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Vegard Malmo,1,2 Arnulf Langhammer,3 Kaare H Bønaa,2,3,4 Jan P Loennechen,1,2 Hanne Ellekjaer5,6 1Department of Circulation and Medical Imaging, Norwegian University of Science and Technology, 2Department of Cardiology, St Olav’s Hospital, 3Department of Public Health and General Practice, Norwegian University of Science and Technology, Trondheim, 4Department of Community Medicine, UiT The Arctic University of Norway, Tromso, 5Stroke Unit, Department of Internal Medicine, St Olav’s Hospital, 6Department of Neuroscience, Norwegian University of Science and Technology, Trondheim, Norway Background: Self-reported atrial fibrillation (AF) and diagnoses from hospital registers are often used to identify persons with AF. The objective of this study was to validate self-reported AF and hospital discharge diagnoses of AF among participants in a population-based study. Materials and methods: Among 50,805 persons who participated in the third survey of the HUNT Study (HUNT3), 16,247 participants from three municipalities were included. Individuals who reported cardiovascular disease, renal disease, or hypertension in the main questionnaire received a cardiovascular-specific questionnaire. An affirmative answer to a question on physician-diagnosed AF in this second questionnaire defined self-reported AF diagnoses in the study. In addition, AF diagnoses were retrieved from hospital and primary care (PC) registers. All AF diagnoses were verified by review of hospital and PC medical records. Results: A total of 502 HUNT3 participants had a diagnosis of AF verified in hospital or PC records. Of these, 249 reported their AF diagnosis in the HUNT3 questionnaires and 370 had an AF diagnosis in hospital discharge registers before participation in HUNT3. The sensitivity of self-reported AF in HUNT3 was 49.6%, specificity 99.2%, positive predictive value (PPV) 66.2%, and negative predictive value (NPV) 98.4%. The sensitivity of a hospital discharge diagnosis of AF was 73.7%, specificity 99.7%, PPV 88.5%, and NPV 99.2%. Conclusion: Use of questionnaires alone to identify cases of AF has low sensitivity. Extraction of diagnoses from health care registers enhances the sensitivity substantially and should be applied when estimates of incidence and prevalence of AF are studied. Keywords: atrial fibrillation, epidemiology, diagnosis, questionnaire, validation

Background: Obstructive sleep apnoea (OSA) can cause left atrial (LA) and left ventricular (LV) remodelling, which is linked to atrial fibrillation (AF). Whether continuous positive airway pressure (CPAP) can reverse LA and LV remodelling in patients with OSA and paroxysmal AF (PAF) has yet to be studied. We assessed the impact of CPAP treatment on LA and LV size and function in patients with OSA and PAF before and after catheter ablation., Methods: In a randomised controlled trial, we screened patients with PAF for OSA. We enrolled patients with an Apnoea-Hypopnoea Index ≥15/hour. The burden of AF was monitored by an implantable loop recorder in all patients. Patients were then randomised to CPAP treatment or standard care. Transthoracic echocardiography was performed at baseline and after 6 and 12 months to assess LV and LA function and remodelling with advanced echocardiographic imaging techniques., Results: We enrolled 109 patients (63±7 years, body mass index 29.6±4.3, 76% men). 83 patients were scheduled for pulmonary vein isolation (PVI) and 26 for clinical follow-up only. 55 patients were randomised to CPAP and 54 to standard care. The burden of AF decreased significantly in patients who underwent PVI irrespective of treatment with CPAP (p for difference ≤0.001). Patients in the study group had LV ejection fraction (LVEF) and LV global longitudinal strain (GLS) within the normal range, increased LA Volume Index (LAVI), LA volume (by speckle tracking) and decreased LA reservoir strain at baseline. We did not observe any improvement in LVEF, GLS, LAVI, LA volume or LA reservoir strain in either group during the 12 months of follow-up., Conclusions: In patients with PAF and OSA, treatment with CPAP was not associated with reverse LA remodelling within 12 months of follow-up., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Studies on the effect of insomnia on atrial fibrillation risk in the general population are limited, therefore we investigated the association between insomnia and the risk of atrial fibrillation in a large-scale population-based study with valid atrial fibrillation measure. A total of 33,983 participants (55% women) reported their insomnia symptoms in the third wave of the HUNT study (between 2006 and 2008) in Norway, and they were followed for their first atrial fibrillation diagnosis until 2020 using hospital registers. Atrial fibrillation diagnoses were validated by physicians based on medical records and electrocardiograms. Insomnia symptoms were assessed by four questions, and analysed both individually and as cumulative symptoms. Cox regression, adjusted for age, sex, social and marital status, working in shiftwork, alcohol consumption, smoking, physical activity, body mass index, systolic blood pressure, and symptoms of anxiety and depression, was conducted. Overall, 1592 atrial fibrillation cases were identified during the follow-up and 31.6% of individuals reported at least one insomnia symptom. In our analysis, we did not detect meaningful associations between insomnia symptoms and the risk of atrial fibrillation. In conclusion, in this population there was no evidence for an association between insomnia symptoms and the risk of subsequent atrial fibrillation., (© 2024 The Authors. Journal of Sleep Research published by John Wiley & Sons Ltd on behalf of European Sleep Research Society.)

Aims: Although parity, infertility, and age at first birth are important for later development of cardiovascular disease, research on their association with atrial fibrillation (AF) is limited., Methods and Results: We linked data from the population-based HUNT study and the Medical Birth Registry of Norway (MBRN) and validated medical records from local hospitals. A total of 24 015 women aged 45 years or older were followed for verified incident AF. Parity and age at first birth were retrieved from the MBRN or from self-reported questionnaires in the HUNT study. A history of infertility was self-reported on the HUNT questionnaire. Cox proportional hazards models were used to calculate hazard ratios (HRs) for the multivariable-adjusted associations of parity, infertility, and age at first birth with risk of AF. During a median follow-up of 12.8 years, 1448 (6.0%) participants developed AF. Women with higher parity (four or more births vs. two births) were at 21% higher risk of AF [HR 1.21, 95% confidence interval (CI) 1.05-1.39]. A history of infertility was also associated with the risk of AF (HR 1.20, 95% CI 1.02-1.42). Among parous women, younger age at first birth (<20 vs. 20-29 years) was associated with a 20% higher risk of AF (HR 1.20, 95% CI 1.03-1.40)., Conclusion: Women with four or more births, or a history of infertility, or younger age at first birth have approximately a 20% higher risk of AF among women over 45 years old., Competing Interests: Conflict of interest: none declared., (© The Author(s) 2024. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Background: Catheter ablation in patients with atrial fibrillation is associated with a transient increase in thromboembolic risk and adequate anticoagulation is highly important. When patients are anticoagulated with apixaban, monitoring of plasma concentrations of the drug is not routinely performed. This study aimed to assess the influence of clinical patient characteristics, concomitant drug treatment and self-reported adherence on apixaban concentrations, and to describe the intra- and inter-individual variability in apixaban concentrations in this group of patients. Method Apixaban concentrations from 141 patients were measured in plasma one week before ablation and two, six and ten weeks after ablation, employing ultra-high performance liquid chromatography coupled with tandem mass spectrometry. In samples not obtained at trough, apixaban concentrations were adjusted to trough levels. Self-reported adherence was registered by means of the 8-item Morisky Medication Adherence Scale before and after ablation., Results: There were statistically significant, positive correlations between apixaban concentrations and increased age, female sex, lower glomerular filtration rate, higher CHA2DS2-VASc score, use of cytochrome P450 3A4 and/or p-glycoprotein inhibitors, and use of amiodarone. Self-reported adherence was generally high. The mean intra-individual and inter-individual coefficients of variation were 29% and 49%, respectively., Conclusion: In patients undergoing catheter ablation for atrial fibrillation, age, sex, renal function, interacting drugs and cerebrovascular risk profile were all associated with altered plasma apixaban concentration. In this group of patients with a generally high self-reported adherence, intra-individual variability was modest, but the inter-individual variability was substantial, and similar to those previously reported in other patient apixaban-treated populations. If a therapeutic concentration range is established, there might be a need for a more flexible approach to apixaban dosing, guided by therapeutic drug monitoring., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Aakerøy et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: Age at menarche, reproductive lifespan, and age at menopause are associated with several cardiovascular diseases, but their relationship with atrial fibrillation (AF) is uncertain., Methods: We linked information on all women who participated in the third survey of the population-based, longitudinal HUNT study in Norway with medical records from all local hospitals. A total of 14,632 women aged 60 or more were followed for validated incident AF. We retrieved age at menarche and age at menopause from the HUNT questionnaires. Reproductive lifespan was defined as the difference between age at menarche and age at menopause. We used Cox proportional hazards regression models to assess associations between AF and age at menarche, reproductive lifespan, and age at menopause., Results: During a median follow-up of 8.17 years (136,494 person-years), 1217 (8.3 %) participants developed AF. In multivariable-adjusted analyses, we observed no associations between early or late age at menarche and AF (hazard ratios (HRs): <12 years: 0.85 [95 % confidence interval (CI), 0.65-1.12]; ≥16 years: 0.99 [95 % CI, 0.80-1.24] compared to those who attained menarche at 13-14 years). The HR for a reproductive lifespan shorter than 30 years was 0.91 [95 % CI, 0.72-1.15] compared to 34-37 years. Likewise, there was no clear association between premature or early age at menopause and AF (HRs: <40 years: 1.21 [95 % CI, 0.83-1.75]; 40-44 years: 0.97 [95 % CI, 0.77-1.22] compared to 50-54 years)., Conclusions: In this population of women aged 60 years and over, the risk of AF was not associated with age at menarche, reproductive lifespan, or age at menopause., Competing Interests: Declaration of competing interest The authors declare that they have no competing interest., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Aims: Gastroesophageal reflux disease (GERD) may influence the risk of atrial fibrillation (AF). We investigated the association between symptoms of GERD and AF in the Trøndelag Health Study (HUNT)., Methods: The study cohort comprised 34,120 adult men and women initially free of AF with information on GERD symptoms. Participants were followed from the baseline clinical examination (1 October 2006 to 30 June 2008) to March 31, 2018., Results: During a median follow-up of 8.9 years, 1,221 cases of AF were diagnosed. When looking at the whole population, participants with much GERD symptoms did not have an increased risk of AF (HR: 1.01; CI: 95%, 0.82 to 1.24) while participants with little GERD symptoms had a 14% lower risk of AF compared those with no GERD symptoms (HR: 0.86; CI: 95%, 0.76 to 0.97). Among younger participants (<40 years of age), the risk of AF had a trend towards increased risk with increasing symptom load of GERD (little GERD symptoms, HR: 3.09; CI: 95%, 0.74 to 12.94 and much GERD symptoms, HR: 5.40; 95% CI: 0.82 to 35.58). Among older participants (≥65 years of age), we saw a slightly reduced risk of AF in participants with little symptoms (HR: 0.84; CI: 0.72 to 0.97) and no association among those with much GERD symptoms (HR: 1.06; 95% CI: 0.82 to 1.36)., Conclusion: We did not find support for a clinically important association between symptoms of GERD and AF across all age groups but for some younger people, GERD might play a role in the development of AF. However, our estimates for this age group were very imprecise and larger studies including younger individuals are warranted., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Drca et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: Data from some population-based studies have indicated an increased risk of atrial fibrillation (AF) among patients with migraine, particularly among individuals with migraine with aura. The present study aimed to assess the association between primary headache disorders and AF., Methods: In a population-based 9-year follow-up design, we evaluated the questionnaire-based headache diagnosis, migraine and tension-type headache (TTH) included, collected in the Trøndelag Health Study (HUNT3) conducted in 2006-2008, and the subsequent risk of AF in the period until December 2015. The population at risk consisted of 39,340 individuals ≥20 years without AF at HUNT3 baseline who answered headache questionnaire during HUNT3. The prospective association was evaluated by multivariable Cox proportional hazard models with 95% confidence intervals (CIs)., Results: Among the 39,340 participants, 1524 (3.8%) developed AF during the 9-year follow up, whereof 91% of these were ≥55 years. In the multivariable analyses, adjusting for known confounders, we did not find any association between migraine or TTH and risk of AF. The adjusted hazard ratios (HRs) were respectively 0.84 (95% CI = 0.64-1.11) for migraine, 1.16 (95% CI = 0.86-1.27) for TTH and 1.04 (95% CI = 0.86-1.27) for unclassified headache. However, in sensitivity analyses of individuals aged ≥55 years, a lower risk of AF was found for migraine (HR = 0.53; 95% CI = 0.39-0.73)., Conclusions: In this large population-based study, no increased risk of AF was found among individuals with migraine or TTH at baseline. Indeed, among individuals aged ≥55 years, migraine was associated with a lower risk for AF., Competing Interests: Declaration of conflicting interestsThe authors declared no potential conflicts of interest with respect to the research, authorship and/or publication of this article.

Ventricular arrhythmias contribute significantly to cardiovascular mortality, with coronary artery disease as the predominant underlying cause. Understanding the mechanisms of arrhythmogenesis is essential to identify proarrhythmic factors and develop novel approaches for antiarrhythmic prophylaxis and treatment. Animal models are vital in basic research on cardiac arrhythmias, encompassing molecular, cellular, ex vivo whole heart, and in vivo models. Most studies use either in vivo protocols lacking important information on clinical relevance or exclusively ex vivo protocols, thereby missing the opportunity to explore underlying mechanisms. Consequently, interpretation may be difficult due to dissimilarities in animal models, interventions, and individual properties across animals. Moreover, proarrhythmic effects observed in vivo are often not replicated in corresponding ex vivo preparations during mechanistic studies. We have established a protocol to perform both an in vivo and ex vivo electrophysiological characterization in an arrhythmogenic rat model with heart failure following myocardial infarction. The same animal is followed throughout the experiment. In vivo methods involve intracardiac programmed electrical stimulation and external defibrillation to terminate sustained ventricular arrhythmia. Ex vivo methods conducted on the Langendorff-perfused heart include an electrophysiological study with optical mapping of regional action potentials, conduction velocities, and dispersion of electrophysiological properties. By exploring the retention of the in vivo proarrhythmic phenotype ex vivo, we aim to examine whether the subsequent ex vivo detailed measurements are relevant to in vivo pathological behavior. This protocol can enhance greater understanding of cardiac arrhythmias by providing a standardized, yet adaptable model for evaluating arrhythmogenicity or antiarrhythmic interventions in cardiac diseases. NEW & NOTEWORTHY Rodent models are widely used in arrhythmia research. However, most studies do not standardize clinically relevant in vivo and ex vivo techniques to support their conclusions. Here, we present a comprehensive electrophysiological protocol in an arrhythmogenic rat model, connecting in vivo and ex vivo programmed electrical stimulation with optical mapping. By establishing this protocol, we aim to facilitate the adoption of a standardized model for investigating arrhythmias, enhancing research rigor and comparability in this field.

Endurance athletes have a high prevalence of atrial fibrillation (AF), probably caused by exercise-induced cardiac remodelling. Athletes diagnosed with AF are often advised to reduce the intensity and amount of training but the efficacy of this intervention has not been investigated in endurance athletes with AF. Effects of detraining in endurance athletes with atrial fibrillation is a two-arm international multicentre randomised (1:1) controlled trial on the effects of a period of training adaption on AF burden in endurance athletes with paroxysmal AF. One-hundred-and-twenty endurance athletes diagnosed with paroxysmal AF are randomised to a 16-week period of intervention (training adaption) or a control group. We define training adaption as training with a heart rate (HR) not exceeding 75% of the individual maximum HR (HRmax), and total duration of weekly training not exceeding 80% of the self-reported average before the study. The control group is instructed to uphold training intensity including sessions with HR ≥85% of HRmax. AF burden is monitored with insertable cardiac monitors, and training intensity with HR chest-straps and connected sports watches. The primary endpoint, AF burden, will be calculated as the cumulative duration of all AF episodes lasting ≥30sec divided by total duration of monitoring. Secondary endpoints include number of AF episodes, adherence to training adaption, exercise capacity, AF symptoms and health-related quality of life, echocardiographic signs of cardiac remodelling and risk of cardiac arrhythmias related to upholding training intensity., Trial Registration Number: NCT04991337., Study Protocol Version: 4.7 (Date 9 March 2023)., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Introduction: Pulseless electrical activity (PEA) is commonly observed in in-hospital cardiac arrest (IHCA). Universally available ECG characteristics such as QRS duration (QRSd) and heart rate (HR) may develop differently in patients who obtain ROSC or not. The aim of this study was to assess prospectively how QRSd and HR as biomarkers predict the immediate outcome of patients with PEA., Method: We investigated 327 episodes of IHCA in 298 patients at two US and one Norwegian hospital. We assessed the ECG in 559 segments of PEA nested within episodes, measuring QRSd and HR during pauses of compressions, and noted the clinical state that immediately followed PEA. We investigated the development of HR, QRSd, and transitions to ROSC or no-ROSC (VF/VT, asystole or death) in a joint longitudinal and competing risks statistical model., Results: Higher HR, and a rising HR, reflect a higher transition intensity ("hazard") to ROSC (p < 0.001), but HR was not associated with the transition intensity to no-ROSC. A lower QRSd and a shrinking QRSd reflect an increased transition intensity to ROSC (p = 0.023) and a reduced transition intensity to no-ROSC (p = 0.002)., Conclusion: HR and QRSd convey information of the immediateoutcome during resuscitation from PEA. These universally available and promising biomarkers may guide the emergency team in tailoring individual treatment., (Copyright © 2023 The Author(s). Published by Elsevier B.V. All rights reserved.)

Background: Obstructive sleep apnea (OSA) is associated with atrial fibrillation (AF). Whether treatment with continuous positive airway pressure (CPAP) reduces AF recurrence after catheter ablation with pulmonary vein isolation (PVI) is unknown., Objective: The purpose of this study was to assess the effect of CPAP treatment on the recurrence and burden of AF after PVI in patients with OSA., Methods: We randomized patients with paroxysmal AF and an apnea-hypopnea index (AHI) ≥15 events/hour to treatment with CPAP or standard care. Heart rhythm was monitored by an implantable loop recorder. AF recurrence after PVI was defined as any episode of AF lasting >2 minutes after a 3-month blanking period., Results: PVI was performed in 83 patients. Thirty-seven patients were randomized to CPAP treatment and 46 patients to standard care. The AHI was reduced from 26.7 ± 14 events/hour to 1.7 ± 1.3 events/hour at follow-up in the CPAP group (P = .001). A total of 57% of patients in both the CPAP group and the standard care group had at least 1 episode of AF 3-12 months after PVI (P for difference = 1). AF burden after ablation was reduced in both groups, with no between-group difference (P = .69)., Conclusion: In patients with paroxysmal AF and OSA, treatment with CPAP did not further reduce the risk of AF recurrence after ablation. PVI considerably reduced the burden of AF in OSA patients, without any difference between groups., (Copyright © 2022 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.)

Rationale: Sleep apnea (SA) is highly prevalent in patients with atrial fibrillation (AF), and both conditions are associated with adverse cardiovascular outcomes. Objectives: To determine the effect of continuous positive airway pressure (CPAP) on AF burden. Methods: This open-label, parallel-group, randomized controlled trial included patients with paroxysmal AF and moderate to severe SA (apnea-hypopnea index ⩾15). A computerized system randomized eligible patients (1:1) to 5 months' treatment with CPAP plus usual care (CPAP, n  = 55) or usual care alone (control, n  = 54). The outcome assessment was blinded. The planned primary outcome was the difference between CPAP treatment and control groups in change of AF burden (percentage of time in AF) as measured by implantable loop recorder. Measurements and Main Results: A total of 579 patients with paroxysmal AF had respiratory polygraphy, of whom 244 (42%) had moderate to severe SA. Of these, 158 (65%) participated in the CPAP run-in period, of whom 39 (25%) patients did not tolerate the treatment. A total of 108 patients were available for the primary analysis. The mean time in AF decreased from 5.6% at baseline to 4.1% during the last 3 months of CPAP intervention and from 5.0% to 4.3% in the control group. The adjusted between-group difference at follow-up was -0.63 (95% confidence interval, -2.55 to 1.30) percentage points ( P  = 0.52). Seven serious adverse events (13%) occurred in the CPAP group, and two (4%) occurred in the control group. Conclusions: In patients with paroxysmal AF and SA, treatment with CPAP did not result in a statistically significant reduction in the burden of AF.Clinical trial registered with www.clinicaltrials.gov (NCT02727192).

Exercise training is generally beneficial for cardiovascular health, improving stroke volume, cardiac output, and aerobic capacity. Despite these benefits, some evidence indicates that endurance training may increase the risk of atrial fibrillation (AF), particularly in highly trained individuals. Among multiple mechanisms, autonomic tone changes and atrial remodeling have been proposed as main contributors for exercise-induced AF. However, the contribution of local and systemic immunity is poorly understood in the development of atrial arrhythmogenic substrates. Here we aim to update the field of immunomodulation in the context of exercise and AF by compiling and reconciling the most recent evidence from preclinical and human studies and rationalize the applicability of "lone" AF terminology in athletes., Competing Interests: Declaration of Competing Interest None., (Copyright © 2021. Published by Elsevier Inc.)

We used sleep monitoring data from a study that investigated the prevalence, characteristics, risk factors and type of sleep apnea (SA) in 579 patients with paroxysmal atrial fibrillation. Most patients were screened for two nights, resulting in 1,043 sleep recordings that each contained data from one night. SA was diagnosed using the Nox T3 portable sleep monitor. An experienced sleep specialist scored the recordings manually using Noxturnal software. A total of 157 women (27%) and 422 men (73%) were examined; 477 (82.7%) had an apnea-hypopnea index (AHI) ≥ 5/hr, whereas moderate to severe SA (AHI ≥ 15/hr) was diagnosed in 243 patients (42.1%). The AHI derived from automatic and manual scoring showed a good agreement (Pearson's r coefficient of 0.96). The median difference in AHI was very small (i.e., 0.72 [mean difference, 1.06]), but was statistically significant (p < .0001). Automatic scoring classified sleep recordings with more than 90% accuracy into SA categories of mild (AHI ≥ 5/hr), moderate (AHI ≥ 15/hr) and severe (AHI ≥ 30/hr). We found a minor (11%-21%) mis-estimation of the number of recordings right above and below the boundary separating mild and moderate SA. The accuracy of automatic scoring differed from recording to recording, especially regarding the sensitivity of detecting disrupted breathing events. We found low to moderate agreement for the duration of disrupted breathing events (r = .53), for which the automatic scoring led to a statistically significant overestimation by 5.22 s (p < .0001)., (© 2020 The Authors. Journal of Sleep Research published by John Wiley & Sons Ltd on behalf European Sleep Research Society.)

Bakgrunn: Implantasjon av hjertestarter (implantable cardioverter defibrillator, ICD) er etablert behandling hos pasienter med høy risiko for plutselig hjertedød. Studiens formål var å kartlegge pasientkarakteristika, indikasjoner, hyppigheten av ICD-støt, komplikasjoner, reoperasjoner samt endringer over tid i ICD-behandlingen ved St. Olavs hospital., Materiale Og Metode: Alle pasienter som fikk implantert hjertestarter ved St. Olavs hospital i perioden 2006-15 ble inkludert. Pasientene ble identifisert i pacemakerregisteret. Data ble hentet fra pacemakerregisteret og elektronisk pasientjournal., Resultater: Studien inkluderte 598 pasienter (82 % menn, medianalder 65 år). Tidligere hjertestans eller alvorlig arytmi forelå hos 401 (67 %) av dem som fikk implantert hjertestarter. Koronarsykdom (n = 383) var vanligste underliggende årsak. I oppfølgingstiden (median 3,6 år) fikk 203 (34 %) av pasientene ICD-støt, 154 (26 %) fikk berettigede og 65 (11 %) fikk uberettigede støt. Hos 139 (23 %) pasienter oppstod komplikasjoner. 101 (17 %) pasienter døde i oppfølgingsperioden., Fortolkning: Studien gir et godt grunnlag for kvalitetssikring av implantasjonsvirksomheten ved St. Olavs hospital. Kjønns- og aldersfordeling, indikasjon og underliggende årsaker for implantasjon samt hyppighet av støt og komplikasjoner samsvarer godt med tidligere publiserte data.

Background: Atrial fibrillation (AF) is the most common sustained cardiac arrhythmia. Anxiety and depression may activate the autonomic nervous system which is likely to play an important role in the etiology of AF. However, little is known about the association between symptoms of anxiety and depression and risk of AF., Objective: This study aimed to assess the association between symptoms of anxiety and depression and risk of AF., Methods: In a population-based study, 37,402 adult residents were followed for incident AF from 2006 to 2008 until 2015. Participants were classified according to data on anxiety and depression symptoms. Cox proportional regression models were used to adjust for common AF risk factors., Results: During a median follow-up of 8.1 years, 1433 (3.8%) participants developed AF. In comparisons with no anxiety symptoms, the multivariable-adjusted hazard ratios (HRs) were 1.1 (95% CI: 0.9-1.5) for mild to moderate anxiety symptoms and 1.0 (95% CI: 0.8-1.4) for severe anxiety symptoms. In comparisons with no depression symptoms, the multivariable-adjusted HRs were 1.5 (95% CI: 1.2-1.8) for mild to moderate depression symptoms and 0.9 (95% CI: 0.6-1.3) for severe depression symptoms. Recurrent anxiety/depression symptoms were not associated with increased AF risk., Conclusions: In this large, population-based study, we found no evidence of an association between symptoms of anxiety or severe depression and AF risk, even for recurrent anxiety or depression symptoms. An unexpected association of symptoms of mild to moderate depression with increased AF risk requires confirmation in other studies. Our findings add to the sparse literature on symptoms of anxiety and depression and risk of AF., Competing Interests: Declaration of competing interest None of the authors have any conflicts of interest., (Copyright © 2019 The Authors. Published by Elsevier B.V. All rights reserved.)

Aims: Atrial fibrillation (AF) confers higher risk of mortality and morbidity, but the long-term impact of physical activity (PA) and cardiorespiratory fitness (CRF) on outcomes in AF patients is unknown. We, therefore, examined the prospective associations of PA and estimated CRF (eCRF) with all-cause mortality, cardiovascular disease (CVD) mortality, morbidity and stroke in individuals with AF., Methods and Results: We followed 1117 AF patients from the HUNT3 study in 2006-08 until first occurrence of the outcomes or end of follow-up in November 2015. We used Cox proportional hazard regression to examine the prospective associations of self-reported PA and eCRF with the outcomes. Atrial fibrillation patients meeting PA guidelines had lower risk of all-cause [hazard ratio (HR) 0.55, 95% confidence interval (CI) 0.41-0.75] and CVD mortality (HR 0.54, 95% CI 0.34-0.86) compared with inactive patients. The respective HRs for CVD morbidity and stroke were 0.78 (95% CI 0.58-1.04) and 0.70 (95% CI 0.42-1.15). Each 1-metabolic equivalent task (MET) higher eCRF was associated with a lower risk of all-cause (HR 0.88, 95% CI 0.81-0.95), CVD mortality (HR 0.85, 95% CI 0.76-0.95), and morbidity (HR 0.88, 95% CI 0.82-0.95)., Conclusion: Higher PA and CRF are associated with lower long-term risk of CVD and all-cause mortality in individuals with AF. The findings support a role for regular PA and improved CRF in AF patients, in order to combat the elevated risk for mortality and morbidity., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2020. For permissions, please email: journals.permissions@oup.com.)

Background: Recent studies have suggested an association between sleep apnea (SA) and atrial fibrillation (AF). We aimed to study the prevalence, characteristics, risk factors and type of sleep apnea (SA) in ablation candidates with paroxysmal AF., Methods/results: We prospectively studied 579 patients with paroxysmal AF, including 157 women (27.1%) and 422 men (72.9%). Mean age was 59.9 ± 9.6 years and mean body mass index (BMI) 28.5 ± 4.5 kg/m 2 . SA was diagnosed using polygraphy for two nights at home. The Epworth Sleepiness Scale (ESS), STOP-Bang Questionnaire, and Berlin Questionnaire (BQ) assessed the degree of SA symptoms. A total of 479 (82.7%) patients had an apnea-hypopnea index (AHI) ≥ 5, whereas moderate-severe SA (AHI ≥ 15) was diagnosed in 244 patients (42.1%). The type of SA was predominantly obstructive, with a median AHI of 12.1 (6.7-20.6) (range 0.4-85.8). The median central apnea index was 0.3 (0.1-0.7). AHI increased with age, BMI, waist and neck circumference, body and visceral fat. Using the Atrial Fibrillation Severity Scale and the SF-36, patients with more severe SA had a higher AF burden, severity and symptom score and a lower Physical-Component Summary score. Age, male gender, BMI, duration of AF, and habitual snoring were independent risk factors in multivariate analysis (AHI ≥ 15). We found no association between ESS and AHI (R 2  = 0.003, p = 0.367)., Conclusions: In our AF population, SA was highly prevalent and predominantly obstructive. The high prevalence of SA detected in this study may indicate that SA is under-recognized in patients with AF. None of the screening questionnaires predicted SA reliably., Competing Interests: Gunn Marit Traaen has received speaker honoraria from ResMed, Norway. The authors declare no other potential conflicts of interest., (© 2019 The Authors.)

Purpose: To investigate the association between estimated cardiorespiratory fitness (eCRF) and risk of atrial fibrillation (AF), and examine how long-term changes in eCRF affects the AF risk., Methods: This prospective cohort study includes data of 39,844 men and women from the HUNT2 (August 15, 1995 to June 18, 1997) and the HUNT3 study (October 3, 2006 to June 25, 2008). The follow-up period was from HUNT3 until AF diagnosis or November 30, 2015. The AF diagnoses were retrieved from hospital registers and validated by medical doctors. A nonexercise test based on age, waist circumference, resting heart rate and self-reported physical activity was used to estimate CRF. Cox regression was performed to assess the association between eCRF and AF., Results: The mean age was 50.6 ± 14.6 yr for men and 50.2 ± 15.2 yr for women. Mean follow-up time was 8.1 yr. One thousand fifty-seven cases of AF were documented. For men, the highest risk reduction of AF was 31% in the fourth quintile of eCRF when compared with the first quintile (hazard ratio [HR], 0.69; 95% confidence interval [CI], 0.53-0.89). For women, the highest risk reduction was 47% in the fifth quintile when compared with the first quintile (HR, 0.53; 95% CI, 0.38-0.74). One metabolic equivalent increase in eCRF over a 10-yr period was associated with 7% lower risk of AF (HR, 0.93; 95% CI, 0.86-1.00). Participants with improved eCRF had 44% lower AF risk compared with those with decreased eCRF (HR, 0.56; 95% CI, 0.36-0.87)., Conclusions: The eCRF was inversely associated with AF, and participants with improved eCRF over a 10-yr period had less risk of AF. These findings support the hypothesis that fitness may prevent AF.

Aims: Although obesity has been associated with risk of atrial fibrillation (AF), the associations of long-term obesity, recent obesity, and weight change with AF risk throughout adulthood are uncertain., Methods and Results: An ambispective cohort study was conducted which included 15 214 individuals. The cohort was created from 2006 to 2008 (the baseline) and was followed for incident AF until 2015. Weight and height were directly measured at baseline. Data on previous weight and height were retrieved retrospectively from measurements conducted 10, 20, and 40 years prior to baseline. Average body mass index (BMI) over time and weight change was calculated. During follow-up, 1149 participants developed AF. The multivariable-adjusted hazard ratios were 1.2 (95% confidence interval 1.0-1.4) for average BMI 25.0-29.9 kg/m2 and 1.6 (1.2-2.0) for average BMI ≥30 kg/m2 when compared with normal weight. The association of average BMI with AF risk was only slightly attenuated after adjustment for most recent BMI. In contrast, current BMI was not strongly associated with the risk of AF after adjustment for average BMI earlier in life. Compared with stable BMI, both loss and gain in BMI were associated with increased AF risk. After adjustment for most recent BMI, the association of BMI gain with AF risk was largely unchanged, while the association of BMI loss with AF risk was weakened., Conclusion: Long-term obesity and BMI change are associated with AF risk. Obesity earlier in life and weight gain over time exert cumulative effects on AF development even after accounting for most recent BMI., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2019. For permissions, please email: journals.permissions@oup.com.)

Background: Despite the high prevalence of atrial fibrillation (AF), there is a lack of recommendations for physical activity and exercise in individuals with AF, including athletes with AF., Methods: With the aim to review studies that have investigated effects and safety of exercise in individuals with AF, we conducted a literature search in Pubmed using the key words atrial fibrillation AND exercise OR physical activity OR exercise/adverse effects OR adverse outcome., Results: Observational data from one registry suggest that regular exercise is associated with reduced mortality in AF patients. Three randomized controlled trials (RCTs) have demonstrated that 12-week exercise interventions might reduce the burden of AF and improve exercise capacity by 10-16% in patients with paroxysmal or persistent AF. Three small RCTs suggest that exercise might improve exercise capacity with 15-41% in patients with permanent AF. Exercise might improve quality of life in patients with AF. Data on safety of exercise are sparse. No studies have evaluated the effect of exercise in athletes with AF., Conclusions: Despite weak evidence, we suggest that individuals with AF should exercise regularly after evaluation of underlying conditions. Recommendations should be individualized. There is a lack of data to support exercise recommendations in athletes with AF.

Introduction: Presence of electrocardiographic rhythm in the absence of palpable pulses defines pulseless electrical activity (PEA) and the electrocardiogram (ECG) may provide a source of information during resuscitation. The aim of this study was to examine the development of ECG characteristics during advanced life support (ALS) from Out-of-hospital cardiac arrest (OHCA) with initial PEA, and to explore the potential effects of adrenaline on these characteristics., Methods: Patients with OHCA and initial PEA, part of randomized controlled trial of ALS with or without intravenous access and medications, were included. A total of 4840 combined observations of QRS complex rate (heart rate) and width were made by examining defibrillator recordings from 170 episodes of cardiac arrest., Results: We found Increased heart rate (47 beats per minute) and reduced QRS complex width (62 ms) during ALS in patients who obtained return of spontaneous circulation (ROSC); while patients who received adrenaline but died increased their heart rate (22 beats per minute) without any concomitant decrease in QRS complex width., Conclusion: ECG changes during ALS in cardiac arrest were associated with prognosis, and the administration of adrenaline impacted on these changes., (Copyright © 2019 The Author(s). Published by Elsevier B.V. All rights reserved.)

Objective: Atrial fibrillation (AF) is the most common arrhythmia and has been described as a global epidemic. Although AF is associated with both obesity and its metabolic consequences, little is known about the association between metabolically healthy obesity and AF., Methods: In a population-based study, 47,870 adults were followed for incident AF from 2006 to 2008 until 2015. Participants were classified according to BMI and metabolic status (using waist circumference, triglycerides, high-density lipoprotein cholesterol, blood pressure, and glucose) at baseline., Results: During a median follow-up of 8.1 years, 1,758 participants developed AF. Compared with metabolically healthy individuals with BMI < 25 kg/m 2 , the multivariable-adjusted hazard ratios for metabolically healthy and unhealthy obesity were 1.6 (95% CI: 1.2 to 2.1) and 1.6 (95% CI: 1.3 to 1.9), respectively. AF risk increased according to the severity of obesity., Conclusions: Metabolically healthy and unhealthy obesity increased AF risk to a similar extent. Severity of obesity was positively associated with AF risk regardless of metabolic status., (© 2019 The Obesity Society.)

Rationale: Atrial fibrillation is associated with increased mortality as well as morbidity. There is strong evidence for an association between atrial fibrillation and sleep apnea. It is not known whether treatment of sleep apnea with continuous positive airway pressure (CPAP) will reduce the burden of atrial fibrillation., Objective: The Treatment of Sleep Apnea in Patients with Paroxysmal Atrial Fibrillation study will investigate the effects of CPAP in patients with paroxysmal atrial fibrillation and sleep apnea., Design: The trial has a dual center, randomized, controlled, open-label, parallel design., Methods: Two centers will enroll a total of 100 patients with both paroxysmal atrial fibrillation and sleep apnea (apnea-hypopnea index [AHI] ≥ 15 events/h) who are scheduled for catheter ablation. Patients will be randomized in a 1:1 ratio to CPAP or control group (50 patients in each arm). The effects of CPAP treatment on atrial fibrillation will be determined using an implanted loop recorder (Reveal LINQ™, Medtronic) that detects all arrhythmia episodes. The primary endpoint is a reduction of the total burden of atrial fibrillation in the intervention group, after 5 months' follow-up (preablation). Reduction in the arrhythmia recurrence rate after ablation is the main secondary endpoint. All patients will be followed up for 12 months after ablation., Conclusion: This study is the first randomized controlled trial that will provide data on the effects of CPAP therapy in patients with paroxysmal atrial fibrillation and sleep apnea. The results are expected to improve our understanding of the interaction between paroxysmal atrial fibrillation and sleep apnea. ClinicalTrials.gov Identifier. NCT02727192.

Background Atrial fibrillation is the most common heart rhythm disorder, and high body mass index is a well-established risk factor for atrial fibrillation. The objective of this study was to examine the associations of physical activity and body mass index and risk of atrial fibrillation, and the modifying role of physical activity on the association between body mass index and atrial fibrillation. Design The design was a prospective cohort study. Methods This study followed 43,602 men and women from the HUNT3 study in 2006-2008 until first atrial fibrillation diagnosis or end of follow-up in 2015. Atrial fibrillation diagnoses were collected from hospital registers and validated by medical doctors. Cox proportional hazard regression analysis was performed to assess the association between physical activity, body mass index and atrial fibrillation. Results During a mean follow-up of 8.1 years (352,770 person-years), 1459 cases of atrial fibrillation were detected (4.1 events per 1000 person-years). Increasing levels of physical activity were associated with gradually lower risk of atrial fibrillation ( p trend 0.069). Overweight and obesity were associated with an 18% (hazard ratio 1.18, 95% confidence interval 1.03-1.35) and 59% (hazard ratio 1.59, 95% confidence interval 1.37-1.84) increased risk of atrial fibrillation, respectively. High levels of physical activity attenuated some of the higher atrial fibrillation risk in obese individuals (hazard ratio 1.53, 95% confidence interval 1.03-2.28 in active and 1.96, 95% confidence interval 1.44-2.67 in inactive) compared to normal weight active individuals. Conclusion Overweight and obesity were associated with increased risk of atrial fibrillation. Physical activity offsets some, but not all, atrial fibrillation risk associated with obesity.

Importance: Asthma, a chronic inflammatory airway disease, and atrial fibrillation (AF) share several common pathophysiological mechanisms. Research on the association between asthma and atrial fibrillation is lacking, and to our knowledge, no previous studies have assessed the dose-response association between levels of asthma control and AF., Objective: To assess the association between asthma, levels of asthma control, and AF., Design, Setting, and Participants: This prospective population cohort analyzed data on adults from a second and third iteration of the survey-based Nord-Trøndelag Health Study (HUNT) in Norway. All included participants were free from AF at baseline. Atrial fibrillation was ascertained by linking HUNT data with hospital records from the 2 hospitals in Nord-Trøndelag County. Data analysis was completed from May 2017 to November 2017., Exposures: Self-reported asthma was categorized into 3 groups: those who had ever had asthma, those who self-report being diagnosed with asthma, and those who had active asthma. Asthma control was defined according to Global Initiative for Asthma guidelines and was categorized into controlled, partly controlled, and uncontrolled cases., Main Outcomes and Measures: Atrial fibrillation., Results: A total of 54 567 adults were included (of whom 28 821 [52.8%] were women). Of these, 5961 participants (10.9%) reported ever having asthma, 3934 participants (7.2%) reported being diagnosed with asthma, and 2485 participants (4.6%) reported having active asthma. During a mean (SD) follow-up of 15.4 (5.8) years, 2071 participants (3.8%) developed AF. Participants with physician-diagnosed asthma had an estimated 38% higher risk of developing AF (adjusted hazard ratio, 1.38 [95% CI, 1.18-1.61]) compared with participants without asthma. There was a dose-response association between levels of asthma control and risk of AF with the highest risk for AF in participants with uncontrolled asthma (adjusted hazard ratio, 1.74 [95% CI, 1.26-2.42]; P for trend < .001)., Conclusions and Relevance: Asthma and lack of asthma control were associated with moderately increased risks of AF in a dose-response manner. Further studies are needed to explore the underlying mechanisms and clarify causal pathways between asthma and AF.

Background: Pulseless electrical activity (PEA) is a frequent initial rhythm in cardiac arrest, and ECG characteristics have been linked to prognosis. The aim of this study was to examine the development of ECG characteristics during advanced life support (ALS) and cardiopulmonary resuscitation (CPR) in cardiac arrest with initial PEA, and to assess any association with survival., Methods: Patients with in-hospital cardiac arrest with initial PEA at St. Olav Hospital (Trondheim, Norway) over a three-year period were included. A total of 2187 combined observations of QRS complex rate (heart rate) and QRS complex width for the duration of ALS were determined from defibrillator recordings from 74 episodes of cardiac arrest., Results: Increasing heart rate and decreasing QRS complex width during ALS was significantly more prevalent in patients who obtained return of spontaneous circulation compared to patients who were declared dead., Conclusion: Changes in ECG characteristics during ALS in cardiac arrest presenting as PEA are related to prognosis. An increase in heart rate was observed in the last 3-6 min before ROSC was obtained., (Copyright © 2018 The Author(s). Published by Elsevier B.V. All rights reserved.)

Aims: Increasing age is the most important risk factor for atrial fibrillation (AF). Very high doses of exercise training might increase AF risk, while moderate levels seem to be protective. This study aimed to examine the effects of age on vulnerability to AF and whether long-term aerobic interval training (AIT) could modify these effects. Methods: Nine months old, male Sprague-Dawley rats were randomized to AIT for 16 weeks (old-ex) or to a sedentary control group (old-sed), and compared to young sedentary males (young-sed). After the intervention, animals underwent echocardiography, testing of exercise capacity (VO 2max ), and electrophysiology with AF induction before ex vivo electrophysiology. Fibrosis quantification, immunohistochemistry and western blotting of atrial tissue were performed. Results: Sustained AF was induced in vivo in 4 of 11 old-sed animals, but none of the old-ex or young-sed rats ( p = 0.006). VO 2max was lower in old-sed, while old-ex had comparable results to young-sed. Fibrosis was increased in old-sed ( p = 0.006), with similar results in old-ex. There was a significantly slower atrial conduction in old-sed ( p = 0.038), with an increase in old-ex ( p = 0.027). Action potential duration was unaltered in old-sed, but prolonged in old-ex ( p = 0.036). There were no differences in amount of atrial connexin 43 between groups, but a lateralization in atrial cardiomyocytes of old-sed, with similar findings in old-ex. Conclusion: AF vulnerability was higher in old-sed animals, associated with increased atrial fibrosis, lateralization of connexin-43, and reduced atrial conduction velocity. AIT reduced the age-associated susceptibility to AF, possibly through increased conduction velocity and prolongation of action potentials.

Background: Compelling evidence suggests that excessive alcohol consumption increases the risk of atrial fibrillation (AF), but the effect of light-moderate alcohol consumption is less certain. We investigated the association between alcohol consumption within recommended limits and AF risk in a light-drinking population., Methods and Results: Among 47 002 participants with information on alcohol consumption in a population-based cohort study in Norway, conducted from October 2006 to June 2008, 1697 validated AF diagnoses were registered during the 8 years of follow-up. We used Cox proportional hazard models with fractional polynomials to analyze the association between alcohol intake and AF. Population attributable risk for drinking within the recommended limit (ie, at most 1 drink per day for women and 2 drinks per day for men without risky drinking) compared with nondrinking was also calculated. The average alcohol intake was 3.8±4.8 g/d. The adjusted hazard ratio for AF was 1.38 (95% confidence interval, 1.06-1.80) when we compared participants consuming >7 drinks per week with abstainers. When we modeled the quantity of alcohol intake as a continuous variable, the risk increased in a curvilinear manner. It was higher with heavier alcohol intake, but there was virtually no association at <1 drink per day for women and <2 drinks per day for men in the absence of risky drinking. The population attributable risk among nonrisky drinkers was 0.07% (95% confidence interval, -0.01% to 0.13%)., Conclusions: Although alcohol consumption was associated with a curvilinearly increasing risk of AF in general, the attributable risk of alcohol consumption within recommended limits among participants without binge or problem drinking was negligible in this population., (© 2017 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley.)

Introduction: Pulseless electrical activity (PEA) is an increasingly common presentation in cardiac arrest. The aim of this study was to investigate possible associations between early ECG patterns in PEA and the underlying causes and survival of in-hospital cardiac arrest (IHCA)., Methods: Prospectively observed episodes of IHCA presenting as PEA between January 2009 and august 2013, with a reliable cause of arrest and corresponding defibrillator ECG recordings, were analysed. QRS width, QT interval, Bazett's corrected QT interval, presence of P waves and heart rate (HR) was determined. QRS width and HR were considered to be normal below 120ms and within 60-100 cardiac cycles per minute, respectively., Results: Fifty-one episodes fulfilled the inclusion criteria. The defibrillator was attached after a median of one minute (75th percentile; 3min) after the onset of arrest. Ninety percent (46/51) had widened QRS complexes, 63% (32/51) were defined as 'wide-slow' due to QRS-widened bradycardia, and only 6% (3/51) episodes were categorized as normal. No unique cause-specific ECG pattern could be identified. Further 7 episodes with a corresponding defibrillator file, but without a reliable cause, were included in analysis of survival. Abnormal ECG patterns were seen in all survivors. None of the patients with 'normal' PEA survived., Conclusion: Abnormal ECG patterns were frequent at the early stage of in-hospital PEA. No unique patterns were associated with the underlying causes or survival., (Copyright © 2016 The Author(s). Published by Elsevier Ireland Ltd.. All rights reserved.)

Background: Exercise training is an effective treatment for important atrial fibrillation (AF) comorbidities. However, a high level of endurance exercise is associated with an increased AF prevalence. We assessed the effects of aerobic interval training (AIT) on time in AF, AF symptoms, cardiovascular health, and quality of life in AF patients., Methods and Results: Fifty-one patients with nonpermanent AF were randomized to AIT (n=26) consisting of four 4-minute intervals at 85% to 95% of peak heart rate 3 times a week for 12 weeks or to a control group (n=25) continuing their regular exercise habits. An implanted loop recorder measured time in AF continuously from 4 weeks before to 4 weeks after the intervention period. Cardiac function, peak oxygen uptake (o2peak), lipid status, quality of life, and AF symptoms were evaluated before and after the 12-week intervention period. Mean time in AF increased from 10.4% to 14.6% in the control group and was reduced from 8.1% to 4.8% in the exercise group (P=0.001 between groups). AF symptom frequency (P=0.006) and AF symptom severity (P=0.009) were reduced after AIT. AIT improved o2peak, left atrial and ventricular ejection fraction, quality-of-life measures of general health and vitality, and lipid values compared with the control group. There was a trend toward fewer cardioversions and hospital admissions after AIT., Conclusions: AIT for 12 weeks reduces the time in AF in patients with nonpermanent AF. This is followed by a significant improvement in AF symptoms, o2peak, left atrial and ventricular function, lipid levels, and QoL., Clinical Trial Registration: URL: http://www.clinicaltrials.gov. Unique identifier: NCT01325675., (© 2016 American Heart Association, Inc.)

Diabetes mellitus (DM) increases the risk of heart failure after myocardial infarction (MI), and aggravates ventricular arrhythmias in heart failure patients. Although exercise training improves cardiac function in heart failure, it is still unclear how it benefits the diabetic heart after MI. To study the effects of aerobic interval training on cardiac function, susceptibility to inducible ventricular arrhythmias and cardiomyocyte calcium handling in DM mice after MI (DM-MI). Male type 2 DM mice (C57BLKS/J Lepr (db) /Lepr (db) ) underwent MI or sham surgery. One group of DM-MI mice was submitted to aerobic interval training running sessions during 6 weeks. Cardiac function and structure were assessed by echocardiography and magnetic resonance imaging, respectively. Ventricular arrhythmias were induced by high-frequency cardiac pacing in vivo. Protein expression was measured by Western blot. DM-MI mice displayed increased susceptibility for inducible ventricular arrhythmias and impaired diastolic function when compared to wild type-MI, which was associated with disruption of cardiomyocyte calcium handling and increased calcium leak from the sarcoplasmic reticulum. High-intensity exercise recovered cardiomyocyte function in vitro, reduced sarcoplasmic reticulum diastolic calcium leak and significantly reduced the incidence of inducible ventricular arrhythmias in vivo in DM-MI mice. Exercise training also normalized the expression profile of key proteins involved in cardiomyocyte calcium handling, suggesting a potential molecular mechanism for the benefits of exercise in DM-MI mice. High-intensity aerobic exercise training recovers cardiomyocyte function and reduces inducible ventricular arrhythmias in infarcted diabetic mice.

Aim: Catecholaminergic polymorphic ventricular tachycardia (CPVT) is an inherited cardiac disease predisposing to life-threatening arrhythmias. We aimed to determine the prevalence of arrhythmias and efficacy of beta-blocker treatment in mutation-positive family members diagnosed by cascade genetic screening., Methods and Results: Relatives of six unrelated CPVT patients were tested for the relevant mutation in the ryanodine receptor-2 gene. Mutation carriers underwent an exercise test at inclusion time and 3 months after the initiation of beta-blocker therapy in the highest tolerable dose. The occurrence of ventricular premature beats, couplets, and non-sustained ventricular arrhythmias (nsVT) were recorded in addition to the heart rate at which they occurred. Thirty family members were mutation carriers and were followed for 22 (13-288) months. Previous undiagnosed CPVT-related symptoms were reported by eight subjects. Exercise test induced ventricular arrhythmias in 23 of the 30 mutation carriers. On beta-blocker treatment, exercise-induced arrhythmias occurred at a lower heart rate (117 +/- 17 vs. 135 +/- 34 beats/min, P = 0.02) but at similar workload (P = 0.78). Beta-blocker treatment suppressed the occurrence of exercise-induced nsVT in three of the four patients, while less severe arrhythmias were unchanged. One patient died during follow-up., Conclusion: Exercise test revealed a high prevalence of arrhythmias in CPVT mutation carriers diagnosed by cascade genetic screening. beta-Blocker therapy appeared to suppress the most severe exercise-induced arrhythmias, while less severe arrhythmias occurred at a lower heart rate.

Objectives: The aim of this study was to investigate whether myocardial strain echocardiography can predict ventricular arrhythmias in patients after myocardial infarction (MI)., Background: Left ventricular (LV) ejection fraction (EF) is insufficient for selecting patients for implantable cardioverter-defibrillator (ICD) therapy after MI. Electrical dispersion in infarcted myocardium facilitates malignant arrhythmia. Myocardial strain by echocardiography can quantify detailed regional and global myocardial function and timing. We hypothesized that electrical abnormalities in patients after MI will lead to LV mechanical dispersion, which can be measured as regional heterogeneity of contraction by myocardial strain., Methods: We prospectively included 85 post-MI patients, 44 meeting primary and 41 meeting secondary ICD prevention criteria. After 2.3 years (range 0.6 to 5.5 years) of follow-up, 47 patients had no and 38 patients had 1 or more recorded arrhythmias requiring appropriate ICD therapy. Longitudinal strain was measured by speckle tracking echocardiography. The SD of time to maximum myocardial shortening in a 16-segment LV model was calculated as a parameter of mechanical dispersion. Global strain was calculated as average strain in a 16-segment LV model., Results: The EF did not differ between ICD patients with and without arrhythmias occurring during follow-up (34 +/- 11% vs. 35 +/- 9%, p = 0.70). Mechanical dispersion was greater in ICD patients with recorded ventricular arrhythmias compared with those without (85 +/- 29 ms vs. 56 +/- 13 ms, p < 0.001). By Cox regression, mechanical dispersion was a strong and independent predictor of arrhythmias requiring ICD therapy (hazard ratio: 1.25 per 10-ms increase, 95% confidence interval: 1.1 to 1.4, p < 0.001). In patients with an EF >35%, global strain showed better LV function in those without recorded arrhythmias (-14.0% +/- 4.0% vs. -12.0 +/- 3.0%, p = 0.05), whereas the EF did not differ (44 +/- 8% vs. 41 +/- 5%, p = 0.23)., Conclusions: Mechanical dispersion was more pronounced in post-MI patients with recurrent arrhythmias. Global strain was a marker of arrhythmias in post-MI patients with relatively preserved ventricular function. These novel parameters assessed by myocardial strain may add important information about susceptibility for ventricular arrhythmias after MI., (Copyright 2010 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

A 20-year-old woman presented with dyspnoea in the Emergency department and subsequently suffered a cardiac arrest. The initial rhythm was PEA (pulseless electrical activity). She had intermittent return of spontaneous circulation. Transthoracic echocardiography showed a dilated hypokinetic right ventricle and a collapsed left ventricle. The tentative diagnosis was pulmonary embolism, but she remained hemodynamically unstable despite thrombolysis. 90 min after the collapse she was put on cardiopulmonary bypass and surgical embolectomy was performed. Large masses of thrombotic material were collected from central parts of the right and left pulmonary artery. Therapeutic hypothermia was applied for 24 hours postoperatively. The remaining hospital stay was uneventful and ten days after the presentation she was transferred to her local hospital. At this point she was without neurological sequelae. The patient had used oral contraceptives (ethinyl estradiol/ drospirenone).

Background: This study aims to investigate changes that occur during progression and establishment of physiological and pathological cardiac hypertrophy, by microarray technology and functional annotations., Design and Methods: Myocardial infarction leading to heart failure was induced in rats, with animals killed 1, 3, 7, 14, 42, and 92 days after coronary artery ligation. A second group was subjected to daily treadmill exercise and killed 1, 4, 24, and 48 h after a single exercise bout, or after 28 or 56 days of exercise training., Results: Physiological hypertrophy was associated with less transcriptional alternation than pathological hypertrophy, indicating that posttranscriptional and translational regulation may be more important. The main difference between the two types of hypertrophy was that myocardial infarction was associated with downregulation of genes related to fatty acid metabolism, whereas no such change occurred after exercise training. Thus, fatty acid metabolism may distinguish adverse maladaptive hypertrophy from beneficial adaptive hypertrophy., Conclusion: This study points to specific genes and gene classes related to biological processes that may be important in these well-characterized rat models of physiological and pathological cardiac hypertrophy.

Regular exercise training is recognized as a powerful tool to improve work capacity, endothelial function and the cardiovascular risk profile in obesity, but it is unknown which of high-intensity aerobic exercise, moderate-intensity aerobic exercise or strength training is the optimal mode of exercise. In the present study, a total of 40 subjects were randomized to high-intensity interval aerobic training, continuous moderate-intensity aerobic training or maximal strength training programmes for 12 weeks, three times/week. The high-intensity group performed aerobic interval walking/running at 85-95% of maximal heart rate, whereas the moderate-intensity group exercised continuously at 60-70% of maximal heart rate; protocols were isocaloric. The strength training group performed 'high-intensity' leg press, abdominal and back strength training. Maximal oxygen uptake and endothelial function improved in all groups; the greatest improvement was observed after high-intensity training, and an equal improvement was observed after moderate-intensity aerobic training and strength training. High-intensity aerobic training and strength training were associated with increased PGC-1alpha (peroxisome-proliferator-activated receptor gamma co-activator 1alpha) levels and improved Ca(2+) transport in the skeletal muscle, whereas only strength training improved antioxidant status. Both strength training and moderate-intensity aerobic training decreased oxidized LDL (low-density lipoprotein) levels. Only aerobic training decreased body weight and diastolic blood pressure. In conclusion, high-intensity aerobic interval training was better than moderate-intensity aerobic training in improving aerobic work capacity and endothelial function. An important contribution towards improved aerobic work capacity, endothelial function and cardiovascular health originates from strength training, which may serve as a substitute when whole-body aerobic exercise is contra-indicated or difficult to perform.

Long-term hyperserotoninemia induces heart valve disease in rats, and cases of cardiac valvulopathies have been reported in patients using ergolines, possibly through activation of the 5-hydroxytryptamine(2B) (5HT(2B)) receptor. The ergoline terguride (transdihydrolisuride) is a 5HT(2B/2C) receptor antagonist. Using a rat model, we have investigated whether terguride could prevent serotonin-induced changes in general and heart disease specifically. During 4 months, twelve Sprague-Dawley rats were given daily subcutaneous serotonin injections; twelve rats received a combination of serotonin injections and terguride by gavage, whereas ten rats were untreated controls. Using echocardiography, rats with aortic insufficiency were found in all 3 groups, while pulmonary insufficiency was only found in two rats injected with serotonin alone. Animals given serotonin alone had significantly higher heart weights compared to the controls (p=0.029) and rats given terguride (p=0.034). Rats injected with serotonin alone developed macroscopic skin changes at the injection sites, histologically identified as orthokeratosis and acanthosis. Terguride completely prevented these changes (p=0.0001, p=0.0003). Liver weights were higher in the animals given serotonin alone compared to controls (p=0.014) and terguride treated animals (p=0.009). Stomach weights were higher in animals given serotonin alone compared to rats given terguride (p=0.012). In the mesenchymal cell-line MC3T3-E1, terguride almost completely inhibited serotonin-induced proliferation (p<0.01). Serotonin increases heart, liver and stomach weights, possibly through enhanced proliferation. Terguride inhibits these effects. We propose that terguride may have beneficial effects in the treatment of diseases such as carcinoid syndrome, where serotonin plays an important pathogenic role.

Aim: To determine whether reduced cardiomyocyte contractility in heart failure is associated with reduced intracellular pH (pH(i)). Involvement of the Na(+)/H(+) exchanger and the H(+)/K(+) ATPase were investigated with specific blockers., Methods: Myocardial infarction and subsequent heart failure in Sprague-Dawley rats were induced by chronic occlusion of the left coronary artery. 6 weeks post-ligation, contractility (cell shortening) and pH(i) (BCECF fluorescence) were recorded in freshly dissociated cardiomyocytes during 2-10 Hz electrical stimulation, with or without either Na(+)/H(+) exchanger or H(+)/K(+) ATPase inhibition., Results: Elevated end-diastolic and reduced peak systolic pressures confirmed heart failure. Increased heart weights (20-30%; P < or = 0.01) and cardiomyocyte lengths and widths (22-25%; P < or = 0.01) confirmed substantial cardiac hypertrophy. In myocytes isolated from sham operated rats, a positive staircase response occurred with stimulation rates from 2 to 7 Hz; further increases in stimulation rate up to 10 Hz reduced contractility. In contrast, pH(i) fell progressively over the entire stimulation range. In failing myocytes, pH(i) was consistently 0.07 pH units lower and contractility 40% lower (P < or = 0.01) than sham control values; the shape of the contractility staircase remained similar to controls. At all stimulation frequencies, Na(+)/H(+) exchanger inhibition reduced pH(i) by 0.05 pH units (P < or = 0.01) and contractility by 22% (P < or = 0.05) in cardiomyocytes from the heart failure group. A significantly smaller decrease of pH(i) and reduction in contractility was observed after inhibition of Na(+)/H(+) exchanger (10 micro m HOE694) in sham myocytes. H(+)/K(+) ATPase inhibition (100 micro m SCH28080) had no effect on pH(i)., Conclusion: Reduced pH(i) is accompanied by reduced cardiomyocyte contractility in isolated myocytes from post-MI heart failure. The data suggest compensatory Na(+)/H(+) exchanger activation in heart failure, whereas H(+)/K(+) ATPase does not appear to contribute significantly to pH(i) maintenance.

Objective: Current guidelines are controversial regarding exercise intensity in cardiovascular prevention and rehabilitation. Although high-intensity training induces larger increases in fitness and maximal oxygen uptake (VO(2max)), moderate intensity is often recommended as equally effective. Controlled preclinical studies and randomized clinical trials are required to determine whether regular exercise at moderate versus high intensity is more beneficial. We therefore assessed relative effectiveness of 10-week HIGH versus moderate (MOD) exercise intensity on integrative and cellular functions., Methods: Sprague-Dawley rats performed treadmill running intervals at either 85%-90% (HIGH) or 65%-70% (MOD) of VO2max 1 h per day, 5 days per week. Weekly VO2max-testing adjusted exercise intensity., Results: HIGH and MOD increased VO2max by 71% and 28%, respectively. This was paralleled by intensity-dependent cardiomyocyte hypertrophy, 14% and 5% in HIGH and MOD, respectively. Cardiomyocyte function (fractional shortening) increased by 45% and 23%, contraction rate decreased by 43% and 39%, and relaxation rate decreased by 20% and 10%, in HIGH and MOD, respectively. Ca2+ transient time-courses paralleled contraction/relaxation, whereas Ca2+ sensitivity increased 40% and 30% in HIGH and MOD, respectively. Carotid artery endothelial function improved similarly with both intensities. EC50 for acetylcholine-induced relaxation decreased 4.3-fold in HIGH (p < 0.05) and 2.8-fold in MOD (p < 0.20) as compared to sedentary; difference HIGH versus MOD 1.5-fold (p = 0.72). Multiple regression identified rate of systolic Ca2+ increase and diastolic myocyte relengthening as main variables associated with VO2max. Cell hypertrophy, contractility and vasorelaxation also correlated significantly with VO2max., Conclusions: The present study demonstrates that cardiovascular adaptations to training are intensity-dependent. A close correlation between VO2max, cardiomyocyte dimensions and contractile capacity suggests significantly higher benefit with high intensity, whereas endothelial function appears equivalent at moderate levels. Thus, exercise intensity emerges as an important variable in future preclinical and clinical investigations.