Publications by authors named "Harry J G M Crijns"

303 Publications

The European TeleCheck-AF project on remote app-based management of atrial fibrillation during the COVID-19 pandemic: centre and patient experiences.

Europace 2021 Apr 2. Epub 2021 Apr 2.

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

Aims: TeleCheck-AF is a multicentre international project initiated to maintain care delivery for patients with atrial fibrillation (AF) during COVID-19 through teleconsultations supported by an on-demand photoplethysmography-based heart rate and rhythm monitoring app (FibriCheck®). We describe the characteristics, inclusion rates, and experiences from participating centres according the TeleCheck-AF infrastructure as well as characteristics and experiences from recruited patients.

Methods And Results: Three surveys exploring centre characteristics (n = 25), centre experiences (n = 23), and patient experiences (n = 826) were completed. Self-reported patient characteristics were obtained from the app. Most centres were academic (64%) and specialized public cardiology/district hospitals (36%). Majority of the centres had AF outpatient clinics (64%) and only 36% had AF ablation clinics. The time required to start patient inclusion and total number of included patients in the project was comparable for centres experienced (56%) or inexperienced in mHealth use. Within 28 weeks, 1930 AF patients were recruited, mainly for remote AF control (31% of patients) and AF ablation follow-up (42%). Average inclusion rate was highest during the lockdown restrictions and reached a steady state at a lower level after easing the restrictions (188 vs. 52 weekly recruited patients). Majority (>80%) of the centres reported no problems during the implementation of the TeleCheck-AF approach. Recruited patients [median age 64 (55-71), 62% male] agreed that the FibriCheck® app was easy to use (94%).

Conclusion: Despite different health care settings and mobile health experiences, the TeleCheck-AF approach could be set up within an extremely short time and easily used in different European centres during COVID-19.
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http://dx.doi.org/10.1093/europace/euab050DOI Listing
April 2021

Effect of a dedicated mitral heart team compared to a general heart team on survival: a retrospective, comparative, non-randomized interventional cohort study based on prospectively registered data.

Eur J Cardiothorac Surg 2021 Mar 30. Epub 2021 Mar 30.

Department of Cardiothoracic Surgery, Maastricht University Medical Center (MUMC+), Maastricht, Netherlands.

Objectives: Although in both the US and European guidelines the 'heart team approach' is a class I recommendation, supporting evidence is still lacking. Therefore, we sought to provide comparative survival data of patients with mitral valve disease referred to the general and the dedicated heart team.

Methods: In this retrospective cohort, patients evaluated for mitral valve disease by a general heart team (2009-2014) and a dedicated mitral valve heart team (2014-2018) were included. Decision-making was recorded prospectively in heart team electronic forms. The end point was overall survival from decision of the heart team.

Results: In total, 1145 patients were included of whom 641 (56%) were discussed by dedicated heart team and 504 (44%) by general heart team. At 5 years, survival probability was 0.74 [95% confidence interval (CI) 0.68-0.79] for the dedicated heart team group compared to 0.70 (95% CI 0.66-0.74, P = 0.040) for the general heart team. Relative risk of mortality adjusted for EuroSCORE II, treatment groups (surgical, transcatheter and non-intervention), mitral valve pathology (degenerative, functional, rheumatic and others) and 13 other baseline characteristics for patients in the dedicated heart team was 29% lower [hazard ratio (HR) 0.71, 95% CI 0.54-0.95; P = 0.019] than for the general heart team. The adjusted relative risk of mortality was 61% lower for patients following the advice of the heart team (HR 0.39, 95% CI 0.25-0.62; P < 0.001) and 43% lower for patients following the advice of the general heart team (HR 0.57, 95% CI 0.37-0.87; P = 0.010) compared to those who did not follow the advice of the heart team.

Conclusions: In this retrospective cohort, patients treated for mitral valve disease based on a dedicated heart team decision have significantly higher survival independent of the allocated treatment, mitral valve pathology and baseline characteristics.
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http://dx.doi.org/10.1093/ejcts/ezab065DOI Listing
March 2021

Cardiovascular magnetic resonance accurately detects obstructive coronary artery disease in suspected non-ST elevation myocardial infarction: a sub-analysis of the CARMENTA Trial.

J Cardiovasc Magn Reson 2021 Mar 22;23(1):40. Epub 2021 Mar 22.

Department of Cardiology, Maastricht UMC+, Maastricht, The Netherlands.

Background: Invasive coronary angiography (ICA) is still the reference test in suspected non-ST elevation myocardial infarction (NSTEMI), although a substantial number of patients do not have obstructive coronary artery disease (CAD). Early cardiovascular magnetic resonance (CMR) may be a useful gatekeeper for ICA in this setting. The main objective was to investigate the accuracy of CMR to detect obstructive CAD in NSTEMI.

Methods: This study is a sub-analysis of a randomized controlled trial investigating whether a non-invasive imaging-first strategy safely reduced the number of ICA compared to routine clinical care in suspected NSTEMI (acute chest pain, non-diagnostic electrocardiogram, high sensitivity troponin T > 14 ng/L), and included 51 patients who underwent CMR prior to ICA. A stepwise approach was used to assess the diagnostic accuracy of CMR to detect (1) obstructive CAD (diameter stenosis ≥ 70% by ICA) and (2) an adjudicated final diagnosis of acute coronary syndrome (ACS). First, in all patients the combination of cine, T2-weighted and late gadolinium enhancement (LGE) imaging was evaluated for the presence of abnormalities consistent with a coronary etiology in any sequence. Hereafter and only when the scan was normal or equivocal, adenosine stress-perfusion CMR was added.

Results: Of 51 patients included (63 ± 10 years, 51% male), 34 (67%) had obstructive CAD by ICA. The sensitivity, specificity and overall accuracy of the first step to diagnose obstructive CAD were 79%, 71% and 77%, respectively. Additional vasodilator stress-perfusion CMR was performed in 19 patients and combined with step one resulted in an overall sensitivity of 97%, specificity of 65% and accuracy of 86%. Of the remaining 17 patients with non-obstructive CAD, 4 (24%) had evidence for a myocardial infarction on LGE, explaining the modest specificity. The sensitivity, specificity and overall accuracy to diagnose ACS (n = 43) were 88%, 88% and 88%, respectively.

Conclusion: CMR accurately detects obstructive CAD and ACS in suspected NSTEMI. Non-obstructive CAD is common with CMR still identifying an infarction in almost one-quarter of patients. CMR should be considered as an early diagnostic approach in suspected NSTEMI.

Trial Registration: The CARMENTA trial has been registered at ClinicalTrials.gov with identifier NCT01559467.
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http://dx.doi.org/10.1186/s12968-021-00723-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7983380PMC
March 2021

Pulmonary vein isolation in a real-world population does not influence QTc interval.

Europace 2021 Mar;23(Supplement_1):i48-i54

Department of Biomedical Engineering, Cardiovascular Research Institute Maastricht (CARIM), Maastricht University, PO Box 616, 6200 MD Maastricht, The Netherlands.

Aims: We aimed to examine whether routine pulmonary vein isolation (PVI) induces significant ventricular repolarization changes as suggested earlier.

Methods And Results: Five-minute electrocardiograms were recorded at hospital's admission (T-1d), 1 day after the PVI-procedure (T+1d) and at 3 months post-procedure (T+3m) from a registry of consecutive atrial fibrillation (AF) patients scheduled for routine PVI with different PVI modalities (radiofrequency, cryo-ablation, and hybrid). Only patients who were in sinus rhythm at all three recordings (n = 117) were included. QT-intervals and QT-dispersion were evaluated with custom-made software and QTc was calculated using Bazett's, Fridericia's, Framingham's, and Hodges' formulas. Both QT- and RR-intervals were significantly shorter at T+1d (399 ± 37 and 870 ± 141 ms) and T+3m (407 ± 36 and 950 ± 140 ms) compared with baseline (417 ± 36 and 1025 ± 164 ms). There was no statistically significant within-subject difference in QTc Fridericia (T-1d 416 ± 28 ms, T+1d 419 ± 33 ms, and T+3m 414 ± 25 ms) and QT-dispersion (T-1d 18 ± 12 ms, T+1d 21 ± 19 ms, and T+3m 17 ± 12 ms) between the recordings. A multiple linear regression model with age, sex, AF type, ablation technique, first/re-do ablation, and AF recurrence to predict the change in QTc at T+3m with respect to QTc at T-1d did not reach significance which indicates that the change in QTc does not differ between all subgroups (age, sex, AF type, ablation technique, first/re-do ablation, and AF recurrence).

Conclusion: Based on our data a routine PVI does not result in a prolongation of QTc in a real-world population. These findings, therefore, suggest that there is no need to intensify post-PVI QT-interval monitoring.
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http://dx.doi.org/10.1093/europace/euaa390DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7943360PMC
March 2021

Both beat-to-beat changes in RR-interval and left ventricular filling time determine ventricular function during atrial fibrillation.

Europace 2021 Mar;23(Supplement_1):i21-i28

Department of Biomedical Engineering, Cardiovascular Research Institute Maastricht, Maastricht University, PO Box 616, 6200 MD Maastricht, Netherlands.

Aims: The irregular atrial electrical activity during atrial fibrillation (AF) is associated with a variable left ventricular (LV) systolic function. The mechanisms determining LV function during AF remain incompletely understood. We aimed at elucidating how changes in RR-interval and LV preload affect LV function during AF.

Methods And Results: Beat-to-beat speckle-tracking echocardiography was performed in 10 persistent AF patients. We evaluated the relation between longitudinal LV peak strain and preceding RR-interval during AF. We used the CircAdapt computational model to evaluate beat-to-beat preload and peak strain during AF for each patient by imposing the patient-specific RR-interval sequences and a non-contractile atrial myocardium. Generic simulations with artificial RR-interval sequences quantified the haemodynamic changes induced by sudden irregular beats. Clinical data and simulations both showed a larger sensitivity of peak strain to changes in preceding RR-interval at slow heart rate (HR) (cycle length, CL <750 ms) than at faster HR. Simulations explained this by a difference in preload of the current beat. Generic simulations confirmed a larger sensitivity of peak strain to preceding RR-interval at fast HR (CL = 600 ms: Δ peak strain = 3.7% vs. 900 ms: Δ peak strain = 0.3%) as in the patients. They suggested that longer LV activation with respect to preceding RR-interval is determinant for this sensitivity.

Conclusions: During AF, longitudinal LV peak strain is highly variable, particularly at fast HR. Beat-to-beat changes in preload explain the differences in LV systolic function. Simulations revealed that a reduced diastolic LV filling time can explain the increased variability at fast HR.
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http://dx.doi.org/10.1093/europace/euaa387DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7943365PMC
March 2021

On-Demand Mobile Health Infrastructure for Remote Rhythm Monitoring within a Wait-and-See Strategy for Recent-Onset Atrial Fibrillation: TeleWAS-AF.

Cardiology 2021 Mar 18:1-5. Epub 2021 Mar 18.

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

Recently, we introduced the TeleCheck-AF approach, an on-demand mobile health (mHealth) infrastructure using app-based heart rate and rhythm monitoring for 7 days, to support long-term atrial fibrillation (AF) management through teleconsultation. Herein, we extend the mHealth approach to patients with recent-onset AF at the emergency department (ED). In the proposed TeleWAS-AF approach, on-demand heart rate and rhythm monitoring are used to support a wait-and-see strategy at the ED. All stable patients who present to the ED with recent-onset symptomatic AF and who are able to use mHealth solutions for heart rate and rhythm monitoring are eligible for this approach. Patients will receive both education on AF and instructions on the use of the mHealth technology before discharge from the ED. A case coordinator will subsequently check whether patients are able to activate the mHealth solution and to perform heart rate and rhythm measurements. Forty hours after AF onset, the first assessment teleconsultation with the physician will take place, determining the need for delayed cardioversion. After maximal 7 days of remote monitoring, a second assessment teleconsultation may occur, in which the rhythm can be reassessed and further treatment strategy can be discussed with the patients. This on-demand mHealth prescription increases patient involvement in the care process and treatment decision-making by encouraging self-management, while avoiding excess data-load requiring work-intensive and expensive data management. Implementation of the TeleWAS-AF approach may facilitate the management of AF in the ED and reduce the burden on the ED system, which enhances the capacity for health care utilization.
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http://dx.doi.org/10.1159/000514156DOI Listing
March 2021

Association of low-voltage areas with the regional wall deformation and the left atrial shape in patients with atrial fibrillation: A proof of concept study.

Int J Cardiol Heart Vasc 2021 Apr 26;33:100730. Epub 2021 Feb 26.

University of Pittsburgh, Pittsburgh, PA, USA.

Background: Left atrium (LA) remodeling is associated with atrial fibrillation (AF) and reduced success after AF ablation, but its relation with low-voltage areas (LVA) is not known. This study aimed to evaluate the relation between regional LA changes and LVAs in AF patients.

Methods: Pre-interventional CT data of patients (n = 24) with LA-LVA (<0.5 mV) in voltage mapping after AF ablation were analyzed (Surgery Explorer, QuantMD LLC). To quantify asymmetry (ASI = LA-A/LAV) a cutting plane parallel to the rear wall and along the pulmonary veins divided the LA-volume (LAV) into anterior (LA-A) and posterior parts. To quantify sphericity (LAS = 1-R/S), a patient-specific best-fit LA sphere was created. The average radius (R) and the mean deviation (S) from this sphere were calculated. The average local deviation (D) was measured for the roof, posterior, septum, inferior septum, inferior-posterior and lateral walls.

Results: The roof, posterior and septal regions had negative local deviations. There was a correlation between roof and septum (r = 0.42, p = 0.04), lateral and inferior-posterior (r = 0.48, p = 0.02) as well as posterior and inferior-septal deviations (r = -0.41, p = 0.046). ASI correlated with septum deformation (r = -0.43, p = 0.04). LAS correlated with dilatation (LAV, r = 0.49, p = 0.02), roof (r = 0.52, p = 0.009) and posterior deformation (r = -0.56, p = 0.005). Extended LVA correlated with local deformation of all LA walls, except the roof and the septum. LVA association with LAV, ASI and LAS did not reach statistical significance.

Conclusion: Extended LVA correlates with local wall deformations better than other remodeling surrogates. Therefore, their calculation could help predict LVA presence and deserve further evaluation in clinical studies.
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http://dx.doi.org/10.1016/j.ijcha.2021.100730DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7933256PMC
April 2021

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

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

Institute of Cardiovascular Sciences, University of Birmingham, UK.

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

Risk Factors for Atrial Fibrillation Progression.

Card Electrophysiol Clin 2021 03 8;13(1):201-209. Epub 2021 Jan 8.

Department of Cardiology, CARIM School for Cardiovascular Diseases, Maastricht University Medical Center+, PO Box 5800, Maastricht 6202 AZ, The Netherlands. Electronic address:

Atrial fibrillation is a chronic, progressive condition that presents a major health burden. This review summarizes recent studies assessing atrial fibrillation progression and its associated risk factors, describes the mechanisms underlying atrial fibrillation progression, and discusses the clinical implications of the progressive nature of atrial fibrillation. Progression of atrial fibrillation burden, and clinical progression from paroxysmal to more advanced (persistent/permanent) forms is common, but progression rates are variable. Atrial fibrillation progression parallels progressive atrial remodeling induced by atrial fibrillation risk factors and atrial fibrillation itself, and is associated with worse clinical outcomes.
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http://dx.doi.org/10.1016/j.ccep.2020.10.011DOI Listing
March 2021

Research Priorities in Atrial Fibrillation Screening: A Report From a National Heart, Lung, and Blood Institute Virtual Workshop.

Circulation 2021 Jan 25;143(4):372-388. Epub 2021 Jan 25.

Division of Cardiology and Duke Clinical Research Institute, Duke University Medical Center, Durham, NC (R.D.L., J.P.P., S.M.A.-K.).

Clinically recognized atrial fibrillation (AF) is associated with higher risk of complications, including ischemic stroke, cognitive decline, heart failure, myocardial infarction, and death. It is increasingly recognized that AF frequently is undetected until complications such as stroke or heart failure occur. Hence, the public and clinicians have an intense interest in detecting AF earlier. However, the most appropriate strategies to detect undiagnosed AF (sometimes referred to as subclinical AF) and the prognostic and therapeutic implications of AF detected by screening are uncertain. Our report summarizes the National Heart, Lung, and Blood Institute's virtual workshop focused on identifying key research priorities related to AF screening. Global experts reviewed major knowledge gaps and identified critical research priorities in the following areas: (1) role of opportunistic screening; (2) AF as a risk factor, risk marker, or both; (3) relationship between AF burden detected with long-term monitoring and outcomes/treatments; (4) designs of potential randomized trials of systematic AF screening with clinically relevant outcomes; and (5) role of AF screening after ischemic stroke. Our report aims to inform and catalyze AF screening research that will advance innovative, resource-efficient, and clinically relevant studies in diverse populations to improve the diagnosis, management, and prognosis of patients with undiagnosed AF.
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http://dx.doi.org/10.1161/CIRCULATIONAHA.120.047633DOI Listing
January 2021

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

Characteristics of patients with atrial fibrillation prescribed edoxaban in Belgium and The Netherlands: insights from the ETNA-AF-Europe study.

Acta Cardiol 2021 Jan 7:1-9. Epub 2021 Jan 7.

Department of Cardiology, Amsterdam Medical Centres/University of Amsterdam, Amsterdam, The Netherlands.

Background: Studies on the use of non-vitamin K antagonist oral anticoagulants in unselected patients with atrial fibrillation (AF) show that clinical characteristics and dosing practices differ per region, but lack data on edoxaban.

Methods: With data from Edoxaban Treatment in routiNe clinical prActice for patients with AF in Europe (ETNA-AF-Europe), a large prospective observational study, we compared clinical characteristics (including the dose reduction criteria for edoxaban: creatinine clearance 15-50 mL/min, weight ≤60 kg, and/or use of strong p-glycoprotein inhibitors) of patients from Belgium and the Netherlands (BeNe) with those from other European countries (OEC).

Results: Of all 13,639 patients in ETNA-AF-Europe, 2579 were from BeNe. BeNe patients were younger than OEC patients (mean age: 72.3 vs 73.9 years), and had lower CHADS-VASc (mean: 2.8 vs 3.2) and HAS-BLED scores (mean: 2.4 vs 2.6). Patients from BeNe less often had hypertension (61.6% vs 80.4%), and/or diabetes mellitus (17.3% vs 23.1%) than patients from OEC. Moreover, relatively fewer patients in BeNe were prescribed the reduced dose of 30 mg edoxaban (14.8%) than in OEC (25.4%). Overall, edoxaban was dosed according to label in 83.1% of patients. Yet, 30 mg edoxaban was prescribed in the absence of any dose reduction criteria in 36.9% of 30 mg users (5.5% of all patients) in BeNe compared with 35.5% (9.0% of all patients) in OEC.

Conclusion: There were several notable differences between BeNe and OEC regarding clinical characteristics and dosing practices in patients prescribed edoxaban, which are relevant for the local implementation of dose evaluation and optimisation.

Trial Registration: NCT02944019; Date of registration: October 24, 2016.
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http://dx.doi.org/10.1080/00015385.2020.1746095DOI Listing
January 2021

The year in cardiovascular medicine 2020: arrhythmias.

Eur Heart J 2021 Feb;42(5):499-507

Cardiovascular Institute, Hospital Clinic, Pediatric Arrhythmia Unit, Hospital Sant Joan de Déu, University of Barcelona, Barcelona, Spain.

of the progress in arrhythmias in 2020. RACE4 and ALL-IN indicated that integrated nurse-led care improves outcomes in AF patients.3,4 The same was reported for early rhythm control therapy15 and cryoablation as initial AF treatment.25,26 Subcutaneous ICD was non-inferior to classical transvenous ICD therapy in PRAETORIAN.54 One mechanistic study showed that autoantibodies against misexpressed actin, keratin, and connexin-43 proteins create a blood-borne biomarker profile enhancing diagnosis of Brugada syndrome.50 Another mechanistic study indicated that transseptal LV pacing yields similar improvement in contractility as His bundle pacing whilst being more easy to execute.44 In PRE-DETERMINE a simple-to-use ECG risk score improved risk prediction in patients with ischemic heart disease possibly enhancing appropriate ICD therapy in high risk patients.58.
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http://dx.doi.org/10.1093/eurheartj/ehaa1091DOI Listing
February 2021

Pacing for repeated vagal reflex-mediated syncope: an old problem with a solution.

Eur Heart J 2021 Feb;42(5):517-519

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

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http://dx.doi.org/10.1093/eurheartj/ehaa975DOI Listing
February 2021

Data on sex differences in one-year outcomes of out-of-hospital cardiac arrest patients without ST-segment elevation.

Data Brief 2020 Dec 12;33:106521. Epub 2020 Nov 12.

Department of Cardiology, Amsterdam University Medical Center, location VUmc, Amsterdam, the Netherlands.

Sex differences in out-of-hospital cardiac arrest (OHCA) patients are increasingly recognized. Although it has been found that post-resuscitated women are less likely to have significant coronary artery disease (CAD) than men, data on follow-up in these patients are limited. Data for this data in brief article was obtained as a part of the randomized controlled Coronary Angiography after Cardiac Arrest without ST-segment elevation (COACT) trial. The data supplements the manuscript "Sex differences in out-of-hospital cardiac arrest patients without ST-segment elevation: A COACT trial substudy" were it was found that women were less likely to have significant CAD including chronic total occlusions, and had worse survival when CAD was present. The dataset presented in this paper describes sex differences on interventions, implantable-cardioverter defibrillator (ICD) shocks and hospitalizations due to heart failure during one-year follow-up in patients successfully resuscitated after OHCA. Data was derived through a telephone interview at one year with the patient or general practitioner. Patients in this randomized dataset reflects a homogenous study population, which can be valuable to further build on research regarding long-term sex differences and to further improve cardiac care.
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http://dx.doi.org/10.1016/j.dib.2020.106521DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7691722PMC
December 2020

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 Feb;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

Left atrial activation and asymmetric anatomical remodeling in patients with atrial fibrillation: The relation between anatomy and function.

Clin Cardiol 2021 Jan 17;44(1):116-122. Epub 2020 Nov 17.

Department of Electrophysiology, Heart Center at University of Leipzig, Leipzig, Germany.

Background: Identifying patients with advanced left atrial (LA) remodeling before catheter ablation (CA) of atrial fibrillation (AF) is crucial.

Hypothesis: This study aimed to identify echocardiographic parameters associated with changes in anatomy and conduction properties of the left atrium (LA).

Methods: We examined 75 AF patients prior to CA and measured the intervals from the P-wave-onset to four mitral annulus sites by pulsed-wave tissue Doppler imaging (PW-TDI). Patients were grouped to an upward U-pattern (delayed anterior activation) and a downward D-pattern (earliest LA activation anterior). CT-data were used to measure the LA volume (LAV). LAV was divided into anterior- (LA-A) and posterior-parts by a plane, parallel to the posterior wall and between the veins and the appendage, to calculate the asymmetry index (ASI = LA-A/LAV).

Results: Patients with U-pattern (n = 66) had a higher ASI (65 ± 6 vs. 61 ± 3%, p = .014), older age (61 ± 11 vs. 51 ± 11 years, p = .03) and more diastolic dysfunction (71 vs. 22%, p = .008) Multivariate regression showed that age (OR 1.1 per year, CI 1.007-1.199) and diastolic dysfunction (OR 6.36, CI 1.132-35.7, p = .036) were independent predictors of the U-pattern. Diastolic dysfunction (B 4.49, CI 1.61-7.37, p = .003) was the only independent predictor of ASI in linear regression analysis.

Conclusion: AF patients with a U-pattern have an increased LA asymmetry. Diastolic dysfunction is a common cause of this LA activation and remodeling. Therefore, detection of a U-pattern signifies patients with advanced AF and may facilitate selection for an appropriate ablation strategy.
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http://dx.doi.org/10.1002/clc.23515DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7803371PMC
January 2021

Sex differences in patients with out-of-hospital cardiac arrest without ST-segment elevation: A COACT trial substudy.

Resuscitation 2021 Jan 12;158:14-22. Epub 2020 Nov 12.

Department of Cardiology, Amsterdam University Medical Centre, location VUmc, Amsterdam, the Netherlands; Department of Cardiology, Radboud University Medical Centre, Nijmegen, the Netherlands.

Background: Whether sex is associated with outcomes of out-of-hospital cardiac arrest (OHCA) is unclear.

Objectives: This study examined sex differences in survival in patients with OHCA without ST-segment elevation myocardial infarction (STEMI).

Methods: Using data from the randomized controlled Coronary Angiography after Cardiac Arrest (COACT) trial, the primary point of interest was sex differences in OHCA-related one-year survival. Secondary points of interest included the benefit of immediate coronary angiography compared to delayed angiography until after neurologic recovery, angiographic and clinical outcomes.

Results: In total, 522 patients (79.1% men) were included. Overall one-year survival was 59.6% in women and 63.4% in men (HR 1.18; 95% CI: 0.76-1.81;p = 0.47). No cardiovascular risk factors were found that modified survival. Women less often had significant coronary artery disease (CAD) (37.0% vs. 71.3%;p < 0.001), but when present, they had a worse prognosis than women without CAD (HR 3.06; 95% CI 1.31-7.19;p = 0.01). This was not the case for men (HR 1.05; 95% CI 0.67-1.65;p = 0.83). In both sexes, immediate coronary angiography did not improve one-year survival compared to delayed angiography (women, odds ratio (OR) 0.87; 95% CI 0.58-1.30;p = 0.49; vs. men, OR 0.97; 95% CI 0.45-2.09;p = 0.93).

Conclusion: In OHCA patients without STEMI, we found no sex differences in overall one-year survival. Women less often had significant CAD, but when CAD was present they had worse survival than women without CAD. This was not the case for men. Both sexes did not benefit from a strategy of immediate coronary angiography as compared to delayed strategy with respect to one-year survival.

Clinical Trial Registration Number: Netherlands trial register (NTR) 4973.
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http://dx.doi.org/10.1016/j.resuscitation.2020.10.026DOI Listing
January 2021

On-demand mobile health infrastructures to allow comprehensive remote atrial fibrillation and risk factor management through teleconsultation.

Clin Cardiol 2020 Nov 8;43(11):1232-1239. Epub 2020 Oct 8.

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

Background: Although novel teleconsultation solutions can deliver remote situations that are relatively similar to face-to-face interaction, remote assessment of heart rate and rhythm as well as risk factors remains challenging in patients with atrial fibrillation (AF).

Hypothesis: Mobile health (mHealth) solutions can support remote AF management.

Methods: Herein, we discuss available mHealth tools and strategies on how to incorporate the remote assessment of heart rate, rhythm and risk factors to allow comprehensive AF management through teleconsultation.

Results: Particularly, in the light of the coronavirus disease 2019 (COVID-19) pandemic, there is decreased capacity to see patients in the outpatient clinic and mHealth has become an important component of many AF outpatient clinics. Several validated mHealth solutions are available for remote heart rate and rhythm monitoring as well as for risk factor assessment. mHealth technologies can be used for (semi-)continuous longitudinal monitoring or for short-term on-demand monitoring, dependent on the respective requirements and clinical scenarios. As a possible solution to improve remote AF care through teleconsultation, we introduce the on-demand TeleCheck-AF mHealth approach that allows remote app-based assessment of heart rate and rhythm around teleconsultations, which has been developed and implemented during the COVID-19 pandemic in Europe.

Conclusion: Large scale international mHealth projects, such as TeleCheck-AF, will provide insight into the additional value and potential limitations of mHealth strategies to remotely manage AF patients. Such mHealth infrastructures may be well suited within an integrated AF-clinic, which may require redesign of practice and reform of health care systems.
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http://dx.doi.org/10.1002/clc.23469DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7661648PMC
November 2020

Cardiac Inflammation Impedes Response to Cardiac Resynchronization Therapy in Patients With Idiopathic Dilated Cardiomyopathy.

Circ Arrhythm Electrophysiol 2020 11 30;13(11):e008727. Epub 2020 Sep 30.

Cardiovascular Research Institute (CARIM), Departments of Cardiology (J.A.J.V., J.J.M., A.M.W.v.S., M.T.H.M.H., V.P.M.v.E., C.K., J.G.L.M.L., H.J.G.M.C., H.-P.B.-L.R., K.V., S.R.B.H., M.R.H.), Maastricht University Medical Center, the Netherlands.

Background: Cardiac resynchronization therapy (CRT) is an established therapy in patients with dilated cardiomyopathy (DCM) and conduction disorders. Still, one-third of the patients with DCM do not respond to CRT. This study aims to depict the underlying cardiac pathophysiological processes of nonresponse to CRT in patients with DCM using endomyocardial biopsies.

Methods: Within the Maastricht and Innsbruck registries of patients with DCM, 99 patients underwent endomyocardial biopsies before CRT implantation, with histological quantification of fibrosis and inflammation, where inflammation was defined as >14 infiltrating cells/mm. Echocardiographic left ventricular end-systolic volume reduction ≥15% after 6 months was defined as response to CRT. RNA was isolated from cardiac biopsies of a representative subset of responders and nonresponders.

Results: Sixty-seven patients responded (68%), whereas 32 (32%) did not respond to CRT. Cardiac inflammation before implantation was negatively associated with response to CRT (25% of responders, 47% of nonresponders; odds ratio 0.3 [0.12-0.76]; =0.01). Endomyocardial biopsies fibrosis did not relate to CRT response. Cardiac inflammation improved the robustness of prediction beyond well-known clinical predictors of CRT response (likelihood ratio test <0.001). Cardiac transcriptomic profiling of endomyocardial biopsies reveals a strong proinflammatory and profibrotic signature in the hearts of nonresponders compared with responders. In particular, , and were significantly higher expressed in the hearts of nonresponders.

Conclusions: Cardiac inflammation along with a transcriptomic profile of high expression of combined proinflammatory and profibrotic genes are associated with a poor response to CRT in patients with DCM.
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http://dx.doi.org/10.1161/CIRCEP.120.008727DOI Listing
November 2020

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

Association of ECG characteristics with clinical and echocardiographic outcome to CRT in a non-LBBB patient population.

J Interv Card Electrophysiol 2020 Sep 12. Epub 2020 Sep 12.

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

Purpose: Effectiveness of cardiac resynchronization therapy (CRT) in patients without left bundle branch block (non-LBBB) QRS morphology is limited. Additional selection criteria are needed to identify these patients.

Methods: Seven hundred ninety consecutive patients with non-LBBB morphology, who received a CRT-device in 3 university centers in the Netherlands, were selected. Pre-implantation 12-lead ECGs were evaluated on morphology, duration, and area of the QRS complex, as well as on PR interval, left ventricular activation time (LVAT), and the presence of fragmented QRS (fQRS). Association of these ECG features with the primary endpoint: a combination of left ventricular assist device (LVAD) implantation, cardiac transplantation and all-cause mortality, and secondary endpoint-echocardiographic reduction of left ventricular end-systolic volume (LVESV)-were evaluated.

Results: The primary endpoint occurred more often in non-LBBB patients with with PR interval ≥ 230ms, QRS area < 109μVs, and with fQRS. Multivariable regression analysis showed independent associations of QRS area (HR 2.33 [1.44, 3.77], p = 0.001) and PR interval (HR 2.03 [1.51, 2.74], p < 0.001) only. Mean LVESV reduction was significantly lower in patients with baseline RBBB, QRS duration < 150 ms, PR interval ≥ 230 ms, and in QRS area < 109 μVs. Multivariable regression analyses only showed significant associations between QRS area ≥ 109 μVs (OR 2.00 [1.09, 3.66] p = 0.025) and probability of echocardiographic response to CRT.

Conclusions: In the heterogeneous non-LBBB patient population, QRS area and PR prolongation rather than traditional QRS duration and morphology are associated to both clinical and echocardiographic outcomes of CRT.
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http://dx.doi.org/10.1007/s10840-020-00866-zDOI Listing
September 2020

Implementation of an on-demand app-based heart rate and rhythm monitoring infrastructure for the management of atrial fibrillation through teleconsultation: TeleCheck-AF.

Europace 2021 03;23(3):345-352

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

During the coronavirus 2019 (COVID-19) pandemic, outpatient visits in the atrial fibrillation (AF) clinic of the Maastricht University Medical Centre (MUMC+) were transferred into teleconsultations. The aim was to develop anon-demand app-based heart rate and rhythm monitoring infrastructure to allow appropriatmanagement of AF through teleconsultation. In line with the fundamental aspects of integrated care, including actively involving patients in the care process and providing comprehensive care by a multidisciplinary team, we implemented a mobile health (mHealth) intervention to support teleconsultations with AF patients: TeleCheck-AF. The TeleCheck-AF approach guarantees the continuity of comprehensive AF management and supports integrated care through teleconsultation during COVID-19. It incorporates three important components: (i) a structured teleconsultation ('Tele'), (ii) a CE-marked app-based on-demand heart rate and rhythm monitoring infrastructure ('Check'), and (iii) comprehensive AF management ('AF'). In this article, we describe the components and implementation of the TeleCheck-AF approach in an integrated and specialized AF-clinic through teleconsultation. The TeleCheck-AF approach is currently implemented in numerous European centres during COVID-19.
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http://dx.doi.org/10.1093/europace/euaa201DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7499572PMC
March 2021

Coronary Angiography After Cardiac Arrest Without ST Segment Elevation: One-Year Outcomes of the COACT Randomized Clinical Trial.

JAMA Cardiol 2020 Sep 2. Epub 2020 Sep 2.

Department of Cardiology, Amsterdam University Medical Center, location VUmc, Amsterdam, the Netherlands.

Importance: Ischemic heart disease is a common cause of cardiac arrest. However, randomized data on long-term clinical outcomes of immediate coronary angiography and percutaneous coronary intervention (PCI) in patients successfully resuscitated from cardiac arrest in the absence of ST segment elevation myocardial infarction (STEMI) are lacking.

Objective: To determine whether immediate coronary angiography improves clinical outcomes at 1 year in patients after cardiac arrest without signs of STEMI, compared with a delayed coronary angiography strategy.

Design, Setting, And Participants: A prespecified analysis of a multicenter, open-label, randomized clinical trial evaluated 552 patients who were enrolled in 19 Dutch centers between January 8, 2015, and July 17, 2018. The study included patients who experienced out-of-hospital cardiac arrest with a shockable rhythm who were successfully resuscitated without signs of STEMI. Follow-up was performed at 1 year. Data were analyzed, using the intention-to-treat principle, between August 29 and October 10, 2019.

Interventions: Immediate coronary angiography and PCI if indicated or coronary angiography and PCI if indicated, delayed until after neurologic recovery.

Main Outcomes And Measures: Survival, myocardial infarction, revascularization, implantable cardiac defibrillator shock, quality of life, hospitalization for heart failure, and the composite of death or myocardial infarction or revascularization after 1 year.

Results: At 1 year, data on 522 of 552 patients (94.6%) were available for analysis. Of these patients, 413 were men (79.1%); mean (SD) age was 65.4 (12.3) years. A total of 162 of 264 patients (61.4%) in the immediate angiography group and 165 of 258 patients (64.0%) in the delayed angiography group were alive (odds ratio, 0.90; 95% CI, 0.63-1.28). The composite end point of death, myocardial infarction, or repeated revascularization since the index hospitalization was met in 112 patients (42.9%) in the immediate group and 104 patients (40.6%) in the delayed group (odds ratio, 1.10; 95% CI, 0.77-1.56). No significant differences between the groups were observed for the other outcomes at 1-year follow-up. For example, the rate of ICD shocks was 20.4% in the immediate group and 16.2% in the delayed group (odds ratio, 1.32; 95% CI, 0.66-2.64).

Conclusions And Relevance: In this trial of patients successfully resuscitated after out-of-hospital cardiac arrest and without signs of STEMI, a strategy of immediate angiography was not found to be superior to a strategy of delayed angiography with respect to clinical outcomes at 1 year. Coronary angiography in this patient group can therefore be delayed until after neurologic recovery without affecting outcomes.

Trial Registration: trialregister.nl Identifier: NTR4973.
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http://dx.doi.org/10.1001/jamacardio.2020.3670DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7489423PMC
September 2020

Early Rhythm-Control Therapy in Patients with Atrial Fibrillation.

N Engl J Med 2020 10 29;383(14):1305-1316. Epub 2020 Aug 29.

From the Department of Cardiology, University Heart and Vascular Center (P.K.), and Institute of Medical Biometry and Epidemiology (A.S., E.V., K.W.), University Medical Center Hamburg-Eppendorf, LANS Cardio (K.-H.K.), and the Department of Cardiology, Asklepios Klinik St. Georg (S.W.), Hamburg, Atrial Fibrillation Network (AFNET) (P.K., A.G., L.E., T.F., D.H., K.-H.K., N.S., U.S., J.T., K.W., S.W., G.B.) and the Department of Cardiology II (Electrophysiology), University Hospital Münster (L.E., G.B.), Münster, the German Center of Cardiovascular Research, Partner Site Hamburg/Lübeck/Kiel (P.K., K.W., S.W.), St. Vincenz Hospital, Paderborn (A.G.), the Working Group of Molecular Electrophysiology, University Hospital Magdeburg, Magdeburg (A.G.), the Clinical Research Institute, Munich (T.F.), Hospital Konstanz, Konstanz (F.H.), the Department of Cardiology and Electrophysiology, University Heart Center-Helios, and Leipzig Heart Institute, Leipzig (G.H.), University Heart Center Schleswig-Holstein, Campus Lübeck, Lübeck (K.-H.K.), Cardiology Practice Schön, Mühldorf (N.S.), and Cardiology Practice Taggeselle, Markkleeberg (J.T.) - all in Germany; the Institute of Cardiovascular Sciences, University of Birmingham, Birmingham (P.K.), the Cardiology Clinical Academic Group, Molecular and Clinical Sciences Research Institute, St. George's University of London, London (A.J.C.), and the Department of Cardiovascular Sciences, University of Leicester, National Institute for Health Research Leicester Biomedical Research Centre, Glenfield Hospital, Leicester (G.A.N.) - all in the United Kingdom; the Department of Cardiology, Odense University Hospital, and Department of Clinical Research, University of Southern Denmark, Odense (A.B.); Isala Hospital and Diagram B.V., Zwolle (A.E.), the University of Groningen, University Medical Center Groningen, Groningen (I.C.G.), and the Department of Physiology, Cardiovascular Research Institute Maastricht (U.S.), and the Department of Cardiology, Maastricht University Medical Center and Cardiovascular Research Institute Maastricht (H.J.G.M.C.), Maastricht - all in the Netherlands; University Hospital Zurich, Zurich (L.M.H.), and the Division of Cardiology, Medical University Department, Kantonsspital Aarau, Aarau (L.M.H.) - both in Switzerland; University Hospital Antwerp and Antwerp University, Antwerp, Belgium (H.H.); the Institute for Clinical and Experimental Medicine, Prague, Czech Republic (J.K.); the Hospital Clinic, University of Barcelona and Institut de Recerca Biomèdica, August Pi-Sunyer, Barcelona (L.M.), and Centro Investigación Biomedica en Red Cardiovascular, Madrid (L.M.); Department of Cardiology, Hospital Wojewódzka Stacja Pogotowia Ratunkowego i Transportu Sanitarnego (WSRiTS) Meditrans, Warsaw, Poland (J.R.); the Department of Cardiology, Ospedale dell'Angelo, Venice, Italy (S.T.); and Heart Sector, Hygeia Hospitals Group, Athens (P.V.).

Background: Despite improvements in the management of atrial fibrillation, patients with this condition remain at increased risk for cardiovascular complications. It is unclear whether early rhythm-control therapy can reduce this risk.

Methods: In this international, investigator-initiated, parallel-group, open, blinded-outcome-assessment trial, we randomly assigned patients who had early atrial fibrillation (diagnosed ≤1 year before enrollment) and cardiovascular conditions to receive either early rhythm control or usual care. Early rhythm control included treatment with antiarrhythmic drugs or atrial fibrillation ablation after randomization. Usual care limited rhythm control to the management of atrial fibrillation-related symptoms. The first primary outcome was a composite of death from cardiovascular causes, stroke, or hospitalization with worsening of heart failure or acute coronary syndrome; the second primary outcome was the number of nights spent in the hospital per year. The primary safety outcome was a composite of death, stroke, or serious adverse events related to rhythm-control therapy. Secondary outcomes, including symptoms and left ventricular function, were also evaluated.

Results: In 135 centers, 2789 patients with early atrial fibrillation (median time since diagnosis, 36 days) underwent randomization. The trial was stopped for efficacy at the third interim analysis after a median of 5.1 years of follow-up per patient. A first-primary-outcome event occurred in 249 of the patients assigned to early rhythm control (3.9 per 100 person-years) and in 316 patients assigned to usual care (5.0 per 100 person-years) (hazard ratio, 0.79; 96% confidence interval, 0.66 to 0.94; P = 0.005). The mean (±SD) number of nights spent in the hospital did not differ significantly between the groups (5.8±21.9 and 5.1±15.5 days per year, respectively; P = 0.23). The percentage of patients with a primary safety outcome event did not differ significantly between the groups; serious adverse events related to rhythm-control therapy occurred in 4.9% of the patients assigned to early rhythm control and 1.4% of the patients assigned to usual care. Symptoms and left ventricular function at 2 years did not differ significantly between the groups.

Conclusions: Early rhythm-control therapy was associated with a lower risk of adverse cardiovascular outcomes than usual care among patients with early atrial fibrillation and cardiovascular conditions. (Funded by the German Ministry of Education and Research and others; EAST-AFNET 4 ISRCTN number, ISRCTN04708680; ClinicalTrials.gov number, NCT01288352; EudraCT number, 2010-021258-20.).
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http://dx.doi.org/10.1056/NEJMoa2019422DOI Listing
October 2020

Dr Hein Wellens MD PhD.

Eur Heart J 2020 08;41(30):2832-2834

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http://dx.doi.org/10.1093/eurheartj/ehaa615DOI Listing
August 2020

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

Differentiating the effects of β-adrenergic stimulation and stretch on calcium and force dynamics using a novel electromechanical cardiomyocyte model.

Am J Physiol Heart Circ Physiol 2020 09 31;319(3):H519-H530. Epub 2020 Jul 31.

Department of Biomedical Engineering, Cardiovascular Research Institute Maastricht, Maastricht University, Maastricht, The Netherlands.

Cardiac electrophysiology and mechanics are strongly interconnected. Calcium is crucial in this complex interplay through its role in cellular electrophysiology and sarcomere contraction. We aim to differentiate the effects of acute β-adrenergic stimulation (β-ARS) and cardiomyocyte stretch (increased sarcomere length) on calcium-transient dynamics and force generation, using a novel computational model of cardiac electromechanics. We implemented a bidirectional coupling between the O'Hara-Rudy model of human ventricular electrophysiology and the MechChem model of sarcomere mechanics through the buffering of calcium by troponin. The coupled model was validated using experimental data from large mammals or human samples. Calcium transient and force were simulated for various degrees of β-ARS and initial sarcomere lengths. The model reproduced force-frequency, quick-release, and isotonic contraction experiments, validating the bidirectional electromechanical interactions. An increase in β-ARS increased the amplitudes of force (augmented inotropy) and calcium transient, and shortened both force and calcium-transient duration (lusitropy). An increase in sarcomere length increased force amplitude even more, but decreased calcium-transient amplitude and increased both force and calcium-transient duration. Finally, a gradient in relaxation along the thin filament may explain the nonmonotonic decay in cytosolic calcium observed with high tension. Using a novel coupled human electromechanical model, we identified differential effects of β-ARS and stretch on calcium and force. Stretch mostly contributed to increased force amplitude and β-ARS to the reduction of calcium and force duration. We showed that their combination, rather than individual contributions, is key to ensure force generation, rapid relaxation, and low diastolic calcium levels. This work identifies the contribution of electrical and mechanical alterations to regulation of calcium and force under exercise-like conditions using a novel human electromechanical model integrating ventricular electrophysiology and sarcomere mechanics. By better understanding their individual and combined effects, this can uncover arrhythmogenic mechanisms in exercise-like situations. This publicly available model is a crucial step toward understanding the complex interplay between cardiac electrophysiology and mechanics to improve arrhythmia risk prediction and treatment.
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http://dx.doi.org/10.1152/ajpheart.00275.2020DOI Listing
September 2020