocks than patients with other CHD (HR 0.29, P = 0.02). CONCLUSION: The ICD provided effective therapy in a quarter of adults with CHD with low complication rates. The incidence of inappropriate shocks, however, appeared to be excessive and warrants further attention.

OBJECTIVES: To evaluate our results of valve-sparing aortic root replacement and associated (multiple) valve repair. METHODS: From September 2003 to September 2013, 97 patients had valve-sparing aortic root replacement procedures. Patient records and preoperative, postoperative and recent echocardiograms were reviewed. Median age was 40.3 (range: 13.4–68.6) years and 67 (69.1%) were male. Seven (7.2%) patients were younger than 18 years, the youngest being 13.4 years. Fifty-four (55.7%) had Marfan syndrome, 2( 2.1%) otherfibrous tissue diseases, 15 (15.5%) bicuspid aortic valve and 3 (3.1%) had earlier Fallot repair. The reimplantation technique was used in all, with a straight vascular prosthesis in 11 (26–34 mm) and the Valsalva prosthesis in 86 (26–32 mm). Concomitant aortic valve repair was performed in 43 (44.3%), mitral valve repair in 10 (10.3%), tricuspid valve repair in 5 (5.2%) and aortic arch replacement in 3 (3.1%). RESULTS: Mean follow-up was 4.2±2.4 years. Follow-up was complete in all. One 14-year old patient died 1.3 years post-surgery presumably of ventricular arrhythmia. One patient underwent reoperation for aneurysm of the proximal right coronary artery after 4.9 years and 4 patients required aortic valve replacement, 3 of which because of endocarditis after 0.1, 0.8 and 1.3 years and 1 because of cusp prolapse after 3.8 years. No thrombo-embolic complications occurred. Mortality, root reoperation and aortic regurgitation were absent in 88.0±0.5% at 5-year follow-up. CONCLUSIONS: Results of valve-sparing root replacement are good, even in association with a high incidence of concomitant valve repair. Valve-sparing aortic root replacement can be performed at a very young age as long as an adult size prosthesis can be implanted.

To evaluate differences in functional parameters and reproducibility between short axis and axial slice orientation in the quantitative evaluation of the systemic right ventricle by cardiovascular magnetic resonance.Cross-sectional evaluation comparing two methods (Bland-Altman).Tertiary care outpatients.Quantitative cardiovascular magnetic resonance evaluation using short axis or axial slice orientation.Intraobserver variance, interobserver variance and systematic differences in systemic right ventricular volumes, ejection fraction, and mass between both methods.Twenty-two patients (mean age 33 ± 7 years) with systemic right ventricle (three with congenitally corrected transposition of the great arteries and 19 with atrially switched transposition of the great arteries).Compared with short axis slices, analysis of axial slices resulted in higher end systolic volume (6.6%, P.01), while mass (-10.8%, P.01) and ejection fraction (-8.9%, P.01) turned out lower. Intraobserver and interobserver reproducibility were similar for both methods when measuring end-diastolic and end-systolic volumes. However, ejection fraction and stroke volume were measured more consistently in axial orientation, while ventricular mass was measured more consistently in short axis orientation.There are significant differences in volume, mass, and function between measurements in axial and short axis orientation. Ejection fraction and stroke volume, which have a high clinical relevance, were measured more consistently in axial slice orientation. Consequently, we recommend using axial slice orientation in patients with a systemic right ventricle.

Objective Patients with repaired tetralogy of Fallot (TOF) experience increased rates of mortality and morbidity in adulthood. This study was designed to identify risk factors for death and ventricular tachycardia (VT) in a large contemporary cohort of patients with repaired TOF. Methods Subjects with repaired TOF from four large congenital heart centres in the USA, Canada and Europe were enrolled. Clinical, ECG, exercise, cardiac magnetic resonance (CMR) and outcome data were analysed. Results Of the 873 patients (median age 24.4 years), 32 (3.7%) reached the primary outcome (28 deaths, 4 sustained VT; median age at outcome 38 years; median time from CMR to outcome 1.9 years). Cox proportional-hazards regression identified RV mass-to-volume ratio >= 0.3 g/mL (HR, 5.04; 95% CI 2.3 to 11.0; p

For adult patients with congenital heart disease (CHD), knowledge about the origin and inheritance of their CHD is important. Clinical geneticists may play a significant role in their care. We explored the diagnostic yield of clinical genetic consultation of adult CHD patients, patients' motivations for the consultation, implications for reproductive decisions, patients' evaluation of the impact of provided information, and satisfaction with counseling. Chart review was performed on all adult patients referred for CHD to our clinical genetics department between 2000 and 2011 (n=90). Additionally, a questionnaire was sent to those patients referred between 2005 and 2011 (n=64), of which 46 useful questionnaires were returned (72% response). Of patients without an etiological diagnosis at referral (n=83), 17 (20%) were eventually diagnosed with syndromic CHD, 6 (7%) with nonsyndromic monogenetic CHD and 45 (54%) with nonsyndromic multifactorial CHD. The diagnosis remained undetermined in 15 (18%) patients. Half of patients who returned the questionnaire had purposefully postponed having children until after genetic consultation and 13% had changed their mind about having children or not after the consultation. Counseling was valued positively. In this study, we showed the added value of clinical genetic consultation in the care for adult CHD patients: it improves diagnostics by establishing an etiological diagnosis and associated recurrence risk in a substantial proportion of patients and leads to more informed reproductive decisions. With new genetic testing technologies an etiological diagnosis may be established in an increasing number of patients in the near future.

To assess the reproducibility of aortic volume estimates and to serially test their use in patients with Marfan syndrome.The study was approved by the medical ethics committee and all subjects gave written informed consent. In 81 patients with Marfan syndrome and seven healthy control subjects, aortic volumes and diameters at baseline were estimated by means of contrast material-enhanced magnetic resonance (MR) imaging. At 3 years of follow-up, aortic expansion rate were calculated in a subgroup of 22 patients with Marfan syndrome. Total aortic volume was defined as volume measurement from the level of the aortic annulus to the aortic bifurcation. Intra- and interobserver agreement of aortic volume were calculated by using the intraclass correlation coefficient. Differences in variables were analyzed with the Student t test and logistic regression. Effect size was calculated.Intra- and interobserver agreement of aortic volume calculation was 0.996 and 0.980, respectively. Mean aortic volume was significantly greater in patients with Marfan syndrome than in control subjects (104 mL/m(2); 95% confidence interval [CI]: 95, 114 mL/m(2) vs 74 mL/m(2); 95% CI: 62, 87 mL/m(2); P.001). In 22 patients with Marfan syndrome, mean aortic volume was increased at 3 years of follow-up (17 mL; 95% CI: 8, 26 mL; P = .001; effect size, 0.29), while mean aortic diameter did not increase significantly (0.4 mm; 95% CI: 0.0, 0.9 mm; P = .171; effect size, 0.13).Assessment of aortic volume is highly reproducible and may be suited for use in the detection of aortic expansion in patients with Marfan syndrome.http://radiology.rsna.org/lookup/suppl/doi:10.1148/radiol.13122310/-/DC1.

Left ventricular noncompaction (LVNC) is a relatively common genetic cardiomyopathy, characterized by prominent trabeculations with deep intertrabecular recesses in mainly the left ventricle. Although LVNC often occurs in an isolated entity, it may also be present in various types of congenital heart disease (CHD). The most prevalent CHD in LVNC is Ebstein anomaly, which is a rare form of CHD characterized by apical displacement and partial fusion of the septal and posterior leaflet of the tricuspid valve with the ventricular septum. Several reports of sporadic as well as familial cases of Ebstein anomaly associated with LVNC have been reported. Recent studies identified mutations in the MYH7 gene, encoding the sarcomeric β-myosin heavy chain protein, in patients harboring this specific phenotype. Here, we will review the association between Ebstein anomaly, LVNC and mutations in MYH7, which seems to represent a subtype of Ebstein anomaly with autosomal dominant inheritance and variable penetrance.

The study objectives were to analyze sex differences in hospital mortality of adult patients with congenital heart disease (CHD) and to determine the impact of health services associated with pregnancy on outcomes in women.The determinants of sex differences in the demographic distribution of CHD are poorly understood.The Quebec CHD database and the Dutch CONCOR (CONgenital CORvitia) registry were used to identify patients with CHD aged 18 to 65 years who were hospitalized between 1996 and 2005. Regression analyses were used to compare 30-day in-hospital mortality in men versus women and in women aged 18 to 45 years with versus without a pregnancy history, after adjustment for age, CHD severity, comorbidities, and admission diagnosis.Of 39,776 patients followed for 259,741 patient years, 19,099 patients (48%) had 54,195 admissions (62% among women). In those aged 18 to 45 years, 30-day in-hospital mortality was higher in men compared with women with nonpregnancy admissions (adjusted rate ratio: 1.36; 95% confidence interval: 1.02 to 1.81). The adjusted rate ratio for 30-day in-hospital mortality in women with a pregnancy history compared with those without was 0.49 (95% confidence interval: 0.24 to 0.99). A history of pregnancy was not associated with an overall increase in medical encounters.We demonstrated a protective effect of sex on in-hospital mortality in women with CHD of reproductive age that did not correlate with increased medical surveillance. Future studies need to explore other mechanisms to account for our observations. Understanding the determinants of the sex distribution of adults with CHD is important for our ability to predict demographic changes in the population with CHD.

Van alle AHA bestaat 5-10% uit een PDB . Op volwassen leeftijd is het tegenwoordig een zeldzame afwijking, omdat deze bij de meeste patienten op kinderleeftijd herkend wordt en de PDB meestal wordt gesloten. Er zijn echter patienten bij wie de diagnose pas op volwassen leeftijd toevallig of door het ontstaan van klachten wordt gesteld.

Het ASD is de meest voorkomende AHA op volwassen leeftijd. Het wordt bovendien vaak laat ontdekt, omdat een ASD gedurende de kinderleeftijd in veel gevallen geen klachten of symptomen veroorzaakt. Het relatief zachte ejectiegeruis over de pulmonalisklep wordt bij kinderen vaak niet gehoord of als onschuldig fysiologisch geruis geduid. Op volwassen leeftijd kunnen complicaties, zoals ritmestoornissen of een paradoxe embolie , maar ook een routinematig cardiaal onderzoek de diagnose aan het licht brengen. Voor een deel omdat een ASD vaak pas op volwassen leeftijd ontdekt wordt, maar ook omdat de prevalentie van andere AHA afneemt op oudere leeftijd (door overlijden, spontaan sluiten van een VSD), is de prevalentie van een ASD bij volwassenen hoger dan bij kinderen. In de landelijke registratie van patienten met een AHA (CONCOR) in Nederland heeft 16% van alle geincludeerde volwassen patienten een ASD.

Pulmonary arterial hypertension due to congenital heart disease (CHD-PAH) has a poor prognosis. We sought to determine whether the biomarker high-sensitivity troponin T (hsTnT) measured on routine visit at the outpatient clinic is associated with prognosis.Consecutive adult CHD-PAH (86% Eisenmenger syndrome) patients referred for advanced medical therapy between January 2005 and March 2007 in the Academic Medical Center in Amsterdam. Patients with severe renal impairment were excluded.The primary outcome was mortality.Of all 31 patients (mean age 45 ± 12 years) with CHD-PAH, eight patients died during a median follow-up of 5.6 (range 1.6 to 6.8) years. A hsTnT level0.014 μg/L was the 99th percentile cutoff of the normal distribution and therefore defined as elevated. At baseline, elevated levels of hsTnT were found in eight patients (26%). In univariate Cox regression, hsTnT elevated at baseline, NT-pro-BNP and right ventricular function were determinants of death (P.05 for all). Patients with elevated levels of hsTnT showed a significantly higher mortality rate as compared to patients with normal hsTnT levels (62% vs. 13%, P = .005).Levels of hsTnT were abnormal in a substantial proportion of CHD-PAH patients. A significant inverse relationship was found between hsTnT and survival.

Identification of adults with congenital heart disease (CHD) who were lost to cardiological follow-up.Cross-sectional study.Adults with CHD and not under cardiological follow-up were asked via a nationwide publicity campaign to contact the CONCOR (CONgenital CORvitia) project group.A total of 593 patients with mild (85%) to moderate-severe (15%) CHD were registered via the nationwide campaign. Of these patients, 66% were examined within 1 year by a cardiologist. Additional cardiac follow-up was necessary within 1 year in 22% of these patients. In 16% of the patients, new residual lesions were found; and in three of these patients the pulmonary valve required replacement.During this comprehensive nationwide campaign it became clear that a considerable number of adults with CDH fail to receive regular cardiac care. However, after surgical correction of CHD in childhood, residual lesions are common in this population. Threatening residual lesions can be present asymptomatically. Cardiological follow-up is therefore almost always necessary, also in patients without symptoms. Patients with CHD as well as their medical care personnel need to be well informed of this.

In the most common form of ToF – a combination of a large, unrestrictive ventricular septal defect (VSD), an overriding aorta and a severe right ventricular outflow tract obstruction (RVOTO) – the prenatal loading conditions are similar to that of the normal heart, but from birth the right ventricle (RV) has abnormal loading conditions.

A first step in the delivery of tailored care is answering the following question: does health care meet the needs of patients? Therefore patients' perspective on health care use and their needs was examined. The design used was cross-sectional questionnaire study.A total of 1109 adult congenital heart defect (CHD) patients attending one of eight Dutch hospitals were randomly selected from a national database (10% of all registered patients).Patient reported questionnaires on in- and outpatient health care use during the past year and need for additional care.A total of 66% and 40% of patients had contact with their cardiologist and general practitioner, respectively. Six to 10 percent were hospitalized, operated upon, or visited the emergency room. For the majority, the amount of contact was sufficient. Most patients indicated that the communication skills and expertise of the cardiologist and general practitioner were sufficient, and health care improvements were not necessary. Frequent health care users had a poor functional status and frequent contact with their cardiologist and general practitioner. Patients who want more contact with their cardiologist rated the communication skills of the cardiologist as insufficient.For most patients, the amount and quality of care are both sufficient. Patients who rate the communication skills of the cardiologist as insufficient have need more contact. In addition to the recommended training program as described in the American College of Cardiology/American Heart Association (ACC/AHA) and European Society of Cardiology (ESC) guidelines, we recommend the incorporation of communication training. This is the first study to provide insight into health care use and needs of CHD patients in countries with a compulsory health insurance system from the patient perspective.

Background— Ebstein anomaly is a rare congenital heart malformation characterized by adherence of the septal and posterior leaflets of the tricuspid valve to the underlying myocardium. An association between Ebstein anomaly with left ventricular noncompaction (LVNC) and mutations in MYH7 encoding β-myosin heavy chain has been shown; in this report, we have screened for MYH7 mutations in a cohort of probands with Ebstein anomaly in a large population-based study. Methods and Results— Mutational analysis in a cohort of 141 unrelated probands with Ebstein anomaly was performed by next-generation sequencing and direct DNA sequencing of MYH7 . Heterozygous mutations were identified in 8 of 141 samples (6%). Seven distinct mutations were found; 5 were novel and 2 were known to cause hypertrophic cardiomyopathy. All mutations except for 1 3-bp deletion were missense mutations; 1 was a de novo change. Mutation-positive probands and family members showed various congenital heart malformations as well as LVNC. Among 8 mutation-positive probands, 6 had LVNC, whereas among 133 mutation-negative probands, none had LVNC. The frequency of MYH7 mutations was significantly different between probands with and without LVNC accompanying Ebstein anomaly ( P MYH7 mutation in the pedigrees of 3 of the probands, 1 of which also included another individual with Ebstein anomaly. Conclusions— Ebstein anomaly is a congenital heart malformation that is associated with mutations in MYH7 . MYH7 mutations are predominantly found in Ebstein anomaly associated with LVNC and may warrant genetic testing and family evaluation in this subset of patients.