Publications by authors named "Dominik Linz"

218 Publications

Sleep arousal burden is associated with long-term all-cause and cardiovascular mortality in 8001 community-dwelling older men and women.

Eur Heart J 2021 Apr 20. Epub 2021 Apr 20.

School of Electrical and Electronic Engineering, The University of Adelaide, Adelaide, Australia.

Aims : To quantify the arousal burden (AB) across large cohort studies and determine its association with long-term cardiovascular (CV) and overall mortality in men and women.

Methods And Results : We measured the AB on overnight polysomnograms of 2782 men in the Osteoporotic Fractures in Men Study (MrOS) Sleep study, 424 women in the Study of Osteoporotic Fractures (SOF) and 2221 men and 2574 women in the Sleep Heart Health Study (SHHS). During 11.2 ± 2.1 years of follow-up in MrOS, 665 men died, including 236 CV deaths. During 6.4 ± 1.6 years of follow-up in SOF, 105 women died, including 47 CV deaths. During 10.7 ± 3.1 years of follow-up in SHHS, 987 participants died, including 344 CV deaths. In women, multivariable Cox proportional hazard analysis adjusted for common confounders demonstrated that AB is associated with all-cause mortality [SOF: hazard ratio (HR) 1.58 (1.01-2.42), P = 0.038; SHHS-women: HR 1.21 (1.06-1.42), P = 0.012] and CV mortality [SOF: HR 2.17 (1.04-4.50), P = 0.037; SHHS-women: HR 1.60 (1.12-2.28), P = 0.009]. In men, the association between AB and all-cause mortality [MrOS: HR 1.11 (0.94-1.32), P = 0.261; SHHS-men: HR 1.31 (1.06-1.62), P = 0.011] and CV mortality [MrOS: HR 1.35 (1.02-1.79), P = 0.034; SHHS-men: HR 1.24 (0.86-1.79), P = 0.271] was less clear.

Conclusions: Nocturnal AB is associated with long-term CV and all-cause mortality in women and to a lesser extent in men.
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http://dx.doi.org/10.1093/eurheartj/ehab151DOI Listing
April 2021

Single Ring Isolation With Inferior Line Sparing for Atrial Fibrillation: A Proof-of-Concept Study.

Circ Arrhythm Electrophysiol 2021 Apr 16;14(4):e009552. Epub 2021 Apr 16.

Centre for Heart Rhythm Disorders, University of Adelaide, Australia (A.T., R.M., S.I., A.G., R.S.M., D.L., M.E., K.K., C.J.O., M.E.M., D.H.L., P.S.).

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http://dx.doi.org/10.1161/CIRCEP.120.009552DOI Listing
April 2021

Early atrial fibrillation detection and the transition to comprehensive management.

Europace 2021 Apr;23(Supplement_2):ii46-ii51

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

Current atrial fibrillation (AF) guidelines recommend screening for AF in individuals above 65 years or with other characteristics suggestive of increased stroke risk. Several mobile health (mHealth) approaches are available to identify AF. Although most wearables or ECG machines include algorithms to detect AF, an ECG confirmation of AF is necessary to establish a suspected diagnosis of AF. Early detection of AF is important to allow early initiation of AF management, and early rhythm control therapy lowered risk of adverse cardiovascular outcomes among patients with early AF aged >75 or with a CHA2DS2-VASc score ≥2 and cardiovascular conditions in the EAST-AFNET 4 study. Strategies for early AF detection should be always linked to a comprehensive work-up infrastructure organized within an integrated care pathway to allow early initiation and guidance of AF treatment in newly detected AF patients. In this review article, we summarize strategies and mHealth approaches for early AF detection and the transition to early AF management including AF symptoms evaluation and assessment of AF progression as well as AF risk factors.
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http://dx.doi.org/10.1093/europace/euaa424DOI Listing
April 2021

Twitter for professional use in electrophysiology: practical guide for #EPeeps.

Europace 2021 Mar 12. Epub 2021 Mar 12.

Hannover Heart Rhythm Center, Department of Cardiology and Angiology, Hannover Medical School, Carl-Neuberg-Straße 1, D-30625 Hannover, Germany.

Social media (SoMe) becomes more and more popular in the cardiological community. Among them, Twitter is an emerging and dynamic medium to connect, communicate and educate academic and clinical cardiologists. However, in contrast to traditional scientific communications, the content provided through SoMe is not peer-reviewed and may not necessarily always represent scientific evidence or may even be used to unjustifiably promote therapies for commercial purposes. For the unintended, this means of communication might be appear difficult to handle. This article aims to provide a practical guide on how to use Twitter efficiently for professional use to keep yourself up-to-date about new techniques, the latest study results and news presented at national or international conferences. Additionally, important limitations will be discussed.
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http://dx.doi.org/10.1093/europace/euab048DOI Listing
March 2021

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
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8083545PMC
April 2021

The walk of life: Remote monitoring provides insights into physical activity during a pandemic.

Int J Cardiol Heart Vasc 2021 Apr 1;33:100772. Epub 2021 Apr 1.

Department of Cardiology, CARIM School for Cardiovascular Diseases, Faculty of Health, Medicine, and Life Sciences, Maastricht University and Maastricht UMC+, Maastricht, the Netherlands.

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http://dx.doi.org/10.1016/j.ijcha.2021.100772DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8012064PMC
April 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

A disproportional rise in the growing submission rate to International Journal of Cardiology Heart & Vasculature during the COVID‑19 pandemic.

Int J Cardiol Heart Vasc 2021 Apr 27;33:100749. Epub 2021 Feb 27.

Institute of Pharmacology, West German Heart and Vascular Center, Faculty of Medicine, University Duisburg-Essen, Essen, Germany.

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http://dx.doi.org/10.1016/j.ijcha.2021.100749DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7957093PMC
April 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

Arrhythmogenic mechanisms of acute obstructive respiratory events in a porcine model of drug-induced long QT.

Heart Rhythm 2021 Mar 15. Epub 2021 Mar 15.

Faculty of Health and Medical Sciences, Department of Biomedical Sciences, University of Copenhagen, Copenhagen, Denmark.

Background: Obstructive sleep apnea is associated with increased risk of sudden cardiac death.

Objective: The purpose of this study was to elucidate changes in ventricular repolarization and electromechanical interaction during obstructive respiratory events simulated by intermittent negative upper airway pressure (INAP) in pigs. We also investigated the effect of a reduced repolarization reserve in drug-induced long QT (LQT) following INAP-induced changes in ventricular repolarization.

Methods: In sedated spontaneously breathing pigs, 75 seconds of INAP was applied by a negative pressure device connected to the endotracheal tube. Ventricular electromechanical coupling was determined by the electromechanical window (EMW) before (pre-INAP), during (INAP), and after INAP (post-INAP). Incidence rates of premature ventricular contractions (PVCs) were measured respectively. A drug-induced LQT was modeled by treating the pigs with the hERG1 blocker dofetilide (DOF).

Results: Whereas QT interval increased during and decreased after INAP (pre-INAP: 273 ± 5 ms; INAP 281 ± 6 ms; post-INAP 254 ± 9 ms), EMW shortened progressively throughout INAP and post-INAP periods (pre-INAP 81 ± 4 ms; post-INAP 44 ± 7 ms). DOF shortened EMW at baseline. Throughout INAP, EMW decreased in a comparable fashion as before DOF (pre-INAP/+DOF 61 ± 7 ms; post-INAP/+DOF 14 ± 9 ms) but resulted in shorter absolute EMW levels. Short EMW levels were associated with increased occurrence of PVCs (pre-INAP 7 ± 2 ms vs post-INAP 26 ± 6 ms; P = .02), which were potentiated in DOF pigs (pre-INAP/+DOF 5 ± 2 ms vs post-INAP/+DOF 40 ± 8 ms; P = .006). Administration of atenolol prevented post-INAP EMW shortening and decreased occurrence of PVCs.

Conclusion: Transient dissociation of ventricular electromechanical coupling during simulated obstructive respiratory events creates a dynamic ventricular arrhythmogenic substrate, which is sympathetically mediated and aggravated by drug-induced LQT.
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http://dx.doi.org/10.1016/j.hrthm.2021.03.017DOI Listing
March 2021

Use and misuse of instant messaging in clinical data sharing: the EHRA-SMS survey.

Europace 2021 Mar 12. Epub 2021 Mar 12.

Department of Cardiology and Angiology, Hannover Heart Rhythm Center, Hannover Medical School, Hannover, Germany.

Instant messaging (IM) enables medical professionals to quickly share clinical data to their peers for counselling. Purpose of this survey is to assess the habits related to IM, their application in clinical practice and the perceived pros and cons. An online survey was distributed to the medical community via newsletters, Twitter, LinkedIn, and Facebook. The survey consisted of 22 questions made on an individual-basis and collected anonymously on SurveyMonkey. A total of 287 subjects from 33 countries responded to the survey (mean age 43 years, 74.8% male). Of all respondents, 88.3% routinely send and 90.3% receive clinical data through IM which was second only to face-to-face contact as the preferred method for sharing clinical data. Twelve-lead electrocardiograms (88.6%), medical history (61.4%), and echo loops (55.7%) were the data shared most often. Nearly half of the clinical data that are sent (43%) or received (44%) are not anonymized. In the same way, 29.3% of the respondents were not aware of the European General Data Protection Regulation (GDPR) at the time of the survey. IM apps are used by medical professionals worldwide to share and discuss clinical data and are preferred to many other methods of data sharing, being second only to face-to-face contact. IM are often used to share many different types of clinical data, being perceived as a fast and easy way of communication. Medical professionals should be aware of the appropriate use of IM to prevent legal and privacy issues.
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http://dx.doi.org/10.1093/europace/euab063DOI Listing
March 2021

NLRP3 inflammasome is a key driver of Obesity-Induced atrial arrhythmias.

Cardiovasc Res 2021 Feb 1. Epub 2021 Feb 1.

Department of Molecular Physiology and Biophysics.

Aims: Obesity, an established risk factor of atrial fibrillation (AF), is frequently associated with enhanced inflammatory response. However, whether inflammatory signaling is causally linked to AF pathogenesis in obesity remains elusive. We recently demonstrated that the constitutive activation of the 'NACHT, LRR & PYD Domains-containing Protein 3' (NLRP3) inflammasome promotes AF susceptibility. In this study, we hypothesized that the NLRP3 inflammasome is a key driver of obesity-induced AF.

Methods And Results: Western blotting was performed to determine the level of NLRP3 inflammasome activation in atrial tissues of obese patients, sheep, and diet-induced obese (DIO) mice. The increased bodyweight in patients, sheep, and mice was associated with enhanced NLRP3-inflammasome activation. To determine whether NLRP3 contributes to the obesity-induced atrial arrhythmogenesis, wildtype (WT) and NLRP3 homozygous knockout (NLRP3-/-) mice were subjected to high-fat diet (HFD) or normal chow (NC) for 10 weeks. Relative to NC-fed WT mice, HFD-fed WT mice were more susceptible to pacing-induced AF with longer AF duration. In contrast, HFD-fed NLRP3-/- mice were resistant to pacing-induced AF. Optical mapping in DIO mice revealed an arrhythmogenic substrate characterized by abbreviated refractoriness and action potential duration (APD), two key determinants of reentry-promoting electrical remodeling. Upregulation of ultra-rapid delayed-rectifier K+-channel (Kv1.5) contributed to the shortening of atrial refractoriness. Increased profibrotic signaling and fibrosis along with abnormal Ca2+ release from sarcoplasmic reticulum (SR) accompanied atrial arrhythmogenesis in DIO mice. Conversely, genetic ablation of Nlrp3 (NLRP3-/-) in HFD-fed mice prevented the increases in Kv1.5 and the evolution of electrical remodeling, the upregulation of profibrotic genes, and abnormal SR Ca2+ release in DIO mice.

Conclusions: These results demonstrate that the atrial NLRP3 inflammasome is a key driver of obesity-induced atrial arrhythmogenesis and establishes a mechanistic link between obesity-induced AF and NLRP3-inflammasome activation.
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http://dx.doi.org/10.1093/cvr/cvab024DOI Listing
February 2021

Sleep Apnea and Atrial Fibrillation.

Card Electrophysiol Clin 2021 03;13(1):87-94

Centre for Heart Rhythm Disorders, South Australian Health and Medical Research Institute, University of Adelaide and Royal Adelaide Hospital, Adelaide, Australia.

Obstructive sleep apnea (OSA) creates a complex and dynamic substrate for atrial fibrillation (AF), which is characterized by structural remodeling as a result of long-term OSA as well as transient and acute apnea-associated transient atrial electrophysiological changes. OSA is present in 21% to 74% of patients with AF, and nonrandomized studies suggest that treatment of OSA by continuous positive airway pressure may help to maintain sinus rhythm after electrical cardioversion and improve catheter ablation success rates. Management of OSA in patients with AF requires a close interdisciplinary collaboration between the electrophysiologist/cardiologist and sleep specialists.
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http://dx.doi.org/10.1016/j.ccep.2020.10.003DOI 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

Nocturnal hypoxemic burden during positive airway pressure treatment across different central sleep apnea etiologies.

Sleep Med 2021 Mar 5;79:62-70. Epub 2021 Jan 5.

University of Adelaide, School of Electrical and Electronic Engineering, Adelaide, Australia.

Introduction: Nocturnal hypoxemia is associated with increased cardiovascular mortality. Here, we assess whether positive airway pressure by adaptive servo-ventilation (ASV) reduces nocturnal hypoxemic burden in patients with primary central sleep apnea (primary CSA), or heart failure related central sleep apnea (CSA-HF) and treatment emergent central sleep apnea (TECSA).

Methods: Overnight oximetry data from 328 consecutive patients who underwent ASV initiation between March 2010 and May 2018 were retrospectively analyzed. Patients were stratified into three groups: primary CSA (n = 14), CSA-HF (n = 31), TECSA (n = 129). Apnea hypopnea index (AHI) and time spent below 90% SpO (T90) was measured. Additionally, T90 due to acute episodic desaturations (T90) and due to non-specific and non-cyclic drifts of SpO (T90) were assessed.

Results: ASV reduced the AHI below 15/h in all groups. ASV treatment significantly shortened T90 in all three etiologies to a similar extent. T90, but not T90, was reduced by ASV across all three patient groups. AHI was identified as an independent modulator for ΔT90 upon ASV treatment (B (95% CI: -1.32 (-1.73; -0.91), p < 0.001), but not for ΔT90 or ΔT90. Body mass index was one independent predictor of T90.

Conclusions: Across different central sleep apnea etiologies, ASV reduced AHI, but nocturnal hypoxemic burden remained high due to a non-specific component of T90 not related to episodic desaturation. Whether adjunct risk factor management such as weight-loss can further reduce T90 warrants further study.
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http://dx.doi.org/10.1016/j.sleep.2021.01.007DOI Listing
March 2021

Associations of anemia with stroke, bleeding, and mortality in atrial fibrillation: A systematic review and meta-analysis.

J Cardiovasc Electrophysiol 2021 Mar 2;32(3):686-694. Epub 2021 Feb 2.

Department of Cardiology, Centre for Heart Rhythm Disorders, University of Adelaide and Royal Adelaide Hospital, Adelaide, South Australia, Australia.

Background: Anemia frequently coexists with atrial fibrillation (AF) and has been variably associated with worse outcomes. We performed a systematic review and meta-analysis to comprehensively assess the effect of anemia on mortality, stroke/systemic thromboembolism, and bleeding events in patients with AF.

Methods: MEDLINE and Embase were searched from inception until May 2020. Studies examining associations of anemia with the above outcomes in AF patients were included, and maximally adjusted hazard ratios (HRs) meta-analysed. PROSPERO registration number CRD42020171113.

Results: Twenty-eight studies involving 365 484 patients (41% female, mean age 74.7 years) were included. The average study follow-up ranged from 0.2 to 4.0 years, and the prevalence of anemia was 16%. Anemia was associated with a 78% increase in all-cause mortality (HR, 1.78; 95% confidence interval [CI], 1.44-2.20), 60% increase in cardiovascular mortality (HR, 1.60; 95% CI, 1.17-2.19), 134% increase in noncardiovascular mortality (HR, 2.34; 95% CI, 1.58-3.47) 15% increase in stroke/systemic thromboembolism (HR, 1.15; 95% CI, 1.01-1.31), 78% increase in major bleeding (HR, 1.78; 95% CI, 1.54-2.05), and 77% increase in gastrointestinal bleeding (HR, 1.77; 95% CI, 1.23-2.55). Sensitivity analyses including studies that reported odds ratios did not result in any material change.

Conclusion: Anemia is a frequently observed comorbidity in patients with AF, and is associated with an increased risk of all-cause, cardiovascular and noncardiovascular mortality, stroke/systemic thromboembolism, and major and gastrointestinal bleeding. Future studies are required to explore the causes of anemia in AF, and whether investigation and treatment may be clinically beneficial in affected individuals.
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http://dx.doi.org/10.1111/jce.14898DOI Listing
March 2021

Sleep apnoea has a dose-dependent effect on atrial remodelling in paroxysmal but not persistent atrial fibrillation: a high-density mapping study.

Europace 2021 Jan 14. Epub 2021 Jan 14.

Department of Cardiology, Royal Melbourne Hospital, Melbourne 3050, Australia.

Aims: Obstructive sleep apnoea (OSA) associates with atrial fibrillation (AF), but the relationship of OSA severity and AF phenotype with the atrial substrate remains poorly defined. We sought to define the atrial substrate across the spectrum of OSA severity utilizing high-density mapping.

Methods And Results: Sixty-six consecutive patients (male 71%, age 61 ± 9) having AF ablation (paroxysmal AF 36, persistent AF 30) were recruited. All patents underwent formal overnight polysomnography and high-density left atrial (LA) mapping (mean 2351 ± 1244 points) in paced rhythm. Apnoea-hypopnoea index (AHI) (mean 21 ± 18) associated with lower voltage (-0.34, P = 0.005), increased complex points (r = 0.43, P < 0.001), more low-voltage areas (r = 0.42, P < 0.001), and greater voltage heterogeneity (r = 0.39, P = 0.001), and persisted after multivariable adjustment. Atrial conduction heterogeneity (r = 0.24, P = 0.025) but not conduction velocity (r = -0.09, P = 0.50) associated with AHI. Patchy regions of low voltage that co-localized with slowed conduction defined the atrial substrate in paroxysmal AF, while a diffuse atrial substrate predominated in persistent AF. The association of AHI with remodelling was most apparent among paroxysmal AF [LA voltage: paroxysmal AF -0.015 (-0.025, -0.005), P = 0.004 vs. persistent AF -0.006 (-0.017, 0.005), P = 0.30]. Furthermore, in paroxysmal AF an AHI ≥ 30 defined a threshold at which atrial remodelling became most evident (nil-mild vs. moderate vs. severe: 1.92 ± 0.42 mV vs. 1.84 ± 0.28 mV vs. 1.34 ± 0.41 mV, P = 0.006). In contrast, significant remodelling was observed across all OSA categories in persistent AF (1.67 ± 0.55 mV vs. 1.50 ± 0.66 mV vs. 1.55 ± 0.67 mV, P = 0.82).

Conclusion: High-density mapping observed that OSA associates with marked atrial remodelling, predominantly among paroxysmal AF cohorts with severe OSA. This may facilitate the identification of AF patients that stand to derive the greatest benefit from OSA management.
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http://dx.doi.org/10.1093/europace/euaa275DOI Listing
January 2021

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

Abnormal electrograms during sinus rhythm for VT ablation: Beware of Fata Morganas.

J Cardiovasc Electrophysiol 2021 Feb 24;32(2):389-390. Epub 2021 Jan 24.

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

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http://dx.doi.org/10.1111/jce.14855DOI Listing
February 2021

Screening for obstructive sleep apnoea in patients with atrial fibrillation: Much more than a screening tool alone.

Int J Cardiol Heart Vasc 2020 Dec 20;31:100655. Epub 2020 Oct 20.

Centre for Heart Rhythm Disorders, South Australian Health and Medical Research Institute, University of Adelaide and Royal Adelaide Hospital, Adelaide, Australia.

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http://dx.doi.org/10.1016/j.ijcha.2020.100655DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7752746PMC
December 2020

Factors Contributing to Exercise Intolerance in Patients With Atrial Fibrillation.

Heart Lung Circ 2020 Dec 16. Epub 2020 Dec 16.

Centre for Heart Rhythm Disorders, University of Adelaide, and the Royal Adelaide Hospital, Adelaide, SA, Australia.

Background: Reduced exercise capacity and exercise intolerance are commonly reported by individuals with atrial fibrillation (AF). Our objectives were to evaluate the contributing factors to reduced exercise capacity and describe the association between subjective measures of exercise intolerance versus objective measures of exercise capacity.

Methods: Two hundred and three (203) patients with non-permanent AF and preserved ejection fraction undergoing cardiopulmonary exercise testing (CPET) were recruited. Clinical characteristics, AF-symptom evaluation, and transthoracic echocardiography measures were collected. Peak oxygen consumption (VO) was calculated during CPET as an objective measure of exercise capacity. We assessed the impact of 16 pre-defined clinical features, comorbidities and cardiac functional parameters on VO.

Results: Across this cohort (Age 66±11 years, 40.4% female and 32% in AF), the mean VO was 20.3±6.3 ml/kg/min. 24.9% of patients had a VO considered low (<16 ml/kg/min). In multivariable analysis, echocardiography-derived estimates of elevated left ventricular (LV) filling pressure (E/E') and reduced chronotropic index were significantly associated with lower VO. The presence of AF at the time of testing was not significantly associated with VO but was associated with elevated minute ventilation to carbon dioxide production indicating impaired ventilatory efficiency. There was a poor association between VO and subjectively reported exercise intolerance and exertional dyspnoea.

Conclusion: Reduced exercise capacity in AF patients is associated with elevated LV filling pressure and reduced chronotropic response rather than rhythm status. Subjectively reported exercise intolerance is not a sensitive assessment of reduced exercise capacity. These findings have important implications for understanding reduced exercise capacity amongst AF patients and the approach to management in this cohort. (ACTRN12619001343190).
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http://dx.doi.org/10.1016/j.hlc.2020.11.007DOI Listing
December 2020

Sleep apnea and atrial fibrillation: Update 2020.

Int J Cardiol Heart Vasc 2020 Dec 27;31:100681. Epub 2020 Nov 27.

Institute of Pharmacology, West German Heart and Vascular Center, University Duisburg-Essen, Germany.

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http://dx.doi.org/10.1016/j.ijcha.2020.100681DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7708811PMC
December 2020

Cerebral Blood Flow and Cognitive Performance in Postural Tachycardia Syndrome: Insights from Sustained Cognitive Stress Test.

J Am Heart Assoc 2020 12 5;9(24):e017861. Epub 2020 Dec 5.

Centre for Heart Rhythm Disorders The University of Adelaide Adelaide Australia.

Background The physiology underlying "brain fog" in the absence of orthostatic stress in postural tachycardia syndrome (POTS) remains poorly understood. Methods and Results We evaluated cognitive and hemodynamic responses (cardiovascular and cerebral: heart rate, blood pressure, end-tidal carbon dioxide, and cerebral blood flow velocity (CBFv) in the middle cerebral artery at baseline, after initial cognitive testing, and after (30-minutes duration) prolonged cognitive stress test (PCST) whilst seated; as well as after 5-minute standing in consecutively enrolled participants with POTS (n=22) and healthy controls (n=18). Symptom severity was quantified with orthostatic hypotensive questionnaire at baseline and end of study. Subjects in POTS and control groups were frequency age- and sex-matched (29±11 versus 28±13 years; 86 versus 72% women, respectively; both ≥0.4). The CBFv decreased in both groups (condition, =0.04) following PCST, but a greater reduction in CBFv was observed in the POTS versus control group (-7.8% versus -1.8%; interaction, =0.038). Notably, the reduced CBFv following PCST in the POTS group was similar to that seen during orthostatic stress (60.0±14.9 versus 60.4±14.8 cm/s). Further, PCST resulted in greater slowing in psychomotor speed (6.1% versus 1.4%, interaction, =0.027) and a greater increase in symptom scores at study completion (interaction, <0.001) in the patients with POTS, including increased difficulty with concentration. All other physiologic responses (blood pressure and end-tidal carbon dioxide) did not differ between groups after PCST (all >0.05). Conclusions Reduced CBFv and cognitive dysfunction were evident in patients with POTS following prolonged cognitive stress even in the absence of orthostatic stress.
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http://dx.doi.org/10.1161/JAHA.120.017861DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7955388PMC
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

Sleep apnea, obesity and COPD depress respiration during catheter ablation procedures: Implications for transcutaneous carbon dioxide monitoring.

Int J Cardiol 2021 Mar 3;327:102-104. Epub 2020 Nov 3.

Department of Pulmonology, Maastricht University Medical Centre, Maastricht, the Netherlands.

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http://dx.doi.org/10.1016/j.ijcard.2020.10.080DOI Listing
March 2021

Inadvertent triggering of supraventricular tachycardia during pacemaker interrogation: Time to lose the magnet?

J Cardiol Cases 2020 Nov 7;22(5):210-211. Epub 2020 Jul 7.

Centre for Heart Rhythm Disorders, The University of Adelaide, Adelaide, Australia.

A 22-year-old male had a dual chamber permanent pacemaker (PPM) implanted for complete heart block following aortic valve replacement for Shone's syndrome 3 months previously. He presented with acute shortness of breath due to severe para-valvular leak with aortic valve dehiscence following a motor vehicle accident. He was scheduled for redo sternotomy and a pre-operative PPM check was undertaken. A programmer wand (Model 2067, Medtronic Inc., Minneapolis, MN, USA) was applied to the patient's PPM site to perform interrogation. During initialization, asynchronous DOO pacing at the magnet rate of 85 bpm was initiated with evidence of both atrial and ventricular capture. Competition from intrinsic rhythm resulted in functional loss of capture. Competitive pacing initiated a narrow complex supraventricular tachycardia at 180 bpm. The tachycardia persisted to result in clinical deterioration until reversion with urgent intravenous metoprolol. Programmer wands from Medtronic (Model 2067 & Encore) and Biotronik (Renamic, Biotronik Inc., Berlin, Germany) have in-built magnets that can cause asynchronous pacing during initialization of interrogation. Removing the magnet in future iterations of PPM programmer wands will mitigate inadvertent arrhythmia induction. < Some pacemaker programmer wands contain in-built magnets that can initiate asynchronous pacing when placed over a cardiac implantable electronic device. This could result in asynchronous pacing and inadvertent triggering of arrhythmia. This risk can be minimized by placing the wand after the programmer is booted up to reduce the duration of asynchronous pacing. Device manufacturers should consider redesigning their products to make magnets redundant in future models of programming wands.>.
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http://dx.doi.org/10.1016/j.jccase.2020.06.016DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7588475PMC
November 2020

Predictors of Anticoagulation Use in Indigenous and Non-Indigenous Australians With Atrial Fibrillation.

Heart Lung Circ 2021 May 31;30(5):707-713. Epub 2020 Oct 31.

Centre for Heart Rhythm Disorders (CHRD), University of Adelaide and Royal Adelaide Hospital, Adelaide, SA, Australia. Electronic address:

Objective: Prior studies have demonstrated that anticoagulation underutilisation for atrial fibrillation (AF) and elevated stroke risk is common. However, there is little data on factors associated with appropriate anticoagulation, particularly in Indigenous Australians who face a disproportionate burden of AF and stroke. We thus sought to determine factors associated with anticoagulation use in Australians with AF.

Design: Administrative, clinical, prescriptive and laboratory data were linked and aggregated over a 12-year period.

Setting: Single tertiary teaching hospital.

Participants: 19,305 (98%) and 308 (2%) consecutive non-Indigenous and Indigenous Australians with AF identified from administrative databases.

Main Outcome Measures: Associations of anticoagulation use according to ethnicity.

Results: Significant independent predictors of anticoagulation use included hypertension (odds ratio [OR] 1.25, 95% confidence interval [CI] 1.17-1.34; p<0.001), diabetes (OR 1.14, 95% CI 1.05-1.24; p=0.002), heart failure (OR 1.54 95% CI 1.43-1.66; p<0.001) and prior stroke or transient ischaemic attack (OR 2.07, 95% CI 1.84-2.33; p<0.001). In contrast, increasing age (OR 0.99, 95% CI 0.98-0.99; p<0.001), female gender (OR 0.88, 95% CI 0.82-0.93; p<0.001), and vascular disease (OR 0.72, 95% CI 0.64-0.80; p<0.001) were significant predictors of no anticoagulation. Hypertension was associated with less anticoagulation use in Indigenous compared to non-Indigenous Australians (p=0.02).

Conclusions: Anticoagulation for AF was suboptimal in both Indigenous and non-Indigenous Australians. Older age, female gender, and comorbid vascular disease were found to be negatively associated with anticoagulation. Importantly, hypertension may also be under-recognised as a stroke risk factor in Indigenous Australians. Future efforts to encourage anticoagulation use in accordance with guideline recommendations is likely to reduce the burden of AF-related stroke in both Indigenous and non-Indigenous populations.
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http://dx.doi.org/10.1016/j.hlc.2020.08.027DOI Listing
May 2021

Central sleep apnea in atrial fibrillation: Risk factor or marker of untreated underlying disease?

Int J Cardiol Heart Vasc 2020 Oct 10;30:100650. Epub 2020 Oct 10.

Centre for Heart Rhythm Disorders, South Australian Health and Medical Research Institute, University of Adelaide and Royal Adelaide Hospital, Adelaide, Australia.

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http://dx.doi.org/10.1016/j.ijcha.2020.100650DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7573638PMC
October 2020

Repeated exposure to transient obstructive sleep apnea-related conditions causes an atrial fibrillation substrate in a chronic rat model.

Heart Rhythm 2021 Mar 17;18(3):455-464. Epub 2020 Oct 17.

Faculty of Health and Medical Sciences, Department of Biomedical Sciences, University of Copenhagen, Copenhagen, Denmark; Klinik für Innere Medizin III, Universität des Saarlandes, Homburg/Saar, Germany; University Maastricht, Cardiovascular Research Institute Maastricht (CARIM), Masstricht, The Netherlands; Centre for Heart Rhythm Disorders, Royal Adelaide Hospital, University of Adelaide, Adelaide, Australia; Department of Cardiology, Maastricht University Medical Centre, Maastricht, The Netherlands. Electronic address:

Background: High night-to-night variability in obstructive sleep apnea (OSA) is associated with atrial fibrillation (AF). Obstructive apneas are characterized by intermittent deoxygenation-reoxygenation and intrathoracic pressure swings during ineffective inspiration against occluded upper airways.

Objective: We elucidated the effect of repeated exposure to transient OSA conditions simulated by intermittent negative upper airway pressure (INAP) on the development of an AF substrate.

Methods: INAP (48 events/4 h; apnea-hypopnea index 12 events/h) was applied in sedated spontaneously breathing rats (2% isoflurane) to simulate mild-to-moderate OSA. Rats without INAP served as a control group (CTR). In an acute test series (ATS), rats were either killed immediately (n = 9 per group) or after 24 hours of recovery (ATS-REC: n = 5 per group). To simulate high night-to-night variability in OSA, INAP applications (n = 10; 24 events/4 h; apnea-hypopnea index 6/h) were repeated every second day for 3 weeks in a chronic test series (CTS).

Results: INAP increased atrial oxidative stress acutely, represented in decreases of reduced to oxidized glutathione ratio (ATS: INAP: 0.33 ± 0.05 vs CTR: 1 ± 0.26; P = .016), which was reversible after 24 hours (ATS-REC: INAP vs CTR; P = .274). Although atrial oxidative stress did not accumulate in the CTS, atrial histological analysis revealed increased cardiomyocyte diameters, reduced connexin 43 expression, and increased interstitial fibrosis formation (CTS: INAP 7.0% ± 0.5% vs CTR 5.1% ± 0.3%; P = .013), which were associated with longer inducible AF episodes (CTS: INAP: 11.65 ± 4.43 seconds vs CTR: 0.7 ± 0.33 seconds; P = .033).

Conclusion: Acute simulation of OSA was associated with reversible atrial oxidative stress. Cumulative exposure to these transient OSA-related conditions resulted in AF substrates and was associated with increased AF susceptibility. Mild-to-moderate OSA with high night-to-night variability may deserve intensive management to prevent atrial substrate development.
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http://dx.doi.org/10.1016/j.hrthm.2020.10.011DOI Listing
March 2021