In the transposition of the great arteries (TGA), alterations in hemodynamics and oxygen saturation could result in fibrotic remodeling, but histological studies are scarce. We aimed to investigate... Show moreIn the transposition of the great arteries (TGA), alterations in hemodynamics and oxygen saturation could result in fibrotic remodeling, but histological studies are scarce. We aimed to investigate fibrosis and innervation state in the full spectrum of TGA and correlate findings to clinical literature. Twenty-two human postmortem TGA hearts, including TGA without surgical correction (n = 8), after Mustard/Senning (n = 6), and arterial switch operation (ASO, n = 8), were studied. In newborn uncorrected TGA specimens (1 day-1.5 months), significantly more interstitial fibrosis (8.6% +/- 3.0) was observed compared to control hearts (5.4% +/- 0.8, p = 0.016). After the Mustard/Senning procedure, the amount of interstitial fibrosis was significantly higher (19.8% +/- 5.1, p = 0.002), remarkably more in the subpulmonary left ventricle (LV) than in the systemic right ventricle (RV). In TGA-ASO, an increased amount of fibrosis was found in one adult specimen. The amount of innervation was diminished from 3 days after ASO (0.034% +/- 0.017) compared to uncorrected TGA (0.082% +/- 0.026, p = 0.036). In conclusion, in these selected postmortem TGA specimens, diffuse interstitial fibrosis was already present in newborn hearts, suggesting that altered oxygen saturations may already impact myocardial structure in the fetal phase. TGA-Mustard/Senning specimens showed diffuse myocardial fibrosis in the systemic RV and, remarkably, in the LV. Post-ASO, decreased uptake of nerve staining was observed, implicating (partial) myocardial denervation after ASO. Show less
BackgroundClinical factors are used to estimate late complication risk in adults after atrial switch operation (AtrSO) for transposition of the great arteries (TGA), but heterogeneity in clinical... Show moreBackgroundClinical factors are used to estimate late complication risk in adults after atrial switch operation (AtrSO) for transposition of the great arteries (TGA), but heterogeneity in clinical course remains. We studied whether common genetic variants are associated with outcome and add value to a clinical risk score in TGA-AtrSO patients.Methods and resultsThis multicenter study followed 133 TGA-AtrSO patients (aged 28 [IQR 24–35] years) for 13 (IQR 9–16) years and examined the association of genome-wide single-nucleotide polymorphisms (SNPs) with a composite endpoint of symptomatic ventricular arrhythmia, heart failure hospitalization, ventricular assist device implantation, heart transplantation, or mortality. Thirty-two patients (24%) reached the endpoint. The genome-wide association study yielded one genome-wide significant (p < 1 × 10−8) locus and 18 suggestive loci (p < 1 × 10−5). A genetic risk score constructed on the basis of independent SNPs with p < 1 × 10−5 was associated with outcome after correction for the clinical risk score (HR = 1.26/point increase [95%CI 1.17–1.35]). Risk stratification improved with a combined risk score (clinical score + genetic score) compared to the clinical score alone (p = 2 × 10−16, C-statistic 0.95 vs 0.85). In 51 patients with a clinical intermediate (5–20%) 5-year risk of events, the combined score reclassified 32 patients to low (<5%) and 5 to high (>20%) risk. Stratified by the combined score, observed 5-year event-free survival was 100%, 79% and 31% for low, intermediate, and high-risk patients, respectively.ConclusionsCommon genetic variants may explain some variation in the clinical course in TGA-AtrSO and improve risk stratification over clinical factors alone, especially in patients at intermediate clinical risk. These findings support the hypothesis that including genetic variants in risk assessment may be beneficial. Show less
Andel, M.M. van; Ooij, P. van; Waard, V. de; Gottwald, L.M.; Kimmenade, R.R.J. van; Scholte, A.J.; ... ; Groenink, M. 2022
Background: It is difficult to assess the risk for aortic dissection beyond the aortic root in patients with Marfan syndrome (MFS). To aid risk assessment in these patients, we investigated aortic... Show moreBackground: It is difficult to assess the risk for aortic dissection beyond the aortic root in patients with Marfan syndrome (MFS). To aid risk assessment in these patients, we investigated aortic flow and wall shear stress (WSS) by 4D flow magnetic resonance imaging (MRI) in patients with MFS and compared the results with healthy volunteers. We hypothesized that MFS patients with a high-risk profile for aortic dissection would show abnormal hemodynamics in aortic regions associated with aortic dissection. Methods: MFS patients (n = 55) and healthy subjects (n = 25), matched for age and sex, prospectively underwent 4D flow MRI. 4D flow maps were constructed to detect elevated (defined as higher than the three-dimensional 95 % confidence interval) and deviant directed (defined as vector angle differences higher than 120) WSS in MFS patients as compared to the controls. Univariate and multivariate associations with risk factors for aortic dissection in MFS patients were assessed. Results: The maximum incidence for elevated WSS was 20 % (CI 9 %-31 %) and found in the ascending aorta. The maximum for deviant directed WSS was 39 % (CI 26 %-52 %) and found in the inner descending aorta. Significantly more male patients had deviant directed WSS in the inner proximal descending aorta (63 % vs 24 %, p = 0.014). Multivariate analysis showed that deviant directed WSS was associated with male sex (p = 0.019), and a haplo-insufficient FBN1 mutation type (p = 0.040). In 60 % of MFS patients with a previous aortic root replacement surgery, abnormal hemodynamics were found in the ascending aorta. No significant differences between hemodynamics were found in the descending aorta between operated and non-operated patients.Conclusion: Deviant directed WSS in the proximal descending aorta is associated with known risk factors for aortic dissection in MFS patients, namely male sex and a haploinsufficient FBN1 mutation type. Show less
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... Show moreMarfan 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 < 0.0001). There were no differences in HADS anxiety or depression scores. In older MFS patients, with a more severe cardiovascular phenotype, chronic pain, and a higher unemployment rate, significantly more symptoms of depression were observed, when compared with the general population (p = 0.027) or compared with younger MFS patients (p = 0.026). Multivariate analysis, showed that anxiety was associated with chronic pain (p = 0.022) and symptoms of depression with unemployment (p = 0.024). MFS patients report significantly more severe fatigue as compared with the general population. Since the cause of fatigue is unclear, more research may be needed. Psychological intervention, for example, cognitive behavioral therapy, may contribute to a reduction in psychological symptoms. Show less
Background Type D personality has been previously shown to increase the risk for mortality in patients with acquired heart disease. Objective We aimed to compare mortality in adult patients with... Show moreBackground Type D personality has been previously shown to increase the risk for mortality in patients with acquired heart disease. Objective We aimed to compare mortality in adult patients with congenital heart disease (CHD) with and without type D. Methods Survival was assessed using prospective data from the Dutch national Congenital Corvitia registry for adults with CHD. Patients were randomly selected from the registry and characterized at inclusion in 2009 for the presence of type D using the DS14 questionnaire. Results One thousand fifty-five patients, with 484 (46%) males, a mean (SD) age of 41 (14) years, 613 (58%) having mild CHD, 348 (33%) having moderate CHD, and 94 (9%) having severe CHD, were included. Type D personality was present in 225 patients (21%). Type D was associated with an increased risk for all-cause mortality independent of age, sex, New York Heart Association class, number of prescribed medications, depression, employment status, and marital status (hazard ratio, 1.94; 95% confidence interval, 1.05-3.57; P = .033). Conclusion Type D personality was associated with an increased risk for all-cause mortality in adult patients with CHD. Show less
Aims: Heart failure is the main threat to long-term health in adults with transposition of the great arteries (TGA) corrected by an atrial switch operation (AtrSO). Current guidelines refrain from... Show moreAims: Heart failure is the main threat to long-term health in adults with transposition of the great arteries (TGA) corrected by an atrial switch operation (AtrSO). Current guidelines refrain from recommending heart failure medication in TGA-AtrSO, as there is insufficient data to support the hypothesis that it is beneficial. Medication is therefore prescribed based on personal judgements. We aimed to evaluate medication use in TGA-AtrSO patients and examine the association of use of renin-angiotensin-aldosterone system (RAAS) inhibitors and beta-blockers with long-term survival. Methods and results: We identified 150 TGA-AtrSO patients [median age 30 years (interquartile range 25-35), 63% male] included in the CONCOR registry from five tertiary medical centres with subsequent linkage to the Dutch Dispensed Drug Register for the years 2006-2014. Use of RAAS inhibitors, beta-blockers, and diuretics increased with age, from, respectively, 21% [95% confidence interval (CI) 14-40], 12% (95% CI 7-21), and 3% (95% CI 2-7) at age 25, to 49% (95% CI 38-60), 51% (95% CI 38-63), and 41% (95% CI 29-54) at age 45. Time-varying Cox marginal structural models that adjusted for confounding medication showed a lower mortality risk with use of RAAS inhibitors and b-blockers in symptomatic patients [hazard ratio (HR) = 0.13 (95% CI 0.03-0.73); P = 0.020 and HR = 0.12 (95% CI 0.02-0.17); P = 0.019, respectively]. However, in the overall cohort, no benefit of RAAS inhibitors and b-blockers was seen [HR = 0.93 (95% CI 0.24-3.63); P = 0.92 and HR = 0.98 (0.23-4.17); P = 0.98, respectively]. Conclusion: The use of heart failure medication is high in TGA-AtrSO patients, although evidence of its benefit is limited. This study showed lower risk of mortality with use of RAAS inhibitors and beta-blockers in symptomatic patients only. These findings can direct future guidelines, supporting use of RAAS inhibitors and b-blockers in symptomatic, but not asymptomatic patients. Show less
Andel, M.M. van; Groenink, M.; Berg, M.P. van den; Timmermans, J.; Scholte, A.J.H.A.; Mulder, B.J.M.; ... ; Waard, V. de 2021
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... Show moreBackground 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 < 10(-8) or p < 10(-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. Show less
Andel, M.M. van; Waard, V. de; Timmermans, J.; Scholte, A.J.H.A.; Berg, M.P. van den; Zwinderman, A.H.; ... ; Groenink, M. 2021
Objectives Patients with Marfan syndrome (MFS) are prone to develop aortic aneurysms due to fragmentation of elastic fibres, resulting in reduced distensibility of the aorta. Reduced distensibility... Show moreObjectives Patients with Marfan syndrome (MFS) are prone to develop aortic aneurysms due to fragmentation of elastic fibres, resulting in reduced distensibility of the aorta. Reduced distensibility was previously shown to predict progressive descending aorta dilatation. Here, we investigated longitudinal changes in distensibility, as a potential predictor of aortic events.Methods This retrospective study included all patients with MFS with at least four cardiac magnetic resonance examinations performed between 1996 and 2012. Aortic distensibility was assessed, in the ascending (level 1), proximal descending (level 2) and distal descending (level 3) aorta. Changes in distensibility were studied using linear mixed-effects regression models.Results In total, 35 patients with MFS (age at inclusion 28 (IQR 23-32) years, 54% men) were included. Mean aortic distensibility was already low (between 2.9x10(-3)/mm Hg/year and 6.4x10(-3)/mm Hg/year) at all levels at baseline, and significantly decreased over time at levels 2 and 3 (respectively, p=0.012 and p=0.002). The rate of distensibility loss per year (x10(-3)/mm Hg/year) was 0.01, 0.03 and 0.06x10(-3)/mm Hg at levels 1, 2 and 3, respectively. At inclusion, men exhibited very low distensibility, whereas women showed moderately reduced distensibility, gradually decreasing with age. Aortic dilatation rate at level 2 was associated with reduced aortic distensibility. However, we could not demonstrate a direct correlation between distensibility and clinical events during a follow-up of 22 years.Conclusion Patients with MFS display reduced aortic distensibility already at an early age, inversely relating to aortic dilatation rate. However, in this selected patient group, distensibility seems less suitable as an individual predictor of aortic events. Show less
Coronary artery status in adults long after the arterial switch operation (ASO) is unclear. We conducted a systematic review to provide an overview of coronary complications during adulthood and to... Show moreCoronary artery status in adults long after the arterial switch operation (ASO) is unclear. We conducted a systematic review to provide an overview of coronary complications during adulthood and to evaluate the value of routine coronary imaging in adults after ASO, in light of current guidelines. Articles were screened for the inclusion of adult ASO patients and data on coronary complications and findings of coronary imaging were collected. A total of 993 adults were followed with a median available follow-up of only 2.0 years after reaching adulthood. Myocardial ischemia was suspected in 17/192 patients (8.9%). The number of coronary interventions was four (0.4%), and coronary death was reported in four (0.4%) patients. A lack of ischemia-related symptoms cannot be excluded because innervation studies indicated deficient cardiac innervation after ASO, although data is limited. Anatomical high-risk features found by routine coronary computed tomography (cCT) included stenosis (4%), acute angle (40%), kinking (24%) and inter-arterial course (11%). No coronary complications were reported during pregnancy (n = 45), although, remarkably, four (9%) patients developed heart failure. The 2020 European Society of Cardiology (ESC) guidelines state that routine screening for coronary pathologies is questionable. Based on current findings and in line with the 2018 American ACC/AHA guidelines a baseline assessment of the coronary arteries in all ASO adults seems justifiable. Thereafter, an individualized coronary follow-up strategy is advisable at least until significant duration of follow-up is available. Show less
BackgroundPatients with transposition of the great arteries corrected by an atrial switch operation experience major clinical events during adulthood, mainly heart failure (HF) and arrhythmias, but... Show moreBackgroundPatients with transposition of the great arteries corrected by an atrial switch operation experience major clinical events during adulthood, mainly heart failure (HF) and arrhythmias, but data on the emerging risks remain scarce. We assessed the risk for events during the clinical course in adulthood, and provided a novel risk score for event-free survival.Methods and ResultsThis multicenter study observed 167 patients with transposition of the great arteries corrected by an atrial switch operation (61% Mustard procedure; age, 28 [interquartile range, 24-36] years) for 13 (interquartile range, 9-16) years, during which 16 (10%) patients died, 33 (20%) had HF events, defined as HF hospitalizations, heart transplantation, ventricular assist device implantation, or HF-related death, and 15 (9%) had symptomatic ventricular arrhythmias. Five-year risk of mortality, first HF event, and first ventricular arrhythmia increased from 1% each at age 25 years, to 6% (95% CI, 4%-9%), 23% (95% CI, 17%-28%), and 5% (95% CI, 2%-8%), respectively, at age 50 years. Predictors for event-free survival were examined to construct a prediction model using bootstrapping techniques. A prediction model combining age >30 years, prior ventricular arrhythmia, age >1 year at repair, moderate or greater right ventricular dysfunction, severe tricuspid regurgitation, and mild or greater left ventricular dysfunction discriminated well between patients at low (<5%), intermediate (5%-20%), and high (>20%) 5-year risk (optimism-corrected C-statistic, 0.86 [95% CI, 0.82-0.90]). Observed 5- and 10-year event-free survival rates in low-risk patients were 100% and 97%, respectively, compared with only 31% and 8%, respectively, in high-risk patients.ConclusionsThe clinical course of patients undergoing atrial switch increasingly consists of major clinical events, especially HF. A novel risk score stratifying patients as low, intermediate, and high risk for event-free survival provides information on absolute individual risks, which may support decisions for pharmacological and interventional management. Show less
Background: Aortic root dilatation is common in adults with repaired tetralogy of Fallot (rTOF) and might lead to aortic dissection. However, little is known on progression of aortic dilatation and... Show moreBackground: Aortic root dilatation is common in adults with repaired tetralogy of Fallot (rTOF) and might lead to aortic dissection. However, little is known on progression of aortic dilatation and the effect of pharmaceutical treatment. This study aims to determine factors associated with aortic growth and investigate effects of losartan.Methods and results: We performed a prespedfied analysis from the 1:1 randomized, double-blind REDEFINE trial. Aortic root diameters were measured at baseline and after 2.0 = 0.3 years of follow-up using cardiovascular magnetic resonance (CMR) imaging. A total of 66 patients were included (68% men, age 40 +/- 12 years, baseline aortic root 37 +/- 6 mm, 32% aortic dilatation (>40 mm)). There was a trend towards slow aortic root growth (+0.6 +/- 2.3 mm after two years, p = 0.06) (n = 60). LV stroke volume was the only factor associated with both a larger baseline aortic root (beta: 0.09 mm/ml (95% C.I.:0.02, 0.15), p - 0.010) and with aortic growth during follow-up (beta: 0.04 rim/rill (95% C.L:0.005, 0.066), p = 0.024), after correction for age, sex, and body surface area using linear regression analysis. No treatment effect of losartan was found (p = 0.17).Conclusions: Aortic root dilatation was present in about one-third of rTOF patients. A larger LV stroke volume was associated with both a larger baseline aortic root and ongoing growth. Our findings provide no arguments for lower aortic diameter thresholds for prophylactic surgery compared to the general population. (C) 2020 Elsevier B.V. All rights reserved. Show less
Baumgartner, H.; Backer, J. de; Babu-Narayan, S.V.; Budts, W.; Chessa, M.; Diller, G.P.; ... ; Zeppenfeld, K. 2021
Background In response to an increased need for patient information in congenital heart disease, we previously developed an online, evidence-based information portal for patients with congenital... Show moreBackground In response to an increased need for patient information in congenital heart disease, we previously developed an online, evidence-based information portal for patients with congenital aortic and pulmonary valve disease. To assess its effectiveness, a stepped-wedge cluster randomised trial was conducted. Methods Adult patients and caregivers of paediatric patients with congenital aortic and/or pulmonary valve disease and/or tetralogy of Fallot who visited the outpatient clinic at any of the four participating centres in the Netherlands between 1 March 2016-1 July 2017 were prospectively included. The intervention (information portal) was introduced in the outpatient clinic according to a stepped-wedge randomised design. One month after outpatient clinic visit, each participant completed a questionnaire on disease-specific knowledge, anxiety, depression, mental quality of life, involvement and opinion/attitude concerning patient information and involvement. Results 343 participants were included (221 control, 122 intervention). Cardiac diagnosis (p=0.873), educational level (p=0.153) and sex (p=0.603) were comparable between the two groups. All outcomes were comparable between groups in the intention-to-treat analyses. However, only 51.6% of subjects in the intervention group (n=63) reported actually visiting the portal. Among these subjects (as-treated), disease-specific knowledge (p=0.041) and mental health (p=0.039) were significantly better than in control subjects, while other baseline and outcome variables were comparable. Conclusion Even after being invited by their cardiologists, only half of the participants actually visited the information portal. Only in those participants that actually visited the portal, knowledge of disease and mental health were significantly better. This underlines the importance of effective implementation of online evidence-based patient information portals in clinical practice. Show less
Aims The COMPARE trial showed a small but significant beneficial effect of 3-year losartan treatment on aortic root dilatation rate in adults with Marfan syndrome (MFS). However, no significant... Show moreAims The COMPARE trial showed a small but significant beneficial effect of 3-year losartan treatment on aortic root dilatation rate in adults with Marfan syndrome (MFS). However, no significant effect was found on clinical endpoints, possibly due to a short follow-up period. The aim of the current study was therefore to investigate the long-term clinical outcomes after losartan treatment.Methods and In the original COMPARE study (inclusion 2008-2009), adult patients with MFS (n=233) were randomly allocated results to either the angiotensin-II receptor blacker losartan on top of regular treatment (beta-blockers in 71% of the patients) or no additional medication. After the COMPARE trial period of 3 years, study subjects chose to continue their losartan medication or not. In a median follow-up period of 8 years, 75 patients continued losartan medication, whereas 78 patients, originally allocated to the control group, never used losartan after inclusion. No differences existed between baseline characteristics of the two groups except for age at inclusion [losartan 34 (interquartile range, IQR 26-43) years, control 41 (IQR 30-52) years; P=0.031], and beta-blacker use (losartan 81%, control 64%; P=0.022). A pathological FBN1 mutation was present in 76% of patients and 58% of the patients were male. Clinical endpoints, defined as all-cause mortality, aortic dissection/rupture, elective aortic root replacement, reoperation, and vascular graft implantation beyond the aortic root, were compared between the two groups. A per-patient composite endpoint was also analysed. Five deaths, 14 aortic dissections, 23 aortic root replacements, 3 reoperations, and 3 vascular graft implantations beyond the aortic root occurred during follow-up. Except for aortic root replacement, all endpoints occurred in patients with an operated aortic root. Patients who used losartan during the entire follow-up period showed a reduced number of events compared to the control group (death: 0 vs. 5, P=0.014; aortic dissection: 3 vs. 11, P=0.013; elective aortic root replacement: 10 vs. 13, P=0.264; reoperation: 1 vs. 2, P=0.463; vascular graft implantations beyond the aortic root 0 vs. 3, P=0.071; and composite endpoint: 14 vs. 26, P=0.019). These results remained similar when corrected for age and beta-blocker use in a multivariate analysis.Conclusion: These results suggest a clinical benefit of combined losartan and beta-blocker treatment in patients with MFS. Show less
Woudstra, O.I.; Dissel, A.C. van; Bom, T. van der; Bruin-Bon, R.H.A.C.M. de; Melle, J.P. van; Dijk, A.P.J. van; ... ; Bouma, B.J. 2020
Background: Predicting heart failure events in patients with a sys-temic right ventricle (sRV) due to transposition of the great arteries (TGA) is important for timely intensification of follow-up.... Show moreBackground: Predicting heart failure events in patients with a sys-temic right ventricle (sRV) due to transposition of the great arteries (TGA) is important for timely intensification of follow-up. This study assessed the value of strain compared with currently used parameters as predictor for heart failureefree survival in patients with sRV.Methods: In participants of a multicentre trial, speckle-tracking echocardiography (STE) was performed to assess global longitudinal strain (GLS), mechanical dispersion (MD), and postsystolic shortening (PSS). Cox regression was used to determine the association of STE parameters with the combined end point of progression of heart failure and death, compared with cardiovascular magnetic resonance (CMR) and computed tomography (CT) derived parameters.Results: Echocardiograms of 60 patients were analyzed (mean age 34 +/- 11 years, 65% male, 35% congenitally corrected TGA). Mean GLS was -13.5 +/- 2.9%, median MD was 49 (interquartile range [IQR] 30-76) ms, and 14 patients (23%) had PSS. During a median 8 (IQR 7-9) years, 15 patients (25%) met the end point. GLS, MD, and PSS were all associated with heart failure -free survival in univariable analysis. After correction for age, only GLS (optimal cutoff 0.001), and HR 4.34, 95% CI 1.48-12.74 (P = 0.007), respectively). Combining GLS and ejection fraction improved prediction, with patients with both GLS -10.5% and sRV ejection fraction < 30% at highest risk (HR 19.69, 95% CI 4.90-79.13; P < 0.001).Conclusions: The predictive value of GLS was similar to that of CMR/ CT-derived ejection fraction. The combination of GLS and ejection fraction identified patients at highest risk of heart failure and death. Easily available STE parameters can be used to guide follow-up in-tensity and can be integrated into future risk prediction scores. Show less
Objective: Little is known about the course of echocardiographic parameters used for the evaluation of valvular heart disease (VHD) during pregnancy, hampering interpretation of possible changes ... Show moreObjective: Little is known about the course of echocardiographic parameters used for the evaluation of valvular heart disease (VHD) during pregnancy, hampering interpretation of possible changes (physiological vs. pathophysiological). Therefore we studied the course of these parameters and ventricular function in pregnant women with aortic and pulmonary VHD.Methods: The cohort comprised 66 pregnant women enrolled in the prospective ZAHARA studies or evaluated by an identical protocol who had pulmonary VHD or aortic VHD (stenosis/prosthetic valve). The control group comprised 46 healthy pregnant women. Echocardiography was performed preconception, during pregnancy and 1 year postpartum. Peak gradient, mean gradient, aortic valve area (AVA)/effective orifice area (EOA), left ventricular ejection fraction (LVEF) and right ventricular function (RVF; TAPSE) were assessed.Results: Peak and mean gradients increased during pregnancy compared to preconception inwomen with aortic VHD and controls (p < 0.0125), but not in women with pulmonary VHD. AVA/EOA remained unchanged. Preconception and postpartum gradients were comparable in all groups. Mean LVEF was normal in pregnant women with VHD and controls. Mean TAPSE was lower (p < 0.001) in women with pulmonary VHD compared to women with aortic VHD and controls (<20 mm vs. >= 23 mm; p < 0.001). In women with pulmonary VHD a decrease of TAPSE was observed during pregnancy (p = 0.005).Conclusion: Physiological changes during pregnancy lead to increased Doppler gradients in women with aortic VHD. This increase was not found inwomen with pulmonary VHD, probably caused by impaired RVF. Therefore, evaluation of RVF during pregnancy might be important to prevent underestimation of the degree of stenosis. (c) 2019 Elsevier B.V. All rights reserved. Show less
Palen, R.L.F. van der; Bom, T. van der; Dekker, A.; Tsonaka, R.; Geloven, N. van; Kuipers, I.M.; ... ; Blom, N.A. 2019
Aims To assess medication use in adult congenital heart disease (ACHD) patients compared to the age- and sex-matched general population, identify patterns of pharmacotherapy, and analyse... Show moreAims To assess medication use in adult congenital heart disease (ACHD) patients compared to the age- and sex-matched general population, identify patterns of pharmacotherapy, and analyse associations between pharmacotherapy and adverse outcomes in ACHD.Methods and results Data of 14 138 ACHD patients from the CONCOR registry [35 (24-48) years, 49% male] and age- and sex-matched referents (1:10 ratio) were extracted from the Dutch Dispensed Drug Register for the years 2006-14. Adult congenital heart disease patients had more cardiovascular and non-cardiovascular drugs than referents (median 3 vs. 1, P<0.001). Polypharmacy, defined as >= 5 dispensed drug types yearly, was present in 30% of ACHD and 15% of referents {odds ratio [OR]=2.47 [95% confidence interval (CI) 2.39-2.54]}. Polypharmacy was independently associated with female sex [OR=1.92 (95% CI 1.88-1.96)], older age [for men: OR=2.3/10years (95% CI 2.2-2.4) and for women: OR=1.6/10years (95% CI 1.5-1.6); P-interaction<0.001], and ACHD severity [mild: OR=2.51 (95% CI 2.40-2.61), moderate: OR=3.22 (95% CI 3.06-3.40), severe: OR=4.87 (95% CI 4.41-5.38)]. Cluster analysis identified three subgroups with distinct medication patterns; a low medication use group (8-year cumulative survival: 98%), and a cardiovascular and comorbidity group with lower survival (92% and 95%, respectively). Cox regression revealed a strong association between polypharmacy and mortality [hazard ratio (HR)=3.94 (95% CI 3.22-4.81)], corrected for age, sex, and defect severity. Polypharmacy also increased the risk of hospitalization for adverse drug events [HR=4.58 (95% CI 2.04-10.29)].Conclusion Both cardiovascular and non-cardiovascular medication use is high in ACHD with twice as much polypharmacy compared with the matched general population. Patients with polypharmacy had a four-fold increased risk of mortality and adverse drug events. Recognition of distinct medication patterns can help identify patients at highest risk. Drug regimens need repeating evaluation to assess the appropriateness of all prescriptions. More high-quality studies are needed to improve ACHD care with more evidence-based pharmacotherapy. Show less
Background: This study describes the different types of congenital vascular rings according to their anatomy, symptoms, and age at clinical onset and reports the surgical outcomes.Methods: A... Show moreBackground: This study describes the different types of congenital vascular rings according to their anatomy, symptoms, and age at clinical onset and reports the surgical outcomes.Methods: A retrospective observational database study was conducted, reviewing the medical charts of 69 adult survivors with a history of a vascular ring, identified from the Dutch Congenital Cor vitia database.Results: Median age at presentation was 8.5 years (0-53.0 years). Thirty patients (43.5%) had a "left aortic arch with aberrant right subclavian artery," 21 patients (30.4%) a "double aortic arch," and 16 patients (23.2%) a "right aortic arch with aberrant left subclavian artery." The main symptomatology at presentation comprised respiratory symptoms (82.9%). Almost three-quarters of patients were also diagnosed with asthma/bronchial hyperreactivity. Patients with a double aortic arch had more symptoms than patients with a left aortic arch with aberrant right subclavian artery and right aortic arch with aberrant left subclavian artery (P < 0.001), requiring surgery most often (P < 0.001). In patients with childhood onset of symptoms, preoperative spirometry (ie, peak expiratory flows) was more often abnormal as compared with adult patients (P = 0.007). Surgery was performed in 42.0% of all patients at a median age of 17 years (0-63.0 years). Twenty-four (92.3%) of the operated patients showed improvement or complete relief of symptoms shortly after surgery. Of 26 asymptomatic nonoperated patients, 3 patients (11.5%) eventually developed symptoms.Conclusions: The low incidence of vascular rings, their anatomic heterogeneity, and a wide range of common symptoms often lead to misdiagnosis. Clinical awareness is warranted as a large subset of patients could benefit from surgery, even at an adult age. Show less
