Search

Background - Prompt myocardial revascularization with percutaneous coronary intervention (PCI) reduces infarct size and improves outcomes in patients with ST-segment elevation myocardial infarction (STEMI). However, as much as 50% of the loss of viable myocardium may be attributed to the reperfusion injury and the associated inflammatory response. Objectives - This study sought to evaluate the effect of the interleukin-6 receptor inhibitor tocilizumab on myocardial salvage in acute STEMI. Methods - The ASSAIL-MI trial was a randomized, double-blind, placebo-controlled trial conducted at 3 high-volume PCI centers in Norway. Patients admitted with STEMI within 6 h of symptom onset were eligible. Consenting patients were randomized in a 1:1 fashion to promptly receive a single infusion of 280 mg tocilizumab or placebo. The primary endpoint was the myocardial salvage index as measured by magnetic resonance imaging after 3 to 7 days. Results - We randomized 101 patients to tocilizumab and 98 patients to placebo. The myocardial salvage index was larger in the tocilizumab group than in the placebo group (adjusted between-group difference 5.6 [95% confidence interval: 0.2 to 11.3] percentage points, p = 0.04). Microvascular obstruction was less extensive in the tocilizumab arm, but there was no significant difference in the final infarct size between the tocilizumab arm and the placebo arm (7.2% vs. 9.1% of myocardial volume, p = 0.08). Adverse events were evenly distributed across the treatment groups. Conclusions - Tocilizumab increased myocardial salvage in patients with acute STEMI. (ASSessing the effect of Anti-IL-6 treatment in Myocardial Infarction [ASSAIL-MI]; NCT03004703)

Sleep apnea is a common and strongly under-diagnosed severe sleep-related respiratory disorder with periods of disrupted or reduced breathing during sleep. To diagnose sleep apnea, sleep data are collected with either polysomnography or polygraphy and scored by a sleep expert. We investigate in this work the use of supervised machine learning to automate the analysis of polygraphy data from the A3 study containing more than 7,400 hours of sleep monitoring data from 579 patients. We conduct a systematic comparative study of classification performance and resource use with different combinations of 27 classifiers and four sleep signals. The classifiers achieve up to 0.8941 accuracy (kappa: 0.7877) when using all four signal types simultaneously and up to 0.8543 accuracy (kappa: 0.7080) with only one signal, i.e., oxygen saturation. Methods based on deep learning outperform other methods by a large margin. All deep learning methods achieve nearly the same maximum classification performance even when they have very different architectures and sizes. When jointly accounting for classification performance, resource consumption and the ability to achieve with less training data high classification performance, we find that convolutional neural networks substantially outperform the other classifiers.

Background We recently showed that interleukin (IL)-6 inhibition by tocilizumab improves myocardial salvage in ST-elevation myocardial infarction (STEMI). However, the mechanisms for this effect are not clear. Methods In this exploratory sub-study of the ASSAIL-MI trial, we examined leukocyte differential counts and their relation to myocardial salvage and peak troponin T (TnT) in STEMI patients randomised to tocilizumab (n = 101) or placebo (n = 98). We performed RNA-sequencing on whole blood (n = 40) and T cells (n = 20). B and T cell subpopulations were examined by flow cytometry (n = 69). Findings (i) STEMI patients had higher neutrophil counts at hospitalisation compared with stable angina patients. (ii) After percutaneous coronary intervention there was a gradual decline in neutrophils, which was significantly more pronounced in the tocilizumab group. (iii) The decrease in neutrophils in the tocilizumab group was associated with improved myocardial salvage and lower peak TnT. (iv) RNA-sequencing suggested that neutrophil function was also attenuated by tocilizumab. (v) B and T cell sub-populations changed only minimally after STEMI with minor effects of tocilizumab, supported as well by RNA-sequencing analyses of T cells. (vi) However, a low CD8+ count was associated with improved myocardial salvage in patients admitted to the hospital > 3 h after symptom onset. Interpretation Tocilizumab induced a rapid reduction in neutrophils and seemed to attenuate neutrophil function in STEMI patients potentially related to the beneficial effects of tocilizumab on myocardial salvage. Funding South-Eastern Norway Regional Health Authority (Nos. 2019067, 2017084), the Central Norway Regional Health Authority and Norwegian Research Council (No. 283867).

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 effec...

Funding Acknowledgements Type of funding sources: Public grant(s) – National budget only. Main funding source(s): South-Eastern Norway Regional Health Authority OnBehalf OUH Background Obstructive sleep apnea (OSA) is common in patients with atrial fibrillation (AF). Studies have reported an association between OSA and increased AF burden, as well as increased recurrence of AF after catheter ablation. However, whether treatment with positive airway pressure (CPAP) can reduce the risk of AF recurrence after pulmonary vein isolation has still not been established. Purpose This is the first randomized study evaluating the effect of CPAP treatment on AF recurrence after pulmonary vein isolation in patients with AF and OSA. Methods Consecutive patients with AF referred for catheter ablation were included after being screened positive for OSA (apnea-hypopnea index [AHI] ≥ 15 events/h). All patients received an implantable loop recorder 6 months prior to ablation to quantify the arrhythmia burden. Patients were randomized to CPAP treatment or no treatment of OSA during five months before and 12 months after ablation. The primary end point was AF recurrence, defined as one episode of AF lasting longer than 30 seconds after catheter ablation, with an initial 90-day blanking period. We also compared AF burden measured in percent of time in AF and assessed five months before and 3-12 months after catheter ablation. Results We included 83 patients (65% male, age 61 ± 7.3 years), of which 37 patients were treated with CPAP and 46 controls. The mean baseline AHI in patients with CPAP was 26.7 ± 14.7 and in patients with usual care 26.3 ± 12.3. AF-burden prior to catheter ablation expressed as median [IQR] percent of time was 2.7 [0.9-9.1] in the CPAP-group compared to 1.8 [0.2-6.4] in the control group (p = 0.24). There was no signal to a difference in AF recurrence rate between patients with or without CPAP treatment. As shown in figure, we found overlapping curves with a final 21 patients [57%] vs. 26 patients (57%) presenting at least 30 seconds of AF. After catheter ablation and blanking period, patients with CPAP treatment had an AF burden of 0.0 [0.0-0.3] % compared to 0.0 [0.0-0.3] % in patients without CPAP (p = 0.64). Conclusion In this randomized study concomitant treatment with CPAP on top of pulmonary vein isolation had no added effect on the risk of AF recurrence in patients with OSA. Although several patients revealed at least 30 seconds of AF 3-12 months after ablation, there was a great reduction in percent AF burden after catheter ablation independent of CPAP treatment. Abstract Figure

Background There is strong evidence for an association between atrial fibrillation (AF) and sleep apnea (SA). Purpose We aimed to examine the effect of treatment with continuous positive airway pressure (CPAP) on the burden of AF. Methods After a run-in period for CPAP-tolerance, we randomly assigned 108 eligible patients between 18–75 years, who had paroxysmal AF and moderate-to-severe obstructive SA (apnea-hypopnea index (AHI)≥15), to receive either CPAP treatment (n=54) plus usual care or usual care alone (n=54) for five months. An implanted loop recorder measured time in AF continuously. The primary endpoint was the difference in change of AF burden (% of time in AF) between CPAP treatment and usual care from baseline (one month prior to randomization) to the last three months of the intervention period. Secondary endpoints were changes in quality of life assessed by the Short Form-36 (SF-36), Epworth Sleepiness Scale (ESS), and the Functional Outcomes of Sleep Questionnaire (FOSQ). Results Mean (SD) age was 62.4 (7.7) years, BMI 29.4 (4.2) kg/m2, ESS 7.9 (3.2), and 76.1% were men. In the intervention group, the mean duration of adherence to CPAP therapy was 4.3 hours/night. During treatment mean AHI decreased from 27.6 events/hour at baseline to 2.3 events/hour during follow-up. Mean time in AF decreased from 5.0%-4.3% in the control group and from 5.6%-4.1% in the CPAP group, but the difference in change was not significant (p=0.52). Sub-analysis of those using CPAP> Conclusion This is the first randomized controlled trial to assess the effect of treatment of SA on the burden of AF, and did not detect a difference between those treated with CPAP compared to usual care alone. Funding Acknowledgement Type of funding source: Public hospital(s). Main funding source(s): Oslo University Hospital is the main funding Source. ResMed Science Center provided an unrestricted grant.

There is strong evidence for an association between atrial fibrillation (AF) and sleep apnea (SA). We aimed to examine the effect of treatment with continuous positive airway pressure (CPAP) on the burden of AF. We randomly assigned 108 patients between 18-75 years, who had paroxysmal AF and moderate-to-severe obstructive SA (apnea-hypopnea index (AHI)≥15) to receive either CPAP treatment (n=54) plus usual care or usual care alone (n=54) for five months. An implanted loop recorder measured time in AF continuously. The primary endpoint was the difference in change of AF burden (% of time in AF) between CPAP treatment and usual care from baseline (one month pre randomization) to the last three months of the intervention period. Secondary endpoints were changes in quality of life assessed by the Short Form-36 (SF-36), Epworth Sleepiness Scale (ESS) and the Functional Outcomes of Sleep Questionnaire (FOSQ) Mean (SD) age was 62.4 (7.7) years, BMI 29.4 (4.2) kg/m², ESS 7.9 (3.2), and 76.1% were men. In the intervention group, the mean duration of adherence to CPAP therapy was 4.3 hours/night. During treatment mean AHI decreased from 27.6 events/hour at baseline to 2.3 events/hour during follow-up. Mean time in AF decreased from 5.0%-4.3% in the control group and from 5.6%-4.1% in the CPAP group, but the difference in change was not significant (p=0.52). Subanalysis of those using CPAP> This is the first randomized controlled trial to assess the effect of treatment of SA on the burden of AF, and did not detect a difference between those treated with CPAP compared to usual care alone.

Background: Prompt myocardial revascularisation with percutaneous coronary intervention (PCI) reduces infarct size and improves outcomes in patients with acute ST segment elevation myocardial infarction (STEMI). However, as much as 50 % of the loss of viable myocardium may be attributed to the subsequent reperfusion injury and the associated inflammatory response. The aim of the ASSessing the effect of Anti-IL-6 treatment in Myocardial Infarction (ASSAIL-MI) trial was to evaluate the effect of interleukin-6 (IL-6) receptor inhibition on myocardial salvage in acute STEMI. Methods: The ASSAIL-MI trial was a randomised, double blind, placebo-controlled trial performed at three high-volume PCI centres in Norway. Patients admitted with STEMI within six hours of symptom onset were eligible if they had had no prior myocardial infarction. Consenting patients were randomised in a 1:1 fashion to receive a single infusion of the IL-6 receptor inhibitor tocilizumab or placebo during PCI. The primary endpoint was the myocardial salvage index as measured by cardiac magnetic resonance imaging three to seven days after randomisation. Findings: Between 16 th March 2017 and 10 th February 2020, 101 patients were randomised to tocilizumab and 98 patients were randomised to placebo. In the intention to treat analysis, the myocardial salvage index was 69 ± 19 % in patients allocated to tocilizumab and 64 ± 21 % in the placebo group (adjusted between-group difference 5.6 percentage points, 95 % confidence interval 0·0 – 11·3 percentage points, p = 0 · 04). There were 34 serious adverse events, 19 of which occurred in patients treated with tocilizumab and 15 in patients receiving placebo.Interpretation: Treatment with tocilizumab significantly improved myocardial salvage in patients presenting with acute STEMI. Funding: The South-Eastern Norway Regional Health Authority, the Central Norway Regional Health Authority, and Roche TM supported the trial. Roche™ provided the investigational medicinal products and an unrestricted grant. Trial registration number: ClinicalTrials.gov (NCT3004703). Funding Statement: The South-Eastern Norway Regional Health Authority, the Central Norway Regional Health Authority, and RocheTM supported the trial. Roche™ provided the investigational medicinal products and an unrestricted grant. Declaration of Interests: Dr Gullestad has received lecture fees from AstraZeneca, Boehringer Ingelheim, Novartis and Amgen and has been a member of local advisory board in AstraZeneca and Boehringer Ingelheim. The other authors do not have conflicts of interest pertaining to this work. Ethics Approval Statement: The trial protocol was approved by the regional ethics committee (REK Sor-Ost 2016/1223), and all participants provided written informed consent. An independent data and safety monitoring board oversaw the safety of the trial. The trial was conducted in compliance with the declaration of Helsinki and with the rules outlined in the guidelines for Good Clinical Practice.

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).

Background: The association between sleep apnea (SA) and atrial fibrillation (AF) is strong. SA is probably underdiagnosed in AF patients. Polysomnography (PSG) is time consuming and costly and a valid screening tool is warranted. Aims and Objectives: The aim was to determine if the Berlin Questionnaire (BQ) and the STOP-Bang Questionnaire (SBQ) can be used as a screening tool in patients with paroxysmal atrial fibrillation (PAF). Methods: We prospectively studied 565 PAF patients. Risk for sleep apnea was assessed with the BQ and the SBQ. SA was defined as an apnea-hypopnea index (AHI) ≥15/h obtained by polygraphy (PG) two nights at home. Sleep studies were analyzed by an experienced specialist, using standard American Academy of Sleep Medicine definitions. A BQ high risk subject was defined as ≥2 of 3 risk factors: (I) snoring; (II) daytime somnolence; and (III) hypertension or a body mass index (BMI) > 30 kg/m². A SBQ high risk subject was defined as ≥5 affirmative answers to the 8 STOP-Bang items. Results: Mean age was 60 (9) years and mean BMI 29 (4) kg/m². 238 (42%) had an AHI ≥ 15/h. According to SBQ low, intermediate and high risk of SA was 7%, 14% and 21% respectively. The SBQ score ≥3 was 84% sensitive and 45 % specific for diagnosis of SA. For those with low risk and high risk according to the BQ score 19% and 23% had SA, respectively. The BQ performed with 56% sensitivity and 70% specificity. Conclusions: Of two commonly used questionnaires to screen for SA, neither the SBQ nor the BQ questionnaire discriminated well between those with or without SA in patients with PAF. Until better screening tools are available PG or PSG needs to be used to detect SA in these patients.

Background: Recent studies have suggested a strong association between sleep apnea (SA) and atrial fibrillation (AF). Aims and Objectives: In this study we aimed to examine clinical predictors to identify SA and the prevalence and type of SA in patients with paroxysmal AF. Methods: We prospectively studied 578 patients with paroxysmal AF. SA was diagnosed using portable polygraphy two nights at home. Sleep studies were analyzed by an experienced specialist, using standard American Academy of Sleep Medicine definitions. The degree of subjective daytime sleepiness was assessed by Epworth Sleepiness Scale (ESS). Body composition data were collected using a body composition analyzer (Tanita BC-545N). We calculated differences in variables between SA categories by Chi-Square Test or ANOVA as appropriate. Results: 158 women (27 %) and 420 men (73%) were enrolled. Mean age (SD) was 60 (10) years and mean BMI 29 (4) kg/m². 477 (83%) of the patients had an apnea-hypopnea index (AHI) ≥ 5/h, while moderate/severe SA (AHI ≥ 15/h) was diagnosed in 243 patients (42%). The type of SA was predominantly obstructive, with mean AHI 15.3/h (12) (range 0.4/h-85.8/h). Mean central apnea index was 0.8/h (2). AHI increased with age, BMI, weight, neck-and waist circumference, body fat, visceral fat and metabolic age. Mean ESS score was 7 (4). There was no association between ESS and AHI/h, r=0.08. Conclusions: In our AF population the prevalence of SA (AHI ≥ 5/h) was 83 %, which is several times higher than in the general population (16%). The high prevalence of SA detected in this study may indicate that SA is under-recognized in patients with AF. We found a positive correlation between body composition and SA severity.