Dysregulation of the complement system has been described in patients with heart failure (HF). However, data on the alternative pathway are scarce and it is unknown if levels of factor B (FB) and the ...C3 convertase C3bBbP are elevated in these patients. We hypothesized that plasma levels of FB and C3bBbP would be associated with disease severity and survival in patients with HF.
We analyzed plasma levels of FB, C3bBbP, and terminal C5b-9 complement complex (TCC) in 343 HF patients and 27 healthy controls.
Compared with controls, patients with HF had elevated levels of circulating FB (1.6-fold, p < 0.001) and C3bBbP (1.3-fold, p < 0.001). In contrast, TCC, reflecting the terminal pathway, was not significantly increased (p = 0.15 vs controls). FB was associated with NT-proBNP, troponin, eGFR, and i.e., C-reactive protein. FB, C3bBbP and TCC were not associated with mortality in HF during a mean follow up of 4.3 years.
Our findings suggest that in patients with HF, the alternative pathway is activated. However, this is not accompanied by activation of the terminal pathway.
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).
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.
This study sought to evaluate the effect of the interleukin-6 receptor inhibitor tocilizumab on myocardial salvage in acute STEMI.
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.
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.
Tocilizumab increased myocardial salvage in patients with acute STEMI. (ASSessing the effect of Anti-IL-6 treatment in Myocardial Infarction ASSAIL-MI; NCT03004703)
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Sleep apnea (SA) is highly prevalent in patients with atrial fibrillation (AF), and both conditions are associated with adverse cardiovascular outcomes.
To determine the effect of continuous positive ...airway pressure (CPAP) on AF burden.
This open-label, parallel-group, randomized, controlled trial included patients with paroxysmal AF and moderate-to-severe SA (apnea-hypopnea index ≥15). Eligible patients were randomized (1:1) to 5 months' treatment with CPAP plus usual care (CPAP, n=55) or usual care alone (control, n=54) by a computerised system. Outcome assessment was blinded. The planned primary outcome was the difference between CPAP treatment and control in change of AF burden (% of time in AF), as measured by implantable loop recorder.
A total of 579 patients with paroxysmal AF had respiratory polygraphy, of whom 244 (42.1%) had moderate-to-severe SA. Of these, 158 (64.8%) participated in the CPAP run-in period, of whom 40 (25.3%) patients did not tolerate the treatment. One-hundred-eight patients were available for the primary analysis. The mean time in AF decreased from 5.6% at baseline to 4.1% during the last three 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.
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 registration available at www.clinicaltrials.gov, ID: NCT02727192.
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.
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.
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.
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).
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.
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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.
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/m2. 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 (R2 = 0.003, p = 0.367).
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.
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.
...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).
(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.
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.
South-Eastern Norway Regional Health Authority (Nos. 2019067, 2017084), the Central Norway Regional Health Authority and Norwegian Research Council (No. 283867).
Abstract only Introduction: Obstructive sleep apnea (OSA) is known to cause left atrial (LA) remodeling. The effect of continuous positive airway pressure (CPAP) on LA remodeling in patients with OSA ...and paroxysmal atrial fibrillation (AF) has not been assessed. Hypothesis: We aimed to assess the impact of CPAP treatment on reverse LA deformation and volume in patients with AF and OSA. Methods: In this secondary analysis of a prospective randomized controlled trial, we screened patients with AF for OSA. The majority of patients were referred for pulmonary vein isolation (PVI). We included AF patients with OSA defined as apnea-hypopnea index (AHI) > 15/h. Patients were randomized to CPAP treatment or standard care. Transthoracic echocardiography was performed to assess atrial remodeling by two-dimensional speckle tracking LA reservoir strain (by AFI LA) and LA volume index (LAVI) in apical 2- and 4-chamber views in sinus rhythm at baseline and at 12 months’ follow-up by an investigator blinded to allocated arm. AF burden was monitored by an implantable loop recorder in all patients. Results: We included 104 patients (62 ±7 years old, 77% men, BMI 30 ± 4) of whom 50 were randomized to CPAP and 54 to standard care. PVI was performed in 83 patients six months after the baseline exam. There was no clear improvement in LA reservoir strain in either group from baseline to follow up (CPAP: 30 ± 8 % vs 32 ± 9 %, p = 0.15; standard care: 28 ± 7 % vs 30 ± 6 %, p = 0.11), and there was no difference between the groups (p=0.41). Similarly, LAVI did not change in the CPAP group (38±8 mL/m 2 vs 36± 10ml/m 2 , p= 0.16) or in the standard care group (39± 10 mL/m 2 vs 37 ± 12 ml/m 2 , p= 0.20) during follow-up, with no difference between the two groups (p =0.62). In patients who underwent PVI, the AF burden decreased in both treatment arms, with no between-group difference (p = 0.69). Conclusions: In AF patients with OSA, treatment with CPAP did not improve reverse left atrial remodeling within 12 months. Although the trial was relatively small, these results suggest that CPAP is unlikely to have a major impact on normalization of LA function after atrial fibrillation ablation in this patient group.
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).
Objective Dysregulation of the complement system has been described in patients with heart failure (HF). However, data on the alternative pathway are scarce and it is unknown if levels of factor B ...(FB) and the C3 convertase C3bBbP are elevated in these patients. We hypothesized that plasma levels of FB and C3bBbP would be associated with disease severity and survival in patients with HF. Methods We analyzed plasma levels of FB, C3bBbP, and terminal C5b-9 complement complex (TCC) in 343 HF patients and 27 healthy controls. Results Compared with controls, patients with HF had elevated levels of circulating FB (1.6-fold, p < 0.001) and C3bBbP (1.3-fold, p < 0.001). In contrast, TCC, reflecting the terminal pathway, was not significantly increased (p = 0.15 vs controls). FB was associated with NT-proBNP, troponin, eGFR, and i.e., C-reactive protein. FB, C3bBbP and TCC were not associated with mortality in HF during a mean follow up of 4.3 years. Conclusion Our findings suggest that in patients with HF, the alternative pathway is activated. However, this is not accompanied by activation of the terminal pathway.
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