Publications by authors named "Barbara J M Mulder"

294 Publications

Cardiovascular Morbidity and Mortality in Adult Patients With Repaired Aortic Coarctation.

J Am Heart Assoc 2021 Nov 10;10(22):e023199. Epub 2021 Nov 10.

Department of Cardiology University Medical Center Utrecht Utrecht The Netherlands.

Background The long-term burden of cardiovascular disease after repair of coarctation of the aorta (CoA) has not been elucidated. We aimed to determine the incidence of and risk factors for cardiovascular events in adult patients with repaired CoA. Additionally, mortality rates were compared between adults with repaired CoA and the general population. Methods and Results Using the Dutch Congenital Corvitia (CONCOR) registry, patients aged ≥16 years with previous surgical or transcatheter CoA repair from 5 tertiary referral centers were included. Cardiovascular events were recorded, comprising coronary artery disease, stroke/transient ischemic attack, aortic complications, arrhythmias, heart failure hospitalizations, endocarditis, and cardiovascular death. In total, 920 patients (median age, 24 years [range 16-74 years]) were included. After a mean follow-up of 9.3±5.1 years, 191 patients (21%) experienced at least 1 cardiovascular event. A total of 270 cardiovascular events occurred, of which aortic complications and arrhythmias were most frequent. Older age at initial CoA repair (hazard ratio [HR], 1.017; 95% CI, 1.000-1.033 [=0.048]) and elevated left ventricular mass index (HR, 1.009; 95% CI, 1.005-1.013 [<0.001]) were independently associated with an increased risk of cardiovascular events. The mortality rate was 3.3 times higher than expected based on an age- and sex-matched cohort from the Dutch general population (standardized mortality ratio, 3.3; 95% CI, 2.3-4.4 [<0.001]). Conclusions This large, prospective cohort of adults with repaired CoA showed a high burden of cardiovascular events, particularly aortic complications and arrhythmias, during long-term follow-up. Older age at initial CoA repair and elevated left ventricular mass index were independent risk factors for the occurrence of cardiovascular events. Mortality was 3.3-fold higher compared with the general population. These results advocate stringent follow-up after CoA repair and emphasize the need for improved preventive strategies.
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http://dx.doi.org/10.1161/JAHA.121.023199DOI Listing
November 2021

Aortic distensibility in Marfan syndrome: a potential predictor of aortic events?

Open Heart 2021 Oct;8(2)

Cardiology, Amsterdam UMC - Location AMC, Amsterdam, The Netherlands

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 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 2.9×10/mm Hg/year and 6.4×10/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 (×10/mm Hg/year) was 0.01, 0.03 and 0.06×10/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.
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http://dx.doi.org/10.1136/openhrt-2021-001775DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8549677PMC
October 2021

Baffle complications in adults after atrial switch for transposition of the great arteries.

Can J Cardiol 2021 Oct 8. Epub 2021 Oct 8.

Department of Cardiology, University Medical Center Utrecht, Heidelberglaan 100, 3584 CX, Utrecht, The Netherlands.

Background: Baffle complications, i.e. leakage or stenosis, after an atrial switch operation(AtrSO) for transposition of the great arteries(TGA) are difficult to detect using routine transthoracic echocardiography(TTE). We examined baffle interventions and the prevalence of baffle complications.

Methods: This dual-center study followed TGA-AtrSO patients for the occurrence of baffle interventions. Additionally, in 2017-2019, prevalence of baffle complications was determined in patients undergoing routine contrast-enhanced (CE) TTE including various hemodynamic conditions and computed tomography(CT). Baffle leaks were defined as right-to-left shunting on CE-TTE and baffle stenosis as a systemic venous baffle diameter of <10mm on CT.

Results: In total, 67 TGA-AtrSO patients were followed up to a median age of 38(IQR 34-42) years, for a median of 9(IQR 6-13) years. Baffle interventions were documented in 24 patients(36%). Cumulative risk of baffle interventions was 25% after 15 years of follow-up. Prevalence of baffle complications was determined in 29/67 patients. In total, 4(14%) had patent baffles, 11(38%) had leakage only, 5(17%) had stenosis only, and 9(31%) had both, while 24/29(84%) were asymptomatic. Although baffle leaks were not associated with clinical characteristics, peak work rate during exercise TTE was lower in patients with vs without stenosis(89±24 vs 123±21 W, p<0.001).

Conclusions: Baffle complications are very common in TGA-AtrSO. The cumulative risk of baffle interventions was 25% after 15 years of follow-up. CE-TTE uncovered asymptomatic baffle leakage in the majority of patients, especially with examination during exercise. CT revealed baffle stenosis in almost half of the patients, associated with decreased exercise tolerance. Awareness of these findings may alter clinical follow-up.
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http://dx.doi.org/10.1016/j.cjca.2021.09.034DOI Listing
October 2021

The Coronary Arteries in Adults after the Arterial Switch Operation: A Systematic Review.

J Cardiovasc Dev Dis 2021 Aug 26;8(9). Epub 2021 Aug 26.

Center for Congenital Heart Disease Amsterdam-Leiden (CAHAL), Department of Cardiology, Leiden University Medical Center, 2333 ZA Leiden, The Netherlands.

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 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.
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http://dx.doi.org/10.3390/jcdd8090102DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8468869PMC
August 2021

Patient information portal for congenital aortic and pulmonary valve disease: a stepped-wedge cluster randomised trial.

Open Heart 2021 03;8(1)

Department of Cardiothoracic Surgery, Erasmus University Medical Center, Rotterdam, The Netherlands.

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 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.
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http://dx.doi.org/10.1136/openhrt-2020-001252DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7993296PMC
March 2021

Clinical Course Long After Atrial Switch: A Novel Risk Score for Major Clinical Events.

J Am Heart Assoc 2021 02 22;10(5):e018565. Epub 2021 Feb 22.

Department of Clinical and Experimental Cardiology Heart Center Amsterdam Cardiovascular SciencesAmsterdam University Medical CenterUniversity of Amsterdam the Netherlands.

Background Patients 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 Results This 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. Conclusions The 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.
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http://dx.doi.org/10.1161/JAHA.120.018565DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8174274PMC
February 2021

Review of Digitalized Patient Education in Cardiology: A Future Ahead?

Cardiology 2021 5;146(2):263-271. Epub 2021 Feb 5.

Department of Cardiology, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands.

Introduction: An increased focus on shared decision-making and patient empowerment in cardiology and on patient outcomes such as quality of life (QoL), depression, and anxiety underline the importance of high-quality patient education. Studies focusing on digital means of patient education performed in other disciplines of medicine demonstrated its positive effect in these areas. Therefore, a review of the current literature was performed to (i) evaluate the status of innovative, digitalized means of patient education in cardiology and (ii) assess the impact of digital patient education on outcome parameters (i.e., patient knowledge (or health literacy), QoL, depression, anxiety, and patient satisfaction).

Method: A review of the current literature was performed to evaluate the effect of digitalized patient education for any purpose in the field of cardiology. Medline and EMBASE were searched for articles reporting any digital educational platform used for patient education up to May 2020. The articles were compared on their effect on patient knowledge or health literacy, QoL, depression or anxiety, and patient satisfaction.

Results: The initial search yielded 279 articles, 34 of which were retained after applying in, and exclusion criteria. After full-text analysis, the total number of articles remaining was 16. Of these, 6 articles discussed the use of smartphone or tablet applications as a means of patient education, whereas 3 reviewed web-based content, and 7 evaluated the use of video (2 three-dimensional videos, from which one on a virtual reality headset).

Conclusion: This review demonstrates that digital patient education increases patient knowledge. Overall, digital education increases QoL and lowers feelings of depression and anxiety. The majority of patients express satisfaction with digital platforms. It remains important that developers of digital patient education platforms remain focused on clear, structured, and comprehensible information presentation.
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http://dx.doi.org/10.1159/000512778DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8117376PMC
August 2021

Identification of patients at risk of sudden cardiac death in congenital heart disease: The PRospEctiVE study on implaNTable cardIOverter defibrillator therapy and suddeN cardiac death in Adults with Congenital Heart Disease (PREVENTION-ACHD).

Heart Rhythm 2021 05 16;18(5):785-792. Epub 2021 Jan 16.

Department of Cardiology, Heart Center, Amsterdam University Medical Centers/University of Amsterdam, Amsterdam, The Netherlands. Electronic address:

Background: Sudden cardiac death (SCD) is the main preventable cause of death in patients with adult congenital heart disease (ACHD). Since robust risk stratification methods are lacking, we developed a risk score model to predict SCD in patients with ACHD: the PRospEctiVE study on implaNTable cardIOverter defibrillator therapy and suddeN cardiac death in Adults with Congenital Heart Disease (PREVENTION-ACHD) risk score model.

Objective: The purpose of this study was to prospectively study predicted SCD risk using the PREVENTION-ACHD risk score model and actual SCD and sustained ventricular tachycardia/ventricular fibrillation (VT/VF) rates in patients with ACHD.

Methods: The PREVENTION-ACHD risk score model assigns 1 point each to coronary artery disease, New York Heart Association class II/III heart failure, supraventricular tachycardia, systemic ejection fraction < 40%, subpulmonary ejection fraction < 40%, QRS duration ≥ 120 ms, and QT dispersion ≥ 70 ms. SCD risk was calculated for each patient. An annual predicted risk of ≥3% constituted high risk. The primary outcome was SCD or VT/VF after 2 years. The secondary outcome was SCD.

Results: The study included 783 consecutive patients with ACHD (n=239 (31%) left-sided lesions; n=138 (18%) tetralogy of Fallot; n=108 (14%) closed atrial septal defect; median age 36 years; interquartile range 28-47 years; n=401 (51%) men). The PREVENTION-ACHD risk score model identified 58 high-risk patients. Eight patients (4 at high risk) experienced the primary outcome. The Kaplan-Meier estimates were 7% (95% confidence interval [CI] 0.1%-13.3%) in the high-risk group and 0.6% (95% CI 0.0%-1.1%) in the low-risk group (hazard ratio 12.5; 95% CI 3.1-50.9; P < .001). The risk score model's sensitivity was 0.5 and specificity 0.93, resulting in a C-statistic of 0.75 (95% CI 0.57-0.90). The hazard ratio for SCD was 12.4 (95% CI 1.8-88.1) (P = .01); the sensitivity and specificity were 0.5 and 0.92, and the C-statistic was 0.81 (95% CI 0.67-0.95).

Conclusion: The PREVENTION-ACHD risk score model provides greater accuracy in SCD or VT/VF risk stratification as compared with current guideline indications and identifies patients with ACHD who may benefit from preventive implantable cardioverter-defibrillator implantation.
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http://dx.doi.org/10.1016/j.hrthm.2021.01.009DOI Listing
May 2021

Bleeding and thrombotic risk in pregnant women with Fontan physiology.

Heart 2021 Sep 24;107(17):1390-1397. Epub 2020 Nov 24.

Adult Congenital Heart Disease, King Faisal Specialist Hospital and Research Centre, Riyadh, Saudi Arabia

Background/objectives: Pregnancy may potentiate the inherent hypercoagulability of the Fontan circulation, thereby amplifying adverse events. This study sought to evaluate thrombosis and bleeding risk in pregnant women with a Fontan.

Methods: We performed a retrospective observational cohort study across 13 international centres and recorded data on thrombotic and bleeding events, antithrombotic therapies and pre-pregnancy thrombotic risk factors.

Results: We analysed 84 women with Fontan physiology undergoing 108 pregnancies, average gestation 33±5 weeks. The most common antithrombotic therapy in pregnancy was aspirin (ASA, 47 pregnancies (43.5%)). Heparin (unfractionated (UFH) or low molecular weight (LMWH)) was prescribed in 32 pregnancies (30%) and vitamin K antagonist (VKA) in 10 pregnancies (9%). Three pregnancies were complicated by thrombotic events (2.8%). Thirty-eight pregnancies (35%) were complicated by bleeding, of which 5 (13%) were severe. Most bleeds were obstetric, occurring antepartum (45%) and postpartum (42%). The use of therapeutic heparin (OR 15.6, 95% CI 1.88 to 129, p=0.006), VKA (OR 11.7, 95% CI 1.06 to 130, p=0.032) or any combination of anticoagulation medication (OR 13.0, 95% CI 1.13 to 150, p=0.032) were significantly associated with bleeding events, while ASA (OR 5.41, 95% CI 0.73 to 40.4, p=0.067) and prophylactic heparin were not (OR 4.68, 95% CI 0.488 to 44.9, p=0.096).

Conclusions: Current antithrombotic strategies appear effective at attenuating thrombotic risk in pregnant women with a Fontan. However, this comes with high (>30%) bleeding risk, of which 13% are life threatening. Achieving haemostatic balance is challenging in pregnant women with a Fontan, necessitating individualised risk-adjusted counselling and therapeutic approaches that are monitored during the course of pregnancy.
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http://dx.doi.org/10.1136/heartjnl-2020-317397DOI Listing
September 2021

Medication in adults after atrial switch for transposition of the great arteries: clinical practice and recommendations.

Eur Heart J Cardiovasc Pharmacother 2020 Sep 25. Epub 2020 Sep 25.

Heart Center; Department of Clinical and Experimental Cardiology, Amsterdam UMC, University of Amsterdam, Amsterdam Cardiovascular Sciences, Meibergdreef 9, AZ, Amsterdam, The Netherlands.

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 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-Angiotension-Aldosteron System(RAAS) inhibitors and β-blockers with long-term survival.

Methods And Results: We identified 150 TGA-AtrSO patients(median age 30 years[IQR 25-35], 63% male) included in the CONCOR registry from five tertiary medical centers with subsequent linkage to the Dutch Dispensed Drug Register for the years 2006-2014. Use of RAAS inhibitors, β-blockers, and diuretics increased with age, from respectively 21%[95%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 β-blockers in symptomatic patients(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 β-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 β-blockers in symptomatic patients only. These findings can direct future guidelines, supporting use of RAAS inhibitors and β-blockers in symptomatic, but not asymptomatic patients.
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http://dx.doi.org/10.1093/ehjcvp/pvaa111DOI Listing
September 2020

Type D Personality Associated With Increased Risk for Mortality in Adults With Congenital Heart Disease.

J Cardiovasc Nurs 2020 Aug 26. Epub 2020 Aug 26.

Dirkjan Kauw, MD PhD student, Department of Cardiology, Amsterdam UMC, University of Amsterdam; and Netherlands Heart Institute, Utrecht, The Netherlands. Dounya Schoormans, PhD Assistant Professor, CoRPS - Center of Research on Psychological and Somatic disorders, Department of Medical and Clinical Psychology, Tilburg University, The Netherlands. Gertjan Tj. Sieswerda, MD, PhD Cardiologist, Department of Cardiology, University Medical Center Utrecht, The Netherlands. Joost P. Van Melle, MD, PhD Cardiologist, Department of Cardiology, University Medical Center Groningen, University of Groningen, The Netherlands. Hubert W. Vliegen, MD, PhD Cardiologist, Department of Cardiology, Leiden University Medical Center, The Netherlands. Arie P.J. Van Dijk, MD, PhD Cardiologist, Department of Cardiology, Radboud University Medical Centre, Nijmegen, The Netherlands. Mariët S. Hulsbergen-Zwarts, MD, PhD Cardiologist, Department of Cardiology, Elisabeth-TweeSteden Hospital, Tilburg, The Netherlands. Marco C. Post, MD, PhD Cardiologist, Department of Cardiology, St. Antonius Hospital, Nieuwegein, The Netherlands. Tieneke J. Ansink, MD, PhD Cardiologist, Department of Cardiology, Zuyderland Hospital, Sittard-Geleen, The Netherlands. Barbara J.M. Mulder, MD, PhD Professor, Department of Cardiology, Amsterdam UMC, University of Amsterdam, The Netherlands. Berto J. Bouma, MD, PhD Cardiologist, Department of Cardiology, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands. Mark J. Schuuring, MD, PhD Postdoctoral researcher, Department of Cardiology, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands. ORCID identifier: 0000-0002-2843-1852.

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 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.
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http://dx.doi.org/10.1097/JCN.0000000000000747DOI Listing
August 2020

Safety and efficacy of non-vitamin K antagonist oral anticoagulants for prevention of thromboembolism in adults with systemic right ventricle: Results from the NOTE international registry.

Int J Cardiol 2021 01 14;322:129-134. Epub 2020 Aug 14.

Adult Congenital Heart Disease Unit, Department of Cardiology, Monaldi Hospital, Naples, Italy.

Background: Patients with systemic right ventricle (sRV), including transposition of great arteries (TGA) after atrial switch procedure and congenitally corrected transposition of great arteries (ccTGA), may require anticoagulation for thromboembolism (TE) prevention. In the absence of data on non-vitamin K antagonist oral anticoagulants (NOACs), vitamin K antagonists (VKAs) remain the agent of choice. We investigated the safety, efficacy and feasibility of NOACs treatment in adults with sRV in a worldwide study.

Methods: This is an international multicentre prospective study, using data from the NOTE registry on adults with sRV taking NOACs between 2014 and 2019. The primary endpoints were TE and major bleeding (MB). The secondary endpoint was minor bleeding.

Results: A total of 76 patients (42.5 ± 10.0 years, 76% male) with sRV (74% TGA, 26% ccTGA) on NOACs were included in the study. During a median follow-up of 2.5 years (IQR1.5-3.9), TE events occurred in 3 patients (4%), while no MB episodes were reported. Minor bleeding occurred in 9 patients (12%). NOAC treatment cessation rate was 1.4% (95%CI:0.3-4%) during the first year of follow-up. All the patients with TE events had a CHADS-VASc score ≥ 2 and impaired sRV systolic function at baseline. The total incidence of major events during follow-up was significantly lower compared to historical use of VKAs or aspirin before study inclusion (1.4% (95%CI:0.29-4%) vs 6,9% (95%CI:2.5-15.2%); p = .01).

Conclusions: In this prospective study, NOACs appear to be well-tolerated, with excellent efficacy and safety at mid-term in patients with sRV.
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http://dx.doi.org/10.1016/j.ijcard.2020.08.034DOI Listing
January 2021

Myocardial Deformation in the Systemic Right Ventricle: Strain Imaging Improves Prediction of the Failing Heart.

Can J Cardiol 2020 09 17;36(9):1525-1533. Epub 2019 Dec 17.

Heart Center, Department of Clinical and Experimental Cardiology, Amsterdam UMC, University of Amsterdam, Amsterdam Cardiovascular Sciences, Amsterdam, The Netherlands. Electronic address:

Background: Predicting heart failure events in patients with a systemic 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 failure-free 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 > -10.5%) and CMR/CT-derived sRV ejection fraction (optimal cutoff < 30%) remained associated with heart failure-free survival: hazard ratio (HR) 8.27, 95% confidence interval (CI) 2.50-27.41 (P < 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 intensity and can be integrated into future risk prediction scores.
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http://dx.doi.org/10.1016/j.cjca.2019.12.014DOI Listing
September 2020

Long-term clinical outcomes of losartan in patients with Marfan syndrome: follow-up of the multicentre randomized controlled COMPARE trial.

Eur Heart J 2020 11;41(43):4181-4187

Department of Cardiology, Amsterdam UMC, University of Amsterdam, Amsterdam Cardiovascular Sciences, Meibergdreef 9, 1105 AZ, Amsterdam, The Netherlands.

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 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 Results: In the original COMPARE study (inclusion 2008-2009), adult patients with MFS (n = 233) were randomly allocated to either the angiotensin-II receptor blocker losartan® on top of regular treatment (β-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 β-blocker 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 β-blocker use in a multivariate analysis.

Conclusion: These results suggest a clinical benefit of combined losartan and β-blocker treatment in patients with MFS.
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http://dx.doi.org/10.1093/eurheartj/ehaa377DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7711887PMC
November 2020

22q11.2 deletion syndrome is associated with increased mortality in adults with tetralogy of Fallot and pulmonary atresia with ventricular septal defect.

Int J Cardiol 2020 05 27;306:56-60. Epub 2020 Feb 27.

Department of Cardiology, Amsterdam UMC, University of Amsterdam, Meibergdreef 9, 1105, AZ, Amsterdam, the Netherlands. Electronic address:

Background: 22q11.2 Deletion syndrome (22q11.2DS) is common in patients with tetralogy of Fallot (TOF) or pulmonary atresia with ventricular septal defect (PA/VSD) and is associated with worse outcomes in children. Whether this impaired prognosis is also translated into adulthood is unknown, as data in adult patients are limited. We aimed to compare long-term outcomes in adults with TOF or PA/VSD both with and without 22q11.2DS.

Methods: This study prospectively followed a nationwide multicenter cohort of TOF or PA/VSD patients with genetically confirmed presence or absence of 22q11.2DS, from inclusion in the Dutch national CONCOR registry for adults with congenital heart disease (CHD) onward. Outcome measures included all-cause mortality, cardiac mortality, need for pulmonary valve replacement (PVR), ventricular arrhythmias (VA), pacemaker implantation, and ICD implantation.

Results: In total, 479 patients were included (277 (58%) male, median age 28 [IQR; 21-37] years, 62 (13%) with PA/VSD, 34 (7%) with 22q11.2DS). During a median follow-up of 11 [IQR; 6-13] years, 52 (11%) patients died (8 with 22q11.2DS and 44 without 22q11.2DS). Patients with 22q11.2DS had significant decreased survival after 12 years (76% [95% CI; 62-93]) compared to patients without 22q11.2DS (89% [95% CI; 86-92], p = 0.008). 22q11.2DS was associated with increased risk of all-cause mortality and cardiac-mortality, independent of age, sex, and PA/VSD. No association was found between 22q11.2DS and late complications i.e. PVR, VA, pacemaker, or ICD implantation.

Conclusions: Adults with TOF or PA/VSD with 22q11.2DS have a significantly worse survival than adults without this deletion. In patients with TOF or PA/VSD, genetic analysis for the presence of 22q11.2DS is important for risk stratification and genetic counseling.
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http://dx.doi.org/10.1016/j.ijcard.2020.02.064DOI Listing
May 2020

Doppler gradients, valve area and ventricular function in pregnant women with aortic or pulmonary valve disease: Left versus right.

Int J Cardiol 2020 05 16;306:152-157. Epub 2019 Nov 16.

Department of Cardiology, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands. Electronic address:

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 (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 in women 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 in women 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.
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http://dx.doi.org/10.1016/j.ijcard.2019.11.118DOI Listing
May 2020

Risk of coronary artery disease in adults with congenital heart disease: A comparison with the general population.

Int J Cardiol 2020 04 18;304:39-42. Epub 2019 Nov 18.

Department of Cardiology, Academic Medical Center, Amsterdam, the Netherlands. Electronic address:

Background: Coronary artery disease (CAD) will increasingly determine outcome in the aging adult congenital heart disease (CHD) population. We aimed to determine sex-specific incidence of CAD in adult CHD patients throughout adulthood, compared to the general population.

Methods And Results: We followed 11,723 adult CHD patients (median age 33 years; 49% male; 57% mild, 34% moderate, 9% severe CHD) from the Dutch CONCOR registry, and two age-sex-matched persons per patient from the general population for first CAD event in national registers (period 2002-2012). Incidence rates were estimated using smoothed hazard functions. CAD risk during follow-up, stratified by CHD severity, was compared using proportional subdistribution hazards regression. In ACHD patients, 103 CAD events (43 women) occurred over 60,456 person-years. Rates per 1000person-years increased from 0.3(95% confidence interval: 0.1-0.6) at age 20 to 5.8(3.7-8.9) at 70 years in female, and from 0.5(0.3-1.0) to 7.8(5.1-11.8) in male patients. Compared to the general population, relative risk was 12.0(2.5-56.3) in women and 4.6(1.7-12.1) in men aged 20 years. Relative risk declined with age, remaining significant up to age ~65 years in women and ~50 years in men. In patients with mild, moderate and severe CHD, CAD risk was 1.3(0.9-1.9), 1.6(1.0-2.5) and 2.9(1.3-6.9) times increased compared to the general population, respectively.

Conclusions: We found increased CAD risk in adult CHD patients, with greater relative risk at younger age, in women and those with more severe CHD. These results underline the importance of screening for and treatment of CAD risk factors in these patients.
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http://dx.doi.org/10.1016/j.ijcard.2019.11.114DOI Listing
April 2020

Advantages of mobile health in the management of adult patients with congenital heart disease.

Int J Med Inform 2019 12 15;132:104011. Epub 2019 Oct 15.

Department of Cardiology, Amsterdam UMC, University of Amsterdam, Amsterdam, the Netherlands; Department of Cardiology, Haga Teaching Hospital, the Hague, the Netherlands. Electronic address:

Background: Adults with congenital heart disease (ACHD) often suffer from deterioration related to cardiac arrhythmias, hypertension (HT) or heart failure (HF), frequently occurring between planned visits. Mobile health (mHealth) could improve management through remote monitoring by enabling swift therapeutic response and detecting new diagnoses.

Methods: We performed a prospective study employing mHealth in ACHD patients, weekly monitoring heart rhythm, weight and blood pressure. In case of consecutive threshold exceeding measurements or in case of new diagnosis, patients were contacted and if needed the treating physician was consulted. Inclusion criteria were: palpitations within the last three years (with or without arrhythmia diagnosis) or HF NYHA class ≥ II. We evaluated the detection of recurrences and new diagnosis of arrhythmias, HT and HF, adherence and patient experience (Net Promotor Score (NPS)).

Results: In total, 109 of the 268 invited ACHD patients were enrolled, 80 with palpitations, 13 with HF, 16 experienced both, mean age 45 (±13) years, 33% male. Median follow-up was 12 (Q1-Q3;9-14) months, 91 patients initiated all measurements (heart rhythm, weight and blood pressure). In 25% of the patients with diagnosed arrhythmias (14/56) recurrences of arrhythmias were detected; 13% of the patients with undiagnosed palpitations (4/32) were diagnosed with novel arrhythmias. In 38% of the patients with HT at baseline (6/16), treatment adjustment was necessary, 4% of the patients without HT (4/76) received novel HT diagnosis. Diuretics were adjusted in 7% of the patients with HF (2/29). Adherence was > 70% in 77% of the patients that started weekly measurements (70/91). Patients that were female, older of age and experienced palpitations at inclusion were more likely to acquire an adherence of > 70%. NPS was completed by 68 patients, 57 patients (84%) were promotors or neutral, and 11 patients (16%) were critics.

Conclusions: mHealth offers advantages in the management of selected ACHD patients; it enabled early detection of recurrences and new diagnosis of arrhythmias, hypertension and heart failure, which lead to swift therapeutic response or remote reassurance. Furthermore, mHealth was well accepted with high adherence and positive patient experience.
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http://dx.doi.org/10.1016/j.ijmedinf.2019.104011DOI Listing
December 2019

Non-Vitamin K Antagonist Oral Anticoagulants in Adult Congenital Heart Disease.

Can J Cardiol 2019 Dec 26;35(12):1686-1697. Epub 2019 Jun 26.

Adult Congenital Heart Center, Department of Medicine, Montreal Heart Institute, Université de Montréal, Montreal, Quebec, Canada; Division of electrophysiology, Department of medicine, Montreal Heart Institute, Université de Montréal, Montreal, Quebec, Canada.

Non-vitamin K antagonist (VKA) oral anticoagulants (NOACs) have several advantages over VKAs that render them an attractive option for adults with congenital heart disease (CHD). Efficacy and safety data specific to the adult CHD population are emerging. Herein, we synthesize the growing literature regarding NOACs in adults with CHD and attempt to identify subgroups for which it appears reasonable to extrapolate data from populations without CHD. Small observational studies suggest that NOACs are safe and effective in selected adults with CHD. NOACs are contraindicated in patients with a mechanical valve, in those with mitral or tricuspid valve stenosis with enlarged and diseased atria, with or without a mitral or tricuspid bioprosthesis, and after recent cardiac surgery (< 3 months). There is currently insufficient evidence to recommend NOACs in patients with a Fontan circulation or cyanotic CHD. Growing literature supports the use of NOACs in patients without CHD who have various forms of valvular heart disease. Therefore, when an indication for oral anticoagulation is established, it appears reasonable to consider a NOAC instead of a VKA in adults with CHD lesions analogous to isolated mitral regurgitation, tricuspid regurgitation, or aortic regurgitation or stenosis. The NOAC agent selected and the prescribed dose should be tailored according to bleeding risk, body weight, renal function, and comedications, especially antiepileptic drugs. The decision to initiate a NOAC should be shared between the patient and care provider. Large-scale research studies are required to further assess safety and efficacy in selected patient subgroups.
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http://dx.doi.org/10.1016/j.cjca.2019.06.022DOI Listing
December 2019

Prolonged T -T interval is a risk factor for sudden cardiac death in adults with congenital heart disease.

Congenit Heart Dis 2019 Nov 1;14(6):952-957. Epub 2019 Oct 1.

Department of Clinical and Experimental Cardiology, Heart Center, Amsterdam University Medical Centers, University of Amsterdam, Amsterdam, the Netherlands.

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 T -T (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 < .001); TpTe-mean was 70 ± 16 vs 63 ± 10 ms (P < .001); and dispersion was 51 ± 22 ms vs 41 ± 16 ms (P = .02), respectively. Assessing each ECG lead separately, TpTe in lead aVR predicted SCD most accurately. TpTe in lead aVR was 71 ± 23 ms in cases vs 61 ± 13 ms in controls (P < .001). After adjusting for impaired ventricular function, heart failure symptoms, and prolonged QRS duration, the OR of SCD of TpTe in lead aVR at an optimal cutoff of 80 ms was 5.8 (95% CI 2.7-12.4, P < .001).

Conclusions: The TpTe interval is associated with SCD in ACHD patients. Particularly, TpTe in lead aVR can be used as an independent risk factor for SCD in ACHD patients and may, therefore, add precision to current risk prediction models.
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http://dx.doi.org/10.1111/chd.12847DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7003836PMC
November 2019

Learning strategies among adult CHD fellows.

Cardiol Young 2019 Nov 10;29(11):1356-1360. Epub 2019 Sep 10.

Department of Cardiology, Heart Institute Cincinnati Children's Hospital Medical Center, OH, USA.

Objective: Subspecialisation is increasingly a fundamental part of the contemporary practice of medicine. However, little is known about how medical trainees learn in the modern era, and particularly in growing and relatively new subspecialties, such as adult CHD. The purpose of this study was to assess institutional-led and self-directed learning strategies of adult CHD fellows.

Methods: This international, cross-sectional online survey was conducted by the International Society for Adult Congenital Heart Disease and consisted primarily of categorical questions and Likert rating scales. All current or recent (i.e., those within 2 years of training) fellows who reported training in adult CHD (within adult/paediatric cardiology training or within subspecialty fellowships) were eligible.

Results: A total of 75 fellows participated in the survey: mean age: 34 ± 5; 35 (47%) female. Most adult CHD subspecialty fellows considered case-based teaching (58%) as "very helpful", while topic-based teaching was considered "helpful" (67%); p = 0.003 (favouring case-based). When facing a non-urgent clinical dilemma, fellows reported that they were more likely to search for information online (58%) than consult a faculty member (29%) or textbook (3%). Many (69%) fellows use their smartphones at least once daily to search for information during regular clinical work.

Conclusions: Fellows receiving adult CHD training reported a preference for case-based learning and frequent use of online material and smartphones. These findings may be incorporated into the design and enhancement of fellowships and development of online training resources.
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http://dx.doi.org/10.1017/S1047951119002063DOI Listing
November 2019

Medium-term systemic blood pressure after stenting of aortic coarctation: a systematic review and meta-analysis.

Heart 2019 10 17;105(19):1464-1470. Epub 2019 Jul 17.

Department of Cardiology, University Medical Center Utrecht, Utrecht, The Netherlands.

Objective: Long-term prognosis of patients with coarctation of the aorta (CoA) is impaired due to the high prevalence of hypertension and consequent cardiovascular complications. Although stent implantation results in acute anatomical and haemodynamic benefit, limited evidence exists regarding the late clinical outcome. In this meta-analysis, we aimed to evaluate the medium-term effect of stent placement for CoA on systemic blood pressure (BP).

Methods: PubMed, EMBASE and Cochrane databases were searched for non-randomised cohort studies addressing systemic BP ≥12 months following CoA stenting. Meta-analysis was performed on the change in BP from baseline to last follow-up using a random-effects model. Subgroup analyses and meta-regression were conducted to identify sources of heterogeneity between studies.

Results: Twenty-six studies with a total of 1157 patients and a median follow-up of 26 months were included for final analysis. Meta-analysis showed a 20.3 mm Hg (95% CI 16.4 to 24.1 mm Hg; p<0.00001) reduction in systolic BP and an 8.2 mm Hg (12 studies; 95% CI 5.2 to 11.3 mm Hg; p<0.00001) reduction in diastolic BP. A concomitant decrease in the use of antihypertensive medication was observed. High systolic BP and peak systolic gradient at baseline and stenting of native CoA were associated with a greater reduction in systolic BP at follow-up.

Conclusions: Stent implantation for CoA is associated with a significant decline in systolic and diastolic BP during medium-term follow-up. The degree of BP reduction appears to be dependent on baseline systolic BP, baseline peak systolic gradient, and whether stenting is performed for native or recurrent CoA.
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http://dx.doi.org/10.1136/heartjnl-2019-314965DOI Listing
October 2019

Glycoproteomic Analysis of the Aortic Extracellular Matrix in Marfan Patients.

Arterioscler Thromb Vasc Biol 2019 09 18;39(9):1859-1873. Epub 2019 Jul 18.

From the King's British Heart Foundation Centre, King's College London, United Kingdom (X.Y., A.L.F., J.B.-B., R.L., M.F., F.B., P.S., Q.X., M.M.).

Objective: Marfan syndrome (MFS) is caused by mutations in FBN1 (fibrillin-1), an extracellular matrix (ECM) component, which is modified post-translationally by glycosylation. This study aimed to characterize the glycoproteome of the aortic ECM from patients with MFS and relate it to aortopathy. Approach and Results: ECM extracts of aneurysmal ascending aortic tissue from patients with and without MFS were enriched for glycopeptides. Direct N-glycopeptide analysis by mass spectrometry identified 141 glycoforms from 47 glycosites within 35 glycoproteins in the human aortic ECM. Notably, MFAP4 (microfibril-associated glycoprotein 4) showed increased and more diverse N-glycosylation in patients with MFS compared with control patients. MFAP4 mRNA levels were markedly higher in MFS aortic tissue. MFAP4 protein levels were also increased at the predilection (convexity) site for ascending aorta aneurysm in bicuspid aortic valve patients, preceding aortic dilatation. In human aortic smooth muscle cells, MFAP4 mRNA expression was induced by TGF (transforming growth factor)-β1 whereas siRNA knockdown of MFAP4 decreased FBN1 but increased elastin expression. These ECM changes were accompanied by differential gene expression and protein abundance of proteases from ADAMTS (a disintegrin and metalloproteinase with thrombospondin motifs) family and their proteoglycan substrates, respectively. Finally, high plasma MFAP4 concentrations in patients with MFS were associated with a lower thoracic descending aorta distensibility and greater incidence of type B aortic dissection during 68 months follow-up.

Conclusions: Our glycoproteomics analysis revealed that MFAP4 glycosylation is enhanced, as well as its expression during the advanced, aneurysmal stages of MFS compared with control aneurysms from patients without MFS.
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http://dx.doi.org/10.1161/ATVBAHA.118.312175DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6727943PMC
September 2019

Progression of aortic root dilatation and aortic valve regurgitation after the arterial switch operation.

Heart 2019 11 10;105(22):1732-1740. Epub 2019 Jul 10.

Division of Pediatric Cardiology, Department of Pediatrics, Leiden University Medical Center, Leiden, The Netherlands.

Objective: To study neo-aortic growth and the evolution of neo-aortic valve regurgitation (AR) in patients with transposition of the great arteries (TGA) after arterial switch operation (ASO) from newborn to adulthood and to identify patients at risk.

Methods: Neo-aortic dimensions (annulus/root/sinotubular junction) and neo-aortic valve regurgitation were assessed serially in 345 patients with TGA who underwent ASO between 1977 and 2015. Linear mixed-effect models were used to assess increase of neo-aortic dimensions over time and to identify risk factors for dilatation. Risk factor analysis for AR by using time-dependent Cox regression models.

Results: After a rapid increase in the first year after ASO and proportional growth in childhood, neo-aortic dimensions continue to increase in adulthood without stabilisation. Annual diameter increase in adulthood was 0.39±0.06, 0.63±0.09 and 0.54±0.11 mm for, respectively, neo-aortic annulus, root and sinotubular junction, all significantly exceeding normal growth. AR continues to develop over time: freedom from AR ≥moderate during the first 25 years post-ASO was 69%. Risk factors for root dilatation were complex TGA anatomy (TGA-ventricular septal defect (VSD), double outlet right ventricle with subpulmonary VSD) and male gender. Risk factors for AR ≥moderate were: complex TGA anatomy and neo-aortic growth. Per millimetre increase in aortic root dimension, there was a 9% increase in the hazard of AR ≥moderate. Bicuspid pulmonary valve did not relate to the presence of root dilatation or AR.

Conclusion: After ASO, neo-aortic dilatation proceeds beyond childhood and is associated with an increase in AR incidence over time. Careful follow-up of the neo-aortic valve and root function is mandatory, especially in males and in patients with complex TGA anatomy.
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http://dx.doi.org/10.1136/heartjnl-2019-315157DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6855793PMC
November 2019

Aortic Root Geometric and Dynamic Changes After Device Closure of Interatrial Shunts.

J Am Soc Echocardiogr 2019 08 17;32(8):1016-1026.e5. Epub 2019 May 17.

Department of Cardiology, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands.

Background: The spatial relationship between atrial septal occluders and the aorta and the subsequent impact on the geometry and mechanics of the aortic root have been underinvestigated. The aim of this study was to evaluate occluder-aorta interaction after device closure of an atrial septal defect (ASD) or a patent foramen ovale (PFO) using three-dimensional transesophageal echocardiography and two-dimensional speckle-tracking echocardiography.

Methods: In 65 adult patients (mean age, 47 ± 14 years; 71% women) who underwent ASD (n = 35) or PFO (n = 30) closure with the Amplatzer Septal Occluder or Amplatzer PFO Occluder, occluder-aorta contact was evaluated on three-dimensional transesophageal echocardiography and defined as continuous, intermittent, or absent. Sinus of Valsalva diameter, height, eccentricity, and strain were measured before and immediately after occluder implantation.

Results: The occluder/total septal length and occluder/body surface area ratios were significantly larger after PFO than after ASD closure. The occluder was in contact with the aorta in 93.8% of cases (ASD, 91.4%; PFO, 96.7%). After ASD closure, occluder-aorta contact was very common, in patients with an aortic rim < 5 mm (100%) and those with an aortic rim ≥ 5 mm (79%). However, continuous occluder-aorta contact was more frequent in those with an aortic rim < 5 mm (95% vs 50%). Factors influencing aortic root strain after occluder implantation included the pattern of occluder-aorta relationship and the occluder/body surface area ratio.

Conclusions: Most interatrial septal occluders are in contact with the aortic root, even in patients with ASDs with a sufficient aortic rim and in patients with PFOs. However, continuous occluder-aorta contact is more likely in patients with ASDs with a deficient aortic rim. The pattern of occluder-aorta relationship and the occluder/body surface area ratio affect aortic root strain.
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http://dx.doi.org/10.1016/j.echo.2019.03.022DOI Listing
August 2019

The Natural and Unnatural History of Congenital Aortic Arch Abnormalities Evaluated in an Adult Survival Cohort.

Can J Cardiol 2019 04 7;35(4):438-445. Epub 2018 Dec 7.

Department of Cardiology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands. Electronic address:

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 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.
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http://dx.doi.org/10.1016/j.cjca.2018.12.004DOI Listing
April 2019

High burden of drug therapy in adult congenital heart disease: polypharmacy as marker of morbidity and mortality.

Eur Heart J Cardiovasc Pharmacother 2019 10;5(4):216-225

Department of Cardiology, Heart Center, Amsterdam UMC, University of Amsterdam, Amsterdam Cardiovascular Sciences, Meibergdreef 9, AZ Amsterdam, The Netherlands.

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 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 = 2.3/10 years (95% CI 2.2-2.4) and for women: OR = 1.6/10 years (95% CI 1.5-1.6); Pinteraction < 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.
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http://dx.doi.org/10.1093/ehjcvp/pvz014DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6749841PMC
October 2019

Electrical remodeling after percutaneous atrial septal defect closure in pediatric and adult patients.

Int J Cardiol 2019 06 23;285:32-39. Epub 2019 Feb 23.

Department of Pediatric Cardiology, Leiden University Medical Center, Leiden, the Netherlands; Department of Pediatric Cardiology, Academic Medical Center, Amsterdam, the Netherlands. Electronic address:

Background: Several studies have reported changes in electrocardiographic variables after atrial septal defect (ASD) closure. However no temporal electro-and vectorcardiographic changes have been described from acute to long-term follow-up at different ages. We aimed to study electrical remodeling after percutaneous ASD closure in pediatric and adult patients.

Methods: ECGs of 69 children and 75 adults (median age 6 [IQR 4-11] years and 45 [IQR 33-54] years, respectively) were retrospectively selected before percutaneous ASD closure and at acute (1-7 days), intermediate (4-14 weeks) and late (6-18 months) follow-up. Apart from electrocardiographic variables, spatial QRS-T angle and ventricular gradient (VG) were derived from mathematically-synthesized vectorcardiograms.

Results: In both pediatric and adult patients, the heart rate decreased immediately post-closure, which persisted to late follow-up. The P-wave amplitude also decreased acutely post-closure, but remained unchanged at later follow-up. The PQ duration shortened immediately in children and at intermediate follow-up in adults. The QRS duration and QTc interval decreased at intermediate-term follow-up in both children and adults. In both groups the spatial QRS-T angle decreased at late follow-up. The VG magnitude increased at intermediate follow-up in children and at late follow-up in adults, after an initial decrease in children.

Conclusion: In both pediatric and adult ASD patients, electrocardiographic changes mainly occurred directly after ASD closure except for shortening of QRS duration and QTc interval, which occurred at later follow-up. Adults also showed late changes in PQ duration. At 6-to-18 month post-closure, the spatial QRS-T angle decreased, reflecting increased electrocardiographic concordance. The initial acute decrease in VG in children, which was followed by a significant increase, may be the effect of action potential duration dynamics directly after percutaneous ASD closure.
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http://dx.doi.org/10.1016/j.ijcard.2019.02.020DOI Listing
June 2019
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