Search

Aims: To investigate if addition of metformin to standard care (life-style advice) reduces the occurrence of cardiovascular events and death after myocardial infarction (MI) in patients with newly detected prediabetes. Methods: The Myocardial Infarction and new treatment with Metformin study (MIMET) is a large multicentre registry-based randomised clinical trial (R-RCT) within the SWEDEHEART registry platform expected to include 5160 patients with MI and newly detected prediabetes (identified with fasting blood glucose, HbA1c or 2-h glucose on oral glucose tolerance test) at similar to 20 study sites in Sweden. Patients 18-80 years, without known diabetes and naive to glucose lowering therapy, will be randomised 1:1 to open-label metformin therapy plus standard care or standard care alone. Outcomes: Patients will be followed for 2 years for the primary outcome new cardiovascular event (first of death, non-fatal MI, hospitalisation for heart failure or non-fatal stroke). Secondary endpoints include individual components of the primary endpoint, diabetes diagnosis, initiation of any glucose lowering therapy, cancer, and treatment safety. Events will be collected from national healthcare registries. Conclusions: The MIMET study will investigate if metformin is superior to standard care after myocardial infarction in preventing cardiovascular events in patients with prediabetes (Clinicaltrials.gov identifier: NCT05182970; EudraCT No: 2019-001487-30).

Rationale Complex endovascular aortic repair often involves multiple major procedures over time with a high risk of complications and little time for recovery. This exposes patients to great stress, both physically and mentally, with potentially long-lasting effects. There is limited knowledge about these effects and who is most at risk – information on this could help vascular nurses and other healthcare professionals anticipate and meet care needs. Aim To investigate the health and quality of life effects of complex endovascular aortic repair, in relation to patients’ demographic and health characteristics. Design A prospective cohort study. Methods Patients undergoing elective complex endovascular aortic repair were consecutively recruited from one university hospital during one year (n=25). Self-report questionnaires on health disability (WHODAS 2.0), quality of life (WHOQoL-BREF) and symptoms of anxiety and depression (HADS) were filled out preoperatively and repeated one and six months postoperatively. Prospective changes in health and quality of life, and associations with patient demographics and preoperative health characteristics, were assessed. Ethical approval was obtained prior to study performance. Results Overall, patients had significantly greater health disability at one month (WHODAS 2.0 score median 31.5, range 1.1–63.0) than preoperatively (median 13.6, range 0.0–41.3) (n=22, p=.017); the majority had recovered at six months (median 11.4, range 3.3–58.7) (n=18, p=.042). No significant effects were seen in quality of life and symptoms of anxiety and depression (p>.05). However, the participants showed heterogeneity, with certain individuals not recovered at six months (n=8). Factors associated with worse six-month outcomes were being female, age < 70 years, postoperative complications, and history of anxiety or depression. Conclusions Complex endovascular aortic repair have limited long-term negative effects on patients’ health and quality o

BackgroundThere are limited comparative data on safety and efficacy within commonly used Vaughan-Williams (VW) class III antiarrhythmic drugs (AADs) for maintenance of sinus rhythm in adults with atrial fibrillation (AF). HypothesisWe hypothesized that dronedarone and sotalol, two commonly prescribed VW class III AADs with class II properties, have different safety and efficacy effects in patients with nonpermanent AF. MethodsA systematic literature review was conducted searching MEDLINE (R), Embase, and Cochrane Central Register of Controlled Trials (CENTRAL) up to June 15, 2021 (NCT05279833). Clinical trials and observational studies that evaluated safety and efficacy of dronedarone or sotalol in adults with AF were included. Bayesian random-effects network meta-analysis (NMA) was used to quantify comparative safety and efficacy. Where feasible, we performed sensitivity analyses by including only randomized controlled trials (RCTs). ResultsOf 3581 records identified through database searches, 37 unique studies (23 RCTs, 13 observational studies, and 1 nonrandomized trial) were included in the NMA. Dronedarone was associated with a statistically significantly lower risk of all-cause death versus sotalol (hazard ratio [HR] = 0.38 [95% credible interval, CrI: 0.19, 0.74]). The association was numerically similar in the sensitivity analysis (HR = 0.46 [95% CrI: 0.21, 1.02]). AF recurrence and cardiovascular death results were not significantly different between dronedarone and sotalol in all-studies and sensitivity analyses. ConclusionThe NMA findings indicate that, across all clinical trials and observational studies included, dronedarone compared with sotalol was associated with a lower risk of all-cause death, but with no difference in AF recurrence.

Background: Patients with type 2 diabetes have an increased risk of death and cardiovascular events and people with diabetes or prediabetes have been found to have increased atherosclerotic burden in the coronary and carotid arteries. This study will estimate the cross-sectional prevalence of atherosclerosis in the coronary and carotid arteries in individuals with prediabetes and diabetes, compared with normoglycaemic individuals in a large population-based cohort. Methods: The 30,154 study participants, 50-64 years, were categorized according to their fasting glycaemic status or self-reported data as normoglycaemic, prediabetes, and previously undetected or known diabetes. Prevalence of affected coronary artery segments, severity of stenosis and coronary artery calcium score (CACS) were determined by coronary computed tomography angiography. Total atherosclerotic burden was assessed in the 11 clinically most relevant segments using the Segment Involvement Score and as the presence of any coronary atherosclerosis. The presence of atherosclerotic plaque in the carotid arteries was determined by ultrasound examination. Results: Study participants with prediabetes (n = 4804, 16.0%) or diabetes (n = 2282, 7.6%) had greater coronary artery plaque burden, more coronary stenosis and higher CACS than normoglycaemic participants (all, p < 0.01). Among male participants with diabetes 35.3% had CACS >= 100 compared to 16.1% among normoglycaemic participants. For women, the corresponding figures were 8.9% vs 6.1%. The prevalence of atherosclerosis in the coronary arteries was higher in participants with previously undetected diabetes than prediabetes, but lower than in patients with known diabetes. The prevalence of any plaque in the carotid arteries was higher in participants with prediabetes or diabetes than in normoglycaemic participants. Conclusions: In this large population-based cohort of currently asymptomatic people, the atherosclerotic burden in the coronary and

Myocardial infarction (MI) with obstructive coronary artery disease (MI-CAD) and MI in the absence of obstructive coronary artery disease (MINOCA) affect different populations and may have separate pathophysiological mechanisms, with greater inflammatory activity in MINOCA compared to MI-CAD. Helicobacter pylori (Hp) can cause systemic inflammation and has been associated with cardiovascular disease (CVD). We aimed to investigate whether Hp infection is associated with concentrations of protein biomarkers of inflammation and CVD. In a case-control study, patients with MINOCA (n = 99) in Sweden were included, complemented by matched subjects with MI-CAD (n = 99) and controls (n = 100). Protein biomarkers were measured with a proximity extension assay in plasma samples collected 3 months after MI. The seroprevalence of Hp and cytotoxin-associated gene A (CagA) was determined using ELISA. The associations between protein levels and Hp status were studied with linear regression. The prevalence of Hp was 20.2%, 19.2%, and 16.0% for MINOCA, MI-CAD, and controls, respectively (p = 0.73). Seven proteins were associated with Hp in an adjusted model: tissue plasminogen activator (tPA), interleukin-6 (IL-6), myeloperoxidase (MPO), TNF-related activation-induced cytokine (TRANCE), pappalysin-1 (PAPPA), soluble urokinase plasminogen activator receptor (suPAR), and P-selectin glycoprotein ligand 1 (PSGL-1). Hp infection was present in one in five patients with MI, irrespective of the presence of obstructive CAD. Inflammatory proteins were elevated in Hp-positive subjects, thus not ruling out that Hp may promote an inflammatory response and potentially contribute to the development of CVD.

Aortic stenosis (AS) is the most common valvular heart disease and most prevalent in the elderly. In the latest decades, a new method for replacement of the aortic valve: transcatheter aortic valve implantation (TAVI) has been introduced. This has enabled treatment of patients who were earlier not candidates for surgery, and has also led to a shift towards TAVI from open surgery for many patients with symptomatic AS. The aims of this thesis were to examine clinical outcomes after TAVI since its implementation in Sweden. In Study I we analysed the burden of disease after TAVI with focus on causes of hospitalisation, hospitalisation patterns and predictors of repeated hospitalisation. We identified that hospitalisations are common and from various indications. Heart failure was the most prevalent diagnosis and efforts should be made to reduce the burden of heart failure hospitalisations. In Study II we performed an external validation of an existing prediction model of risk for short-term hospitalisations after TAVI. The model underperformed in a Swedish setting and it is therefore not recommended for clinical use in its current state. The findings highlight the challenges of developing reliable models that are valid after transportation into a new setting. In Study III we investigated regional differences in availability to TAVI in Sweden with focus on regional procedure rates, short-term mortality and waiting times. The findings indicated no major regional differences. Hence, despite that Sweden is a geographically large and sparsely populated country the current system with a few specialised TAVI centres seems sufficient for providing national coverage of TAVI procedures. In Study IV we examined the need for and indications for coronary interventions after TAVI. We concluded that most patients do not need interventions after TAVI and in case an intervention is needed, the outcome is in a majority of cases successful, even though the success rates are lower than in

Aims Low-dose rivaroxaban has been indicated for the management of atherosclerotic cardiovascular disease (ASCVD) after recent (2019-2020) updates to European guidelines. We aimed to describe prescription trends of low-dose rivaroxaban in ASCVD patients over the period 2015-2022 in two European countries, to compare the trends before and after guideline changes, and to determine the characteristics of users. Methods In a cross-sectional interrupted time series analysis, utilization of low-dose rivaroxaban (2.5 mg, twice daily) was measured in Clinical Practice Research Datalink Aurum (United Kingdom [UK]) and the PHARMO Database Network (the Netherlands) from 1 January 2015 to 28 February 2022 in patients with an ASCVD diagnosis. Incidence rates (IRs) and incidence rate ratios (IRRs) of new use (within 182 days) compared to the reference period, 2015-2018, were calculated. Age, sex and comorbidities of users were compared to those of nonusers. Results In the UK, from 721 271 eligible subjects the IR of new use of low-dose rivaroxaban in the period 2015-2018, before guideline changes, was 12.4 per 100 000 person-years and after guideline changes in 2020-2022 was 124.0 (IRR 10.0, 95% confidence interval [CI] 8.5, 11.8). In the Netherlands from 394 851 subjects, the IR in 2015-2018 was 2.4 per 100 000 person-years and in 2020 was 16.3 (IRR 6.7, 95% CI 4.0, 11.4). Users were younger (UK mean difference [MD] −6.1 years, Netherlands −2.4 years; P < .05) and more likely to be male (UK difference 11.5%, Netherlands 13.4%; P < .001) than nonusers. Conclusions There was a statistically significant increase in the use of low-dose rivaroxaban for the management of ASCVD after guideline changes in the UK and the Netherlands. There were international differences, but low-dose rivaroxaban has not been put into widespread practice.

Background Pain increases the risk for cardiovascular diseases, including myocardial infarction (MI). However, the impact of pain on mortality after MI has not yet been investigated in large studies with long‐term follow‐up periods. Thus, we aimed to examine various levels of pain severity 1 year after an MI as a potential risk for all‐cause mortality. Methods and Results We collected data from 18 376 patients, aged <75 years, who had a registered MI event during the period from 2004 to 2013 and with measurements of potential cardiovascular risk indicators at hospital discharge from the Swedish quality register SWEDEHEART (Swedish Web System for Enhancement and Development of Evidence‐Based Care in Heart Disease Evaluated According to Recommended Therapies). Self‐reported levels of experienced pain according to EuroQol‐5 dimension instrument were recorded in secondary prevention clinics 1 year after hospital discharge. We collected all‐cause mortality data up to 8.5 years (median, 3.4 years) after the 1‐year visit. The Cox proportional hazard regression was used to estimate hazard ratio (HR) and 95% CI. Moderate pain and extreme pain were reported by 38.2% and 4.5%, respectively, of included patients. There were 1067 deaths. Adjusted HR was 1.35 (95% CI, 1.18–1.55) and 2.06 (95% CI, 1.63–2.60) for moderate and extreme pain, respectively. Pain was a stronger mortality predictor than smoking. Conclusions Pain 1 year after MI is highly prevalent, and its effect on mortality 1 year after MI was found to be more pronounced than smoking. Clinicians managing patients after MI should recognize the need to consider experienced pain when making prognosis or treatment decisions.

Background The incidence of atherosclerotic cardiovascular disease increases with levels of low-density lipoprotein cholesterol (LDL-C). Yet, a paradox may exist where lower LDL-C levels at myocardial infarction (MI) are associated with poorer prognoses. Objective To assess the association between LDL-C levels at MI with risk factor burden and cause-specific outcomes. Methods Statin-naive patients hospitalized for a first MI and registered in SWEDEHEART were included. Data were linked to Swedish registers. Primary outcomes were all-cause mortality and nonfatal MI. Associations between LDL-C and outcomes were assessed using adjusted proportional hazards models. Results Among 63,168 patients (median age, 66 years), the median LDL-C level was 3.0 mmol/L (interquartile range 2.4–3.6). Patient age and comorbidities increased as LDL-C decreased. During a median follow-up of 4.5 years, 10,236 patients died, and 4973 had nonfatal MI. Patients with the highest LDL-C had a lower risk of mortality (hazard ratio [HR] 0.75; 95% confidence interval [CI] 0.71–0.80). The risk of hospitalization for pneumonia, hip fracture, chronic obstructive pulmonary disease, and new cancer diagnosis was lower with higher LDL-C (HR range, 0.40–0.81). Patients with the highest LDL-C had a greater risk of recurrent MI (HR 1.16; 95% CI 1.07–1.26). Conclusions Patients with the highest LDL-C levels at MI had the lowest incidence of mortality and morbidity. This seems to reflect lower age at MI, less underlying morbidities, paired with the modifiability of LDL-C. However, supporting the causal association between LDL-C and ischemic heart disease, elevated LDL-C was simultaneously associated with an increased risk of nonfatal MI.

Background and aims: Several different scoring systems for early risk stratification after out-of-hospital cardiac arrest have been developed, but few have been validated in large datasets. The aim of the present study was to compare the well-validated Out-of-hospital Cardiac Arrest (OHCA) and Cardiac Arrest Hospital Prognosis (CAHP)-scores to the less complex MIRACLE2- and Target Temperature Management (TTM)-scores. Methods: This was a post-hoc analysis of the Targeted Hypothermia versus Targeted Normothermia after Out-of-Hospital Cardiac Arrest (TTM2) trial. Missing data were handled by multiple imputation. The primary outcome was discriminatory performance assessed as the area under the receiver operating characteristics-curve (AUROC), with the outcome of interest being poor functional outcome or death (modified Rankin Scale 4-6) at 6 months after OHCA. Results: Data on functional outcome at 6 months were available for 1829 cases, which constituted the study population. The pooled AUROC for the MIRACLE2-score was 0.810 (95% CI 0.790-0.828), 0.835 (95% CI 0.816-0.852) for the TTM-score, 0.820 (95% CI 0.800-0.839) for the CAHPscore and 0.770 (95% CI 0.748-0.791) for the OHCA-score. At the cut-offs needed to achieve specificities >95%, sensitivities were <40% for all four scoring systems. Conclusions: The TTM-, MIRACLE2- and CAHP-scores are all capable of providing objective risk estimates accurate enough to be used as part of a holistic patient assessment after OHCA of a suspected cardiac origin. Due to its simplicity, the MIRACLE2-score could be a practical solution for both clinical application and risk stratification within trials.

BACKGROUND: Aberrant subclavian artery (ASA) with or without Kommerell's diverticulum (KD) is a rare anatomic aortic arch anomaly that can cause dysphagia and/or life-threatening rupture. The objective of this study is to compare outcomes of ASA/KD repair in patients with a left versus right aortic arch. METHODS: Using the Vascular Low Frequency Disease Consortium methodology, a retrospective review was performed of patients ≥18 years old with surgical treatment of ASA/KD from 2000 to 2020 at 20 institutions. RESULTS: 288 patients with ASA with or without KD were identified; 222 left-sided aortic arch (LAA), and 66 right-sided aortic arch (RAA). Mean age at repair was younger in LAA 54 vs. 58 years (P = 0.06). Patients in RAA were more likely to undergo repair due to symptoms (72.7% vs. 55.9%, P = 0.01), and more likely to present with dysphagia (57.6% vs. 39.1%, P < 0.01). The hybrid open/endovascular approach was the most common repair type in both groups. Rates of intraoperative complications, death within 30 days, return to the operating room, symptom relief and endoleaks were not significantly different. For patients with symptom status follow-up data, in LAA, 61.7% had complete relief, 34.0% had partial relief and 4.3% had no change. In RAA, 60.7% had complete relief, 34.4% had partial relief and 4.9% had no change. CONCLUSIONS: In patients with ASA/KD, RAA patients were less common than LAA, presented more frequently with dysphagia, had symptoms as an indication for intervention, and underwent treatment at a younger age. Open, endovascular and hybrid repair approaches appear equally effective, regardless of arch laterality.

Objective: The significance of the inflammatory response in the natural course of acute type B aortic dissection (ATBAD) is unknown. The aim was to characterise inflammation and its transformation over time in ATBAD using F-18-fluorodeoxyglucose (FDG) positron emission tomography (PET) with contrast enhanced magnetic resonance imaging (MRI). Methods: Ten patients underwent FDG-PET/MRI within two weeks of ATBAD (acute phase), three to four months (subacute phase), nine to 12 months (early chronic phase), and 21 to 24 months (late chronic phase) after ATBAD. Target background ratios (TBRs) were measured in the ascending aorta, aortic arch, and descending aorta. MRI inflammatory markers were assessed in the descending aorta. Results: Ten patients were included: median age 69 years, median clinical follow up 32 months. In the acute phase there was increased FDG uptake in the descending aorta (maximum TBR 5.8, SD [standard deviation] 1.3) compared with the ascending aorta (TBR 3.3, SD 0.8, p < .010) and arch (TBR 4.2, SD 0.6, p = .010). The maximum TBR of the descending aorta decreased from the acute to subacute phase (TBR 3.5, SD 0.6, p = .010) and further to the early chronic phase (TBR 2.9, SD 0.4, p = .030) but was stable thereafter. The acute phase maximum TBR in the ascending aorta (TBR 3.3) and arch (TBR 4.2) decreased to the subacute phase (ascending: TBR 2.8, SD 0.6, p = .020; arch: TBR 2.7, SD 0.4, p = .010) and was stable thereafter. Four patients underwent surgical aortic repair (three for aortic dilatation at one, five, and 28 months and one for visceral ischaemia at three weeks). MRI signs of inflammation were present in all surgically treated patients vs. two of six of medically treated patients (p= .048). Conclusion: ATBAD is associated with increased FDG uptake in the acute phase primarily in the descending aorta, but also involving the aortic arch and ascending aorta, indicating an inflammatory response in the whole aorta. Inflammation subsides early

Objective; Digital healthcare systems could provide insights into the global prevalence of heart failure (HF). We designed the CardioRenal and Metabolic disease (CaReMe) HF study to estimate the prevalence, key clinical adverse outcomes and costs of HF across 11 countries. Methods: Individual level data from a contemporary cohort of 6 29 624 patients with diagnosed HF was obtained from digital healthcare systems in participating countries using a prespecified, common study plan, and summarised using a random effects meta-analysis. A broad definition of HF (any registered HF diagnosis) and a strict definition (history of hospitalisation for HF) were used. Event rates were reported per 100 patient years. Cumulative hospital care costs per patient were calculated for a period of up to 5 years. Results: The prevalence of HF was 2.01% (95% CI 1.65 to 2.36) and 1.05% (0.85 to 1.25) according to the broad and strict definitions, respectively. In patients with HF (broad definition), mean age was 75.2 years (95% CI 74.0 to 76.4), 48.8% (40.9-56.8%) had ischaemic heart disease and 34.5% (29.4-39.6%) had diabetes. In 51 442 patients with a recorded ejection fraction (EF), 39.1% (30.3-47.8%) had a reduced, 18.8% (13.5-24.0%) had a mildly reduced and 42.1% (31.5-52.8%) had a preserved left ventricular EF. In 1 69 518 patients with recorded estimated glomerular filtration rate, 49% had chronic kidney disease (CKD) stages III-V. Event rates were highest for cardiorenal disease (HF or CKD) and all cause mortality (19.3 (95% CI 11.3 to 27.1) and 13.1 (11.1 to 15.1), respectively), and lower for myocardial infarction, stroke and peripheral artery disease. Hospital care costs were highest for cardiorenal diseases. Conclusions: We estimate that 1-2% of the contemporary adult population has HF. These individuals are at significant risk of adverse outcomes and associated costs, predominantly driven by hospitalisations for HF or CKD. There is considerable public health potential in unders

Background Supervised exercise is an integral part of the recommended first-line treatment for patients with intermittent claudication (IC). By reflecting the patients’ perspectives, patient-reported outcome measurements provide additional knowledge to the biomedical endpoints and are important outcomes to include when evaluating exercise interventions in patients with IC. We aimed to evaluate the one-year impact of three strategies: unsupervised Nordic pole walk advice (WA), WA + six months of home-based structured exercise (HSEP) or WA + six months of hospital-based supervised exercise (SEP) on health-related quality of life and patient-reported physical function in patients with IC. Methods This secondary exploratory analysis of a multi-center, randomized clinical trial compared three exercise strategies. The primary outcome of the secondary analysis was the one-year change in the 36-Item Short-Form (SF-36). Secondary outcomes were three- and six-months SF-36 changes alongside three, six- and 12-months changes in the disease-specific Vascular Quality of Life instrument (VascuQoL) and the Patient-Specific Functional Scale (PSFS). The Kruskal–Wallis test with Bonferroni-adjusted post-hoc tests were used for between-group comparisons. Effect size calculations were used to describe the size of observed treatment effects, and the clinical meaningfulness of observed changes in the VascuQoL summary score at one year was studied using established minimally important difference (MID) thresholds. Results A total of 166 patients with IC, mean age: 72.1 (SD 7.4) years, 41% women, were randomized. No significant between-group differences were observed over time for the SF-36 or the PSFS scores whereas some significant between-group differences were observed in the VascuQoL domain and summary scores over time, favoring SEP and/or HSEP over WA. The observed SF-36 and VascuQoL domain and summary score effect sizes were small to moderate, and many domain score effect sizes also r

Aims This study aims to survey current educational experience and the individual requirements for electrophysiologists in training. Methods and results The European Heart Rhythm Association (EHRA) e-Communication Committee and the Scientific Initiatives Committee prepared a questionnaire and distributed it via newsletters, Twitter, LinkedIn, and Facebook. The survey consisted of 22 questions collected on an individual basis anonymously. Two hundred and forty-three responders from 35 countries (32% female, age 38 ± 6 years old) completed the survey. This EHRA electrophysiology (EP) fellowship survey showed that (i) hands-on participation and observation of EP procedures are very important; (ii) the main motivations to choose the EP fellowship institution are centre reputation and volume as well as the availability of a structured EP fellowship programme; (iii) 59% passed the EHRA exam and 46% took a national certification exam; (iv) respondents are overall satisfied with their own fellowships, but there are areas of less confidence such as conduction system pacing implantation and cardiac resynchronization therapy implantation; (v) 78% of respondents performed research during their fellowship, (vi) the optimal duration of an EP fellowship should be at least 2 years; and (viii) doing fellowships abroad is beneficial, but significant obstacles exist. Conclusion The results of this EHRA survey may help to refine current EP fellowship programmes to improve the quality of EP training and early career building of young electrophysiologists.

BackgroundLimited studies have explored the association between visceral adipose tissue (VAT) mass and fat-to-muscle mass ratio (FMR) and mortality. We aimed to evaluate the sex-specific association of VAT and FMR with all-cause and cause-specific mortality by age. MethodsA total of 438 896 participants (49.8% men, mean age +/- standard deviation: 57 +/- 8 years for men; 56 +/- 8 years for women) were included from the UK Biobank cohort. The nature of VAT was predictive, as obtained by sex-stratified, non-linear prediction models. Fat and muscle mass were estimated using a bioelectrical impedance assessment device. FMR was calculated as the fat mass divided by the muscle mass in the whole body. VAT and FMRs were divided into quintiles in ascending order, and the 3rd quintile was used as the reference. Cox regression analyses were used to estimate the associations between VAT, FMR and mortality. ResultsDuring a median of 12.4 years of follow-up, we documented 29 903 deaths. After adjusting for various covariates, the individuals in the highest quintiles of VAT and FMR had the highest hazard ratios (HRs) of all-cause mortality [1.24 (95% confidence interval: 1.17-1.33) for VAT and 1.24 (1.17-1.31) for FMR in men; and 1.11 (1.03-1.21) for VAT in women], except that the 1st quintile of FMR in women had the greatest HR [1.18 (1.09-1.27)]. Significant interactions were observed in both sexes according to age category (P for interaction < 0.05). Among men <50 years, participants in the 1st and 5th quintiles of VAT and FMR had significantly higher risks of mortality [1.30 (1.02-1.66) and 1.67 (1.27-2.19) in VAT; 1.25 (0.99-1.56) and 1.41 (1.11-1.79) in FMR, respectively]; in women, this phenomenon was observed in the >= 60 age group [1.16 (1.06-1.27) and 1.19 (1.08-1.31) in VAT; 1.18 (1.08-1.29) and 1.11 (1.01-1.22) in FMR, respectively]. VAT showed a linear positive association with mortality in women <60 years and a J-shaped association from respiratory diseas

Objectives: NT-proBNP is frequently used for ruling out heart failure. Different cut-offs are used depending on the clinical context, e.g. an acute or chronic condition. Medical decision limits have been suggested at 125 and 300 ng/L or 400 ng/L in international guidelines. However, there is limited standardization between NT-proBNP methods and using the same blood sample might cause different treatment of patients. Methods: Data from the external quality assessment program for NT-proBNP from Equalis, Sweden, were extracted for the period 2011-2021, and categorized according to manufacturer. Manufacturer median NT-proBNP values were compared to total median values. CV% was calculated for each manufacturer and in comparison to different levels of NT-proBNP. Results: Roche was the most common method, and its median results were closest to the median consensus results. When looking at the total CV at NT-proBNP levels in the range of 0-500 ng/L, the total CV varied from 4 to 27%. During 2019-2021, Siemens (Immulite, Centaur, Atellica) yielded results 16-20% above the consensus median depending on sample level. Similarly, Abbott was 5-7% above, while Roche and Siemens Stratus were 1% respectively 6-10% below the consensus median. Conclusions: The introduction of new manufacturers and methods in 2017 have caused the agreement between manufacturers to decline. This highlights the need for a common calibrator and reference materials, particularly since medical decision limits in guidelines, e.g. European Society of Cardiology 2021, which are mostly based on Roche methods, do not take these method differences into account.

Background Resuscitative Endovascular Balloon Occlusion of the Aorta (REBOA) may be considered for stabilization of patients with hemorrhage from below the diaphragm. Occluding the aorta is a powerful means of hemorrhagic control but is also associated with acute kidney injury, which increases mortality in trauma patients. Allowing for intermittent distal blood flow during REBOA application (iREBOA) could decrease this risk, but circulatory consequences have not been sufficiently elucidated. Therefore, we investigated circulatory effects and the renal artery blood flow (RBF) in iREBOA versus continuous, complete aortic occlusion (cREBOA). Methods In a porcine model of uncontrolled class III hemorrhage (34% estimated total blood volume, mean 1360 mL), swine (n = 12, mean weight 60.3 kg) were randomly assigned to iREBOA: 3-min full deflation every 10 min (n = 6), or cREBOA (n = 6), for 60 min of thoracic (zone I) application. The animals then underwent 60 min of reperfusion (critical care phase). Results Survival was 100% in iREBOA and 83% in cREBOA. The intermittent balloon deflation protocol was hemodynamically tolerable in 63% of reperfusion intervals. Systolic blood pressure decreased during the reperfusion intervals in iREBOA animals (mean 108 mm Hg versus 169 mm Hg; p < 0.005). No differences were detected in heart rate, cardiac output or stroke volume between methods. Troponin I increased in cREBOA after 60 min (mean 666-187 ng/L, p < 0.05). The norepinephrine requirement increased in cREBOA during reperfusion (mean infusion time 12.5-5.5 min; p < 0.05). Total ischemic time decreased in iREBOA (60.0-48.6 min; p < 0.001). RBF increased in iREBOA during balloon deflations and after 60 min reperfusion (61%-39% of baseline RBF; p < 0.05). Urine output increased in iREBOA (mean 135-17 mL; p < 0.001). Nephronal osteopontin, a marker of ischemic injury, increased in cREBOA (p < 0.05). Conclusion iREBOA was survivable, did not cause rebleeding, dec

The International Federation of Clinical Chemistry Committee on Clinical Applications of Cardiac Biomarkers (IFCC C-CB) provides educational documents to facilitate the interpretation and use of cardiac biomarkers in clinical laboratories and practice. Our aim is to improve the understanding of certain key analytical and clinical aspects of cardiac biomarkers and how these may interplay. Measurements of cardiac troponin (cTn) have a prominent place in the clinical work-up of patients with suspected acute coronary syndrome. It is therefore important that clinical laboratories know how to recognize and assess analytical issues. Two emerging analytical issues resulting in falsely high cTn concentrations, often several fold higher than the upper reference limit (URL), are antibody-mediated assay interference due to long-lived cTn-antibody complexes, called macrotroponin, and crosslinking antibodies that are frequently referred to as heterophilic antibodies. We provide an overview of antibody-mediated cTn assay interference and provide recommendations on how to confirm the interference and interpret the results.

Objective THALES demonstrated that ticagrelor plus aspirin reduced the risk of stroke or death but increased bleeding versus aspirin during the 30 days following a mild-to-moderate acute non-cardioembolic ischaemic stroke (AIS) or high-risk transient ischaemic attack (TIA). There are no cost-effectiveness analyses supporting this combination in Europe. To address this, a cost-effectiveness analysis was performed. Methods Cost-effectiveness was evaluated using a decision tree and Markov model with a short-term and long-term (30-year) horizon. Stroke, mortality, bleeding and EuroQol-5 Dimension (EQ-5D) data from THALES were used to estimate short-term outcomes. Model transitions were based on stroke severity (disabling stroke was defined as modified Rankin Scale >2). Healthcare resource utilisation and EQ-5D data beyond 30 days were based on SOCRATES, another trial in AIS/TIA that compared ticagrelor with aspirin. Long-term costs, survival and disutilities were based on published literature. Unit costs were derived from national databases and discounted at 3% annually from a Swedish healthcare perspective. Results One-month treatment with ticagrelor plus aspirin resulted in 12 fewer strokes, 4 additional major bleeds and cost savings of euro95 000 per 1000 patients versus aspirin from a Swedish healthcare perspective. This translated into increased quality-adjusted life-years (0.04) and reduced societal costs (-euro1358) per patient over a lifetime horizon. Key drivers of cost-effectiveness were number of patients experiencing subsequent disabling stroke and degree of disability. Findings were robust over a range of input assumptions. Conclusion One month of treatment with ticagrelor plus aspirin is likely to improve outcomes and reduce costs versus aspirin in mild-to-moderate AIS or high-risk TIA.Trial registration number NCT03354429.

Background 15O-water PET is the gold standard for noninvasive quantification of myocardial blood flow. In addition to evaluation of ischemia, the assessment of cardiac function and remodeling is important in all cardiac diseases. However, since 15O-water is freely diffusible and standard uptake images show little contrast between the myocardium and blood pool, the assessment of left-ventricular (LV) volumes and ejection fraction (EF) is challenging. Therefore, the aim of the present study was to investigate the feasibility of calculating LV volumes and EF from first-pass analysis of 15O-water PET, by comparison with cardiac magnetic resonance imaging (CMR) using a hybrid PET/MR scanner. Methods Twenty-four patients with known or suspected CAD underwent a simultaneous ECG-gated cardiac PET/MR scan. The 15O-water first-pass images (0-50 seconds) were analyzed using the CarPET software and the CMR images were analyzed using the software Segment, for LV volumes and EF calculations. The LV volumes and EF were compared using correlation and Bland–Altman analysis. In addition, inter- and intra-observer variability of LV volumes and EF were assessed for both modalities. Results The correlation between PET and CMR was strong for volumes (r > 0.84) and moderate for EF (r = 0.52), where the moderate correlation for EF was partly due to the small range of EF values. Agreement was high for all parameters, with a slight overestimation of PET values for end-diastolic volume but with no significant mean bias for other parameters. Inter- and intra-observer agreement of volumes was high and comparable between PET and CMR. For EF, inter-observer agreement was higher for PET and intra-observer agreement was higher for CMR. Conclusion LV volumes and EF can be calculated by first-pass analysis of a 15O-water PET scan with high accuracy and comparable precision as with CMR.

Objective: Abdominal aortic graft and endograft infections (AGIs) are rare complications following aortic surgery. Radical surgery (RS) with resection of the infected graft and reconstruction with extra-anatomical bypass or in situ reconstruction is the preferred therapy. For patients unfit for RS, a semi-conservative (SC), graft preserving strategy is possible. This paper aimed to compare survival and infection outcomes between RS and SC treatment for AGI in a nationwide cohort. Methods: Patients with abdominal AGI related surgery in Sweden between January 1995 and May 2017 were identified. The Management of Aortic Graft Infection Collaboration (MAGIC) criteria were used for the definition of AGI. Multivariable regression was performed to identify factors associated with mortality. Results: One hundred and sixty-nine patients with surgically treated abdominal AGI were identified, comprising 43 SC (14 endografts; 53% with a graft enteric fistula [GEF] in total) and 126 RS (26 endografts; 50% with a GEF in total). The SC cohort was older and had a higher frequency of cardiac comorbidities. There was a non-significant trend towards lower Kaplan -Meier estimated five year survival for SC vs. RS (30.2% vs. 48.4%; p = .066). A non-significant trend was identified towards worse Kaplan -Meier estimated five year survival for SC patients with a GEF vs. without a GEF (21.7% vs. 40.1%; p = .097). There were significantly more recurrent graft infections comparing SC with RS (45.4% vs. 19.3%; p < .001). In a Cox regression model adjusting for confounders, there was no difference in five year survival comparing SC vs. RS (HR 1.0, 95% CI 0.6 -1.5). Conclusion: In this national AGI cohort, there was no mortality difference comparing SC and RS for AGI when adjusting for comorbidities. Presence of GEF probably negatively impacts survival outcomes of SC patients. Rates of recurrent infection remain high for SC treated patients.

Aortic valve degeneration (AVD) is a life-threatening condition that has no medical treatment and lacks individual therapies. Although extensively studied with standard approaches, aetiologies behind AVD are unclear. We compared abundances of extracellular matrix (ECM) proteins from excised valve tissues of 88 patients with isolated AVD of normal tricuspid (TAV) and congenital bicuspid aortic valves (BAV), quantified more than 1400 proteins per ECM sample by mass spectrometry, and demonstrated that local ECM preserves molecular cues of the pathophysiological processes. The BAV ECM showed enrichment with fibrosis markers, namely Tenascin C, Osteoprotegerin, and Thrombospondin-2. The abnormal physical stress on BAV may cause a mechanical injury leading to a continuous Tenascin C-driven presence of myofibroblasts and persistent fibrosis. The TAV ECM exhibited enrichment with Annexin A3 (p = 1.1 x 10(-16) and the fold change 6.5) and a significant deficit in proteins involved in high-density lipid metabolism. These results were validated by orthogonal methods. The difference in the ECM landscape suggests distinct aetiologies between AVD of BAV and TAV; warrants different treatments of the patients with BAV and TAV; elucidates the molecular basis of AVD; and implies possible new therapeutic approaches. Our publicly available database (human_avd_ecm.surgsci. uu.se) is a rich source for medical doctors and researchers who are interested in AVD or heart ECM in general. Systematic proteomic analysis of local ECM using the methods described here may facilitate future studies of various tissues and organs in development and disease.

BACKGROUND: Trigeminal neuralgia (TN), a severe type of facial pain, is mainly caused by a neurovascular conflict (NVC). The severity of the NVC seems associated with the outcome following microvascular decompression (MVD) surgery. This study aimed to investigate the outcome after MVD and whether it is affected by NVC severity and sex. METHODS: TN patients (n = 109) were followed for 5 to 10 years after MVD. Barrow Neurology Index (BNI), Patients Global Impression of Change (PGIC), complications, and time to relapse were evaluated. The NVC severity was retrospectively reviewed from presurgical MRI. Demographic and clinical factors and NVC severity were analyzed for potential association with outcome after MVD. RESULTS: The success rate (BNI ≤ 2) was 80% after 5 to 10 years follow-up for TN patients with severe NVC (grade 2-3) and 56% for TN patients with mild NVC (grade 0-1, P = 0.003). No sex difference was observed in outcome for patients with both mild (P = 0.924) and severe NVC (P = 0.883) respectively. Three patients (2.8%) during the hospital stay, and two patients (1.8%) at 6 weeks, experienced a complication requiring invasive treatment. At long-term 52/109 patients (47.7%) reported some type of persistent adverse event, of which the majority were mild and required no treatment. CONCLUSIONS: MVD offers an 80% probability of long-term pain relief in TN patients with severe NVC, with low frequency of serious complications. NVC severity significantly affects outcome after MVD, while no sex differences in outcome were found. In consistency with previous work, the results stress the importance of adequate neuroradiological assessment of the NVC for preoperative patient selection.

Background The History, Electrocardiogram (ECG), Age, Risk factors and Troponin, (HEART) score is useful for early risk stratification in chest pain patients. The aim was to validate previous findings that a simplified score using history, ECG and troponin (HET-score) has similar ability to stratify risk. Methods Patients presenting with chest pain with duration of ≥10 min and an onset of last episode ≤12 h but without ST-segment elevation on ECG at 6 emergency departments were eligible for inclusion. The HEART-score and the simplified HET-score were calculated. The endpoint was a composite of myocardial infarction (MI) as index diagnosis, readmission due to new MI or death within 30 days. Results HEART-score identified 32% as low risk (0-2p), 47% as intermediate risk (3-5p), and 20% as high risk (6-10p) patients. The endpoint occurred in 0.5%, 7.3% and 35.7%, respectively. HET-score identified 39%, 42% and 19% as low- (0p), intermediate- (1-2p) and high-risk (3-6p) patients, with the endpoint occurring in 0.6%, 6.2% and 43.2%, respectively. When all variables included in the HEART-score were included in a multivariable logistic regression analysis, only History (OR, CI [95%]): 2.97(2.16–4.09), ECG (1.61[1.14–2.28]) and troponin level (5.21[3.91–6.95]) were significantly associated with cardiovascular events. When HEART- and HET-score were compared in a ROC-analysis, HET-score had a significantly larger AUC (0.887 vs 0.853, p < 0.001). Conclusions Compared with HEART-score, HET-score is simpler and appears to have similar ability to discriminate between chest pain patients with and without cardiovascular event.

Objective Pre-eclampsia and gestational diabetes mellitus (GDM) are two common pregnancy complications that affect birth outcomes and are associated with a long-term risk of cardiovascular disease (CVD). The aims of this study were to investigate if the pre-eclampsia association with CVD is independent of GDM and modified by body mass index (BMI) or GDM. Design Case–control study. Setting Sweden. Population Cases were women with a first CVD event between 1991 and 2008 and a previous pregnancy who were matched with controls without CVD (1:5) by year of birth, age and region of birth. Methods Conditional logistic regression was used to evaluate the associations of GDM, pre-eclampsia and maternal BMI with CVD adjusted for potential confounders and effect modifications with interaction tests. Main outcome measures CVD. Results There were 2639 cases and 13 310 controls with complete data. Pre-eclampsia and GDM were independent risk factors for CVD (adjusted odds ratio [aOR] 2.59, 95% CI 2.12–3.17 and aOR 1.47, 95% CI 1.04–2.09, respectively). After stratifying by maternal BMI, the adjusted association of pre-eclampsia with CVD did not differ notably between BMI groups: normal weight (aOR 2.65, 95% CI 1.90–3.69), overweight (aOR 2.67, 95% CI 1.52–4.68) and obesity (aOR 3.03, 95% CI 0.74–12.4). Similar findings were seen when stratifying on GDM/non-GDM. Conclusions Pre-eclampsia and GDM are independent risk factors for later CVD and having both during pregnancy is a major risk factor for later CVD. The association between pre-eclampsia and CVD is not modified by BMI. Effective CVD preventive programs for high-risk women are urgently needed in order to improve women's long-term health.

Importance: Cardiovascular risk factors in youth have been associated with future cardiovascular disease (CVD), but conventional observational studies are vulnerable to genetic and environmental confounding. Objective: To examine the role of genetic and environmental factors shared by full siblings in the association of adolescent cardiovascular risk factors with future CVD. Design, Setting, and Participants: This is a nationwide cohort study with full sibling comparisons. All men who underwent mandatory military conscription examinations in Sweden between 1972 and 1995 were followed up until December 31, 2016. Data analysis was performed from May 1 to November 10, 2022. Exposures: Body mass index (BMI), cardiorespiratory fitness, blood pressure, handgrip strength, and a combined risk z score in late adolescence. Main Outcomes and Measures: The primary outcome was fatal or nonfatal CVD, as recorded in the National Inpatient Register or the Cause of Death Register before 2017. Results: A total of 1138833 men (mean [SD] age, 18.3 [0.8] years), of whom 463995 were full brothers, were followed up for a median (IQR) of 32.1 (26.7-37.7) years, during which 48606 experienced a CVD outcome (18598 among full brothers). All risk factors were associated with CVD, but the effect of controlling for unobserved genetic and environmental factors shared by full siblings varied. In the sibling analysis, hazard ratios for CVD (top vs bottom decile) were 2.10 (95% CI, 1.90-2.32) for BMI, 0.77 (95% CI, 0.68-0.88) for cardiorespiratory fitness, 1.45 (95% CI, 1.32-1.60) for systolic blood pressure, 0.90 (95% CI, 0.82-0.99) for handgrip strength, and 2.19 (95% CI, 1.96-2.46) for the combined z score. The percentage attenuation in these hazard ratios in the sibling vs total cohort analysis ranged from 1.1% for handgrip strength to 40.0% for cardiorespiratory fitness. Consequently, in the sibling analysis, the difference in cumulative CVD incidence at age 60 years (top vs bottom decile) was

Risk stratification is valuable in patients with cardiovascular disease (CVD). Proteins involved in different pathophysiological processes in atherosclerosis have shown prognostic capacity. A new technology, Proximity Extension Assay (PEA), enables the simultaneous analysis of numerous plasma proteins from a minimal amount of plasma. In this thesis, the overall aim was to identify and study prognostic protein biomarkers that could become useful in risk stratification. We used PEA to identify the biomarkers with the best prediction of long-term mortality among patients with acute myocardial infarction (AMI) and peripheral arterial disease (PAD). The study populations included consecutive patients with AMI from the Västmanland Myocardial Infarction Study (VaMIS), outpatients with carotid or lower extremity PAD from the Peripheral Arterial Disease Study in Västmanland (PADVa), and a population-based control cohort. A set of 92 proteins was analysed with PEA and related to follow-up data in the populations. The biomarkers which were best at predicting all-cause mortality were identified using LASSO regression analyses. The added value of the identified biomarkers to clinical risk markers was evaluated by logistic or Cox regression models. The associations between the plasma concentrations of growth differentiation factor 15 (GDF-15) to clinical risk factors, indicators of atherosclerotic burden, and variables of cardiac geometry and function were analysed with linear regression models. Spearman’s rank correlation coefficients compared the plasma concentrations obtained from conventional immunoassays and PEA for GDF-15 and N-terminal pro-brain natriuretic peptide (NT-proBNP) in the PAD population and the population-based cohort without PAD. The association between the two assay data and outcome was evaluated separately with Cox regression. GDF-15 and tumour necrosis factor-related apoptosis-inducing ligand receptor 2 (TRAIL-R2) had the best prognostic performance for

Sleep apnea is a common disorder that can cause pauses in breathing and can last from a few seconds to several minutes, as well as shallow breathing or complete cessation of breathing. Obstructive sleep apnea is strongly associated with the risk of developing several heart diseases, including coronary heart disease, heart attack, heart failure, and stroke. In addition, obstructive sleep apnea increases the risk of developing irregular heartbeats (arrhythmias), which can lead to low blood pressure. To prevent these conditions, this study presents a novel machine-learning (ML) model for predicting sleep apnea based on electronic health data that provides accurate predictions and helps in identifying the risk factors that contribute to the development of sleep apnea. The dataset used in the study includes 75 features and 10,765 samples from the Swedish National Study on Aging and Care (SNAC). The proposed model is based on two modules: the XGBoost module assesses the most important features from feature space, while the Bidirectional Long Short-Term Memory Networks (BiLSTM) module classifies the probability of sleep apnea. Using a cross-validation scheme, the proposed XGBoost_BiLSTM algorithm achieves an accuracy of 97% while using only the six most significant features from the dataset. The model’s performance is also compared with conventional long-short-term memory networks (LSTM) and other state-of-the-art ML models. The results of the study suggest that the proposed model improved the diagnosis and treatment of sleep apnea by identifying the risk factors., CC BY 4.0 DEED© 2023, The Author(s)Correspondence Address: A. Javeed; Department of Health, Blekinge Institute of Technology, Karlskrona, Valhallavägen 1, Blekinge, 37179, Sweden; email: ajv@bth.seOpen access funding provided by Blekinge Institute of Technology.

Sleep apnea is a common disorder that can cause pauses in breathing and can last from a few seconds to several minutes, as well as shallow breathing or complete cessation of breathing. Obstructive sleep apnea is strongly associated with the risk of developing several heart diseases, including coronary heart disease, heart attack, heart failure, and stroke. In addition, obstructive sleep apnea increases the risk of developing irregular heartbeats (arrhythmias), which can lead to low blood pressure. To prevent these conditions, this study presents a novel machine-learning (ML) model for predicting sleep apnea based on electronic health data that provides accurate predictions and helps in identifying the risk factors that contribute to the development of sleep apnea. The dataset used in the study includes 75 features and 10,765 samples from the Swedish National Study on Aging and Care (SNAC). The proposed model is based on two modules: the XGBoost module assesses the most important features from feature space, while the Bidirectional Long Short-Term Memory Networks (BiLSTM) module classifies the probability of sleep apnea. Using a cross-validation scheme, the proposed XGBoost_BiLSTM algorithm achieves an accuracy of 97% while using only the six most significant features from the dataset. The model’s performance is also compared with conventional long-short-term memory networks (LSTM) and other state-of-the-art ML models. The results of the study suggest that the proposed model improved the diagnosis and treatment of sleep apnea by identifying the risk factors., CC BY 4.0 DEED© 2023, The Author(s)Correspondence Address: A. Javeed; Department of Health, Blekinge Institute of Technology, Karlskrona, Valhallavägen 1, Blekinge, 37179, Sweden; email: ajv@bth.seOpen access funding provided by Blekinge Institute of Technology.

ObjectiveBeta-blockers (BB) are an established treatment following myocardial infarction (MI). However, there is uncertainty as to whether BB beyond the first year of MI have a role in patients without heart failure or left ventricular systolic dysfunction (LVSD). MethodsA nationwide cohort study was conducted including 43 618 patients with MI between 2005 and 2016 in the Swedish register for coronary heart disease. Follow-up started 1 year after hospitalisation (index date). Patients with heart failure or LVSD up until the index date were excluded. Patients were allocated into two groups according to BB treatment. Primary outcome was a composite of all-cause mortality, MI, unscheduled revascularisation and hospitalisation for heart failure. Outcomes were analysed using Cox and Fine-Grey regression models after inverse propensity score weighting. ResultsOverall, 34 253 (78.5%) patients received BB and 9365 (21.5%) did not at the index date 1 year following MI. The median age was 64 years and 25.5% were female. In the intention-to-treat analysis, the unadjusted rate of primary outcome was lower among patients who received versus not received BB (3.8 vs 4.9 events/100 person-years) (HR 0.76; 95% CI 0.73 to 1.04). Following inverse propensity score weighting and multivariable adjustment, the risk of the primary outcome was not different according to BB treatment (HR 0.99; 95% CI 0.93 to 1.04). Similar findings were observed when censoring for BB discontinuation or treatment switch during follow-up. ConclusionEvidence from this nationwide cohort study suggests that BB treatment beyond 1 year of MI for patients without heart failure or LVSD was not associated with improved cardiovascular outcomes., Funding Agencies|Swedish State under the agreement between the Swedish Government and the County Councils (the ALF-agreement)

Aims Cardiac resynchronization therapy (CRT) is effective in heart failure with reduced ejection fraction (HFrEF) and dyssynchrony but is underutilized. In a cohort study, we identified clinical, organizational, and level of care factors linked to CRT implantation. Methods and results We included HFrEF patients fulfilling study criteria in the ESC-HF-Long Term Registry (ESC-HF-LT, n = 1031), the Swedish Heart Failure Registry (SwedeHF) (n = 5008), and the ESC-CRT Survey II (n = 11 088). In ESC-HF-LT, 36% had a CRT indication of which 47% had CRT, 53% had indication but no CRT, and the remaining 54% had no indication and no CRT. In SwedeHF, these percentages were 30, 25, 75, and 70%. Median age of patients with CRT indication and CRT present vs. absent was 68 vs. 65 years with 24% vs. 22% women in ESC-HF-LT, 76 vs. 74 years with 26% vs. 26% women in SwedeHF, and 70 years with 24% women in CRT Survey II (all had CRT). For ESC-HF-LT, independent predictors of having CRT were guideline-directed medical therapy (GDMT), atrial fibrillation (AF), prior HF hospitalization, and NYHA class. For SwedeHF, they were GDMT, age, AF, previous myocardial infarction, lower NYHA class, enrolment at university hospital, and follow-up at HF centre/Hospital. In SwedeHF, above median income and higher education level were also independently associated with having CRT. In the ESC-CRT Survey II (n = 11 088), all patients received CRT but with differences in the clinical characteristics between countries. Conclusion CRT was used in a minority of eligible patients and more used in ESC-HF-LT than in SwedeHF.

Aims The Heart Failure Association of the European Society of Cardiology has recently proposed to optimize guideline-directed medical treatments according to patient s profiles. The aim of this analysis was to investigate prevalence/characteristics/treatments/outcomes for individual profiles Methods and results Patients with heart failure (HF) with reduced ejection fraction (HFrEF) enrolled in the Swedish Heart Failure Registry (SwedeHF) between 2013 and 2021 were considered. Among 108 profiles generated by combining different strata of renal function (by estimated glomerular filtration rate [eGFR]), systolic blood pressure (sBP), heart rate, atrial fibrillation (AF) status and presence of hyperkalaemia, 93 were identified in our cohort. Event rates for a composite of cardiovascular (CV) mortality or first HF hospitalization were calculated for each profile. The nine most frequent profiles accounting for 70.5% of the population had eGFR 30- 60 or =60 ml/min/1.73m(2), sBP 90-140mmHg and no hyperkalaemia. Heart rate and AF were evenly distributed. The highest risk of CV mortality/first HF hospitalization was observed in those with concomitant eGFR 30- 60ml/min/1.73m(2) and AF. We also identified nine profiles with the highest event rates, representing only 5% of the study population, characterized by no hyperkalaemia, even distribution among the sBP strata, predominance of eGFR < 30 ml/min/1.73m(2) and AF. The three profiles with eGFR 30- 60ml/min/1.73m(2) also showed sBP < 90 mmHg Conclusions In a real-world cohort, most patients fit in a few easily identifiable profiles; the nine profiles at highest risk of mortality/morbidity accounted for only 5% of the population. Our data might contribute to identifying profile-tailored approaches to guide drug implementation and follow-up., Funding Agencies|Swedish Heart and Lung Foundation; [20220680]

Background: Women with Turner syndrome (TS) have an increased risk of aortic dissection. The current recommended cutoff to prevent aortic dissection in TS is an aortic size index (ASI) of >= 2.5 cm/m2. This study estimated which aortic size had the best predictive value for the risk of aortic dissection, and whether adjusting for body size improved risk prediction.Methods: A prospective, observational study in Sweden, of women with TS, n = 400, all evaluated with echocardiography of the aorta and data on medical history for up to 25 years. Receiver operating characteristic (ROC) curves, sensitivity and specificity were calculated for the absolute ascending aortic diameter (AAD), ascending ASI and TS specific z-score.Results: There were 12 patients (3%) with aortic dissection. ROC curves demonstrated that absolute AAD and TS specific z-score were superior to ascending ASI in predicting aortic dissection. The best cutoff for absolute AAD was 3.3 cm and 2.12 for the TS specific z-score, respectively, with a sensitivity of 92% for both. The ascending ASI cutoff of 2.5 cm/m2 had a sensitivity of 17% only. Subgroup analyses in women with an aortic diameter >= 3.3 cm could not demonstrate any association between karyotype, aortic coarctation, bicuspid aortic valve, BMI, antihypertensive medication, previous growth hormone therapy or ongoing estrogen replacement treatment and aortic dissection. All models failed to predict a dissection in a pregnant woman.Conclusions: In Turner syndrome, absolute AAD and TS-specific z-score were more reliable predictors for aortic dissection than ASI. Care should be taken before and during pregnancy.

Acute exacerbations of chronic obstructive pulmonary disease (AECOPD) are the most devastating events in the course of the disease. Our aim was to investigate the value of early warning scoring systems: National Early Warning Score (NEWS) and Modified Early Warning Score (MEWS) in AECOPD. This is a prospective observational study of patients with AECOPD who were admitted at hospital. The NEWS and MEWS scores were registered at admission (NEWS-d1, MEWS-d1) and on the second day (NEWS-d2, MEWS-d2). A nasopharyngeal and sputum sample was taken for culture. Follow-up was done at 3 and 6 months after hospitalization. Any possible correlations between NEWS and MEWS and other parameters of COPD were explored. A cohort of 64 patients were included. In-hospital mortality was 4.7% while total mortality at 6 months was 26%. We did not find any significant correlation between in-hospital mortality and any of the scores but we could show a higher mortality and more frequent AECOPD at 6 months of follow-up for those with higher NEWS-d2. NEWS-d2 was associated with higher pCO(2) at presentation and a more frequent use of NIV. Higher NEWS-d1 and NEWS-d2 were predictive of a longer hospital stay. The presence of pathogens in the nasopharyngeal sample was related with a higher reduction of both scores on the second day. We therefore support the superiority of NEWS in the evaluation of hospitalized patients with AECOPD. A remaining high NEWS at the second day of hospital stay signals a high risk of hypercapnia and need of NIV but also higher mortality and more frequent exacerbations at 6 months after AECOPD.

IntroductionAdverse left ventricular remodelling (AR) develops over time in approximately 30% of patients with a history of coronary artery disease. AR manifests as a structural change in the left ventricle (LV) in terms of increased volumes and reduced left ventricular ejection fraction (LVEF). Manganese dipyridoxyl diphosphate (mangafodipir) has demonstrated interesting cardioprotective features in acute myocardial ischaemia. Pharmacological postconditioning (PP) with mangafodipir as an adjunct to primary percutaneous coronary intervention may possibly reduce the development of AR over time in ST-elevation myocardial infarction (STEMI). The aim of this 4-7-year follow-up study is to investigate the potential benefits of PP with mangafodipir in STEMI patients. MethodThirteen out of the initial 20 patients that were included in the primary study of Karlsson et al. were followed up between April and June 2017. The study group underwent review of the hospital records, a clinical examination with ECG and blood sample analysis before cardiac magnetic resonance examination of the patient. LVEF, left ventricular diastolic volume, left ventricular end systolic volume, LV mass and myocardial strain in all directions were computed. ResultsThe PP group showed a decrease in LV volume, mass and higher LVEF at follow-up (p < 0.05) while the individual response of the placebo group showed features that are seen in AR. Although there was no difference in myocardial strain, measurement for the PP-group was higher in absolute terms. ConclusionPharmacological postconditioning with mangafodipir in STEMI demonstrated cardioprotective features compared to the placebo group at follow-up. This article is protected by copyright. All rights reserved., Funding Agencies|Futurum-Academy for Health and Care, Region Jonkoeping County [414891, 598791, 635951, 851331]

Aims: Sodium-glucose cotransporter 2 inhibitors (SGLT2i) reduce mortality/morbidity in heart failure (HF). We explored the implementation of SGLT2i over time, and patient characteristics associated with their use, in a large, nationwide population with HF with reduced ejection fraction (HFrEF).Methods and results: Patients with HFrEF (ejection fraction <40%), no type 1 diabetes, estimated glomerular filtration rate (eGFR) <20 ml/min/1.73 m(2) and/or on dialysis, registered in the Swedish HF Registry between 1 November 2020 and 5 August 2022 were included. Independent predictors of use were investigated by multivariable logistic regressions. Of 8192 patients, 37% received SGLT2i. Use increased overall from 20.5% to 59.0% over time, from 46.2% and 12.5% to 69.8% and 55.4% in patients with and without type 2 diabetes, from 14.7% and 22.3% to 58.0% and 59.8% in eGFR <60 versus =60 ml/min/1.73 m(2), from 21.0% and 18.9% to 61.6% and 52.0% in males versus females, from 24.2% and 18.0% to 60.8% and 57.7% in patients with versus without recent HF hospitalization, from 26.1% and 19.8% to 54.7% and 59.6% in inpatients versus outpatients, and from 20.2% and 21.2% to 59.2% and 58.7% in those with HF duration <6 versus =6 months, respectively. Important characteristics associated with SGLT2i use were male sex, recent HF hospitalization, specialized HF follow-up, lower ejection fraction, type 2 diabetes, higher education level, use of other HF/cardiovascular interventions. Older age, higher blood pressure, atrial fibrillation and anaemia were associated with less use. Discontinuation rate at 6 and 12 months was 13.1% and 20.0%, respectively.Conclusions: Use of SGLT2i increased three-fold over 2 years. Although this indicates a more rapid translation of trial results and guidelines into clinical practice compared to previous HF drugs, further efforts are advocated to complete the implementation process while avoiding inequities across different patient, Funding Agencies|Swedish Heart and Lung Foundation; [20220680]

Background: Acute or new-onset atrial fibrillation (NOAF) is the most common cardiac arrhythmia in critically ill adult patients, and observational data suggests that NOAF is associated to adverse outcomes. Methods: We prepared this guideline according to the Grading of Recommendations Assessment, Development and Evaluation methodology. We posed the following clinical questions: (1) what is the better first-line pharmacological agent for the treatment of NOAF in critically ill adult patients?, (2) should we use direct current (DC) cardioversion in critically ill adult patients with NOAF and hemodynamic instability caused by atrial fibrillation?, (3) should we use anticoagulant therapy in critically ill adult patients with NOAF?, and (4) should critically ill adult patients with NOAF receive follow-up after discharge from hospital? We assessed patient-important outcomes, including mortality, thromboembolic events, and adverse events. Patients and relatives were part of the guideline panel. Results: The quantity and quality of evidence on the management of NOAF in critically ill adults was very limited, and we did not identify any relevant direct or indirect evidence from randomized clinical trials for the prespecified PICO questions. We were able to propose one weak recommendation against routine use of therapeutic dose anticoagulant therapy, and one best practice statement for routine follow-up by a cardiologist after hospital discharge. We were not able to propose any recommendations on the better first-line pharmacological agent or whether to use DC cardioversion in critically ill patients with hemodynamic instability induced by NOAF. An electronic version of this guideline in layered and interactive format is available in MAGIC: https://app.magicapp.org/#/guideline/7197. Conclusions: The body of evidence on the management of NOAF in critically ill adults is very limited and not informed by direct evidence from randomized clinical trials. Practice variation appear, Funding Agencies|Scandinavian Society of Anaesthesiology and Intensive Care Medicine (SSAI)

Aims Hypertrophic cardiomyopathy (HCM) is characterized by hypercontractility and diastolic dysfunction, which alter blood flow haemodynamics and are linked with increased risk of adverse clinical events. Four-dimensional flow cardiac magnetic resonance (4D-flow CMR) enables comprehensive characterization of ventricular blood flow patterns. We characterized flow component changes in non-obstructive HCM and assessed their relationship with phenotypic severity and sudden cardiac death (SCD) risk. Methods and results Fifty-one participants (37 non-obstructive HCM and 14 matched controls) underwent 4D-flow CMR. Left-ventricular (LV) end-diastolic volume was separated into four components: direct flow (blood transiting the ventricle within one cycle), retained inflow (blood entering the ventricle and retained for one cycle), delayed ejection flow (retained ventricular blood ejected during systole), and residual volume (ventricular blood retained for >two cycles). Flow component distribution and component end-diastolic kinetic energy/mL were estimated. HCM patients demonstrated greater direct flow proportions compared with controls (47.9 +/- 9% vs. 39.4 +/- 6%, P = 0.002), with reduction in other components. Direct flow proportions correlated with LV mass index (r = 0.40, P = 0.004), end-diastolic volume index (r = -0.40, P = 0.017), and SCD risk (r = 0.34, P = 0.039). In contrast to controls, in HCM, stroke volume decreased with increasing direct flow proportions, indicating diminished volumetric reserve. There was no difference in component end-diastolic kinetic energy/mL. Conclusion Non-obstructive HCM possesses a distinctive flow component distribution pattern characterised by greater direct flow proportions, and direct flow-stroke volume uncoupling indicative of diminished cardiac reserve. The correlation of direct flow proportion with phenotypic severity and SCD risk highlight its potential as a novel and sensitive haemodynamic measure of cardiovascular risk, Funding Agencies|British Heart Foundation [FS/CRTF/21/24144]; National Institute of Health and Care Research Oxford Biomedical Research Centre; British Heart Foundation, Oxford Centre of Research Excellence [RE/18/3/34214]; Swedish Research Council; Swedish Heart and Lung Foundation; ALF Grant Region Ostergotland; Oxford British Heart Foundation Centre of Research Excellence

Aims Eating a varied diet promotes adequate micronutrient intake. Poor appetite could decrease the desire to eat a varied diet leading to dietary micronutrient insufficiencies. The interrelationships among appetite, diet variety, and dietary micronutrient intake have not been investigated in patients with heart failure (HF). The purpose of the study was to determine whether the relationship between appetite and micronutrient insufficiency was mediated through diet variety. Methods and results A total of 238 patients with HF, mean age 61 +/- 12.1; 68% male, and 45% NYHA class III/IV were included in this secondary analysis. Data collection consisted of a 4-day food diary and self-reported appetite on a 10-point visual analogue scale. Micronutrient insufficiency was defined as the total number of 17 minerals and vitamins that were insufficient in the diet. Diet variety was calculated as the number of 23 food types consumed over the 4 days. Mediation analysis, controlling for covariates age, gender, NYHA class, and body mass index showed that diet variety mediated the relationship between appetite and micronutrient insufficiencies [indirect effect = -0.0828, 95% confidence interval (CI): -0.1585 to -0.0150]. There was no direct effect of appetite on micronutrient insufficiency (c = -0.1802; 95% CI = -0.3715 to.0111). Conclusions Diet variety played a previously unrecognized role in the relationship between appetite and dietary micronutrient intake in patients with HF. More research is needed to validate these associations in patients with HF., Funding Agencies|NIH [R01 NR 009280, P20 NR 010679, UL1 RR025008, UL1TR000117, MO1 RR000750]; Clarion Health Partners (Indiana); Atlanta Veterans Administration Medical Center

Atrial fibrillation (AF) is the most common arrhythmia seen in clinical practice. In cardiac surgery, the negative influence of AF on short- and long-term outcomes has made concomitant ablation procedures more common. The indications, clinical aspects, results, risks, and benefits of the additional surgical ablation are still valuable topics for discussion. This compilation thesis consists of four papers aiming to investigate some of the clinical, biochemical, and echocardiographic aspects of surgical ablation for AF (Cox-Maze IV) when performed concomitant to mitral valve surgery (MVS). Through a retrospective, case-control, single-center study, we described the impact of the Cox-Maze IV procedure added to MVS with focus on postoperative heart failure (paper I). Cryoenergy (cryo) and radiofrequency (RF) are the two different energy sources mainly used in Cox-Maze IV for AF ablation. To achieve linear scars in the atrial wall, the RF procedure uses heat damage, whereas the cryo method freezes down to -150°C. Through a prospective, randomized, longitudinal, controlled study, we compared the biochemical responses of the two ablative methods in concomitant MVS and the release of enzymes expressing myocardial injury, as well as inflammatory, cell stress, and apoptosis-specific proteins. We could show that cryo results in a larger release of markers for myocardial damage but has no impact on the early inflammatory response (paper II). Extended scar lesions resulting after maze may influence atrial function. As the left atrium plays a key role in the altered cardiac hemodynamics in AF, an echocardiographic analysis of the effects of the Cox-Maze IV procedure concomitant to MVS on the left atrium was carried out. The impacts of the two energy sources (cryo and RF) on left atrial remodeling and function had not been compared previously. Their direct effect on left atrial remodeling and mechanical function were assessed 1 year after surgery in patients with restored sinus rh, Förmaksflimmer (FF) är den vanligaste arytmin som ses i klinisk praxis. Inom hjärtkirurgi har den negativa inverkan på kort- och långtidsutfall för patienter med FF gjort samtidiga ablationsprocedurer vanligare. Indikationerna, de kliniska aspekterna, resultaten, riskerna och fördelarna med den extra kirurgiska ablationen är fortfarande under diskussion. Den aktuella avhandligen består av fyra artiklar som syftar till att undersöka några av de kliniska, biokemiska och ekokardiografiska aspekterna av kirurgisk ablation vid förmaksflimmer (Cox-Maze IV) när det utförs samtidigt med mitralisklaffkirurgi. I en retrospektiv fallkontrollstudie beskrev vi effekten av Cox-Maze IVproceduren som tillägg till mitralisklaffkirurgin med fokus på postoperativ hjärtsvikt (första artikeln). Kryo och Radiofrekvens är de två olika energikällorna som huvudsakligen används vid Cox-Maze IV för FF-ablation. För att uppnå ärrlinjer i förmaksväggen använder Radiofrekvens-proceduren värmeskada, medan Kryo-metoden fryser ner vävnader till minus 150º C grader Celsius. En jämförelse av de biokemiska svaren presenteras mellan de två ablativa metoderna vid samtidig mitralisklaffkirurgi. Frisättningen av biokemiska markörer som uttrycker myokardskada samt inflammatoriska, cellstress- och apoptosspecifika (celldödsspecifika) proteiner rapporteras. Genom en prospektiv randomiserad longitudinell kontrollerad studie kunde vi visa att Kryo hade en större frisättning av hjärtskademarkörer, men ingen inverkan på tidig inflammatorisk respons (andra artikeln). Ärrskador som uppstår efter Cox-Maze IV kan påverka förmaksfunktionen. Eftersom det vänstra förmaket spelar en nyckelroll vid förmaksflimmer förändrade hemodynamiken, genomfördes en ekokardiografisk analys av effekterna av Cox-Maze IV-proceduren samtidigt med mitralisklaffkirurgi på vänster förmak. Effekten av de två energikällorna (Kryo och Radiofrekvens) på vänster förmaks remodeling och funktion har inte jämförts tidigare på ett prospektivt sätt.

BackgroundDespite the proven cost effectiveness of mechanical thrombectomy (MT) in patients with acute ischemic stroke (AIS) due to large vessel occlusion, treatment within 6 hours from symptom onset remains inaccessible for many patients. We aimed to find the optimal number and location of treatment facilities with respect to the cost effectiveness of MT in patients with AIS, first by the most cost effective implementation of comprehensive stroke centers (CSCs), and second by the most cost effective addition of complementary thrombectomy capable stroke centers (TSCs). MethodsThis study was based on nationwide observational data comprising 18 793 patients with suspected AIS potentially eligible for treatment with MT. The most cost effective solutions were attained by solving the p median facility location-allocation problem with the objective function of maximizing the incremental net monetary benefit (INMB) of MT compared with no MT in patients with AIS. Deterministic sensitivity analysis (DSA) was used as the basis of the results analysis. ResultsThe implementation strategy with seven CSCs produced the highest annual INMB per patient of all possible solutions in the base case scenario. The most cost effective implementation strategy of the extended scenario comprised seven CSCs and four TSCs. DSA revealed sensitivity to variability in MT rate and the maximum willingness to pay per quality adjusted life year gained. ConclusionThe combination of optimization modeling and cost effectiveness analysis provides a powerful tool for configuring the extent and locations of CSCs (and TSCs). The most cost effective implementation of CSCs in Sweden entails 24/7 MT services at all seven university hospitals., Funding Agencies|Center for Advanced Research in Emergency Response (CARER) at Linkoeping University, Sweden; Region Ostergotland, Sweden

BACKGROUND Prognostic assessment of ventricular tachycardia (VT) or ventricular fibrillation (VF) in ST-segment elevation myocardial infarction (STEMI) is based mainly on distinguishing between early (,48 hours) and late arrhythmias, and does not take into account its time distribution with regard to reperfusion, or type of arrhythmia.OBJECTIVE We analyzed the prognostic value of early ventricular arrhythmias (VAs) in STEMI with regard to their type and timing. METHODS The prespecified analysis of the multicenter prospective Bivalirudin versus Heparin in ST-Segment and Non-ST-Segment Eleva-tion Myocardial Infarctionin Patients on Modern Antiplatelet Therapy in the Swedish Web System for Enhancement and Development of Ev-idence-based Care in Heart Disease evaluated according to Recom-mended Therapies Registry Trial included 2886 STEMI patients undergoing primary percutaneous coronary intervention (PCI). VA episodes were characterized regarding their type and timing. Survival status at 180 days was assessed through the population registry.RESULTS Nonmonomorphic VT or VF was observed in 97 (3.4%) and monomorphic VT in 16 (0.5%) patients. Only 3 (2.7%) early VA epi-sodes occurred after 24 hours from symptom onset. VA was associated with higher risk of death (hazard ratio 3.59; 95% confidence interval [CI] 2.01-6.42) after adjustment for age, sex, and STEMI localization. VA after PCI was associated with an increased mortality compared with VA before PCI (hazard ratio 6.68; 95% CI 2.90-15.41). Early VA was associated with in-hospital mortality (odds ratio 7.39; 95% CI 3.68-14.83) but not with long-term prognosis in patients dis-charged alive. The type of VA was not associated with mortality.CONCLUSION VA after PCI was associated with an increased mortal-ity compared with VA before PCI. Long-term prognosis did not differ between patients with monomorphic VT and nonmonomorphic VT or VF, but events were few. VA incidence during 24 to 48 hours of STEMI is negligibly low, thus, Funding Agencies|Swedish Heart Lung Foundation [20180222, 20200674]; Swedish government

Background Guideline recommendations for the treatment of heart failure with mildly reduced ejection fraction (HFmrEF) derive from small subgroups in post-hoc analyses of randomized trials. Objectives We investigated predictors of renin-angiotensin system inhibitors/angiotensin receptor neprilysin inhibitors (RASI/ARNI) and beta-blockers use, and the associations between these medications and mortality/morbidity in a large real-world cohort with HFmrEF. Methods and results Patients with HFmrEF (EF 40-49%) from the Swedish HF Registry were included. The associations between medications and cardiovascular (CV) mortality/HF hospitalization (HFH), and all-cause mortality were assessed through Cox regressions in a 1:1 propensity score-matched cohort. A positive control analysis was performed in patients with EF < 40%, while a negative control outcome analysis had cancer-related hospitalization as endpoint. Of 12 421 patients with HFmrEF, 84% received RASI/ARNI and 88% beta-blockers. Shared-independent predictors of RASI/ARNI and beta-blockers use were younger age, being an outpatient, follow-up in specialty care, and hypertension. In the matched cohorts, use of both RASI/ARNI and beta-blocker use was separately associated with lower risk of CV mortality/HFH [hazard ratio (HR) = 0.90, 95% confidence interval (CI): 0.83-0.98 and HR = 0.82, 95% CI: 0.74-0.90, respectively] and of all-cause mortality (HR = 0.75, 95% CI: 0.69-0.81 and HR = 0.79, 95% CI: 0.72-0.87, respectively). Results were consistent at the positive control analysis, and there were no associations between treatment use and the negative control outcome. Conclusions RASI/ARNI and beta-blockers were extensively used in this large real-world cohort with HFmrEF. Their use was safe since associated with lower mortality and morbidity. Our findings confirm the real-world evidence from previous post-hoc analyses of trials, and represent a further call for implementing guideline recommendations.

BACKGROUND: Swimming is a genotype-specific trigger in long QT syndrome type 1 (LQT1). OBJECTIVE: To examine the autonomic response to water activities in children and adolescents with LQT1. METHODS: In this cross-sectional study, LQT1 patients were age and sex matched to one healthy control subject. Electrocardiograms (ECGs) were recorded during face immersion (FI), swimming, diving, and whole-body submersion (WBS). Heart rate (HR) and heart rate variability (HRV) was measured. The high frequency (HF) component of HRV was interpreted to reflect parasympathetic activity, while the low frequency (LF) component was interpreted as reflecting the combined influence of sympathetic and parasympathetic activity on autonomic nervous modulation of the heart. RESULTS: Fifteen LQT1 patients (aged 7-19 years, all on beta-blocker therapy) and fifteen age and sex matched non-medicated controls were included. No significant ventricular arrhythmias were observed in the LQT1 population during the water activities. Out of these 15 matched pairs, 12 pairs managed to complete FI and WBS for more than 10 seconds and were subsequently included in HR and HRV analyses. In response to FI, the LQT1 group experienced a drop in HR of 48 bpm, compared to 67 bpm in the control group (p = 0.006). In response to WBS, HR decreased by 48 bpm in the LQT1 group and 70 bpm in the control group (p = 0.007). A significantly lower PTOT (p < 0.001) and HF (p = 0.011) component was observed before, during and after FI in LQT1 patients compared with the controls. Before, during and after WBS, a significantly lower total power (p < 0.001), LF (p = 0.002) and HF (p = 0.006) component was observed in the LQT1 patients. CONCLUSION: A significantly lower HR decrease in response to water activities was observed in LQT1 subjects on beta-blocker therapy, compared to matched non-medicated controls. The data suggests an impaired parasympathetic response in LQT1 children and adolescents. An aberrant autonomic ner

Introduction: Carotid-Fetal-Posterior (CFP) syndrome is a posterior cerebral artery (PCA) territory ischemic stroke/TIA caused by symptomatic >= 50% carotid stenosis or occlusion via fetal posterior communicating artery. We aimed to assess the incidence of CFP syndrome and prevalence of CFP syndrome among symptomatic >= 50% carotid stenosis or occlusion as these are unknown. Methods: We reassessed consecutive CTAs from 4042 persons, and included locally admitted patients with >= 50% carotid stenosis or occlusion. These were assessed for symptoms and signs of possible posterior circulation stroke/TIA (suspicion of CFP syndrome). Among these, those with unilateral PCA territory stroke/TIA, ipsilateral stenosis and fetal/fetal type PCA were considered CFP syndrome. Results: We included 208 locally admitted patients with >= 50% carotid stenosis or occlusion, 33 (16%) patients had suspicion of CFP syndrome, of which 3 (9%) had CFP syndrome. The prevalence of CFP syndrome was 2.9% of symptomatic >= 50% carotid stenosis or occlusion; incidence was 4.23 per 1 000 000 person-years. Also, we found a lower prevalence of CFP-syndrome (0.9%, p=0.047) among referred patients with symptomatic >= 50% carotid stenosis or occlusion than among locally admitted patients with symptomatic >= 50% carotid stenosis or occlusion. Discussion/Conclusion: CFP syndrome has a low incidence and low prevalence among symptomatic carotid stenosis cases. Given lower prevalence of CFP syndrome among referred cases than local, CFP-syndrome seems susceptible to underdiagnosis. On the other hand, few cases with suspicion of CFP syndrome had CFP syndrome, why CFP syndrome also seems susceptible to overdiagnosis if detailed assessment is not employed.

Background: Takotsubo syndrome (TS) is a life-threatening acute heart failure syndrome without any evidence-based treatment options. No treatment for TS has been examined in a randomized trial. Study design and objectives: BROKEN-SWEDEHEART is a multicenter, randomized, open-label, registry-based 2 × 2 factorial clinical trial in patients with TS designed to test whether treatment with adenosine and dipyridamole accelerates cardiac recovery and improves clinical outcomes compared to standard care (study 1); and apixaban reduces the risk of thromboembolic events compared to no treatment with antithrombotic drugs (study 2). The trial will enroll 1,000 patients. Study 1 (adenosine hypothesis) will evaluate 2 coprimary end points: (1) wall motion score index at 48 to 96 hours (evaluated in the first 200 patients); and (2) the composite of death, cardiac arrest, need for mechanical assist device or heart failure hospitalization within 30 days or left ventricular ejection fraction <50% at 48 to 96 hours (evaluated in 1,000 patients). The primary end point in study 2 (apixaban hypothesis) is the composite of death or thromboembolic events within 30 days or the presence of intraventricular thrombus on echocardiography at 48 to 96 hours. Conclusions: BROKEN-SWEDEHEART will be the first prospective randomized multicenter trial in patients with TS. It is designed as 2 parallel studies to evaluate whether adenosine accelerates cardiac recovery and improves cardiac function in the acute phase and the efficacy of anticoagulation therapy for preventing thromboembolic complications in TS. If either of its component studies is successful, the trial will provide the first evidence-based treatment recommendation in TS. Clinical trials identifier: The trial has been approved by the Swedish Medicinal Product Agency and the Swedish Ethical Board and is registered at ClinicalTrials.gov (NCT04666454).

BACKGROUND: Cerebral blood flow (CBF) is believed to be relatively constant within an upper and lower blood pressure limit. Different methods are available to monitor CBF autoregulation during surgery. This study aims to critically analyze the application of the cerebral oxygenation index (COx), one of the commonly used techniques, using a reference to data from a series of clinical registrations. METHOD: CBF was monitored using near-infrared spectroscopy, while cerebral blood pressure was estimated by recordings obtained from either the radial or femoral artery in 10 patients undergoing cardiopulmonary bypass. The association between CBF and blood pressure was calculated as a moving continuous correlation coefficient. A COx index > 0.4 was regarded as a sign of abnormal cerebral autoregulation (CA). Recordings were examined to discuss reliability measures and clinical feasibility of the measurements, followed by interpretation of individual results, identification of possible pitfalls, and suggestions of alternative methods. RESULTS AND CONCLUSION: Monitoring of CA during cardiopulmonary bypass is intriguing and complex. A series of challenges and limitations should be considered before introducing this method into clinical practice.