To Örebro University

BACKGROUND: The clinical utility of risk scores to guide treatment decisions and improve clinical outcomes has rarely been prospectively evaluated. This study aimed to evaluate whether a biomarker-based ABC-AF risk score-guided multidimensional treatment strategy improves long-term outcomes in patients with atrial fibrillation (AF).

METHODS: The multicenter, registry-based, randomized, controlled, open-label study enrolled adults with AF. In the active arm, the investigator was informed of each individual's ABC-AF-score risks for stroke and bleeding, which were used as decision support to tailor treatment recommendations, including preference for type of direct OAC. In the control arm, patient management was at the discretion of the investigator. Primary outcome was a composite of stroke or death. Secondary outcomes included stroke, death, major bleeding events, and their composite outcome.

RESULTS: The intention-to-treat population comprised 3933 patients, median age 73.9 years, 33.6% women, 51.3% had paroxysmal AF, 11.2% had prior stroke or TIA, and 85.7% had OAC treatment. After randomization, 97.8% in active and 92.6% in control arm received OAC, p<0.0001. Enrollment was prematurely terminated owing to safety concerns with a trend towards higher mortality in patients with CHA2DS2-VASc scores of 3 or above, and the study was therefore underpowered for its primary objective. Over a median follow-up of 2.6 years, 175 primary events (3.18/100 patient-years [100PY]) occurred in the active and 148 (2.67/100PY) in the control arm, hazard ratio with 95% confidence interval (HR) 1.19, 0.96-1.48, p=0.12. Major bleeding events were 152 (2.82/100PY) versus 141 (2.61/100PY), HR 1.08; 0.86-1.36, p=0.50; stroke 48 (0.87/100PY) versus 41 (0.74/100PY), HR 1.18, 0.78-1.79, p=0.44; death 136 (2.44/100PY) versus 113 (2.02/100PY), HR 1.21, 0.94-1.55, p=0.13, and rates of the composite stroke, death, or major bleeding 277 (5.21/100PY) versus 244 (4.55/100PY), HR 1.14; 0.96-1.36, p=0.13. Primary outcome results were similar across ABC-AF-score subgroups (interaction p=0.98).

CONCLUSIONS: The individually tailored multidimensional treatment strategy, based on ABC-AF risk scores, did not improve clinical outcomes as compared with usual guideline-based care in patients with AF. The results emphasize the need for prospective testing of the utility of risk stratification and precision medicine tools in different clinical settings before implementation in routine care.

ST-elevation myocardial infarction (STEMI) triggers a significant inflammatory response. Sweat may offer a novel, non-invasive medium for monitoring inflammation. In this prospective study, we characterized the inflammatory signatures in plasma and sweat collected from the skin surface of two patient groups: (1) 18 STEMI patients immediately following percutaneous coronary intervention (exposure) and (2) six patients who underwent outpatient angiography without subsequent intervention (control). Levels of 92 biomarkers were measured using a high-throughput proteomic assay and reassessed after 4-6 weeks in STEMI patients. Adjusting for patient group, sweat biomarkers did not show significant changes over time. In plasma, hepatocyte growth factor and interleukin-6 showed a significant decrease from the acute phase to follow-up, adjusted for patient group. STAM binding protein was significantly higher in the sweat of STEMI patients compared to controls, adjusted for time effects. While sweat was less sensitive than plasma for detecting biomarker levels in the setting of STEMI, its longitudinal analysis via wearable sensors holds promise for detecting specific markers.Trial registration: The trial is registered on www.clinicaltrials.gov with the trial registration number NCT05843006.

OBJECTIVES: To establish the prevalence of clinically significant chronic obstructive pulmonary disease (COPD) and relevant characteristics in individuals with a significant smoking history who are hospitalised for acute myocardial infarction (MI).

DESIGN: Cross-sectional study.

SETTING: Hospital inpatients at 8 European centres (7 in Sweden, 1 in the UK). PARTICIPANTS: 518 men or women (302 in Sweden, 216 in the UK) hospitalised for acute MI, aged 40 years or older, with a smoking history of at least 10 pack-years.

PRIMARY AND SECONDARY OUTCOME MEASURES: The primary outcome was prevalence of detected significant COPD (Global Initiative for Chronic Obstructive Lung Disease stages 2-4), defined as a ratio of forced expiratory volume in 1 and 6 s (FEV1/FEV6) <0.7 and FEV1 <80% of the predicted value, measured using microspirometry. Secondary outcome measures were prior diagnosis of COPD, prescription of inhaled corticosteroids (ICS), symptom burden (COPD Assessment Test (CAT)) and blood eosinophil count.

RESULTS: The prevalence of significant COPD was 91/518 (18% (95% CI 14 to 21)) with no difference between the countries. Of those with detected significant COPD, 69 (76%) had no previous COPD diagnosis. A CAT score >10 was found in 65%, and a blood eosinophil count of ≥100/mm3 and ≥300/mm3 was found in 76% and 20%, respectively. Inhaled corticosteroids were used by 15% of the patients.

CONCLUSIONS: In a cohort of patients hospitalised for acute MI in Sweden and the UK, one in five patients with a history of smoking was found to have significant COPD based on microspirometry. Symptom burden was high and treatment rates with ICS low. Among those diagnosed with COPD, three out of four had not been previously diagnosed with COPD.

BACKGROUND: Stroke and reduced survival are devastating complications of atrial fibrillation (AF). Biomarker-based ABC-AF risk scores improve risk prediction in AF, and risk-guided treatment recommendations may improve patient outcomes.

DESIGN: The ABC AF-study is a national, multicenter, prospective, registry-based, randomized controlled, parallel-group, open-label study. Its primary objective is to evaluate whether ABC-AF risk score-guided treatment recommendations improve outcomes in patients with AF. Consenting patients with AF registered in the Swedish national quality register for AF, AURICULA AF, will be randomized in a 1:1 ratio to either ABC-AF risk score-guided treatment recommendations or standard care. For participants in the active arm, investigators will receive a visual presentation of stroke and bleeding risks along with recommendations regarding the choice of oral anticoagulant (OAC) and additional treatments for stroke and bleeding prevention. In the control arm, patients are managed at the discretion of the investigator.

OUTCOMES: The primary outcome is a composite of stroke or death. Secondary outcomes include the composite of stroke, death, and major bleeding, and the individual components of the primary outcome, myocardial infarction, and hospitalization for heart failure; and a safety endpoint of major bleeding. Study enrollment commenced on October 25, 2018, and terminated on May 12, 2023, after 3,933 patients had been recruited. Study results are expected in 2025.

SUMMARY: The ABC AF-study evaluates whether a personalized treatment recommendation strategy - guided by the biomarker-based ABC-AF risk score decision support - improves outcomes in AF.

In humans, hypothermia prolongs ventricular repolarization and associates with sustained ventricular tachyarrhythmias. In bears, body temperature drops during hibernation similar to moderate human hypothermia, yet they rarely face fatal outcomes during the winter. This suggests protective adaptations in bear electrophysiology. We studied seasonality in ursine ventricular repolarization by analyzing >1 year electrocardiogram (ECG) recordings from loop recorders implanted in 57 free-ranging Eurasian brown bears. In sinus rhythm, bears exhibited significantly longer RR, QT, and Tpeak-Tend intervals (2441 ± 470, 508 ± 50, and 53 ± 8 ms, respectively) during hibernation than in the active period (649 ± 323, 232 ± 39, and 29 ± 5 ms, respectively). Optimal heart rate correction of QT interval (QT/RR0.435) demonstrated significant prolongation during hibernation. QT and Tpeak-Tend intervals remained longer during hibernation than in the active period, even when comparing ECGs with similar RR intervals in the two periods. Ventricular fibrillation occurred in four bears shot during licensed hunting in summer, which led to death. In conclusion, seasonal variations in ventricular repolarization in bears appear, at least partially, independently of heart rate. Compared to humans, ventricular repolarization is slower but more homogeneous. These findings, combined with the absence of fatalities during hibernation, support the theory of protective electrophysiological adaptations in bears. Insights into the underlying mechanisms have biomimetic potential for human therapy.

Background: Education level is an important socioeconomic factor affecting the incidence, symptoms, and treatment of atrial fibrillation (AF). Despite this, data on the association between education level and the incidence of major AF consequences – heart failure (HF), acute myocardial infarction (AMI), and stroke – are limited.     

Aim: To investigate the association between education level and the risk of HF, AMI, and stroke in patients hospitalized with AF.  

Methods: This retrospective cohort study is based on data generated by crosslinking of several Swedish national registries. All patients hospitalized between 1998 and 2003 with a diagnosis of AF were included. The relative risk for incident HF, AMI, and stroke were assessed according to education level categories during a 5–year follow–up. Education levels were categorised as primary, secondary, and academic. Kaplan-Meier curves and Cox regression models adjusted for age, sex, time of AF diagnosis, and the variables of Charlson´s Comorbidity Index were used to estimate the relative risk of the examined outcomes. Hazard ratios (HR) with 95% confidence intervals (CI) were used as estimate of associations and statistical significance level was 5%.Results: The study included 263,172 patients (56.2% male; mean age 72.5±10.4 years). There was a statistically significant dose-dependent association between education level and the risk of AMI and HF in both sexes. Compared to primary education, the HR for AMI was 0.89 (95% CI: 0.85-0.93) for secondary education and 0.71 (95% CI: 0.65-0.78) for academic education in women; and 0.91 (95% CI: 0.87-0.94) for secondary education and 0.75 (95% CI: 0.71-0.80) for academic education in men. The relative risk for HF was similar, with HRs of 0.96 (95% CI: 0.93-1.00) for secondary and 0.82 (95% CI: 0.77-0.87) for academic education in women, and HRs of 0.93 (95% CI: 0.90-0.96) for secondary and 0.76 (95% CI: 0.72-0.80) for academic education in men). Patients with academic education had a significantly lower risk for stroke compared to those with primary education (HR 0.77 (95% CI: 0.71-0.84) in women; HR 0.84 (95% CI: 0.79-0.90) in men), while patients with secondary education did not have a significantly different relative risk for stroke compared to those with primary education.    

Conclusion:  Secondary and academic education levels were associated with a significantly lower risk of HF and AMI in both women and men with AF compared to primary education. Furthermore, academic education was associated with a lower risk of stroke. In conclusion, higher education levels were associated with a lower 5-year risk of HF, AMI, and stroke compared to primary education.

A woman in her 80s experienced a life-threatening complication of pacemaker implant consisting of subacute right ventricular lead perforation causing iatrogenic injury to an intercostal artery, resulting in a large haemothorax. A CT scan confirmed active bleeding from the fourth intercostal artery. The patient underwent cardiothoracic surgery via a median sternotomy approach, during which the source of the bleeding was sealed, a new epicardial lead was positioned, and the original lead was extracted. This case emphasises the potentially severe consequences of pacemaker lead perforation and secondary injury to adjacent structures. It underscores the importance of early recognition and timely intervention, preferably in a tertiary specialist unit equipped for cardiothoracic surgery and confirms the value of pacemaker interrogation and CT scans for diagnosis.

The association of socioeconomic status with cardiovascular morbidity and mortality is well known, but data on the influence of education level on mortality in individuals with atrial fibrillation (AF) are scarce. We investigated education level as a predictor of all-cause mortality in patients diagnosed with AF. This retrospective cohort study used a database created from several Swedish nationwide registries to identify all patients hospitalized with a diagnosis of AF hospitalized from 1995 to 2008. Education level was categorized as primary, secondary, and academic. All-cause mortality risk was estimated in subpopulations defined by the Charlson Comorbidity Index and several comorbidities. A total of 272,182 patients (56% male; mean age 72 ± 10 years) were followed for five years. Cox regression models showed a reduction in all-cause mortality risk with increased education level. Hazard ratios (HR) relative to primary education remained significant after stratification and adjustment for several confounders: secondary education HR = 0.88; 95% CI: 0.86-0.89; P < 0.001; academic education HR = 0.70; 95% CI: 0.67-0.72; P < 0.001. Subpopulation analyses confirmed a significant reduction in relative risk with higher education level. Targeted screening and education programs could be effective in reducing mortality in AF patients with fewer years of formal education.

Introduction: Smoking is a major risk factor for both chronic obstructive pulmonary disease (COPD) and myocardial infarction (MI). Systemic inflammation also contributes to both diseases and has been suggested as a potential target for intervention. Prevalence of COPD in those with a significant smoking history hospitalised for MI has not been well-characterised. We sought to obtain an accurate estimate of COPD burden in this group and characterise the population.

Methods: Two consecutive cohorts of patients hospitalised for MI with a smoking history of ≥10 pack-years were recruited in Sweden and the United Kingdom (UK). Baseline characteristics were recorded, including treatment with inhaled corticosteroids (ICS) and eosinophil count in blood. Microspirometry was performed using the Vitalograph COPD-6 device and symptom burden assessed using the COPD Assessment Test (CAT). The primary outcome was the prevalence of a preliminary diagnosis of clinically-significant COPD, here defined as a ratio of forced expiratory volume in 1 and 6 seconds (FEV1/FEV6) <0.7 and with FEV1 <80% of predicted value.

Results: In the UK cohort, 216 participants with MI (26% female, median age 60 (IQR 53–67) years, smoking history 32 (23–45) pack-years) were recruited. The proportion with any COPD was 36%. Clinically-significant COPD was found in 30 participants (13.9%, 95% CI 9.5–19.2). Of these, 43% had a prior COPD diagnosis, 20% had an eosinophil count ≥300 cells/mm3, mean CAT score was 14.4 ± 9.3), 80% had high symptom burden (CAT score >10) and 23% were receiving ICS. The Swedish cohort included 302 participants with MI (24% female, median age 68 (IQR 61–76) years, 26 (15–38) pack years), and clinically-significant COPD was found in 52 (17.2%; 12.9–21.5). In these 52 participants, 17% had a prior COPD diagnosis, 20% had an eosinophil count ≥300 cells/mm3, mean CAT score was 12.9 ± 7.2, 63% had CAT score ≥10 and 15% had treatment with ICS.

Conclusions: The prevalence of preliminary diagnosis of clinically-significant COPD in patients with a ≥10 pack-year smoking history hospitalised for MI is similar between two European cohorts and under-recognised. Further work is warranted to determine whether identification and treatment of COPD improves clinical outcomes following MI.

Introduction:

The association between social status and cardiovascular morbidity and mortality is well–known. Education level is an important socioeconomic factor which influences the incidence, symptoms, and treatments of atrial fibrillation (AF). However, data about the effects of education level on all-cause mortality in patients with AF are scarce.

Aim:

To explore any association between education level and all-cause mortality in patients hospitalized with AF.

Methods:

This retrospective cohort study is based on a database created by linking Swedish nationwide registries including all patients hospitalized with an AF diagnosis between 1995 and 2003. In all, 158 577 patients were included in the study (56% male and 44% female; mean age 72 ± 11 years). The follow-up was 5 years with an observation time of 636 597 person–years. Education level was described by 3 categories representing primary, secondary, and academic education. Kaplan-Meier curves and Cox proportional hazard models adjusted with age, sex, time of index hospitalization, categorized Charlson´s Comorbidity Index (CCI) score, and CHA2DS2-VASc score were used for statistical analysis. Hazard ratio (HR) with 95% confidence interval (CI) was used as estimate of association and P < 0.05 was regarded as statistically significant. The risk of all-cause mortality was estimated in subpopulations defined by mortality risk factors as CCI, CHA2DS2-VASc score, heart failure, coronary artery disease, chronic obstructive pulmonary disease, diabetes, chronic kidney disease, and cancer.

Results:

Patients with academic education had the lowest all–cause mortality, which was seen early during follow–up. Compared to patients with primary education, those with secondary or academic education showed lower relative mortality risk in the adjusted Cox regression model (secondary education HR: 0.875, 95% CI: 0.86 – 0.89, p<0.001; academic education HR: 0.695, 95% CI: 0.67 – 0.72; p<0.001). Among the subpopulations, the HR varied between 0.72 and 0.95 for secondary and between 0.43 and 0.79 for academic education respectively. All risk differences were statistically significant.

Conclusion:

Academic education was associated with the lowest and primary education with the highest risk of all-cause mortality. This pattern was consistent through all analyzed subpopulations.