Publications by authors named "Michiel Rienstra"

212 Publications

Gut microbiota, dysbiosis and atrial fibrillation. Arrhythmogenic mechanisms and potential clinical implications.

Cardiovasc Res 2021 Sep 22. Epub 2021 Sep 22.

Department of Cardiology, Maastricht University Medical Centre and Cardiovascular Research Institute Maastricht, Maastricht, the Netherlands.

Recent preclinical and observational cohort studies have implicated imbalances in gut microbiota composition as a contributor to atrial fibrillation (AF). The gut microbiota is a complex and dynamic ecosystem containing trillions of microorganisms, which produces bioactive metabolites influencing host health and disease development. In addition to host-specific determinants, lifestyle-related factors such as diet and drugs are important determinants of the gut microbiota composition. In this review, we discuss the evidence suggesting a potential bidirectional association between AF and gut microbiota, identifying gut microbiota-derived metabolites as possible regulators of the AF substrate. We summarize the effect of gut microbiota on the development and progression of AF risk-factors, including heart failure, hypertension, obesity and coronary artery disease. We also discuss the potential antiarrhythmic effects of pharmacological and diet-induced modifications of gut microbiota composition, which may modulate and prevent the progression to AF. Finally, we highlight important gaps in knowledge and areas requiring future investigation. Although data supporting a direct relationship between gut microbiota and AF are very limited at the present time, emerging preclinical and clinical research dealing with mechanistic interactions between gut microbiota and AF is important as it may lead to new insights into AF pathophysiology and the discovery of novel therapeutic targets for AF.
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http://dx.doi.org/10.1093/cvr/cvab292DOI Listing
September 2021

Myocardial Scar Characterization and Future Ventricular Arrhythmia in Patients With Ischemic Cardiomyopathy and an Implantable Cardioverter-Defibrillator.

Front Cardiovasc Med 2021 17;8:708406. Epub 2021 Aug 17.

Department of Cardiology, Heart Center, University of Groningen, University Medical Center Groningen, Groningen, Netherlands.

Implantable cardioverter-defibrillator (ICD) therapy is associated with several deleterious effects, which can be reduced by antiarrhythmic drugs or catheter ablation. However, it is largely unknown which patients might benefit from these therapies. Therefore, this study aimed to investigate whether myocardial scar characterization improves risk stratification for ventricular arrhythmia (VA) occurrence in patients with ischemic cardiomyopathy and an ICD. In this study, 82 patients with ischemic cardiomyopathy who received an ICD were enrolled retrospectively. Late gadolinium enhancement cardiac magnetic resonance (LGE-CMR) images were analyzed using an investigational software tool to obtain quantitative data regarding the total scar, core, and border zone (BZ). Data regarding the QRS complex was obtained from electrocardiography (ECG). The primary endpoint was appropriate ICD therapy. During a median follow-up duration of 3.98 years [interquartile range (IQR) 2.89-5.14 years], appropriate therapy occurred in 24 (29.3%) patients. Patients with appropriate ICD therapy had a significantly larger total scar mass [60.0 (IQR 41.2-73.4) vs. 43.3 (IQR 31.2-61.2) g; = 0.009] and BZ mass [32.9 (IQR 26.9-42.4) vs. 24.5 (IQR 18.8-32.5) g; = 0.001] than those without appropriate therapy. In multivariable Cox regression analyses, total scar mass [hazard ratio (HR) 1.02 [95% confidence interval (CI) 1.00-1.04]; = 0.014] and BZ mass (HR 1.04 [95% CI 1.01-1.07]; = 0.009) independently predicted appropriate ICD therapy. Core mass and the QRS complex, however, were not significantly associated with the primary endpoint. LGE-CMR-based, but not ECG-based myocardial scar characterization improves risk stratification for VA occurrence in patients with ischemic cardiomyopathy who received an ICD.
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http://dx.doi.org/10.3389/fcvm.2021.708406DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8415981PMC
August 2021

Early Thromboembolic Stroke Risk of Postoperative Atrial Fibrillation Following Cardiac Surgery.

J Cardiothorac Vasc Anesth 2021 Jul 21. Epub 2021 Jul 21.

Department of Critical Care, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands.

Objective: The authors aimed to study the association between postoperative atrial fibrillation (POAF) and thromboembolic stroke and to determine risk factors for thromboembolic stroke after cardiac surgery.

Design: The authors performed a secondary analysis from a randomized controlled trial (GRIP-COMPASS). The patients with thromboembolic stroke were compared with those without thromboembolic stroke, and the difference in the incidence of POAF between these groups was assessed. Odds ratios (OR) were calculated using logistic regression analyses. Brain imaging was studied for the occurrence of thromboembolic stroke during hospital admission, and POAF was monitored for seven days. To assess which characteristics were associated with occurrence of thromboembolic stroke, stepwise backward regression analysis was performed.

Participants: All adult consecutive cardiac surgery patients admitted postoperatively to the intensive care unit.

Setting: Academic tertiary care medical center.

Interventions: None.

Measurements And Main Results: Of the 910 patients included in this study, 26 patients (2.9%) had a thromboembolic stroke during hospital admission. The incidence of POAF during the first seven days after cardiac surgery in those with thromboembolic stroke was 65%, compared with 39% in those without thromboembolic stroke: adjusted OR 3.01 (95% confidence interval, 1.13-8.00). POAF, a history of peripheral vascular disease, a higher EuroSCORE, and a longer duration of surgery were associated with thromboembolic stroke.

Conclusions: POAF within seven days after cardiac surgery was associated with a three-fold increased risk for a thromboembolic stroke during hospital admission. Expeditious treatment of POAF may, therefore, reduce early stroke risk after cardiac surgery.
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http://dx.doi.org/10.1053/j.jvca.2021.07.030DOI Listing
July 2021

AV junction ablation and cardiac resynchronization for patients with permanent atrial fibrillation and narrow QRS: the APAF-CRT mortality trial.

Eur Heart J 2021 Aug 28. Epub 2021 Aug 28.

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

Aims : In patients with atrial fibrillation (AF) and heart failure (HF), strict and regular rate control with atrioventricular junction ablation and biventricular pacemaker (Ablation + CRT) has been shown to be superior to pharmacological rate control in reducing HF hospitalizations. However, whether it also improves survival is unknown.

Methods And Results : In this international, open-label, blinded outcome trial, we randomly assigned patients with severely symptomatic permanent AF >6 months, narrow QRS (≤110 ms) and at least one HF hospitalization in the previous year to Ablation + CRT or to pharmacological rate control. We hypothesized that Ablation + CRT is superior in reducing the primary endpoint of all-cause mortality. A total of 133 patients were randomized. The mean age was 73 ± 10 years, and 62 (47%) were females. The trial was stopped for efficacy at interim analysis after a median of 29 months of follow-up per patient. The primary endpoint occurred in 7 patients (11%) in the Ablation + CRT arm and in 20 patients (29%) in the Drug arm [hazard ratio (HR) 0.26, 95% confidence interval (CI) 0.10-0.65; P = 0.004]. The estimated death rates at 2 years were 5% and 21%, respectively; at 4 years, 14% and 41%. The benefit of Ablation + CRT of all-cause mortality was similar in patients with ejection fraction (EF) ≤35% and in those with >35%. The secondary endpoint combining all-cause mortality or HF hospitalization was significantly lower in the Ablation + CRT arm [18 (29%) vs. 36 (51%); HR 0.40, 95% CI 0.22-0.73; P = 0.002].

Conclusions : Ablation + CRT was superior to pharmacological therapy in reducing mortality in patients with permanent AF and narrow QRS who were hospitalized for HF, irrespective of their baseline EF.

Study Registration: ClinicalTrials.gov Identifier: NCT02137187.
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http://dx.doi.org/10.1093/eurheartj/ehab569DOI Listing
August 2021

Rate control drugs differ in the prevention of progression of atrial fibrillation.

Europace 2021 Aug 20. Epub 2021 Aug 20.

Department of Cardiology, Martini Hospital, Van Swietenplein 1, 9728 NT Groningen, The Netherlands.

Aims: We hypothesize that in patients with paroxysmal atrial fibrillation (AF), verapamil is associated with lower AF progression compared to beta blockers or no rate control.

Methods And Results: In this pre-specified post hoc analysis of the RACE 4 randomized trial, the effect of rate control medication on AF progression in paroxysmal AF was analysed. Patients using Vaughan-Williams Class I or III antiarrhythmic drugs were excluded. The primary outcome was a composite of first electrical cardioversion (ECV), chemical cardioversion (CCV), or atrial ablation. Event rates are displayed using Kaplan-Meier curves and multivariable Cox regression analyses are used to adjust for baseline differences. Out of 666 patients with paroxysmal AF, 47 used verapamil, 383 used beta blockers, and 236 did not use rate control drugs. The verapamil group was significantly younger than the beta blocker group and contained more men than the no rate control group. Over a mean follow-up of 37 months, the primary outcome occurred in 17% in the verapamil group, 33% in the beta blocker group, and 33% in the no rate control group (P = 0.038). After adjusting for baseline characteristics, patients using verapamil have a significantly lower chance of receiving ECV, CCV, or atrial ablation compared to patients using beta blockers [hazard ratio (HR) 0.40, 95% confidence interval (CI) 0.19-0.83] and no rate control (HR 0.64, 95% CI 0.44-0.93).

Conclusion: In patients with newly diagnosed paroxysmal AF, verapamil was associated with less AF progression, as compared to beta blockers and no rate control.
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http://dx.doi.org/10.1093/europace/euab191DOI Listing
August 2021

Is catheter ablation of atrial fibrillation as first-line treatment ready for prime time?

Heart 2021 Oct 12;107(20):1605-1606. Epub 2021 Aug 12.

University Medical Center Groningen, Groningen, The Netherlands.

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http://dx.doi.org/10.1136/heartjnl-2021-319832DOI Listing
October 2021

Research Priorities in the Secondary Prevention of Atrial Fibrillation: A National Heart, Lung, and Blood Institute Virtual Workshop Report.

J Am Heart Assoc 2021 Aug 5;10(16):e021566. Epub 2021 Aug 5.

Division of Research Kaiser Permanente Northern California Oakland CA.

There has been sustained focus on the secondary prevention of coronary heart disease and heart failure; yet, apart from stroke prevention, the evidence base for the secondary prevention of atrial fibrillation (AF) recurrence, AF progression, and AF-related complications is modest. Although there are multiple observational studies, there are few large, robust, randomized trials providing definitive effective approaches for the secondary prevention of AF. Given the increasing incidence and prevalence of AF nationally and internationally, the AF field needs transformative research and a commitment to evidenced-based secondary prevention strategies. We report on a National Heart, Lung, and Blood Institute virtual workshop directed at identifying knowledge gaps and research opportunities in the secondary prevention of AF. Once AF has been detected, lifestyle changes and novel models of care delivery may contribute to the prevention of AF recurrence, AF progression, and AF-related complications. Although benefits seen in small subgroups, cohort studies, and selected randomized trials are impressive, the widespread effectiveness of AF secondary prevention strategies remains unknown, calling for development of scalable interventions suitable for diverse populations and for identification of subpopulations who may particularly benefit from intensive management. We identified critical research questions for 6 topics relevant to the secondary prevention of AF: (1) weight loss; (2) alcohol intake, smoking cessation, and diet; (3) cardiac rehabilitation; (4) approaches to sleep disorders; (5) integrated, team-based care; and (6) nonanticoagulant pharmacotherapy. Our goal is to stimulate innovative research that will accelerate the generation of the evidence to effectively pursue the secondary prevention of AF.
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http://dx.doi.org/10.1161/JAHA.121.021566DOI Listing
August 2021

Different circulating biomarkers in women and men with paroxysmal atrial fibrillation: results from the AF-RISK and RACE V studies.

Europace 2021 07 30. Epub 2021 Jul 30.

Department of Cardiology, University of Groningen, University Medical Centre Groningen, Groningen, Hanzeplein 1, 9713 GZ, The Netherlands.

Aims: The clinical risk profile of atrial fibrillation (AF) patients is different in men and women. Our aim was to identify sex differences in blood biomarkers in patients with paroxysmal AF.

Methods And Results: Sex differences in 92 blood biomarkers were measured in 364 patients included in our discovery cohort, the identification of a risk profile to guide atrial fibrillation therapy (AF-RISK) study, assessed by multivariable logistic regression and enrichment pathway analysis. Findings were subsequently confirmed in 213 patients included in our validation cohort, the Reappraisal of Atrial Fibrillation: Interaction between HyperCoagulability, Electrical remodelling, and Vascular Destabilisation in the Progression of AF (RACE V) study. In the discovery cohort, mean age was 59 ± 12 years, 41% were women. CHA2DS2-VASc-score was 1.6 ± 1.4. A total of 46% had hypertension, 10% diabetes, and 50% had heart failure, predominantly with preserved ejection fraction (47%). In women, activated leucocyte cell adhesion molecule (ALCAM) and fatty acid binding protein-4 (FABP-4) were higher. In men, matrix metalloproteinase-3 (MMP-3), C-C motif chemokine-16 (CCL-16), and myoglobin were higher. In the validation cohort, four out of five biomarkers could be confirmed: levels of ALCAM (P = 1.73 × 10-4) and FABP-4 (P = 2.46 × 10-7) and adhesion biological pathways [false discovery rate (FDR) = 1.23 × 10-8] were higher in women. In men, levels of MMP-3 (P = 4.31 × 10-8) and myoglobin (P = 2.10 × 10-4) and markers for extracellular matrix degradation biological pathways (FDR = 3.59 × 10-9) were higher.

Conclusion: In women with paroxysmal AF, inflammatory biomarkers were more often higher, while in men with paroxysmal AF, biomarkers for vascular remodelling were higher. Our data support the clinical notion that pathophysiological mechanisms in women and men with AF may differ.

Trial Registration: Clinicaltrials.gov identifier NCT01510210 for AF-RISK; Clinicaltrials.gov NCT02726698 for RACE V.
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http://dx.doi.org/10.1093/europace/euab179DOI Listing
July 2021

The clinical and prognostic value of late Gadolinium enhancement imaging in heart failure with mid-range and preserved ejection fraction.

Heart Vessels 2021 Jul 22. Epub 2021 Jul 22.

Department of Cardiology, University of Groningen, University Medical Centre Groningen, Hanzeplein 1, PO Box 30.001, 9700 RB, Groningen, The Netherlands.

Heart failure (HF) with mid-range or preserved ejection fraction (HFmrEF; HFpEF) is a heterogeneous disorder that could benefit from strategies to identify subpopulations at increased risk. We tested the hypothesis that HFmrEF and HFpEF patients with myocardial scars detected with late gadolinium enhancement (LGE) are at increased risk for all-cause mortality. Symptomatic HF patients with left ventricular ejection fraction (LVEF) > 40%, who underwent cardiac magnetic resonance (CMR) imaging were included. The presence of myocardial LGE lesions was visually assessed. T1 mapping was performed to calculate extracellular volume (ECV). Multivariable logistic regression analyses were used to determine associations between clinical characteristics and LGE. Cox regression analyses were used to assess the association between LGE and all-cause mortality. A total of 110 consecutive patients were included (mean age 71 ± 10 years, 49% women, median N-terminal brain natriuretic peptide (NT-proBNP) 1259 pg/ml). LGE lesions were detected in 37 (34%) patients. Previous myocardial infarction and increased LV mass index were strong and independent predictors for the presence of LGE (odds ratio 6.32, 95% confidence interval (CI) 2.07-19.31, p = 0.001 and 1.68 (1.03-2.73), p = 0.04, respectively). ECV was increased in patients with LGE lesions compared to those without (28.6 vs. 26.6%, p = 0.04). The presence of LGE lesions was associated with a fivefold increase in the incidence of all-cause mortality (hazards ratio 5.3, CI 1.5-18.1, p = 0.009), independent of age, sex, New York Heart Association (NYHA) functional class, NT-proBNP, LGE mass and LVEF. Myocardial scarring on CMR is associated with increased mortality in HF patients with LVEF > 40% and may aid in selecting a subpopulation at increased risk.
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http://dx.doi.org/10.1007/s00380-021-01910-2DOI Listing
July 2021

First-line treatment of persistent and long-standing persistent atrial fibrillation with single-stage hybrid ablation: a 2-year follow-up study.

Europace 2021 Jun 18. Epub 2021 Jun 18.

Department of Cardiology, University of Groningen, University Medical Center Groningen, PO Box 30.001, 9700 RB Groningen, The Netherlands.

Aims: This study evaluates the efficacy and safety of first-line single-stage hybrid ablation of (long-standing) persistent atrial fibrillation (AF), over a follow-up period of 2 years, and provides additional information on arrhythmia recurrences and electrophysiological findings at repeat ablation.

Methods And Results: This is a prospective cohort study that included 49 patients (65% persistent AF; 35% long-standing persistent AF) who underwent hybrid ablation as first-line ablation treatment (no previous endocardial ablation). Patients were relatively young (57.0 ± 8.5 years) and predominantly male (89.8%). Median CHA2DS2-VASc score was 1.0 (0.5; 2.0) and mean left atrium volume index was 43.7 ± 10.9 mL/m2. Efficacy was assessed by 12-lead electrocardiography and 72-h Holter monitoring after 3, 6, 12, and 24 months. Recurrence was defined as AF/atrial flutter (AFL)/tachycardia (AT) recorded by electrocardiography or Holter monitoring lasting >30 s during 2-year follow-up. At 2-year follow-up, single and multiple procedure success rates were 67% and 82%, respectively. Two (4%) patients experienced a major complication (bleeding) requiring intervention following hybrid ablation. Among the 16 (33%) patients who experienced an AF/AFL/AT recurrence, 13 (81%) were ATs/AFLs and only 3 (19%) were AF. Repeat ablation was performed in 10 (20%) patients and resulted in sinus rhythm in 7 (70%) at 2-year follow-up.

Conclusion: First-line single-stage hybrid AF ablation is an effective treatment strategy for patients with persistent and long-standing persistent AF with an acceptable rate of major complications. Recurrences are predominantly AFL/AT that can be successfully ablated percutaneously. Hybrid ablation seems a feasible approach for first-line ablation of (long-standing) persistent AF.
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http://dx.doi.org/10.1093/europace/euab093DOI Listing
June 2021

Incidence of atrial fibrillation, ischaemic heart disease and heart failure in patients with diabetes.

Cardiovasc Diabetol 2021 06 16;20(1):123. Epub 2021 Jun 16.

Dept. General Practice, Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht University, Universiteitsweg 100, 3584 CG, Utrecht, The Netherlands.

Background: Diabetes has strongly been linked to atrial fibrillation, ischaemic heart disease and heart failure. The epidemiology of these cardiovascular diseases is changing, however, due to changes in prevalence of obesity-related conditions and preventive measures. Recent population studies on incidence of atrial fibrillation, ischaemic heart disease and heart failure in patients with diabetes are needed.

Methods: A dynamic longitudinal cohort study was performed using primary care databases of the Julius General Practitioners' Network. Diabetes status was determined at baseline (1 January 2014 or upon entering the cohort) and participants were followed-up for atrial fibrillation, ischaemic heart disease and heart failure until 1 February 2019. Age and sex-specific incidence and incidence rate ratios were calculated.

Results: Mean follow-up was 4.2 years, 12,168 patients were included in the diabetes group, and 130,143 individuals in the background group. Incidence rate ratios, adjusted for age and sex, were 1.17 (95% confidence interval 1.06-1.30) for atrial fibrillation, 1.66 (1.55-1.83) for ischaemic heart disease, and 2.36 (2.10-2.64) for heart failure. Overall, incidence rate ratios were highest in the younger age categories, converging thereafter.

Conclusion: There is a clear association between diabetes and incidence of the major chronic progressive heart diseases, notably with heart failure with a more than twice increased risk.
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http://dx.doi.org/10.1186/s12933-021-01313-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8210360PMC
June 2021

Update on management of atrial fibrillation in heart failure: a focus on ablation.

Heart 2021 Jun 4. Epub 2021 Jun 4.

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

Atrial fibrillation is increasingly encountered in patients with heart failure. Both diseases have seen tremendous rises in incidence in recent years. In general, the treatment of atrial fibrillation is focused on relieving patients from atrial fibrillation-related symptoms and risk reduction for thromboembolism and the occurrence or worsening of heart failure. Symptomatic relief may be accomplished by either (non-)pharmacological rate or rhythm control in combination with optimal therapy of underlying cardiovascular morbidities and risk factors. Atrial fibrillation ablation has been performed in patients without overt heart failure successfully for many years. However, in recent years, attempts have been made for patients with heart failure as well. In this review, we discuss the current literature describing the treatment of atrial fibrillation in heart failure. We highlight the early rate versus rhythm control studies, the importance of addressing underlying conditions and treatment of risk factors. A critical evaluation will be performed of the catheter ablation studies that have been performed so far in light of larger (post-hoc) ablation studies. Furthermore, we will hypothesise the role of patient selection as next step in optimising outcome for patient with atrial fibrillation and heart failure.
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http://dx.doi.org/10.1136/heartjnl-2020-318081DOI Listing
June 2021

Importance of epicardial adipose tissue localization using cardiac magnetic resonance imaging in patients with heart failure with mid-range and preserved ejection fraction.

Clin Cardiol 2021 Jul 4;44(7):987-993. Epub 2021 Jun 4.

Department of Cardiology, University of Groningen, University Medical Center Groningen, Groningen, Netherlands.

Background: Epicardial adipose tissue (EAT) has been implicated in the pathophysiology of heart failure (HF) with left ventricular ejection fraction (LVEF) >40%, but whether this is due to a regional or global effect of EAT remains unclear.

Hypothesis: Regional EAT is associated with alterations in local cardiac structure and function.

Methods: Patients with HF and LVEF >40% were studied. Cardiac Magnetic Resonance imaging was used to localize EAT surrounding the right ventricle (RV) and LV separately, using anterior- and posterior interventricular grooves as boundaries. Atrial- and ventricular EAT were differentiated using the mitral-valve position. All EAT depots were related to the adjacent myocardial structure.

Results: 102 consecutive HF patients were enrolled. The majority of EAT was present around the RV (42% of total EAT, p < .001). RV-EAT showed a strong association with increased RV mass (β = 0.60, p < .001) and remained associated with RV mass after adjusting for total EAT, sex, N-terminal prohormone of brain natriuretic peptide (NT-proBNP), renal function and blood glucose. LV-EAT showed a similar association with LV mass in univariable analysis, albeit less pronounced (β = 0.24, p = .02). Atrial EAT was increased in patients with atrial fibrillation compared to those without atrial fibrillation (30 vs. 26 ml/m , p = .04), whereas ventricular EAT was similar (74 vs. 75 ml/m , p = .9).

Conclusions: Regional EAT is strongly associated with local cardiac structure and function in HF patients with LVEF >40%. These data support the hypothesis that regional EAT is involved in the pathophysiology of HF with LVEF >40%.
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http://dx.doi.org/10.1002/clc.23644DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8259147PMC
July 2021

Sudden cardiac death in heart failure: more than meets the eye.

Eur J Heart Fail 2021 08 14;23(8):1361-1363. Epub 2021 May 14.

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

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http://dx.doi.org/10.1002/ejhf.2212DOI Listing
August 2021

Antiarrhythmic drugs in patients with early persistent atrial fibrillation and heart failure: results of the RACE 3 study.

Europace 2021 Sep;23(9):1359-1368

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

Aims: Maintaining sinus rhythm in patients with persistent atrial fibrillation (AF) is challenging. We explored the efficacy of class I and III antiarrhythmic drugs (AADs) in patients with persistent AF and mild to moderate heart failure (HF).

Methods And Results: In the RACE 3 trial, patients with early persistent symptomatic AF and short history of mild to moderate HF with preserved or reduced left ventricular ejection fraction (LVEF) were randomized to targeted or conventional therapy. Both groups received AF and HF guideline-driven treatment. Additionally, the targeted-group received mineralocorticoid receptor antagonists, statins, angiotensin-converting enzyme inhibitors and/or receptor blockers, and cardiac rehabilitation. Class I and III AADs could be instituted in case of symptomatic recurrent AF. Eventually, pulmonary vein isolation could be performed. Primary endpoint was sinus rhythm on 7-day Holter after 1-year. Included were 245 patients, age 65 ± 9 years, 193 (79%) men, AF history was 3 (2-6) months, HF history 2 (1-4) months, 72 (29.4%) had HF with reduced LVEF. After baseline electrical cardioversion (ECV), 190 (77.6%) had AF recurrences; 108 (56.8%) received class I/III AADs; 19 (17.6%) flecainide, 36 (33.3%) sotalol, 3 (2.8%) dronedarone, 50 (46.3%) amiodarone. At 1-year 73 of 108 (68.0%) patients were in sinus rhythm, 44 (40.7%) without new AF recurrences. Maintenance of sinus rhythm was significantly better with amiodarone [n = 29/50 (58%)] compared with flecainide [n = 6/19 (32%)] and sotalol/dronedarone [n = 9/39 (23%)], P = 0.0064. Adverse events occurred in 27 (25.0%) patients, were all minor and reversible.

Conclusion: In stable HF patients with early persistent AF, AAD treatment was effective in nearly half of patients, with no serious adverse effects reported.
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http://dx.doi.org/10.1093/europace/euab062DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8427339PMC
September 2021

Atrial fibrillation and left atrial size and function: a Mendelian randomization study.

Sci Rep 2021 Apr 19;11(1):8431. Epub 2021 Apr 19.

Department of Cardiology, University Medical Center Groningen, University of Groningen, Hanzeplein 1, P.O. Box 30.001, 9700 RB, Groningen, The Netherlands.

Atrial fibrillation (AF) patients have enlarged left atria (LA), but prior studies suggested enlarged atria as both cause and consequence of AF. The aim of this study is to investigate the causal association between AF and LA size and function. In the UK Biobank, all individuals with contoured cardiovascular magnetic resonance data were selected. LA maximal volume (LA max), LA minimal volume (LA min), LA stroke volume and LA ejection fraction were measured and indexed to body surface area (BSA). Two-sample Mendelian randomization analyses were performed using 84 of the known genetic variants associated with AF to assess the association with all LA size and function in individuals without prevalent AF. A total of 4274 individuals (mean age 62.0 ± 7.5 years, 53.2% women) were included. Mendelian randomization analyses estimated a causal effect between genetically determined AF and BSA-indexed LA max, LA min, and LA ejection fraction, but not between AF and LA stroke volume. Leave-one-out analyses showed that the causal associations were attenuated after exclusion of rs67249485, located near PITX2 gene. Our results suggest that AF causally increases LA size and decreases LA ejection fraction. The AF risk allele of rs67249485, located near the PITX2 gene, contributes strongly to these associations.
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http://dx.doi.org/10.1038/s41598-021-87859-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8055882PMC
April 2021

Role of genetics in atrial fibrillation management.

Europace 2021 04;23(23 Suppl 2):ii4-ii8

Cardiovascular Disease Initiative, The Broad Institute of MIT and Harvard, Cambridge, MA, USA.

Atrial fibrillation (AF) management has significantly improved during the career of professor Crijns. Research was implemented into guidelines and clinical practice. However, despite advances in AF management, large differences between individual treatment responses still exist and the mechanisms underlying initiation and perpetuation of AF are not completely understood. International collaborations have revealed the genetic contribution to AF and steps towards improving AF management are being made. In this short review, the most important paradigms shifts in the field of AF genetics are recognized and the future role of genetics in personalized management of AF is discussed.
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http://dx.doi.org/10.1093/europace/euaa366DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8035706PMC
April 2021

Dynamic risk assessment to improve quality of care in patients with atrial fibrillation: the 7th AFNET/EHRA Consensus Conference.

Europace 2021 03;23(3):329-344

Atrial Fibrillation NETwork (AFNET), Münster, Germany.

Aims: The risk of developing atrial fibrillation (AF) and its complications continues to increase, despite good progress in preventing AF-related strokes.

Methods And Results: This article summarizes the outcomes of the 7th Consensus Conference of the Atrial Fibrillation NETwork (AFNET) and the European Heart Rhythm Association (EHRA) held in Lisbon in March 2019. Sixty-five international AF specialists met to present new data and find consensus on pressing issues in AF prevention, management and future research to improve care for patients with AF and prevent AF-related complications. This article is the main outcome of an interactive, iterative discussion between breakout specialist groups and the meeting plenary. AF patients have dynamic risk profiles requiring repeated assessment and risk-based therapy stratification to optimize quality of care. Interrogation of deeply phenotyped datasets with outcomes will lead to a better understanding of the cardiac and systemic effects of AF, interacting with comorbidities and predisposing factors, enabling stratified therapy. New proposals include an algorithm for the acute management of patients with AF and heart failure, a call for a refined, data-driven assessment of stroke risk, suggestions for anticoagulation use in special populations, and a call for rhythm control therapy selection based on risk of AF recurrence.

Conclusion: The remaining morbidity and mortality in patients with AF needs better characterization. Likely drivers of the remaining AF-related problems are AF burden, potentially treatable by rhythm control therapy, and concomitant conditions, potentially treatable by treating these conditions. Identifying the drivers of AF-related complications holds promise for stratified therapy.
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http://dx.doi.org/10.1093/europace/euaa279DOI Listing
March 2021

Incidence and outcome of atrial fibrillation: diversity throughout Europe.

Eur Heart J 2021 02;42(8):858-860

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

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http://dx.doi.org/10.1093/eurheartj/ehaa1078DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7897461PMC
February 2021

Risk prediction of atrial fibrillation in the community combining biomarkers and genetics.

Europace 2021 05;23(5):674-681

Department of Cardiology, University Heart and Vascular Centre Hamburg-Eppendorf, Martinistr. 52, 20246 Hamburg, Germany.

Aims: Classical cardiovascular risk factors (CVRFs), biomarkers, and common genetic variation have been suggested for risk assessment of atrial fibrillation (AF). To evaluate their clinical potential, we analysed their individual and combined ability of AF prediction.

Methods And Results: In N = 6945 individuals of the FINRISK 1997 cohort, we assessed the predictive value of CVRF, N-terminal pro B-type natriuretic peptide (NT-proBNP), and 145 recently identified single-nucleotide polymorphisms (SNPs) combined in a developed polygenic risk score (PRS) for incident AF. Over a median follow-up of 17.8 years, n = 551 participants (7.9%) developed AF. In multivariable-adjusted Cox proportional hazard models, NT-proBNP [hazard ratio (HR) of log transformed values 4.77; 95% confidence interval (CI) 3.66-6.22; P < 0.001] and the PRS (HR 2.18; 95% CI 1.88-2.53; P < 0.001) were significantly related to incident AF. The discriminatory ability improved asymptotically with increasing numbers of SNPs. Compared with a clinical model, AF risk prediction was significantly improved by addition of NT-proBNP and the PRS. The C-statistic for the combination of CVRF, NT-proBNP, and the PRS reached 0.83 compared with 0.79 for CVRF only (P < 0.001). A replication in the Dutch Prevention of REnal and Vascular ENd-stage Disease (PREVEND) cohort revealed similar results. Comparing the highest vs. lowest quartile, NT-proBNP and the PRS both showed a more than three-fold increased AF risk. Age remained the strongest risk factor with a 16.7-fold increased risk of AF in the highest quartile.

Conclusion: The PRS and the established biomarker NT-proBNP showed comparable predictive ability. Both provided incremental predictive value over standard clinical variables. Further improvements for the PRS are likely with the discovery of additional SNPs.
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http://dx.doi.org/10.1093/europace/euaa334DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8139818PMC
May 2021

Segment length in cine (SLICE) strain analysis: a practical approach to estimate potential benefit from cardiac resynchronization therapy.

J Cardiovasc Magn Reson 2021 01 11;23(1). Epub 2021 Jan 11.

Department of Cardiology, Amsterdam Cardiovascular Sciences (ACS), Amsterdam University Medical Centers (AUMC), Location VU University Medical Center, De Boelelaan 1118, 1081 HV, Amsterdam, The Netherlands.

Background: Segment length in cine (SLICE) strain analysis on standard cardiovascular magnetic resonance (CMR) cine images was recently validated against gold standard myocardial tagging. The present study aims to explore predictive value of SLICE for cardiac resynchronization therapy (CRT) response.

Methods And Results: Fifty-seven patients with heart failure and left bundle branch block (LBBB) were prospectively enrolled in this multi-center study and underwent CMR examination before CRT implantation. Circumferential strains of the septal and lateral wall were measured by SLICE on short-axis cine images. In addition, timing and strain pattern parameters were assessed. After twelve months, CRT response was quantified by the echocardiographic change in left ventricular (LV) end-systolic volume (LVESV). In contrast to timing parameters, strain pattern parameters being systolic rebound stretch of the septum (SRS), systolic stretch index (SSI), and internal stretch factor (ISF) all correlated significantly with LVESV change (R - 0.56; R - 0.53; and R - 0.58, respectively). Of all strain parameters, end-systolic septal strain (ESS) showed strongest correlation with LVESV change (R - 0.63). Multivariable analysis showed ESS to be independently related to LVESV change together with age and QRS.

Conclusion: The practicable SLICE strain technique may help the clinician to estimate potential benefit from CRT by analyzing standard CMR cine images without the need for commercial software. Of all strain parameters, end-systolic septal strain (ESS) demonstrates the strongest correlation with reverse remodeling after CRT. This parameter may be of special interest in patients with non-strict LBBB morphology for whom CRT benefit is doubted.
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http://dx.doi.org/10.1186/s12968-020-00701-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7798189PMC
January 2021

Heart Size Corrected Electrical Dyssynchrony and Its Impact on Sex-Specific Response to Cardiac Resynchronization Therapy.

Circ Arrhythm Electrophysiol 2021 01 9;14(1):e008452. Epub 2020 Dec 9.

Department of Cardiology (O.A.E.S., M.J.C., M.M.), University Medical Center Utrecht, Utrecht University, the Netherlands.

Background: Women are less likely to receive cardiac resynchronization therapy, yet, they are more responsive to the therapy and respond at shorter QRS duration. The present study hypothesized that a relatively larger left ventricular (LV) electrical dyssynchrony in smaller hearts contributes to the better cardiac resynchronization therapy response in women. For this, the vectorcardiography-derived QRS area is used, since it allows for a more detailed quantification of electrical dyssynchrony compared with conventional electrocardiographic markers.

Methods: Data from a multicenter registry of 725 cardiac resynchronization therapy patients (median follow-up, 4.2 years [interquartile range, 2.7-6.1]) were analyzed. Baseline electrical dyssynchrony was evaluated using the QRS area and the corrected QRS area for heart size using the LV end-diastolic volume (QRSarea/LVEDV). Impact of the QRSarea/LVEDV ratio on the association between sex and LV reverse remodeling (LV end-systolic volume change) and sex and the composite outcome of all-cause mortality, LV assist device implantation, or heart transplantation was assessed.

Results: At baseline, women (n=228) displayed larger electrical dyssynchrony than men (QRS area, 132±55 versus 123±58 μVs; =0.043), which was even more pronounced for the QRSarea/LVEDV ratio (0.76±0.46 versus 0.57±0.34 μVs/mL; <0.001). After multivariable analyses, female sex was associated with LV end-systolic volume change (β=0.12; =0.003) and a lower occurrence of the composite outcome (hazard ratio, 0.59 [0.42-0.85]; =0.004). A part of the female advantage regarding reverse remodeling was attributed to the larger QRSarea/LVEDV ratio in women (25-fold change in β from 0.12 to 0.09). The larger QRSarea/LVEDV ratio did not contribute to the better survival observed in women. In both volumetric responders and nonresponders, female sex remained strongly associated with a lower risk of the composite outcome (adjusted hazard ratio, 0.59 [0.36-0.97]; =0.036; and 0.55 [0.33-0.90]; =0.018, respectively).

Conclusions: Greater electrical dyssynchrony in smaller hearts contributes, in part, to more reverse remodeling observed in women after cardiac resynchronization therapy, but this does not explain their better long-term outcomes.
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http://dx.doi.org/10.1161/CIRCEP.120.008452DOI Listing
January 2021

Effects of a simple cardiac rehabilitation program on improvement of self-reported physical activity in atrial fibrillation - Data from the RACE 3 study.

Int J Cardiol Heart Vasc 2020 Dec 16;31:100673. Epub 2020 Nov 16.

Department of Cardiology, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands.

Background And Aim: Physical inactivity is associated with an increased prevalence of atrial fibrillation (AF). We aim to evaluate whether cardiac rehabilitation (CR) motivates patients to become and stay physical active, and whether CR affects sinus rhythm maintenance and quality of life (QoL) in patients with persistent AF and moderate heart failure.

Methods: In the Routine versus Aggressive risk factor driven upstream rhythm Control for prevention of Early atrial fibrillation in heart failure study patients were randomized to conventional or targeted therapy. Targeted therapy contained next to optimal risk factor management a 3-month CR program, including self-reported physical activity and counseling. Successful physical activity was assessed in the targeted group, defined as activity of moderate intensity ≥ 150 min/week, or ≥ 75 min/week of vigorous intensity. AF was assessed at 1 year on 7-days Holter monitoring, QoL using general health, fatigue and AF symptom questionnaires.

Results: All 119 patients within the targeted group participated in the CR program, 106 (89%) completed it. At baseline 80 (67%) patients were successfully physical active, 39 (33%) were not. NTproBNP was lower in active patients. During 1-year follow-up physical active patients stayed active: 72 (90%) at 12 weeks, 72 (90%) at 1 year. Inactive patients became active: at 12 weeks 25 (64%) patients and 30 (77%) at 1 year. No benefits were seen on sinus rhythm maintenance and QoL for successful physical active patients.

Conclusion: In patients with persistent AF and moderate heart failure participation in CR contributes to improve and to maintain physical activity.
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http://dx.doi.org/10.1016/j.ijcha.2020.100673DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7683261PMC
December 2020

Chronic obstructive pulmonary disease and atrial fibrillation: an interdisciplinary perspective.

Eur Heart J 2021 02;42(5):532-540

Centre for Heart Rhythm Disorders, University of Adelaide and Royal Adelaide Hospital, 1 Port Road, SA 5000 Adelaide, Australia.

Chronic obstructive pulmonary disease (COPD) is highly prevalent among patients with atrial fibrillation (AF), shares common risk factors, and adds to the overall morbidity and mortality in this population. Additionally, it may promote AF and impair treatment efficacy. The prevalence of COPD in AF patients is high and is estimated to be ∼25%. Diagnosis and treatment of COPD in AF patients requires a close interdisciplinary collaboration between the electrophysiologist/cardiologist and pulmonologist. Differential diagnosis may be challenging, especially in elderly and smoking patients complaining of unspecific symptoms such as dyspnoea and fatigue. Routine evaluation of lung function and determination of natriuretic peptides and echocardiography may be reasonable to detect COPD and heart failure as contributing causes of dyspnoea. Acute exacerbation of COPD transiently increases AF risk due to hypoxia-mediated mechanisms, inflammation, increased use of beta-2 agonists, and autonomic changes. Observational data suggest that COPD promotes AF progression, increases AF recurrence after cardioversion, and reduces the efficacy of catheter-based antiarrhythmic therapy. However, it remains unclear whether treatment of COPD improves AF outcomes and which metric should be used to determine COPD severity and guide treatment in AF patients. Data from non-randomized studies suggest that COPD is associated with increased AF recurrence after electrical cardioversion and catheter ablation. Future prospective cohort studies in AF patients are needed to confirm the relationship between COPD and AF, the benefits of treatment of either COPD or AF in this population, and to clarify the need and cost-effectiveness of routine COPD screening.
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http://dx.doi.org/10.1093/eurheartj/ehaa822DOI Listing
February 2021

Evaluation and treatment of premature ventricular contractions in heart failure with reduced ejection fraction.

Heart 2021 01 19;107(1):10-17. Epub 2020 Oct 19.

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

Premature ventricular complexes (PVCs) are often observed in patients presenting with heart failure with a reduced ejection fraction (HFrEF). PVCs may in some patients be considered to be the cause of heart failure, while in others it may be the consequence of heart failure. PVCs are important prognostic markers in HFrEF. The uncertainty whether PVCs are the cause or effect in HFrEF impacts clinical decision making. In this review, we discuss the complexity of the cause-effect relationship between PVCs and HFrEF. We demonstrate a workflow with the use of a trial period of amiodarone that may discover whether the reduced LVEF is reversible, the symptoms are due to PVCs and whether biventricular pacing can be increased by the reduction of PVCs. The use of non-invasive and invasive (high-density) mapping techniques may help to improve accuracy and efficacy in the treatment of PVC, which will be demonstrated. With these results in mind, we conclude this review highlighting the future directions for PVC research and treatment.
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http://dx.doi.org/10.1136/heartjnl-2020-317491DOI Listing
January 2021

Preoperative cardiac screening using NT-proBNP in obese patients 50 years and older undergoing bariatric surgery: a study of 310 consecutive patients.

Surg Obes Relat Dis 2021 Jan 2;17(1):64-71. Epub 2020 Sep 2.

Department of Surgery, Vitalys Clinic, Rijnstate Hospital, Arnhem, the Netherlands; Division of Human Nutrition and Health, Wageningen University & Research, Wageningen, the Netherlands.

Background: Obesity is associated with cardiovascular (CV) risk factors and diseases. Because bariatric surgery is increasingly performed in relatively elderly patients, a risk for pre- and postoperative CV complications exists.

Objectives: We aimed to assess the value of plasma N-terminal-probrain natriuretic peptide (NT-proBNP) as a CV screening tool.

Setting: High-volume bariatric center.

Methods: Between June 2019 and January 2020, all consecutive bariatric patients 50 years and older underwent preoperative NT-proBNP assessment in this cohort study to screen for CV disease. Patients with elevated NT-proBNP (≥125 pg/mL) were referred for further cardiac evaluation, including electrocardiography and echocardiography.

Results: We included 310 consecutive patients (median age, 56 years; 79% female; body mass index = 43±6.5 kg/m). A history of CV disease was present in 21% of patients, mainly atrial fibrillation (7%) and coronary artery disease (10%). A total of 72 patients (23%) had elevated NT-proBNP levels, and 67 of them underwent further cardiac workup. Of these 67 patients, electrocardiography (ECG) showed atrial fibrillation in 7 patients (10%). On echocardiography, 3 patients had left ventricular ejection fraction (LVEF) <40%, 9 patients had LVEF 40%-49%, and 13 patients had LVEF ≥50% with structural and/or functional remodeling. In 2 patients, elevated NT-proBNP prompted workup leading to a diagnosis of coronary artery disease and consequent percutaneous coronary intervention in 1 patient.

Conclusions: Elevated NT-proBNP levels are present in 23% of patients 50 years and older undergoing bariatric surgery. In 37% of them, there was echocardiographic evidence for structural and/or functional remodeling. Further studies are needed to assess if these preliminary results warrant routine application of NT-proBNP to identify patients at risk for CV complications after bariatric surgery.
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http://dx.doi.org/10.1016/j.soard.2020.08.036DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7467016PMC
January 2021

Emergency department cardioversion of acute atrial fibrillation.

Lancet 2020 09;396(10255):884-885

Department of Cardiology and Cardiovascular Research Institute Maastricht, Maastricht University Medical Center, 6229HX Maastricht, Netherlands.

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http://dx.doi.org/10.1016/S0140-6736(20)31311-8DOI Listing
September 2020

Design and rationale of DUTCH-AF: a prospective nationwide registry programme and observational study on long-term oral antithrombotic treatment in patients with atrial fibrillation.

BMJ Open 2020 08 24;10(8):e036220. Epub 2020 Aug 24.

Department of Cardiology, Martini Hospital, Groningen, Netherlands.

Introduction: Anticoagulation therapy is pivotal in the management of stroke prevention in atrial fibrillation (AF). Prospective registries, containing longitudinal data are lacking with detailed information on anticoagulant therapy, treatment adherence and AF-related adverse events in practice-based patient cohorts, in particular for non-vitamin K oral anticoagulants (NOAC). With the creation of DUTCH-AF, a nationwide longitudinal AF registry, we aim to provide clinical data and answer questions on the (anticoagulant) management over time and of the clinical course of patients with newly diagnosed AF in routine clinical care. Within DUTCH-AF, our current aim is to assess the effect of non-adherence and non-persistence of anticoagulation therapy on clinical adverse events (eg, bleeding and stroke), to determine predictors for such inadequate anticoagulant treatment, and to validate and refine bleeding prediction models. With DUTCH-AF, we provide the basis for a continuing nationwide AF registry, which will facilitate subsequent research, including future registry-based clinical trials.

Methods And Analysis: The DUTCH-AF registry is a nationwide, prospective registry of patients with newly diagnosed 'non-valvular' AF. Patients will be enrolled from primary, secondary and tertiary care practices across the Netherlands. A target of 6000 patients for this initial cohort will be followed for at least 2 years. Data on thromboembolic and bleeding events, changes in antithrombotic therapy and hospital admissions will be registered. Pharmacy-dispensing data will be obtained to calculate parameters of adherence and persistence to anticoagulant treatment, which will be linked to AF-related outcomes such as ischaemic stroke and major bleeding. In a subset of patients, anticoagulation adherence and beliefs about drugs will be assessed by questionnaire.

Ethics And Dissemination: This study protocol was approved as exempt for formal review according to Dutch law by the Medical Ethics Committee of the Leiden University Medical Centre, Leiden, the Netherlands. Results will be disseminated by publications in peer-reviewed journals and presentations at scientific congresses.

Trial Registration Number: Trial NL7467, NTR7706 (https://www.trialregister.nl/trial/7464).
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http://dx.doi.org/10.1136/bmjopen-2019-036220DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7449286PMC
August 2020
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