Publications by authors named "Bob Weijs"

26 Publications

  • Page 1 of 1

Frequency and Determinants of Spontaneous Conversion to Sinus Rhythm in Patients Presenting to the Emergency Department with Recent-onset Atrial Fibrillation: A Systematic Review.

Arrhythm Electrophysiol Rev 2020 Dec;9(4):195-201

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

The exact frequency and clinical determinants of spontaneous conversion (SCV) in patients with symptomatic recent-onset AF are unclear. The aim of this systematic review is to provide an overview of the frequency and determinants of SCV of AF in patients presenting at the emergency department. A comprehensive literature search for studies about SCV in patients presenting to the emergency department with AF resulted in 25 articles - 12 randomised controlled trials and 13 observational studies. SCV rates range between 9-83% and determinants of SCV also varied between studies. The most important determinants of SCV included short duration of AF (<24 or <48 hours), low number of episodes, normal atrial dimensions and absence of previous heart disease. The large variation in SCV rate and determinants of SCV was related to differences in duration of the observation period, inclusion and exclusion criteria and in variables used in the prediction models.
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http://dx.doi.org/10.15420/aer.2020.34DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7788393PMC
December 2020

Long-term intermittent versus short continuous heart rhythm monitoring for the detection of atrial fibrillation recurrences after catheter ablation.

Int J Cardiol 2021 Apr 4;329:105-112. Epub 2021 Jan 4.

Department of Cardiology, Maastricht University Medical Center and Cardiovascular Research Institute Maastricht, Maastricht, the Netherlands; Department of Cardiology, Radboud University Medical Center, Nijmegen, the Netherlands. Electronic address:

Background: The utility of long-term intermittent heart rhythm monitoring after atrial fibrillation (AF) ablation remains unclear. Therefore, we compared the efficacy and usability of long-term intermittent (AliveCor Kardia® (ACK)) versus short continuous (Holter) heart rhythm monitoring for the detection of AF recurrences after AF ablation and evaluated ACK accuracy to detect AF.

Methods: Patients were provided with Holter (for ≥24 h) simultaneously with an ACK (4 weeks) used three times a day and in case of symptoms. The primary endpoint was the difference in proportion of patients diagnosed with recurrent AF by ACK as compared to Holter monitoring. Secondary endpoints were the usability (System Usability Scale and a four-item questionnaire) of ACK and Holter monitoring; and the accuracy of the ACK algorithm for AF detection.

Results: Out of 126 post-ablation patients, 115 (91.3%; 35 females, median age 64.0 [58.0-68.0] years) transmitted overall 7838 ACK ECG recordings. ACK and Holter monitoring detected 29 (25.2%) and 17 (14.8%) patients with AF recurrences, respectively (p < 0.001). More than 2 weeks of ACK monitoring did not have additional diagnostic yield for detection of AF recurrences. Patients graded ACK higher than Holter monitoring and found ACK more convenient in daily usage than Holter (p < 0.001). Sensitivity and specificity of ACK for AF detection were 95.3% and 97.5%, respectively.

Conclusions: Long-term intermittent monitoring by ACK more effectively detects AF recurrences after AF ablation and has a higher patients' usability than short continuous Holter monitoring. ACK showed a high accuracy to detect AF.
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http://dx.doi.org/10.1016/j.ijcard.2020.12.077DOI Listing
April 2021

Biomarkers Associated With Aortic Valve Calcification: Should We Focus on Sex Specific Processes?

Front Cell Dev Biol 2020 10;8:604. Epub 2020 Jul 10.

Department of Biochemistry and CARIM, Maastricht University, School for Cardiovascular Diseases, Maastricht, Netherlands.

Objective: Circulating biomarkers are useful in detection and monitoring of cardiovascular diseases. However, their role in aortic valve disease is unclear. Mechanisms are rapidly elucidated and sex differences are suggested to be involved. Therefore, we sought to identify biomarkers involved in aortic valve calcification (AVC) stratified by sex.

Methods: Blood samples of 34 patients with AVC (without further overt cardiovascular disease, including absence of hemodynamic consequences of valvular calcification) were compared with 136 patients without AVC. AVC was determined using computed tomography calcium scoring. Circulating biomarkers were quantified using a novel antibody-based method (Olink Proseek Multiplex Cardiovascular Panel I) and 92 biomarkers were compared between patients with and without AVC.

Results: In the overall population, Interleukin-1 Receptor Antagonist and pappalysin-1 were associated with increased and decreased odds of having AVC. These differences were driven by the male population [IL1RA: OR 2.79 (1.16-6.70), = 0.022; PAPPA: OR 0.30 (0.11-0.84), = 0.021]. Furthermore, TNF-related activation-induced cytokine (TRANCE) and fibroblast growth factor-23 were associated decreased odds of having AVC, and monocyte chemotactic protein-1 was associated with increased odds of having AVC [TRANCE: OR 0.32 (0.12-0.80), = 0.015; FGF23: OR 0.41 (0.170-0.991), = 0.048; MCP1: OR 2.64 (1.02-6.81), = 0.045]. In contrast, galanin peptides and ST2 were associated with increased odds of having AVC in females [GAL: OR 12.38 (1.31-116.7), = 0.028; ST2: OR13.64 (1.21-153.33), = 0.034].

Conclusion: In this exploratory study, we identified biomarkers involved in inflammation, fibrosis and calcification which may be associated with having AVC. Biomarkers involved in fibrosis may show higher expression in females, whilst biomarkers involved in inflammation and calcification could associate with AVC in males.
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http://dx.doi.org/10.3389/fcell.2020.00604DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7366171PMC
July 2020

Variation in the Association between Antineoplastic Therapies and Venous Thromboembolism in Patients with Active Cancer.

Thromb Haemost 2020 May 5;120(5):847-856. Epub 2020 May 5.

Department of Haematology, Guy's and St Thomas' NHS Foundation Trust, King's College London, London, United Kingdom.

Background:  Venous thromboembolism (VTE) is a major cause of death in cancer patients. Although patients with cancer have numerous risk factors for VTE, the relative contribution of cancer treatments is unclear.

Objective:  The objective of this study is to evaluate the association between cancer therapies and the risk of VTE.

Methods:  From UK Clinical Practice Research Datalink, data on patients with first cancer diagnosis between 2008 and 2016 were extracted along with information on hospitalization, treatments, and cause of death. Primary outcome was active cancer-associated VTE. To establish the independent effects of risk factors, adjusted subhazard ratios (adj-SHR) were calculated using Fine and Gray regression analysis accounting for death as competing risk.

Results:  Among 67,801 patients with a first cancer diagnosis, active cancer-associated VTE occurred in 1,473 (2.2%). During a median observation time of 1.2 years, chemotherapy, surgery, hormonal therapy, radiation therapy, and immunotherapy were given to 71.1, 37.2, 17.2, 17.5, and 1.4% of patients with VTE, respectively. The active cancers associated with the highest risk of VTE-as assessed by incidence rates-included pancreatic cancer, brain cancer, and metastatic cancer. Chemotherapy was associated with an increased risk of VTE (adj-SHR: 3.17, 95% confidence interval [CI]: 2.76-3.65) while immunotherapy with a not significant reduced risk (adj-SHR: 0.67, 95% CI: 0.30-1.52). There was no association between VTE and radiation therapy (adj-SHR: 0.91, 95% CI: 0.65-1.27) and hormonal therapies.

Conclusion:  VTE risk varies with cancer type. Chemotherapy was associated with an increased VTE risk, whereas with radiation and immunotherapy therapy, an association was not confirmed.
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http://dx.doi.org/10.1055/s-0040-1709527DOI Listing
May 2020

Short-Term Hemodynamic and Electrophysiological Effects of Cardiac Resynchronization by Left Ventricular Septal Pacing.

J Am Coll Cardiol 2020 02;75(4):347-359

Department of Cardiology, Cardiovascular Research Institute Maastricht (CARIM), Maastricht University Medical Center (MUMC+), Maastricht, the Netherlands; Department of Cardiology, Radboud University Medical Centre (Radboudumc), Nijmegen, the Netherlands.

Background: Cardiac resynchronization therapy (CRT) is usually performed by biventricular (BiV) pacing. Previously, feasibility of transvenous implantation of a lead at the left ventricular (LV) endocardial side of the interventricular septum, referred to as LV septal (LVs) pacing, was demonstrated.

Objectives: The authors sought to compare the acute electrophysiological and hemodynamic effects of LVs with BiV and His bundle (HB) pacing in CRT patients.

Methods: Temporary LVs pacing (transaortic approach) alone or in combination with right ventricular (RV) (LVs+RV), BiV, and HB pacing was performed in 27 patients undergoing CRT implantation. Electrophysiological changes were assessed using electrocardiography (QRS duration), vectorcardiography (QRS area), and multielectrode body surface mapping (standard deviation of activation times [SDAT]). Hemodynamic changes were assessed as the first derivative of LV pressure (LVdP/dtmax).

Results: As compared with baseline, LVs pacing resulted in a larger reduction in QRS area (to 73 ± 22 μVs) and SDAT (to 26 ± 7 ms) than BiV (to 93 ± 26 μVs and 31 ± 7 ms; both p < 0.05) and LVs+RV pacing (to 108 ± 37 μVs; p < 0.05; and 29 ± 8 ms; p = 0.05). The increase in LVdP/dtmax was similar during LVs and BiV pacing (17 ± 10% vs. 17 ± 9%, respectively) and larger than during LVs+RV pacing (11 ± 9%; p < 0.05). There were no significant differences between basal, mid-, or apical LVs levels in LVdP/dtmax and SDAT. In a subgroup of 16 patients, changes in QRS area, SDAT, and LVdP/dtmax were comparable between LVs and HB pacing.

Conclusions: LVs pacing provides short-term hemodynamic improvement and electrical resynchronization that is at least as good as during BiV and possibly HB pacing. These results indicate that LVs pacing may serve as a valuable alternative for CRT.
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http://dx.doi.org/10.1016/j.jacc.2019.11.040DOI Listing
February 2020

Vitamin K Antagonists, Non-Vitamin K Antagonist Oral Anticoagulants, and Vascular Calcification in Patients with Atrial Fibrillation.

TH Open 2018 Oct 10;2(4):e391-e398. Epub 2018 Nov 10.

Department of Cardiology, Maastricht University Medical Center+ and CARIM, Maastricht, The Netherlands.

 Vitamin K antagonists (VKAs) are associated with coronary artery calcification in low-risk populations, but their effect on calcification of large arteries remains uncertain. The effect of non-vitamin K antagonist oral anticoagulants (NOACs) on vascular calcification is unknown. We investigated the influence of use of VKA and NOAC on calcification of the aorta and aortic valve.  In patients with atrial fibrillation without a history of major adverse cardiac or cerebrovascular events who underwent computed tomographic angiography, the presence of ascending aorta calcification (AsAC), descending aorta calcification (DAC), and aortic valve calcification (AVC) was determined. Confounders for VKA/NOAC treatment were identified and propensity score adjusted logistic regression explored the association between treatment and calcification (Agatston score > 0). AsAC, DAC, and AVC differences were assessed in propensity score-matched groups.  Of 236 patients (33% female, age: 58 ± 9 years), 71 (30%) used VKA (median duration: 122 weeks) and 79 (34%) used NOAC (median duration: 16 weeks). Propensity score-adjusted logistic regression revealed that use of VKA was significantly associated with AsAC (odds ratio [OR]: 2.31; 95% confidence interval [CI]: 1.16-4.59;  = 0.017) and DAC (OR: 2.38; 95% CI: 1.22-4.67;  = 0.012) and a trend in AVC (OR: 1.92; 95% CI: 0.98-3.80;  = 0.059) compared with non-anticoagulation. This association was absent in NOAC versus non-anticoagulant (AsAC OR: 0.51; 95% CI: 0.21-1.21;  = 0.127; DAC OR: 0.80; 95% CI: 0.36-1.76;  = 0.577; AVC OR: 0.62; 95% CI: 0.27-1.40;  = 0.248). A total of 178 patients were propensity score matched in three pairwise comparisons. Again, use of VKA was associated with DAC (  = 0.043) and a trend toward more AsAC (  = 0.059), while use of NOAC was not (AsAC  = 0.264; DAC  = 0.154; AVC  = 0.280).  This cross-sectional study shows that use of VKA seems to contribute to vascular calcification. The calcification effect was not observed in NOAC users.
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http://dx.doi.org/10.1055/s-0038-1675578DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6524908PMC
October 2018

The Biomarkers NT-proBNP and CA-125 are Elevated in Patients with Idiopathic Atrial Fibrillation.

J Atr Fibrillation 2018 Dec 31;11(4):2058. Epub 2018 Dec 31.

Maastricht University Medical Center+ and Cardiovascular Research Institute Maastricht (CARIM), Department of Cardiology, Maastricht, the Netherlands.

Background: Blood biomarkers related to AF could be useful to detect silent AF and to develop stratified strategies for AF prevention. Previous studies identified markers that predict incident AF. However, it is difficult to differentiate whether biomarkers relate to underlying cardiovascular diseases, are generated by the atria in response to an AF episode, or both. We therefore measured a panel of blood biomarkers in patients without overt CVD with and without AF to investigate the association between biomarkers and atrial fibrillation (AF) in patients without overt cardiovascular disease (CVD).

Methods: Blood samples - drawn remote from an AF episode - of 60 patients with AF but without overt forms of CVD (idiopathic AF; iAF) were compared to 120 matched patients with sinus rhythm only. A novel antibody-based method for quantification of blood biomarkers (OlinkProseek Multiplex Cardiovascular) was used to compare 92 biomarkers between the two groups.

Results: N-terminal pro-B-type natriuretic peptide (NT-proBNP), Cathepsin L1, Endothelial cell-specific molecule 1, Cancer Antigen-125 (CA-125), Heat shock 27kDa protein, Galanin peptides, Proteinase-activated receptor 1, Stem cell factor, and CD40-ligand were all higher in iAF patients than in SR controls. Both NT-proBNP (OR1.55(1.07-2.25);p=0.022) and CA-125 (OR1.68(1.07-2.64);p=0.026) were independently associated with iAF.

Conclusions: This exploratory study, investigating over 90 cardiovascular blood biomarkers in patients without known CVD, identified one established biomarker for paroxysmal AF, NT-proBNP, and a novel marker, CA-125. CA-125 - previously unrelated to paroxysmal AF in an otherwise healthy population - may thus be a potential indicator of remote paroxysms of AF.
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http://dx.doi.org/10.4022/jafib.2058DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6533832PMC
December 2018

Incident Atrial Fibrillation, Dementia and the Role of Anticoagulation: A Population-Based Cohort Study.

Thromb Haemost 2019 Jun 27;119(6):981-991. Epub 2019 Mar 27.

Institute for Epidemiology, Statistics and Informatics GmbH, Frankfurt, Germany.

Introduction:  Atrial fibrillation (AF) is associated with dementia. Anticoagulation may modify this relationship, but it is unclear if this is due to stroke reduction alone.

Methods:  Age- and sex-matched individuals from the U.K. Clinical Practice Research Datalink (2008-2016) with and without an incident diagnosis of AF were followed for a new dementia diagnosis. We estimated adjusted hazard ratios (aHRs) for incident dementia diagnosis in the AF cohort, overall and stratified by anticoagulation status, using the matched non-AF cohorts as reference. We performed a sensitivity analysis excluding individuals with stroke/transient ischaemic attack (TIA) before the observation period.

Results:  Over 193,082 person-years (mean follow-up 25.7 ± 0.1 months), 347/15,276 AF (2.3%) and 1,085/76,096 non-AF (1.4%) were newly diagnosed with dementia (aHR, 1.31, 95% confidence interval, 1.15-1.49). The AF group had more co-morbidity and higher rates of dementia, both with and without anticoagulation, than non-AF. When those with history of stroke/ TIA before the observation period were excluded and those with incident stroke/TIA during the observation period were censored, AF individuals not on anticoagulation had significantly higher rates of dementia compared with non-AF, aHR 1.30 (1.06-1.58).

Conclusion:  Our findings support the hypothesis that AF is a distinct risk factor for dementia, independent of stroke/TIA and other vascular risk factors. In those without stroke/TIA, risk of dementia is increased only in those who are not on anticoagulation, suggesting anticoagulation is protective presumably through reduction of sub-clinical embolic events. Further prospective research is needed to better ascertain the role of anticoagulation amongst targeted therapeutic strategies to reduce cognitive decline in AF.
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http://dx.doi.org/10.1055/s-0039-1683429DOI Listing
June 2019

Targeted therapy of underlying conditions improves quality of life in patients with persistent atrial fibrillation: results of the RACE 3 study.

Europace 2019 Apr;21(4):563-571

Department of Cardiology, University Medical Centre Groningen, University of Groningen, RB Groningen, Netherlands.

Aims: Atrial fibrillation (AF) reduces quality of life (QoL). We aim to evaluate effects of targeted therapy of underlying conditions on QoL in patients with AF and heart failure (HF).

Methods And Results: The Routine versus Aggressive risk factor driven upstream rhythm Control for prevention of Early atrial fibrillation in heart failure (RACE 3) study randomized patients with early persistent AF and HF to targeted or conventional therapy. Both groups received guideline-driven treatment. The targeted group received four additional therapies: mineralocorticoid receptor antagonists; statins; angiotensin converting enzyme inhibitors and/or receptor blockers; and cardiac rehabilitation including physical activity, dietary restrictions, and counselling. Quality of life was analysed in 230 patients at baseline and 1 year with available Medical Outcomes Study Short-Form Health Survey (SF-36), University of Toronto AF Severity Scale (AFSS) questionnaires, and European Heart Rhythm Association (EHRA) class. Improvements in SF-36 subscales were larger in the targeted group for physical functioning (Δ12 ± 19 vs. Δ6 ± 22, P = 0.007), physical role limitations (Δ32 ± 41 vs. Δ17 ± 45, P = 0.018), and general health (Δ8 ± 16 vs. Δ0 ± 17, P < 0.001). Dyspnoea at rest improved more (Δ-0.8 ± 1.3 vs. Δ-0.4 ± 1.2, P = 0.018) and EHRA class was lower at 1-year follow-up in the targeted group. Patients with AF at 1 year, improvement in physical functioning (Δ9 ± 9 vs. Δ-3 ± 16, P = 0.001), general health (Δ7 ± 16 vs. Δ-7 ± 19, P = 0.004), and social functioning (Δ6 ± 23 vs. Δ-4 ± 16, P = 0.041) were larger in the targeted group.

Conclusion: A strategy aiming to treat underlying conditions improved QoL more compared with conventional therapy in patients with early persistent AF and HF. Its benefit was even observed in patients in AF at 1 year.

Trial Registration Number: Clinicaltrials.gov NCT00877643.
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http://dx.doi.org/10.1093/europace/euy311DOI Listing
April 2019

Agatston score of the descending aorta is independently associated with coronary events in a low-risk population.

Open Heart 2018;5(2):e000893. Epub 2018 Nov 24.

Department of Cardiology, Maastricht University Medical Center (MUMC+) and Cardiovascular Research Institute Maastricht (CARIM), Maastricht, The Netherlands.

Objectives: A standard coronary artery calcium scan includes part of the aorta. This additional information is often not included in routine analyses. We aimed to determine the feasibility of assessing the Agatston score of the descending aorta calcification (DAC) on standard coronary calcium scans and the association of this score with coronary events in a low-risk study population.

Methods: Between January 2008 and March 2011, 390 consecutive patients who were referred for cardiac CT as part of work-up for pulmonary vein isolation (n=115) or assessment of presence of coronary artery disease (n=275) were included. At baseline, all patients were free of a history of cardiovascular disease. Two independent observers determined the Agatston score of the ascending aorta and descending aorta.

Results: A total of 16 patients (4.1%) developed coronary events (acute coronary syndrome (n=6) and symptomatic significant coronary artery disease requiring treatment (n=10)) during a follow-up of 67±12 months, with more events in patients with calcifications in the descending aorta than in those without (8.4% vs 3.7 %; p=0.08). Multivariable Cox regression, corrected for Framingham Risk Score (FRS) and coronary Agatston score (CAC), revealed that DAC was independently associated with coronary events (per 100 units; HR: 1.06, 95% CI 1.02 to 1.09; p=0.001). DAC furthermore increased the identification of patients that will experience a coronary event (area under the curve: 0.68 for FRS only, 0.75 for FRS+CAC and 0.78 for FRS+CAC+DAC).

Conclusions: The Agatston score of the descending aorta could be included in the standard analysis of cardiac CT scans of low-risk patients since it holds valuable information for the prediction of coronary events.
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http://dx.doi.org/10.1136/openhrt-2018-000893DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6269642PMC
November 2018

Vascular Calcification and not Arrhythmia in Idiopathic Atrial Fibrillation Associates with Sex Differences in Diabetic Microvascular Injury miRNA Profiles.

Microrna 2019 ;8(2):127-134

Department of Internal Medicine (Nephrology), Leiden University Medical Center and Einthoven Laboratory for Vascular and Regenerative Medicine, Albinusdreef 2, 2333 ZA, Leiden, Netherlands.

Background: Atrial Fibrillation (AF) in patients without concomitant cardiovascular pathophysiological disease, is called idiopathic Atrial Fibrillation (iAF). Nonetheless, iAF patients have often times subclinical coronary (micro) vascular dysfunction and, particularly in women, a higher prevalence of subsequent cardiovascular comorbidities. Previously, we identified a plasma miRNA association with diabetes and microvascular injury in Diabetic Nephropathy (DN) patients. Therefore, in this study we assessed whether plasma levels of these diabetic, microvascular injury associated miRNAs reflect microvascular integrity in iAF patients, associated with the presence of paroxysmal arrhythmia or instead are determined by concealed coronary artery disease.

Methods: Circulating levels of a pre-selected set of diabetic, (micro) vascular injury associated miRNAs, were measured in 59 iAF patients compared to 176 Sinus Rhythm (SR) controls. Furthermore, the presence of coronary artery and aortic calcification in each patient was assessed using Cardiac Computed Tomography Angiography (CCTA).

Results: Paroxysmal arrhythmia in iAF patients did not result in significant miRNA expression profile differences in iAF patients compared to SR controls. Nonetheless, coronary artery calcification (CAC) was associated with higher levels of miRNAs-103, -125a-5p, -221 and -223 in men. In women, CAC was associated with higher plasma levels of miRNA-27a and miRNA-126 and correlated with Agatston scores. Within the total population, ascending Aortic Calcification (AsAC) patients displayed increased plasma levels of miRNA-221, while women, in particular, demonstrated a Descending Aorta Calcification (DAC) associated increase in miRNA-212 levels.

Conclusions: Diabetic microvascular injury associated miRNAs in iAF are associated with subclinical coronary artery disease in a sex-specific way and confirm the notion that biological sex identifies iAF subgroups that may require dedicated clinical care.
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http://dx.doi.org/10.2174/2211536608666181122125208DOI Listing
April 2019

Late complications of an atrial septal occluder provoked by anticoagulant therapy.

J Cardiol Cases 2018 Feb 7;17(2):68-71. Epub 2017 Nov 7.

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

Late complications of an atrial septal occluder device (ASO) are rare but may be serious. We report a case with extensive hemopericardium five years after ASO implantation most likely triggered by anticoagulant therapy. Although not surgically confirmed, indirect clues for erosion of the atrial wall by the device were the exclusion of other etiologies, lack of recurrence after pericardial drainage and withdrawal of anticoagulants. In addition, multimodality imaging using echocardiography, computed tomography, and cardiac magnetic resonance imaging were helpful to elucidate this unusual cause. Initiation of anticoagulant treatment in patients with an ASO should be carefully balanced and may warrant more frequent echocardiographic follow-up. < Late complications of an atrial septal occlude device (ASO) are rare. Initiation of anticoagulant therapy in patients with an ASO may lead to late hemopericardium, suggesting that more frequent echocardiographic follow-up is warranted.>.
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http://dx.doi.org/10.1016/j.jccase.2017.09.010DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6149637PMC
February 2018

Multi-ethnic genome-wide association study for atrial fibrillation.

Authors:
Carolina Roselli Mark D Chaffin Lu-Chen Weng Stefanie Aeschbacher Gustav Ahlberg Christine M Albert Peter Almgren Alvaro Alonso Christopher D Anderson Krishna G Aragam Dan E Arking John Barnard Traci M Bartz Emelia J Benjamin Nathan A Bihlmeyer Joshua C Bis Heather L Bloom Eric Boerwinkle Erwin B Bottinger Jennifer A Brody Hugh Calkins Archie Campbell Thomas P Cappola John Carlquist Daniel I Chasman Lin Y Chen Yii-Der Ida Chen Eue-Keun Choi Seung Hoan Choi Ingrid E Christophersen Mina K Chung John W Cole David Conen James Cook Harry J Crijns Michael J Cutler Scott M Damrauer Brian R Daniels Dawood Darbar Graciela Delgado Joshua C Denny Martin Dichgans Marcus Dörr Elton A Dudink Samuel C Dudley Nada Esa Tonu Esko Markku Eskola Diane Fatkin Stephan B Felix Ian Ford Oscar H Franco Bastiaan Geelhoed Raji P Grewal Vilmundur Gudnason Xiuqing Guo Namrata Gupta Stefan Gustafsson Rebecca Gutmann Anders Hamsten Tamara B Harris Caroline Hayward Susan R Heckbert Jussi Hernesniemi Lynne J Hocking Albert Hofman Andrea R V R Horimoto Jie Huang Paul L Huang Jennifer Huffman Erik Ingelsson Esra Gucuk Ipek Kaoru Ito Jordi Jimenez-Conde Renee Johnson J Wouter Jukema Stefan Kääb Mika Kähönen Yoichiro Kamatani John P Kane Adnan Kastrati Sekar Kathiresan Petra Katschnig-Winter Maryam Kavousi Thorsten Kessler Bas L Kietselaer Paulus Kirchhof Marcus E Kleber Stacey Knight Jose E Krieger Michiaki Kubo Lenore J Launer Jari Laurikka Terho Lehtimäki Kirsten Leineweber Rozenn N Lemaitre Man Li Hong Euy Lim Henry J Lin Honghuang Lin Lars Lind Cecilia M Lindgren Marja-Liisa Lokki Barry London Ruth J F Loos Siew-Kee Low Yingchang Lu Leo-Pekka Lyytikäinen Peter W Macfarlane Patrik K Magnusson Anubha Mahajan Rainer Malik Alfredo J Mansur Gregory M Marcus Lauren Margolin Kenneth B Margulies Winfried März David D McManus Olle Melander Sanghamitra Mohanty Jay A Montgomery Michael P Morley Andrew P Morris Martina Müller-Nurasyid Andrea Natale Saman Nazarian Benjamin Neumann Christopher Newton-Cheh Maartje N Niemeijer Kjell Nikus Peter Nilsson Raymond Noordam Heidi Oellers Morten S Olesen Marju Orho-Melander Sandosh Padmanabhan Hui-Nam Pak Guillaume Paré Nancy L Pedersen Joanna Pera Alexandre Pereira David Porteous Bruce M Psaty Sara L Pulit Clive R Pullinger Daniel J Rader Lena Refsgaard Marta Ribasés Paul M Ridker Michiel Rienstra Lorenz Risch Dan M Roden Jonathan Rosand Michael A Rosenberg Natalia Rost Jerome I Rotter Samir Saba Roopinder K Sandhu Renate B Schnabel Katharina Schramm Heribert Schunkert Claudia Schurman Stuart A Scott Ilkka Seppälä Christian Shaffer Svati Shah Alaa A Shalaby Jaemin Shim M Benjamin Shoemaker Joylene E Siland Juha Sinisalo Moritz F Sinner Agnieszka Slowik Albert V Smith Blair H Smith J Gustav Smith Jonathan D Smith Nicholas L Smith Elsayed Z Soliman Nona Sotoodehnia Bruno H Stricker Albert Sun Han Sun Jesper H Svendsen Toshihiro Tanaka Kahraman Tanriverdi Kent D Taylor Maris Teder-Laving Alexander Teumer Sébastien Thériault Stella Trompet Nathan R Tucker Arnljot Tveit Andre G Uitterlinden Pim Van Der Harst Isabelle C Van Gelder David R Van Wagoner Niek Verweij Efthymia Vlachopoulou Uwe Völker Biqi Wang Peter E Weeke Bob Weijs Raul Weiss Stefan Weiss Quinn S Wells Kerri L Wiggins Jorge A Wong Daniel Woo Bradford B Worrall Pil-Sung Yang Jie Yao Zachary T Yoneda Tanja Zeller Lingyao Zeng Steven A Lubitz Kathryn L Lunetta Patrick T Ellinor

Nat Genet 2018 06 11;50(9):1225-1233. Epub 2018 Jun 11.

Program in Medical and Population Genetics, The Broad Institute of MIT and Harvard, Cambridge, MA, USA.

Atrial fibrillation (AF) affects more than 33 million individuals worldwide and has a complex heritability. We conducted the largest meta-analysis of genome-wide association studies (GWAS) for AF to date, consisting of more than half a million individuals, including 65,446 with AF. In total, we identified 97 loci significantly associated with AF, including 67 that were novel in a combined-ancestry analysis, and 3 that were novel in a European-specific analysis. We sought to identify AF-associated genes at the GWAS loci by performing RNA-sequencing and expression quantitative trait locus analyses in 101 left atrial samples, the most relevant tissue for AF. We also performed transcriptome-wide analyses that identified 57 AF-associated genes, 42 of which overlap with GWAS loci. The identified loci implicate genes enriched within cardiac developmental, electrophysiological, contractile and structural pathways. These results extend our understanding of the biological pathways underlying AF and may facilitate the development of therapeutics for AF.
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http://dx.doi.org/10.1038/s41588-018-0133-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6136836PMC
June 2018

Cardioversion of persistent atrial fibrillation is associated with a 24-hour relapse gap: Observations from prolonged postcardioversion rhythm monitoring.

Clin Cardiol 2018 Mar 22;41(3):366-371. Epub 2018 Mar 22.

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

Background: Many recurrences occur after electrical cardioversion (ECV) of atrial fibrillation (AF). Assessment of extent of remodeling and continuous prolonged rhythm monitoring might reveal actionable recurrence mechanisms.

Hypothesis: After ECV of AF specific patterns of arrhythmia recurrence can be distinguished.

Methods: All patients who underwent successful ECV due to persistent AF were included. Tissue velocity echocardiography during AF was performed before ECV to study atrial fibrillatory cycle length and fibrillatory velocity. After ECV, the heart rhythm of all patients was monitored 3 times daily during 4 weeks, and timing of recurrence was noted.

Results: In total, 50 patients (68% male) were included; mean age was 68 ± 9 years. Median duration of the current AF episode was 102 (range, 74-152) days. Twenty-one (42%) patients showed recurrence of persistent AF. No recurrences occurred during the first 24 hours. There were no differences in clinical characteristics between patients with or without recurrence of AF. However, patients with early recurrence of AF had significantly higher precardioversion wall-motion velocity compared with patients who remained in sinus rhythm (2.8 [1.6-3.6] vs 1.4 [0.9-3.3] cm/s; P = 0.017), whereas atrial fibrillatory cycle length did not differ.

Conclusions: In this study on 50 patients successfully cardioverted for persistent AF, there was a relapse gap of ≥24 hours. This phenomenon has not been well appreciated before and offers an AF-free window of opportunity for electrocardiographically triggered cardiac imaging or complex electrophysiological procedures. Echocardiographic tissue velocity imaging may visualize atrial remodeling relevant to AF recurrence.
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http://dx.doi.org/10.1002/clc.22877DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6489937PMC
March 2018

The influence of progression of atrial fibrillation on quality of life: a report from the Euro Heart Survey.

Europace 2018 06;20(6):929-934

Department of Cardiology, Maastricht University Medical Center (MUMC+) and Cardiovascular Research Institute Maastricht (CARIM), P. Debyelaan 25, 6229 HX Maastricht, the Netherlands.

Aims: Progression of atrial fibrillation (AF) from paroxysmal to persistent forms is an active field of research. The influence of AF progression on health related quality of life (HRQoL) is currently unknown. We aimed to assess the influence of AF progression on HRQoL, and whether this association is mediated through symptoms, treatment, and major adverse events.

Methods And Results: In the Euro Heart Survey, 967 patients were included with paroxysmal AF who filled out EuroQoL-5D at baseline and at 1 year follow-up. Those who progressed (n = 132, 13.6%) developed more problems during follow-up than those who did not, on all EuroQoL-5D domains (increase in problems on mobility 20.5% vs. 11.4%; self-care 12.9% vs. 6.2%; usual activities 23.5% vs. 14.0%; pain/discomfort 20.5% vs. 13.7%; and anxiety/depression 22.7% vs. 15.7%; all P < 0.05), leading to a decrease in utility [baseline 0.744 ± 0.26, follow-up 0.674 ± 0.36; difference -0.07 (95% CI [-0.126,-0.013], P = 0.02)]. Multivariate analysis showed that the effect of progression on utility is mediated by a large effect of adverse events [stroke (-0.27 (95% CI [-0.43,-0.11]); P = 0.001], heart failure [-0.12 (95% CI [-0.20,-0.05]); P = 0.001], malignancy (-0.31 (95% CI [-0.56,-0.05]); P = 0.02] or implantation of an implantable cardiac defibrillator [-0.12 (95% CI [-0.23,-0.02]); P = 0.03)], as well as symptomatic AF [-0.04 (95% CI [-0.08,-0.01]); P = 0.008].

Conclusion: AF progression is associated with a decrease in HRQoL. However, multivariate analysis revealed that AF progression itself does not have a negative effect on HRQoL, but that this effect can be attributed to a minor effect of the associated symptoms and a major effect of associated adverse events.
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http://dx.doi.org/10.1093/europace/eux217DOI Listing
June 2018

Acute cardioversion vs a wait-and-see approach for recent-onset symptomatic atrial fibrillation in the emergency department: Rationale and design of the randomized ACWAS trial.

Am Heart J 2017 Jan 2;183:49-53. Epub 2016 Oct 2.

Department of Cardiology, Maastricht University Medical Center and Cardiovascular Research Institute Maastricht, Maastricht, the Netherlands. Electronic address:

Background: Current standard of care for patients with recent-onset atrial fibrillation (AF) in the emergency department aims at urgent restoration of sinus rhythm, although paroxysmal AF is a condition that resolves spontaneously within 24 hours in more than 70% of the cases. A wait-and-see approach with rate-control medication only and when needed cardioversion within 48 hours of onset of symptoms is hypothesized to be noninferior, safe, and cost-effective as compared with current standard of care and to lead to a higher quality of life.

Design: The ACWAS trial (NCT02248753) is an investigator-initiated, randomized, controlled, 2-arm noninferiority trial that compares a wait-and-see approach to the standard of care. Consenting adults with recent-onset symptomatic AF in the emergency department without urgent need for cardioversion are eligible for participation. A total of 437 patients will be randomized to either standard care (pharmacologic or electrical cardioversion) or the wait-and-see approach, consisting of symptom reduction through rate control medication until spontaneous conversion is achieved, with the possibility of cardioversion within 48 hours after onset of symptoms. Primary end point is the presence of sinus rhythm on 12-lead electrocardiogram at 4 weeks; main secondary outcomes are adverse events, total medical and societal costs, quality of life, and cost-effectiveness for 1 year.

Conclusions: The ACWAS trial aims at providing evidence for the use of a wait-and-see approach for patients with recent-onset symptomatic AF in the emergency department.
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http://dx.doi.org/10.1016/j.ahj.2016.09.009DOI Listing
January 2017

Poor anticoagulation relates to extended access times for cardioversion and is associated with long-term major cardiac and cerebrovascular events.

Int J Cardiol 2016 Dec 11;225:337-341. Epub 2016 Oct 11.

Department of Cardiology, Maastricht University Medical Centre, PO Box 5800, 6202 AZ, Maastricht, The Netherlands; Cardiovascular Research Institute Maastricht (CARIM), Maastricht University, PO Box 616, 6200 MD, Maastricht, The Netherlands.

Background: Patients undergoing elective electrical cardioversion (ECV) for atrial fibrillation have a temporarily increased risk of thromboembolism. Current guidelines recommend adequate anticoagulation for ≥3 consecutive weeks precardioversion, i.e. consecutive INR values 2.0-3.0 in patients with vitamin K antagonists (VKA). We aimed to evaluate the occurrence and impact of subtherapeutic INRs precardioversion and to study factors associated with these unwanted fluctuations.

Methods: We recruited 346 consecutive patients undergoing elective ECV in the Maastricht University Medical Centre between 2008 and 2013. Predictors of subtherapeutic INR values were identified and incorporated into a logistic regression model.

Results: A subtherapeutic INR precardioversion occurred in 55.2% of patients. The only statistically significant predictor was VKA-naivety (Odds Ratio (OR) 4.78, 95% Confidence Interval (CI) 2.67-8.58, p<0.001). In patients with ≥1 subtherapeutic INR precardioversion, time from referral until cardioversion was 91.1±42.8days, compared to 41.7±26.6days (p<0.001) in patients without subtherapeutic INRs. No thromboembolic events occurred <30days after the ECV. Independent predictors for the combined endpoint of cardiovascular death, ischemic stroke and the need of blood transfusion (n=30, median follow-up of 374days) were coronary artery disease in the history (OR 3.35, 95%CI 1.54-7.25, p=0.002) and subtherapeutic INR precardioversion (OR 3.64, 95%CI 1.43-9.24, p=0.007).

Conclusions: The use of VKA often results in subtherapeutic INRs precardioversion and is associated with a significant delay until cardioversion, especially in patients with recent initiation of VKA therapy. Furthermore, subtherapeutic INR levels prior to ECV are associated with the combined endpoint of cardiovascular death, ischemic stroke and the need of blood transfusion.
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http://dx.doi.org/10.1016/j.ijcard.2016.10.018DOI Listing
December 2016

Termination of Ventricular Arrhythmia Using Acetaminophen in a Nonagenarian.

J Am Geriatr Soc 2016 Apr;64(4):914-6

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

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http://dx.doi.org/10.1111/jgs.14060DOI Listing
April 2016

Clinical correlates of echocardiographic tissue velocity imaging abnormalities of the left atrial wall during atrial fibrillation.

Europace 2014 Nov 25;16(11):1546-53. Epub 2014 Mar 25.

Department of Cardiology, Maastricht University Medical Centre, PO Box 5800, Maastricht 6202 AZ, The Netherlands.

Aims: In patients with atrial fibrillation (AF), echocardiographic tissue velocity imaging (TVI) enables assessment of electrical and structural remodelling by measuring, respectively, the AF cycle length (AFCL-TVI) and the atrial fibrillatory wall motion velocity (AFV-TVI). We investigated the clinical and echocardiographic correlates of atrial remodelling assessed by TVI.

Methods And Results: We studied 215 patients presenting with AF. In all patients, we measured the AFCL-TVI and the AFV-TVI in the left atrium. Standard baseline characteristics were recorded. We divided patients by median value of AFV-TVI and AFCL-TVI to evaluate the determinants of atrial remodelling. A low AFV-TVI was related with a longer median duration of the current AF episode, a higher prevalence of significant mitral regurgitation and a thicker left ventricle (LV). Multivariate analysis revealed that a low AFV-TVI was independently associated with a longer median duration of the current AF episode [OR 0.09 (95% CI 0.03-0.027); P < 0.001]. Univariately, a short AFCL-TVI was associated with a long median duration of the current AF episode, the use of anti-arrhythmic drugs, a lower LV ejection fraction (LVEF) and a smaller left atrial volume index (LAVI). Multivariate analysis revealed that LVEF [OR 1.48 (95% CI 1.09-2.01); P = 0.013] and LAVI [OR 1.37 (95% CI 1.08-1.74); P = 0.010] were independently associated with AFCL-TVI.

Conclusion: This study investigated the clinical and echocardiographic correlates of atrial remodelling assessed by TVI. The AFV-TVI is reduced in patients with a long AF duration and who have mitral regurgitation. In addition, the AFCL is long if LAVI is high and LVEF preserved. Tissue velocity imaging parameters measured during AF may be helpful to characterize the degree of atrial remodelling and optimize treatment.
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http://dx.doi.org/10.1093/europace/euu047DOI Listing
November 2014

Contemporary real life cardioversion of atrial fibrillation: Results from the multinational RHYTHM-AF study.

Int J Cardiol 2014 04 25;172(3):588-94. Epub 2014 Jan 25.

Hôpital Européen Georges Pompidou, René Descartes University, Paris, France.

Aims: Electrical and pharmacological cardioversion (ECV, PCV) are important treatment options for symptomatic patients with recent onset atrial fibrillation (AF). RHYTHM-AF is an international registry of present-day cardioversion providing information that is not currently available on country differences and acute and long-term arrhythmia outcomes of ECV and PCV.

Methods And Results: 3940 patients were enrolled, of whom 75% underwent CV. All patients were followed for 2 months. There were large variations concerning mode of CV used, ECV being heterogeneous. A choice of PCV drug depended on the clinical patient profile. Sinus rhythm was restored in 89.7% of patients by ECV and in 69.1% after PCV. Among patients not undergoing CV during admission, 34% spontaneously converted to sinus rhythm within 24h. ECV was most successful in patients pretreated with antiarrhythmic drugs (mostly amiodarone). PCV was enhanced by class Ic antiarrhythmic drugs; conversion rate on amiodarone was similar to that seen with rate control drugs. Female patients and those with paroxysmal and first detected AF as well as those without previous ECV responded well to PCV. The median duration of hospital stay was 16.2 and 24.0 h for ECV and PCV patients, respectively. There were very few CV-related complications regardless of mode of CV. Chronic maintenance of sinus rhythm was enhanced in patients on chronic antiarrhythmic drugs, beta-blockers or inhibitors of the renin-angiotensin system.

Conclusions: Mode of CV varied significantly, but both PCV and ECV were safe and effective. Class Ic drugs were most effective conversion drugs, but amiodarone is used most frequently despite providing merely rate control rather than shorten time to conversion.
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http://dx.doi.org/10.1016/j.ijcard.2014.01.099DOI Listing
April 2014

Tissue velocity imaging of the left atrium predicts response to flecainide in patients with acute atrial fibrillation.

Heart Rhythm 2014 Mar 7;11(3):478-84. Epub 2013 Dec 7.

Maastricht University Medical Centre, Maastricht, The Netherlands.

Background: Acute atrial fibrillation (AF) is often treated with the administration of intravenous flecainide; however, this treatment may not always be successful and is potentially hazardous. Previous studies suggest that electro-echocardiographic tissue velocity imaging (TVI) of the atrial wall may reflect atrial remodeling.

Objective: To study whether atrial TVI can be used to identify nonresponders of flecainide administered intravenously in patients with acute AF.

Methods: We used atrial TVI to measure atrial fibrillatory cycle length determined by using tissue velocity imaging (AFCL-TVI) and atrial fibrillatory wall motion velocity determined by using tissue velocity imaging (AFV-TVI) in the left atrium in 52 (55%) patients presenting with acute AF in the emergency department. These 2 parameters reflect electrical and structural remodeling, respectively. Standard baseline characteristics were recorded.

Results: Patients were predominantly men (76%) and 64 ± 11 years old. Thirty-six (69%) patients had successful cardioversion after flecainide infusion. There were no significant differences in baseline characteristics between responders and nonresponders. Patients with a successful cardioversion had a longer mean AFCL-TVI and higher median (interquartile range) AFV-TVI compared with patients with failed cardioversion: 172 ± 29 ms vs 137 ± 35 ms (P < .001) and 4.2 (3.3-6.2) cm/s vs 2.3 (1.9-3.5) cm/s (P = .001).

Conclusions: Electro-echocardiographic atrial TVI measurement is a promising noninvasive tool for predicting outcome of pharmacological cardioversion. A short AFCL-TVI and a low AFV-TVI are related to failure of cardioversion of AF using flecainide.
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http://dx.doi.org/10.1016/j.hrthm.2013.12.010DOI Listing
March 2014

Patients originally diagnosed with idiopathic atrial fibrillation more often suffer from insidious coronary artery disease compared to healthy sinus rhythm controls.

Heart Rhythm 2012 Dec 8;9(12):1923-9. Epub 2012 Aug 8.

Maastricht University Medical Center & Cardiovascular Research Institute Maastricht, The Netherlands.

Background: Idiopathic atrial fibrillation (AF) refers to a clinically lacking cardiovascular or pulmonary disease generating the pathophysiologic substrate for the arrhythmia. However, because idiopathic AF is associated with an increased event rate, it could be a harbinger of as-yet undetected underlying heart disease.

Objective: The purpose of this study was to determine the prevalence of coronary artery disease (CAD) in patients diagnosed with idiopathic paroxysmal AF.

Methods: Of the 3243 patients who underwent cardiac computed tomographic angiography (CTA) in our center between January 2008 and March 2011, we identified a total of 115 consecutive idiopathic paroxysmal AF patients who underwent CTA before electrophysiologic ablation. Patients were compared with 275 age-, sex-, and PROCAM risk score-matched healthy controls in permanent sinus rhythm. All patients were free of hypertension, diabetes, congestive heart failure, previous known coronary artery and peripheral vascular disease, previous stroke, thyroid, pulmonary, and renal disease, and structural abnormalities on echocardiography.

Results: Controls more often showed a family history of CAD (38% vs 15%, P <.001), had a higher prevalence of smoking (25% vs 14%, P = .021), higher fasting blood glucose levels (5.5 ± 0.7 mmol/L vs 5.4 ± 0.6 mmol/L, P = .025), and smaller atrial diameters (37 ± 4 mm vs 40 ± 5 mm, P <.001) compared to AF patients. Notwithstanding the above, idiopathic AF patients significantly more often suffered from subclinical CAD compared to controls (49% vs 34%, P = .008). Multivariable regression analysis revealed that beside (as expected) age and gender, a history of AF and left atrial diameter were significant predictors of underlying CAD.

Conclusion: Half of patients originally diagnosed with idiopathic paroxysmal AF show concealed underlying CAD. The detection and treatment of CAD at an early stage could improve the prognosis of these patients.
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http://dx.doi.org/10.1016/j.hrthm.2012.08.013DOI Listing
December 2012

Idiopathic atrial fibrillation revisited in a large longitudinal clinical cohort.

Europace 2012 Feb 1;14(2):184-90. Epub 2011 Dec 1.

Department of Cardiology, Cardiovascular Research Institute Maastricht, Maastricht University Medical Centre, PO Box 5800, Maastricht 6202 AZ, The Netherlands.

Aims: An age of 60 years is often used as cut-off for the diagnosis of idiopathic atrial fibrillation (AF). We investigated the importance of age and atrial size in patients with idiopathic AF and AF patients with isolated hypertension.

Methods And Results: Out of 3978 AF patients in the Euro Heart Survey on AF with known follow-up, 119 (3%) patients had idiopathic AF. We disregarded age and atrial size when selecting idiopathic AF patients since the atria may enlarge by AF itself. For comparison, we selected 152 patients with isolated hypertension from the database. A total of 57 (48%) of the patients were older than 60 years. Persistent or permanent AF was more prevalent in the older idiopathic AF patients (34% in the age <60 vs. 66% in the age >60 years group, P= 0.002) but mean duration of known AF did not differ between these groups [310 days (inter-quartile range, IQR) 60-1827) vs. 430 days (IQR 88-1669), P= 0.824]. Left atrial size did not differ significantly in relation to age (1.50 ± 0.29 mm/kg/m² in the age <60 vs. 1.56 ± 0.31 mm/kg/m² in the age >60 years group, P= 0.742). Only two paroxysmal AF patients progressed to permanent AF. No cardiovascular events occurred during the 1-year follow-up. In contrast, strokes occurred in five patients (6%) with isolated hypertension despite similar clinical profile and comparable atrial size as idiopathic AF patients.

Conclusion: Idiopathic AF may present at advanced age and is even then not associated with significant atrial enlargement, AF progression, or an adverse short-term prognosis. In contrast, elevated blood pressure even when found in the absence of significant atrial remodelling, seems of prognostic importance.
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http://dx.doi.org/10.1093/europace/eur379DOI Listing
February 2012

Clinical and echocardiographic correlates of intra-atrial conduction delay.

Europace 2011 Dec 15;13(12):1681-7. Epub 2011 Aug 15.

Department of Cardiology, Maastricht University Medical Centre, Maastricht, The Netherlands.

Aims: The total atrial conduction time (TACT) is an important electrophysiological parameter. We developed a new transthoracic echocardiographic tool (PA-TDI). The PA-TDI interval is a reflection of the TACT. In the present study, we evaluated the clinical and echocardiographic correlates of intra-atrial conduction delay.

Methods And Results: We studied 427 patients without class I anti-arrhythmic agents or amiodarone. All patients underwent an echocardiogram and the PA-TDI interval was measured. Patient characteristics were recorded. The mean PA-TDI was 157 ± 22 ms. Multivariate linear regression analysis revealed that atrial fibrillation (AF) in history (B = 9.7; 95%CI 5.7-13.8; P < 0.001), hypertension (B = 5.5; 95%CI 1.4-9.8; P = 0.01), clinically relevant valve disease (B = 5.7; 95%CI 0.5-10.8; P = 0.03), age (B = 5; 95%CI 3.3-6.6; P < 0.001), and body mass index (BMI; B = 2.6; 95%CI 0.3-4.9; P = 0.026) were independently associated with the PA-TDI interval. On the echocardiogram: the aortic diameter (B = 0.7; 95%CI 0.2-1.2; P = 0.009), left atrial dimension (B = 0.9; 95%CI 0.5-1.3; P < 0.001), mitral valve E-wave deceleration time (B = 0.1; 95%CI 0.1-0.1; P < 0.001), aortic incompetence (B = 13; 95%CI 3.3-22.6; P = 0.008), and mitral incompetence (B = 11; 95%CI 3.6-17.5; P < 0.003) were independently associated with the PA-TDI interval.

Conclusion: This study is the largest to investigate the relation between the atrial conduction time, underlying heart diseases, and echocardiographic parameters. We found that the PA-TDI was independently prolonged in patients with a history of AF, hypertension, valve disease, higher age, and a higher BMI. Signs of diastolic dysfunction, valve incompetence, and enlarged atrium or aortic root on the echocardiogram were associated with a prolonged PA-TDI. This suggests that early and aggressive treatment of hypertension, diastolic dysfunction, and obesity could prevent intra-atrial conduction delay.
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http://dx.doi.org/10.1093/europace/eur261DOI Listing
December 2011

Patients using vitamin K antagonists show increased levels of coronary calcification: an observational study in low-risk atrial fibrillation patients.

Eur Heart J 2011 Oct 20;32(20):2555-62. Epub 2011 Jul 20.

Department of Cardiology, Maastricht University Medical Centre and Cardiovascular Research Institute Maastricht (CARIM), P.O. Box 5800, 6202 AZ Maastricht, The Netherlands.

Aims: Vitamin K antagonists (VKA) are currently the most frequently used drug to prevent ischaemic stroke in atrial fibrillation (AF) patients. However, VKA use has been associated with increased vascular calcification. The aim of this study was to investigate the contribution of VKA use to coronary artery calcification in low-risk AF patients.

Methods And Results: A prospective coronary calcium scan was performed in 157 AF patients without significant cardiovascular disease (108 males; mean age 57 ± 9 years). A total of 71 (45%) patients were chronic VKA users. The duration of VKA treatment varied between 6 and 143 months (mean 46 months). No significant differences in clinical characteristics were found between patients on VKA treatment and non-anticoagulated patients. However, median coronary artery calcium scores differed significantly between patients without and patients with VKA treatment [0, inter-quartile range (IQR) 0-40, vs. 29, IQR 0-184; P = 0.001]. Mean coronary calcium scores increased with the duration of VKA use (no VKA: 53 ± 115, 6-60 months on VKA: 90 ± 167, and >60 months on VKA: 236 ± 278; P < 0.001). Multivariable logistic regression analysis revealed that age and VKA treatment were significantly related to increased coronary calcium score.

Conclusion: Patients using VKA show increased levels of coronary calcification. Age and VKA treatment were independently related to increased coronary calcium score.
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http://dx.doi.org/10.1093/eurheartj/ehr226DOI Listing
October 2011