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Background: A novel risk calculator based on clinical characteristics and noninvasive tests that predicts the onset of clinical sustained ventricular arrhythmias (VA) in patients with arrhythmogenic right ventricular cardiomyopathy (ARVC) has been proposed and validated by recent studies. It remains unknown whether programmed ventricular stimulation (PVS) provides additional prognostic value. Methods: All patients with a definite ARVC diagnosis, no history of sustained VAs at diagnosis, and PVS performed at baseline were extracted from 6 international ARVC registries. The calculator-predicted risk for sustained VA (sustained or implantable cardioverter defibrillator treated ventricular tachycardia [VT] or fibrillation, [aborted] sudden cardiac arrest) was assessed in all patients. Independent and combined performance of the risk calculator and PVS on sustained VA were assessed during a 5-year follow-up period. Results: Two hundred eighty-eight patients (41.0 +/- 14.5 years, 55.9% male, right ventricular ejection fraction 42.5 +/- 11.1%) were enrolled. At PVS, 137 (47.6%) patients had inducible ventricular tachycardia. During a median of 5.31 [2.89-10.17] years of follow-up, 83 (60.6%) patients with a positive PVS and 37 (24.5%) with a negative PVS experienced sustained VA (PFunding Agencies|Leonie-Wild Foundation; Leyla Erkan Family Fund for ARVD Research; Hugh Calkins, Marvin H. Weiner, and Jacqueline J. Bernstein Cardiac Arrhythmia Center; Marvin H. Weiner, and Jacqueline J. Bernstein Cardiac Arrhythmia Center; Dr. Francis P. Chiramonte Private Foundation; Dr. Satish, Rupal, and Robin Shah ARVD Fund at Johns Hopkins; Bogle Foundation; Healing Hearts Foundation; Campanella Family; Patrick J. Harrison Family; Peter French Memorial Foundation; Wilmerding Endowments; Fondation Leducq; National Center for Advancing Translational Sciences [UL1TR001079]; Philippa and Marvin Carsley cardiology research chair; Montreal Heart Institute Foundation; Georg und Bertha Schwyzer-Winiker Foundation; Baugarten Foundation; Swiss Heart Foundation [FF17019, FF21073]; Swiss National Science Foundation [160327]; Swedish Heart Lung Foundation [20200674]; Swedish state under the Avtal om lakarutbildning och forsknin (ALF)-agreement; Netherlands Cardiovascular Research Initiative; Dutch Heart Foundation [CVON201512/2018-30]

Background: The relationship between blood pressure (BP) trajectories and outcomes in patients with peripartum cardiomyopathy (PPCM) is not clear. Aim: The study aimed to assess the clinical features and outcomes (all-cause mortality and unrecovered left ventricular [LV] systolic function) of PPCM patients grouped according to their baseline systolic BP (SBP). Patients and Methods: PPCM patients presenting to 14 tertiary hospitals in Nigeria were consecutively recruited between June 2017 and March 2018 and then followed up till March 2019. SBP at first presentation was used to categorize the patients into seven groups

Aims The 10-year risk of recurrent atherosclerotic cardiovascular disease (ASCVD) events in patients with established ASCVD can be estimated with the Secondary Manifestations of ARTerial disease (SMART) risk score, and may help refine clinical management. To broaden generalizability across regions, we updated the existing tool (SMART2 risk score) and recalibrated it with regional incidence rates and assessed its performance in external populations. Methods and results Individuals with coronary artery disease, cerebrovascular disease, peripheral artery disease, or abdominal aortic aneurysms were included from the Utrecht Cardiovascular Cohort-SMART cohort [n = 8355; 1706 ASCVD events during a median follow-up of 8.2 years (interquartile range 4.2-12.5)] to derive a 10-year risk prediction model for recurrent ASCVD events (non-fatal myocardial infarction, non-fatal stroke, or cardiovascular mortality) using a Fine and Gray competing risk-adjusted model. The model was recalibrated to four regions across Europe, and to Asia (excluding Japan), Japan, Australia, North America, and Latin America using contemporary cohort data from each target region. External validation used data from seven cohorts [Clinical Practice Research Datalink, SWEDEHEART, the international REduction of Atherothrombosis for Continued Health (REACH) Registry, Estonian Biobank, Spanish Biomarkers in Acute Coronary Syndrome and Biomarkers in Acute Myocardial Infarction (BACS/BAMI), the Norwegian COgnitive Impairment After STroke, and Bialystok PLUS/Polaspire] and included 369 044 individuals with established ASCVD of whom 62 807 experienced an ASCVD event. C-statistics ranged from 0.605 [95% confidence interval (CI) 0.547-0.664] in BACS/BAMI to 0.772 (95% CI 0.659-0.886) in REACH Europe high-risk region. The clinical utility of the model was demonstrated across a range of clinically relevant treatment thresholds for intensified treatment options. Conclusion The SMART2 risk score provides an updated, validated tool for the prediction of recurrent ASCVD events in patients with established ASCVD across European and non-European populations. The use of this tool could allow for a more personalized approach to secondary prevention based upon quantitative rather than qualitative estimates of residual risk. Key objective To improve upon prediction of 10-year residual atherosclerotic cardiovascular disease (ASCVD) event risk in individuals with established ASCVD, by taking into account competing risks and geographical differences in ASCVD incidence. Key findings Derivation in 8355 individuals with established ASCVD from the Utrecht Cardiovascular Cohort-Secondary Manifestations of ARTerial disease (SMART) cohort. C-statistics ranged from 0.605 [95% confidence interval (CI) 0.547-0.664] to 0.772 (95% CI 0.659-0.886). Clinical utility was demonstrated across a range of treatment thresholds relevant to therapy intensification. Take-home messages The SMART2 risk score can be used to estimate 10-year residual risk of fatal and non-fatal ASCVD in individuals with established ASCVD. Adapted to the CVD incidence in several global regions. Facilitates shared decision-making on Step 2 prevention goals as recommended by the 2021 ESC Guidelines on cardiovascular prevention.

ObjectiveThe onset of new conduction abnormalities requiring permanent pacemaker implantation (PPI) after transcatheter aortic valve implantation (TAVI) is still a relevant adverse event. The main objective of this registry was to identify modifiable procedural risk factors for an improved outcome (lower rate of PPI) after TAVI in patients at high risk of PPI.MethodsPatients from four European centres receiving a balloon-expandable TAVI (Edwards SAPIEN 3/3 Ultra) and considered at high risk of PPI (pre-existing conduction disturbance, heavily calcified left ventricular outflow tract or short membranous septum) were prospectively enrolled into registry.ResultsA total of 300 patients were included: 42 (14.0%) required PPI after TAVI and 258 (86.0%) did not. Patients with PPI had a longer intensive care unit plus intermediate care stay (65.7 vs 16.3 hours, pConclusionValve oversizing is a strong procedure-related risk factor for PPI following TAVI. The clinical impact of the valve type (SAPIEN 3), implantation depth, and postdelivery balloon dilatation did not reach significance and may reflect already refined procedures in the participating centres, giving attention to these avoidable risk factors.Trial registration numberNCT03497611.

BackgroundTriglyceride-glucose (TyG) index is a useful low-cost marker of insulin resistance. We aimed to evaluate the association between TyG index and arterial stiffness, incidence of diabetes, adverse cardiovascular outcomes, and all-cause and cardiovascular mortality in two large prospective Swedish cohorts, the Malmö Diet and Cancer Study-Cardiovascular Cohort (MDCS-CV) and the Malmö Preventive Project (MPP).MethodsAssociation between baseline TyG index and arterial stiffness, measured by carotid femoral pulse wave velocity (c-f PWV), was assessed using linear regression and general linear models, adjusting for covariates. Cox proportional hazard regression was used to assess the association between TyG index and incidence of diabetes, coronary events (CE), stroke, atrial fibrillation (AF), heart failure, and all-cause and cardiovascular mortality.ResultsAfter multivariable adjustment, baseline TyG index was significantly associated with increased arterial stiffness (β for c-f PWV = 0.61, p = 0.018). Participants in the highest quartile of TyG index vs. lowest quartile had an increased incidence of diabetes (HR: 3.30, 95% CI: 2.47–4.41), CE (HR: 1.53, 95% CI: 1.41–1.68), stroke (HR: 1.30, 95% CI: 1.18–1.44), all-cause mortality (HR: 1.22, 95% CI: 1.16–1.28), and cardiovascular mortality (HR: 1.37, 95% CI: 1.26–1.49) after adjustment for covariates. Per unit increase in TyG index was associated with increased heart failure risk. No significant association was observed for incident AF.ConclusionElevated TyG index is positively associated with increased arterial stiffness and increased incidence of diabetes, CE, stroke, and all-cause and cardiovascular mortality. The results suggest that TyG index can potentially be useful in the identification of those at increased long-term risk of adverse health outcomes.

Background Decisions on stroke prevention strategies in patients with atrial fibrillation (AF) depend on the perceived risks of stroke and bleeding with different antithrombotic treatment strategies. The study objectives were to evaluate net clinical outcome with oral anticoagulation (OAC) for the individual patient with AF and to identify clinically relevant thresholds for OAC treatment. Methods Patients with AF receiving OAC treatment in the randomized ARISTOTLE and RE-LY trials, with available biomarkers for calculation of ABC-AF scores at baseline, were included (n = 23,121). Observed 1-year risk on OAC was compared with predicted 1-year risk if the same patients would not have received OAC using the ABC-AF scores calibrated for aspirin. Net clinical outcome was defined as the sum of stroke and major bleeding risks. Results The ratio between the 1-year incidence of major bleeding and stroke/systemic embolism events ranged from 1.4 to 10.6 according to different ABC-AF risk profiles. Net clinical outcome analyses showed that in patients with an ABC-AF-stroke risk >1% per year on OAC (>3% without OAC), treatment with OAC consistently provides larger net clinical benefit than no-OAC treatment. In patients with an ABC-AF-stroke risk

ObjectivesTo describe the perceived importance of suggested hamstring injury risk factors according to chief medical officers (CMOs) of European male professional football clubs. A secondary objective was to compare if these perceptions differed between teams with a lower-than-average hamstring injury burden and teams with a higher than average hamstring injury burden.MethodsFirst, CMOs of 15 European professional male football clubs were asked to suggest risk factors for hamstring injury in their club. The perceived importance of the suggested risk factors was then rated by all participants on a 5-graded Likert scale. Participating teams were divided in two groups depending on their hamstring injury burden during the 2019/2020 and 2020/2021 seasons. The LOW group consisted of seven teams that had a lower than average hamstring injury burden. The HIGH group consisted of eight teams that had a higher-than-average hamstring injury burden.ResultsTwenty-one risk factors were suggested. The majority were extrinsic in nature, associated with coaching staff, team or club rather than players themselves. ‘Lack of communication between medical staff and coaching staff’ had the highest average importance (weighted average=3.7) followed by ‘Lack of regular exposure to high-speed football during training sessions’ (weighted average=3.6). The HIGH group perceived the player factors fatigue and wellness as more important than the LOW group.ConclusionAccording to CMOs recruited in this study, most risk factors for hamstring injuries are extrinsic and associated with the club and coaching staff, and not the players themselves.

This commentary refers to 'Effects of a comprehensive lifestyle intervention on cardiovascular health: the TANSNIP-PESA trial', by I. Garcia-Lunar et al., https://doi.org/10.1093/eurheartj/ehac378 and the discussion piece 'Motivational interview and imaging of subclinical atherosclerosis for cardiovascular disease prevention: a winning combination?', by I. Garcia-Lunar et al., https://doi.org/10.1093/eurheartj/ehad126.

Background: Selenium and coenzyme Q10 (SeQ10) possess antioxidant and anti-inflammatory properties, potentially mediated via Sirtuin1 (SIRT1). We aimed to investigate the influence of a SeQ10 intervention on SIRT1 concentration, with potential interactions with microRNAs. Methods: In this sub-study of a prospective double-blind placebo-controlled clinical trial, healthy subjects (mean age 76 years) were randomized to receive an active treatment (n = 165, combined 200 µg/day of Se and 200 mg/day of Q10) or a placebo (n = 161). SIRT1 concentration and microRNAs were measured with ELISA and PCR, respectively. Results: After four years, SIRT1 concentration was increased in the active treatment group, with mean (SD) ng/mL of 469 (436) vs. 252 (162), p < 0.001, and decreased in the placebo group, 190 (186) vs. 269 (172), p = 0.002, and the differences between the groups were significant (p = 0.006, adjusted). Those who suffered CV death during a 10-year follow-up (n = 25 and n = 52 in the active treatment and placebo groups, respectively) had significantly lower baseline SIRT1 concentrations compared to the survivors (p < 0.001). MiR-130a-3p was significantly downregulated during the intervention and correlated inversely with SIRT1 at baseline (r = -0.466, p = 0.007). Conclusion: The increased SIRT1 concentration after the SeQ10 intervention associated with reduced CV mortality, partly mediated via miR-1303a-3p, suggests that SIRT1 is an additional mediator of the intervention, preventing vascular ageing. This research was funded by the Stein Erik Hagen Foundation for Clinical Heart Research, Oslo, Norway. Part of the analysis cost was funded by grants from Pharma Nord Aps, Vejle, Denmark, and the County Council of Östergötland, Linköping University, Sweden. The selenium and coenzyme Q10 tablets were provided by Pharma Nord Aps, Vejle, Denmark.

Pulmonary arterial hypertension (PAH) is an uncommon but serious disease that causes increased pressure in the pulmonary vessels and increased pulmonary vascular resistance (PVR), which in turn leads to right heart failure. At diagnosis, mean pulmonary artery pressure (mPAP) must be >20 mmHg, pulmonary artery wedge pressure (PAWP) ≤15 mmHg and PVR >2 Wood units (WU). Calculation of cardiac output (CO) is an important hemodynamic parameter to be measured and assessed in these patients during a right heart catheterization (RHC). Prevailing ESC guidelines recommend using direct Fick's principle (dFp), which is considered the gold standard, or thermodilution when calculating CO. The aim of this study was to compare these two methods to see if there is a significant difference in the calculation of CO in patients with PAH. The aim was also to see if calculated cardiac index (CI) and PVR differ significantly depending on which of the methods for calculating CO is used. A retrospective study was conducted in which 34 patients who underwent RHC at the University Hospital in Örebro were included. The result showed a significant difference between dFp and thermodilution (p

BACKGROUND: Epidemiological studies have shown that impaired lung function is common and associated with increased risk of cardiovascular disease. Increased levels of several inflammatory and cardiovascular disease-related plasma proteins have been associated with impaired lung function. The aim was to study the association between plasma proteomics and forced expiratory volume in 1 s (FEV1), forced vital capacity (FVC) and FEV1/FVC ratio. METHODS: We used a discovery and replication approach in two community-based cohorts, EpiHealth and the Malmö Offspring Study (total n=2874), to cross-sectionally study 242 cardiovascular disease- and metabolism-linked proteins in relation to FEV1, FVC (both % predicted) and FEV1/FVC ratio. A false discovery rate of 5% was used as the significance threshold in the discovery cohort. RESULTS: Plasma fatty acid-binding protein 4, interleukin-1 receptor antagonist, interleukin-6 and leptin were negatively associated with FEV1 and paraoxonase 3 was positively associated therewith. Fatty acid-binding protein 4, fibroblast growth factor 21, interleukin-1 receptor antagonist, interleukin-6 and leptin were negatively associated with FVC and agouti-related protein, insulin-like growth factor-binding protein 2, paraoxonase 3 and receptor for advanced glycation end products were positively associated therewith. No proteins were associated with FEV1/FVC ratio. A sensitivity analysis in EpiHealth revealed only minor changes after excluding individuals with known cardiovascular disease, diabetes or obesity. CONCLUSIONS: Five proteins were associated with both FEV1 and FVC. Four proteins associated with only FVC and none with FEV1/FVC ratio, suggesting associations mainly through lung volume, not airway obstruction. However, additional studies are needed to investigate underlying mechanisms for these findings.

Direct oral anticoagulants (DOACs) used in nonvalvular atrial fibrillation (NVAF) are dose-reduced in elderly and patients with impaired renal function. Only reduced dose dabigatran is concluded as having similar stroke risk reduction and lower risk of major bleeding than warfarin in the pivotal studies. In clinical practice, reduced dose is prescribed more often than expected making this an important issue. The objective of this study was to compare effectiveness and safety between reduced dose DOACs and high TTR warfarin treatment (TTR ≥ 70%) in NVAF. A Swedish anticoagulation registry was used in identifying eligible patients from July 2011 to December 2017. The study cohort consisted of 40,564 patients with newly initiated DOAC (apixaban, dabigatran, or rivaroxaban) (11,083 patients) or warfarin treatment (29,481 patients) after exclusion of 374,135 patients due to not being warfarin or DOAC naïve, not being prescribed reduced dose, having previous mechanical heart valve (MHV), or being under 18 years old. The median durations of follow up were 365, 419, 432 and 473 days for apixaban, dabigatran, rivaroxaban and warfarin, respectively. Warfarin TTR identified from Auricula was 70.0%. Endpoints (stroke and major bleeding) and baseline characteristics were collected from hospital administrative registers using ICD-10 codes. Cohorts were compared using weighted adjusted Cox regression after full optimal matching based on propensity scores. DOACs are associated with lower risk of major bleeding (HR with 95% CI) 0.85 (0.78–0.93), intracranial bleeding HR 0.64 (0.51–0.80), hemorrhagic stroke HR 0.68 (0.50–0.92), gastrointestinal bleeding HR 0.81 (0.69–0.96) and all-cause stroke HR 0.87 (0.76–0.99), than warfarin. Apixaban and dabigatran are associated with lower risk of major bleeding, HR 0.70 (0.63–0.78) and HR 0.80 (0.69–0.94), and rivaroxaban is associated with lower risk of ischemic stroke, HR 0.73 (0.59–0.96), with higher major bleeding risk, HR 1.31 (1.15–1.48), compared to warfarin. Apixaban is associated with higher all-cause mortality compared to warfarin, HR 1.12 (1.03–1.21). DOACs are associated with lower risk of major bleeding and all-cause stroke, than high quality warfarin treatment, with exception of rivaroxaban that carried higher risk of major bleeding and lower risk of stroke or systemic embolism. In this large observational registry-based NVAF cohort, DOACs are preferred treatment in patients with indication for DOAC dose reduction, even in a high TTR setting.

AIMS: To investigate the association of iatrogenic cardiac tamponades as a complication of invasive electrophysiology procedures (EPs) and mortality as well as serious cardiovascular events in a nationwide patient cohort during long-term follow-up. METHODS: From the Swedish Catheter Ablation Registry between 2005 and 2019, a total of 58 770 invasive EPs in 44 497 patients were analysed. From this, all patients with periprocedural cardiac tamponades related to invasive EPs were identified (n = 200; tamponade group) and matched (1:2 ratio) to a control group (n = 400). Over a follow-up of 5 years, the composite primary endpoint-death from any cause, acute myocardial infarction, transitory ischaemic attack (TIA)/stroke, and hospitalization for heart failure-revealed no statistically significant association with cardiac tamponade [hazard ratio (HR) 1.22 (95% CI, 0.79-1.88)]. All single components of the primary endpoint as well as cardiovascular death revealed no statistically significant association with cardiac tamponade. Cardiac tamponade was associated with a significantly higher risk with hospitalization for pericarditis [HR 20.67 (95% CI, 6.32-67.60)]. CONCLUSION: In this nationwide cohort of patients undergoing invasive EPs, iatrogenic cardiac tamponade was associated with an increased risk of hospitalization for pericarditis during the first months after the index procedure. In the long-term, however, cardiac tamponade revealed no significant association with mortality or other serious cardiovascular events.

Objective: After alerts on EndoVascular Aneurysm Seal (EVAS) failure were raised, the European Society for Vascular Surgery (ESVS) Abdominal Aortic Aneurysm (AAA) Clinical Practice Guidelines Writing Committee (WC) initiated a task force with the aim to provide guidance on surveillance and management of patients with implanted EVAS devices.Methods: Based on a scoping review of risk for late serious aortic-related adverse events in patients treated with EVAS for AAA, the ESVS AAA Guidelines WC agreed on recommendations graded according to the European Society of Cardiology (ESC) grading system.Results: EVAS has a very high incidence of late endograft migration resulting in proximal type 1 endoleak with risk of rupture, requiring open conversion with device explantation. The reported mortality rate for elective explantation varies between 0% and 14%, while acute conversion for rupture has a very dismal prognosis with a 67 -75% mortality rate.Conclusion: It is recommended that all patients in whom a Nellix device has been implanted should be identified, properly informed, and enrolled in enhanced surveillance. If device failure is detected, early elective device explantation should be considered in surgically fit patients. The authors, on behalf of the ESVS AAA Guidelines Writing Committee and the ESVS Guidelines Steering Committee.

Objectives: The risk of cardiovascular disease is associated with the echo intensity of carotid plaques in ultrasound images and their cardiac cycle-induced intensity variations. In this study, we aimed to 1) explore the underlying origin of echo intensity variations by using simulations and 2) evaluate the association between the two-dimensional (2D) spatial distribution of these echo intensity variations and plaque vulnerability. Methods: First, we analyzed how out-of-plane motion and compression of simulated scattering spheres of different sizes affect the ultrasound echo intensity. Next, we propose a method to analyze the features of the 2D spatial distribution of interframe plaque echo intensity in carotid ultrasound image sequences and explore their associations with plaque vulnerability in experimental data. Results: The simulations showed that the magnitude of echo intensity changes was similar for both the out-of-plane motion and compression, but for scattering objects smaller than 1 mm radius, the out-of-plane motion dominated. In experimental data, maps of the 2D spatial distribution of the echo intensity variations had a low correlation with standard B-mode echo intensity distribution, indicating complementary information on plaque tissue composition. In addition, we found the existence of ∼1 mm diameter subregions with pronounced echo intensity variations associated with plaque vulnerability. Conclusions: The results indicate that out-of-plane motion contributes to intra-plaque regions of high echo intensity variation. The 2D echo intensity variation maps may provide complementary information for assessing plaque composition and vulnerability. Further studies are needed to verify this method's role in identifying vulnerable plaques and predicting cardiovascular disease risk.

Background and AimsGhrelin is an endogenous appetite-stimulating peptide hormone with potential cardiovascular benefits. Effects of acylated (activated) ghrelin were assessed in patients with heart failure and reduced ejection fraction (HFrEF) and in ex vivo mouse cardiomyocytes.Methods and resultsIn a randomized placebo-controlled double-blind trial, 31 patients with chronic HFrEF were randomized to synthetic human acyl ghrelin (0.1 µg/kg/min) or placebo intravenously over 120 min. The primary outcome was change in cardiac output (CO). Isolated mouse cardiomyocytes were treated with acyl ghrelin and fractional shortening and calcium transients were assessed. Acyl ghrelin but not placebo increased cardiac output (acyl ghrelin: 4.08 ± 1.15 to 5.23 ± 1.98 L/min; placebo: 4.26 ± 1.23 to 4.11 ± 1.99 L/min, P < 0.001). Acyl ghrelin caused a significant increase in stroke volume and nominal increases in left ventricular ejection fraction and segmental longitudinal strain and tricuspid annular plane systolic excursion. There were no effects on blood pressure, arrhythmias, or ischaemia. Heart rate decreased nominally (acyl ghrelin: 71 ± 11 to 67 ± 11 b.p.m.; placebo 69 ± 8 to 68 ± 10 b.p.m.). In cardiomyocytes, acyl ghrelin increased fractional shortening, did not affect cellular Ca2+ transients, and reduced troponin I phosphorylation. The increase in fractional shortening and reduction in troponin I phosphorylation was blocked by the acyl ghrelin antagonist D-Lys 3.ConclusionIn patients with HFrEF, acyl ghrelin increased cardiac output without causing hypotension, tachycardia, arrhythmia, or ischaemia. In isolated cardiomyocytes, acyl ghrelin increased contractility independently of preload and afterload and without Ca2+ mobilization, which may explain the lack of clinical side effects. Ghrelin treatment should be explored in additional randomized trials.Clinical Trial RegistrationClinicalTrials.gov Identifier: NCT05277415

Background Surgery on the aortic arch and proximal descending thoracic aorta can be lifesaving but is also associated with significant morbidity, ranging from minor infections to severe neurological impairments as well as a substantial risk of mortality. The aim of this study is to clinically assess outcomes, with special regards to neurologic injury, as well as to seek to identify predictors of in-hospital mortality in two patient groups with different underlying aortic pathology, aneurysms and dissections, undergoing arch/descending aortic repair. Methods 34 patients (17 aneurysms, 17 dissections) underwent surgery involving the arch and/or descending aorta, using the Thoraflex or E-Vita frozen elephant trunk graft. 40% were female. Subgroup analysis of aneurysms compared to dissections were performed. Mean follow-up time was 53.9 months and mean age 63.5 years. Results In-hospital mortality was 18%. Survival was comparable between aneurysms and dissections. Incidence of spinal cord injury was 9% and stroke 9%. 67% suffered any form of neurological affection, when also cognitive afflictions were included. Perioperative reoperation rate was 29% (bleeding 21%, visceral ischemia 6%, infection 2%), the need for postoperative dialysis was 11% and a series of other minor complications such as atrial fibrillation and pleurocentesis were common. Conclusion Postoperative dialysis was found to be a predictor of in-hospital mortality, while both dialysis as well as reoperation due to bleeding and/or visceral ischemia increased the risk for overall mortality, irrespective of preoperative diagnosis. Previous or current smoking appeared to be associated with negative outcomes regarding both in-hospital and overall mortality during follow-up. Trial registration Retrospectively enrolled.

Aims Management of comorbidities represents a critical step in optimal treatment of heart failure (HF) patients. However, minimal attention has been paid whether comorbidity burden and their prognostic value changes over time. Therefore, we examined the association between comorbidities and clinical outcomes in HF patients between 2002 and 2017. Methods and results The 2002-HF cohort consisted of patients from The Coordinating Study Evaluating Outcomes of Advising and Counseling in Heart Failure (COACH) trial (n = 1,032). The 2017-HF cohort were outpatient HF patients enrolled after hospitalization for HF in a tertiary referral academic hospital (n = 382). Kaplan meier and cox regression analyses were used to assess the association of comorbidities with HF hospitalization and all-cause mortality. Patients from the 2017-cohort were more likely to be classified as HF with preserved ejection fraction (24 vs 15%, p p for interaction 0.026). Conclusion Despite major advances in HF treatment over the past decades, comorbidity burden remains high in HF and influences outcome to a large extent. Obesity emerges as a prominent comorbidity, and efforts should be made for prevention and treatment. Graphical abstract Created with BioRender.com.

Women with a history of pregnancy complications have an increased risk of cardiovascular disease (CVD) later in life. The overall aims were to investigate pregnancy complications as cardiovascular risk factors; whether they have predictive value for the spread of atherosclerosis in older women, whether they are associated with atherosclerotic CVD after adjusting for major confounders, both at the population-level and in women with structural heart disease; and to investigate cardiovascular biomarkers in women with spontaneous preterm birth. Among 307 postmenopausal women with and without CVD, the self-reported frequency of pregnancy complications was assessed, and three vascular beds were examined (peripheral, carotid and coronary arteries). The self-reported complications were evaluated as possible predictors of spreading atherosclerosis. Exposures to pregnancy complications of a population-based cohort, including 2 134 239 women from the national Medical Birth Register from 1973 to 2014, were evaluated as a risk factor for atherosclerotic cardiovascular outcomes (hospitalizations and mortality) after adjustment for major confounders. The associations were further analyzed in 2554 women from the same cohort identified as having structural heart disease, and also for hospitalizations for heart failure and arrhythmias. A first screening phase used comparative mass spectrometry to examine differences in protein expression in mid-pregnancy plasma samples, from the Uppsala Biobank for Pregnant Women, from a subset of women with spontaneous preterm birth in first pregnancy and controls. Seven protein biomarkers differed significantly between cases and controls. In a second validation phase, plasma samples and data on cardiovascular risk factors were collected from 65 women who agreed to participate in a follow-up visit 4–15 years after pregnancy. Concentrations of the selected biomarkers were analyzed, as well as lipid profiles from samples from both pregnancy (Biobank) and follow-up. In conclusion, an association between pregnancy complications and the spread of atherosclerosis in older women was not found. Pregnancy complications were associated with an increased risk of atherosclerotic cardiovascular outcomes, both at the population level and in women with structural heart disease, after adjustment for major confounding factors. Compared with women without preterm birth, those with spontaneous preterm birth had higher concentrations of fibrinogen and triglycerides, both at mid-pregnancy and a decade after pregnancy.

During interventional cardiology (IC), medical staff are exposed to scattered ionizing radiation from the patient, potentially leading to various radiation-induced health effects. Therefore, shielding devices are routinely used to reduce occupational exposure during IC procedures. This study explores how the positioning of shielding devices impacts radiation protection efficiency in clinical scenarios. The study aims to determine optimal setups and potential pitfalls that might significantly reduce the efficiency of the shielding devices. It also explores the relationship between DICOM-based production data, clinical observations, and phantom-based measurements to add knowledge to the research field of radiation protection in IC. Clinical DICOM-based production data from 4976 procedures were analyzed to identify C-arm projection angles used during different procedure types. This data and the results of an observational study were used to determine a scattered radiation measurement setup. A survey meter was used to measure air kerma at seven heights in the operator position while an anthropomorphic phantom was irradiated. The measurements were distributed over seven projections with 56 position combinations of the shielding devices. A total of 3171 measurements were performed. The measurements suggest significant variations in the operator dose depending on the projection and how the shielding devices are positioned. The most optimal combination of shielding devices was achieved when placing the table-mounted shield along the table, the ceiling-suspended shield caudal close to the phantom, and without the patient drape. Conversely, the least optimal combination was achieved when placing the table-mounted shield flared out, the ceiling-suspended shield cranial 10 cm above the phantom, and without the patient drape. The air kerma rate for these two shielding setups with the LAO25/CAUD30 projection was reduced from 0.19 μGy/s to 0.05 μGy/s at 110 cm from the floor. This height was shown to be the hardest to properly shield. Despite the implementation of the most optimal shielding combination, it is evident that certain heights present difficulties in effectively protecting the operator from scattered radiation.

ObjectivesRegistries have been highlighted as means to improve quality of care. Here, we describe temporal trends in risk factors, lifestyle and preventive medication for patients after myocardial infarction (MI) registered in the quality registry Swedish Web-system for Enhancement and Development of Evidence-based care in Heart disease Evaluated According to Recommended Therapies (SWEDEHEART).DesignA registry-based cohort study.SettingAll coronary care units and cardiac rehabilitation (CR) centres in Sweden.ParticipantsPatients attending a CR visit at 1-year post-MI 2006–2019 were included (n=81 363, 18–74 years, 74.7% men).Outcome measuresOutcome measures at 1-year follow-up included blood pressure (BP) ResultsThe proportion of patients attaining the targets for BP90.0% of patients were prescribed statins and approximately 98% antiplatelet and/or anticoagulant therapy. Angiotensin-converting enzyme inhibitor/angiotensin receptor blocker prescription increased from 68.7% (2006) to 80.2% (2019, pConclusionsWhile little change was observed for persistent smoking and overweight/obesity, large improvements were observed for LDL-C and BP target achievements and prescription of preventive medication for Swedish patients after MI 2006–2019. Compared with published results from patients with coronary artery disease in Europe during the same period, these improvements were considerably larger. Continuous auditing and open comparisons of CR outcomes might possibly explain some of the observed improvements and differences.

BACKGROUND: Isolated systolic hypertension (ISH) in middle-aged and elderly is associated with high cardiovascular risk, but no randomised controlled trial has assessed the effect of antihypertensive treatment in ISH using today's definition, i.e. systolic blood pressure (SBP) ≥140 mmHg and diastolic blood pressure (DBP)

Background: Masked hypertension is associated with cardiovascular disease (CVD). However, previous large studies have not used the same device to measure office and home blood pressure (BP) and adhered to current home BP measurement recommendations of the European Society of Hypertension. We aimed to characterize masked hypertension and explore its relation to manifestations of CVD. Methods: A randomly selected cohort of 5057 participants aged 50–64 years from the Swedish CardioPulmonary BioImage Study (SCAPIS) was evaluated with office and home BP using the semi-automatic Omron M10-IT oscillometric device. Additional analyses included pulse wave velocity (PWV) and coronary artery calcium score (CACS). Results: Of participants, 4122 did not have current antihypertensive treatment, and were thus included in our analyses. Of these, 2634 (63.9%) had sustained normotension, and 172 (4.2%) had masked hypertension. Participants with masked hypertension vs. sustained normotension were more often men (66.9 vs. 46.2%, P < 0.001). Those with masked hypertension had higher mean PWV [9.3 (95% confidence interval, 95% CI 9.1–9.5) vs. 8.3 (95% CI 8.2–8.4) m/s, P < 0.001] and odds ratio for CACS at least 100 [1.65 (95% CI 1.02–2.68), P = 0.040]. These associations were similar in a posthoc analysis of masked hypertension and sustained normotension, matched for age, sex and systolic office BP. Conclusion: Masked hypertension was associated with markers of CVD. This suggests that home BP is a better predictor of risk, even when the recordings are performed with the same measurement device, in a population-based setting with randomized recruitment. Funding: Swedish Heart and Lung Foundation [20160315]; Knut and Alice Wallenberg Foundation [20140047]; Swedish Research Council [82220132000]; VINNOVA (Swedens Innovation agency) [201204476]; University of Gothenburg; Sahlgrenska University Hospital; Karolinska Institutet; Stockholm County council; Linkoping University; Linkoping University Hospital; Lund University; Skane University Hospital; Umea~University; Umea University Hospital; Uppsala University; Uppsala University Hospital; Strategic Research Network in Circulation and Metabolism at Linkoping University (LiU-CircM); King Gustaf V and Queen Victoria Freemason Foundation

Aims Sacubitril/valsartan is a first-in-class angiotensin receptor–neprilysin inhibitor (ARNI) with a class-1 guideline recommendation. We assessed the real-world effectiveness of ARNI versus angiotensin-converting enzyme inhibitor/angiotensin receptor blocker (ACEi/ARB) on all-cause and cardiovascular (CV)-related mortality and hospitalizations in heart failure (HF) with reduced or mildly reduced ejection fraction (EF). Methods Patient-level clinical, laboratory, drug dispensation, hospitalization, and mortality data were derived from the Swedish Heart Failure Registry (SwedeHF) and interlinked databases (1 April 2016–31 December 2020). Eligible ARNI:ACEi/ARB patients (n = 7275:24,604) had a left ventricular EF n = 1506) versus ACEi/ARB (≤ 3 months post-index; n = 17,108) were assessed using propensity score matching (1:1 ratio) with clinical variables, and sensitivity analysis (1:2/1:3 with, and 1:2 without clinical variables). Results ARNI induced a 23% reduction in all-cause mortality versus ACEi/ARB (1:1 hazard ratio [HR; 95% confidence interval (CI)]: 0.77 [0.63–0.95], p = 0.013), and a non-significant 23% relative risk reduction in CV-related mortality (0.77 [0.54–1.09], p = 0.13), but no difference in all-cause or CV-related hospitalization (1.02 [0.91–1.13]; p = 0.76; 1.01 [0.91–1.15]; p = 0.84, respectively). Sensitivity analyses confirmed all-cause mortality was reduced for ARNI versus ACEi/ARB (HR 0.90 [95% CI 0.82–0.99], p = 0.026), but not CV-related mortality (HR 1.04 [95% CI 0.89–1.22], p = 0.63). Conclusions In this nationwide real-world study including a population of patients with HF with reduced or mildly reduced EF, ARNI as part of guideline-led Swedish clinical practice was associated with a statistically significant relative risk reduction in all-cause mortality compared with ACEi/ARB.

Aims Primary acute heart failure (AHF) is a common cause of hospitalization. AHF may also develop postoperatively (pAHF). The aim of this study was to assess the incidence, phenotypes, determinants and outcomes of pAHF following non-cardiac surgery.Methods and results A total of 9164 consecutive high-risk patients undergoing 11 262 non-cardiac inpatient surgeries were prospectively included. The incidence, phenotypes, determinants and outcome of pAHF, centrally adjudicated by independent cardiologists, were determined. The incidence of pAHF was 2.5% (95% confidence interval [CI] 2.2-2.8%); 51% of pAHF occurred in patients without known heart failure (de novo pAHF), and 49% in patients with chronic heart failure. Among patients with chronic heart failure, 10% developed pAHF, and among patients without a history of heart failure, 1.5% developed pAHF. Chronic heart failure, diabetes, urgent/emergent surgery, atrial fibrillation, cardiac troponin elevations above the 99th percentile, chronic obstructive pulmonary disease, anaemia, peripheral artery disease, coronary artery disease, and age, were independent predictors of pAHF in the logistic regression model. Patients with pAHF had significantly higher all-cause mortality (44% vs. 11%, p < 0.001) and AHF readmission (15% vs. 2%, p < 0.001) within 1 year than patients without pAHF. After Cox regression analysis, pAHF was an independent predictor of all-cause mortality (adjusted hazard ratio [aHR] 1.7 [95% CI 1.3-2.2]; p < 0.001) and AHF readmission (aHR 2.3 [95% CI 1.5-3.7]; p < 0.001). Findings were confirmed in an external validation cohort using a prospective multicentre cohort of 1250 patients (incidence of pAHF 2.4% [95% CI 1.6-3.3%]).Conclusions Postoperative AHF frequently developed following non-cardiac surgery, being de novo in half of cases, and associated with a very high mortality. Funding Agencies|Swiss National Science Foundation; Swiss Heart Foundation; University Hospital Basel; University of Basel; AstraZeneca; Abbott; Roche; Clinical Research Program of the University of Basel; Spezialprogramm Nachwuchsforderung Klinische Forschung; Forderung Exzellenter Junger Forschender; Forschung fond Kantonsspital Aarau; Swiss Academy of Medical Sciences; Bangerter Foundation; Fundacao de Amparo a Pesquisa do Estado de Sao Paulo; Brazil [FAPESP] [2015/23731-6]; Swedish Research Council [2019-02833]; South Eastern Sweden Research Council [746981, 712291]; LinkopingUniversity-Region_Osterg_otland ALF [687681, 792291]

Background We aimed to compare absolute plasma concentrations of N-terminal pro-brain natriuretic peptide (NT-proBNP) and growth differentiation factor 15 (GDF-15) obtained by a conventional immunoassay with the corresponding relative concentrations from a proximity extension assay (PEA) and compare the prognostic impact of the protein levels obtained from these assays. Methods We evaluated 437 patients with peripheral arterial disease (PAD) and a population-based cohort of 643 individuals without PAD. Correlations were calculated using Spearman’s rank correlation coefficients (rho). The discriminatory accuracy of the protein levels to predict future cardiovascular events was analyzed with Cox regression and presented as time-dependent areas under the receiver-operator-characteristic curves (tdAUCs). Results For NT-proBNP, the two assays correlated with rho 0.93 and 0.93 in the respective cohort. The PEA values leveled off at higher values in both cohorts. The corresponding correlations for GDF-15 were 0.91 and 0.89. At 5 years follow-up, the tdAUCs in the patient cohort were similar for NT-proBNP and GDF-15 regardless of assay used (0.65–0.66). The corresponding tdAUCs in the population-based cohort were between 0.72 and 0.77. Conclusion Except for the highest levels of NT-proBNP, we suggest that PEA data for NT-proBNP and GDF-15 reliably reflects absolute plasma levels and contains similar prognostic information.

Researchers have proposed several automated diagnostic systems based on machine learning and data mining techniques to predict heart failure. However, researchers have not paid close attention to predicting cardiac patient mortality. We developed a clinical decision support system for predicting mortality in cardiac patients to address this problem. The dataset collected for the experimental purposes of the proposed model consisted of 55 features with a total of 368 samples. We found that the classes in the dataset were highly imbalanced. To avoid the problem of bias in the machine learning model, we used the synthetic minority oversampling technique (SMOTE). After balancing the classes in the dataset, the newly proposed system employed a (Formula presented.) statistical model to rank the features from the dataset. The highest-ranked features were fed into an optimized random forest (RF) model for classification. The hyperparameters of the RF classifier were optimized using a grid search algorithm. The performance of the newly proposed model ((Formula presented.) _RF) was validated using several evaluation measures, including accuracy, sensitivity, specificity, F1 score, and a receiver operating characteristic (ROC) curve. With only 10 features from the dataset, the proposed model (Formula presented.) _RF achieved the highest accuracy of 94.59%. The proposed model (Formula presented.) _RF improved the performance of the standard RF model by 5.5%. Moreover, the proposed model (Formula presented.) _RF was compared with other state-of-the-art machine learning models. The experimental results show that the newly proposed decision support system outperforms the other machine learning systems using the same feature selection module ((Formula presented.)). CC BY 4.0© 2023 by the authors.(This article belongs to the Special Issue Opinion Mining and Sentiment Analysis Using Deep Neural Network)This research received no external funding.

A proportion of patients with the acute coronary syndrome (ACS) will suffer progressive remodeling of the left ventricular (LV). The aim was to screen for important biomarkers from a large-scale protein profiling in 420 ACS patients and define biomarkers associated with reduced LV function early and 1 year after the ACS. Transferrin receptor protein 1 and NT-proBNP were associated with LV function early and after 1 year, whereas osteopontin and soluble ST2 were associated with LV function in the early phase and, tissue-type plasminogen activator after 1 year. Fatty-acid-binding protein and galectin 3 were related to worse GLS but not to LVEF 1 year after the ACS. Proteins involved in remodeling and iron transport in cardiomyocytes were related to worse LV function after ACS. Biomarkers for energy metabolism and fibrosis were exclusively related to worse LV function by GLS. Studies on the functions of these proteins might add knowledge to the biological processes involved in heart failure in long term after ACS.

AimsA high intake of salt raises blood pressure and the risk of cardiovascular disease. Previous studies have reported on the association between salt intake and carotid stenosis, but the association with coronary atherosclerosis has not been reported. Therefore, this project aimed at studying the association between salt intake and both carotid and coronary atherosclerosis in a contemporary community-based cohort.Methods and resultsEstimated 24-h sodium excretion (est24hNa) was calculated by the Kawasaki formula for participants of two sites (Uppsala and Malmö) of the Swedish Cardiopulmonary bioImage Study, who underwent a coronary computed tomography (n = 9623) and measurement of coronary artery calcium score (CACS, n = 10 289). Carotid ultrasound was used to detect carotid plaques (n = 10 700). Ordered logistic regression was used to calculate odds ratios (OR) per 1000 mg increase in est24hNa. We also investigated potential J-formed associations using quintiles of est24hNa. Increased est24hNa was associated with increased occurrence of carotid plaques [OR: 1.09, P < 0.001, confidence interval (CI): 1.06–1.12], higher CACS (OR: 1.16, P < 0.001, CI: 1.12–1.19), and coronary artery stenosis (OR: 1.17, P < 0.001, CI: 1.13–1.20) in minimal adjusted models. Associations were abolished when adjusting for blood pressure. When adjusting for established cardiovascular risk factors (not including blood pressure), associations remained for carotid plaques but not for coronary atherosclerosis. There was no evidence of J-formed associations.ConclusionHigher est24hNa was associated with both coronary and carotid atherosclerosis in minimal adjusted models. The association seemed mainly mediated by blood pressure but to some degree also influenced by other established cardiovascular risk factors.

ObjectivesLittle is known about figure skaters’ mental health. This study aimed to describe anxiety and depression caseness (defined as a screening condition qualifying for psychiatric examination) in competitive figure skaters and analyse factors associated with such caseness.MethodsA cross-sectional study was performed in April 2019 among all competitive figure skaters in the south-eastern region of Sweden (N=400). The primary outcomes were anxiety caseness, measured using the short-form Spielberger State-Trait Anxiety Inventory and depression caseness, measured using the WHO-5 index. Multivariable logistic regression models were employed to determine the association between anxiety caseness and explanatory factors.ResultsIn total, 36% (n=142) of the invited skaters participated. Only females (n=137), mean age 12.9 (SD 3.0) years) were selected for analysis. Of the participating skaters, 47% displayed anxiety caseness and 10% depression caseness. Overweight body image perception (OR 5.9; 95% CI 2.0 to 17.6; p=0.001) and older age (OR 1.2; 95% CI 1.1 to 1.4; p=0.005) were associated with anxiety caseness. Skaters reporting no caseness were younger than those reporting only anxiety caseness (mean age difference −1.9 years; 95% CI −3.1 to −0.7; p=0.001) or anxiety and depression caseness (OR −3.5 years; 95% CI −5.6 to −1.5 years; pConclusionAnxiety caseness was associated with overweight body image perception and older age in female competitive figure skaters. Older skaters reported generally worse mental health. More research on the mental health of figure skaters is warranted, considering comorbidity and focusing on those needing further assessment and support.

BACKGROUND: The health effects of rest-activity rhythm are of major interest to public health, but its associations with health outcomes remain elusive. We aimed to examine the associations between accelerometer-measured rest-activity rhythm amplitude and health risks among the general UK population. METHODS: We did a prospective cohort analysis of UK Biobank participants aged 43-79 years with valid wrist-worn accelerometer data. Low rest-activity rhythm amplitude was defined as the first quintile of relative amplitude; all other quintiles were classified as high rest-activity rhythm amplitude. Outcomes of interest were defined using International Classification of Diseases 10th Revision codes and consisted of incident cancer and cardiovascular, infectious, respiratory, and digestive diseases, and all-cause and disease-specific (cardiovascular, cancer, and respiratory) mortality. Participants with a current diagnosis of any outcome of interest were excluded. We assessed the associations between decreased rest-activity rhythm amplitude and outcomes using Cox proportional hazards models. FINDINGS: Between June 1, 2013, and Dec 23, 2015, 103 682 participants with available raw accelerometer data were enrolled. 92 614 participants (52 219 [56·4%] women and 40 395 [42·6%] men) with a median age of 64 years (IQR 56-69) were recruited. Median follow-up was 6·4 years (IQR 5·8-6·9). Decreased rest-activity rhythm amplitude was significantly associated with increased incidence of cardiovascular diseases (adjusted hazard ratio 1·11 [95% CI 1·05-1·16]), cancer (1·08 [1·01-1·16]), infectious diseases (1·31 [1·22-1·41]), respiratory diseases (1·26 [1·19-1·34]), and digestive diseases (1·08 [1·03-1·14]), as well as all-cause mortality (1·54 [1·40-1·70]) and disease-specific mortality (1·73 [1·34-2·22] for cardiovascular diseases, 1·32 [1·13-1·55] for cancer, and 1·62 [1·25-2·09] for respiratory diseases). Most of these associations were not modified by age older than 65 years or sex. Among 16 accelerometer-measured rest-activity parameters, low rest-activity rhythm amplitude had the strongest or second- strongest associations with nine health outcomes. INTERPRETATION: Our results suggest that low rest-activity rhythm amplitude might contribute to major health outcomes and provide further evidence to promote risk-modifying strategies associated with rest-activity rhythm to improve health and longevity.

Data regarding adherence and minor bleeding on direct oral anticoagulants in everyday life are still sparse. Inclusion criteria: treatment initiated with dabigatran, rivaroxaban or apixaban in non-valvular atrial fibrillation patients from a center in northern Sweden between 2011 and 2019 (n = 668). Exclusion criteria: cognitive impairment, dose dispensing, need of interpreter or hospital admission (n = 67). By a telephone interview adherence was measured in 569 patients (response rate 94.8%) using the 8-item Morisky medication adherence scale and minor bleeding was asked for. CHA2DS2-VASc and HAS-BLED scores were collected from medical records. The number (n), mean age, mean treatment duration, mean (points) CHA2DS2-VASc and HAS-BLED scores was with dabigatran (n = 175, 73.3 years, 17.8 months, 3.6 p and 2.2 p), rivaroxaban (n = 198, 73.7 years, 21months, 3.8 p and 2.1 p) and apixaban (n = 196, 72.7 years, 15.2 months, 3.4 p and 2.1 p). Adherence was high for dabigatran, rivaroxaban and apixaban in 54%, 76% and 53%; intermediate in 37%, 20% and 37% or low in 9%, 4% and 10% respectively. High adherence (Morisky score 8) distinguished rivaroxaban (p 2DS2-VASc ≥ 4 p, (p

According to the World Health Organization, cardiovascular disease (CVD) is a group of disorders of the heart and blood vessels, and it is the leading cause of death worldwide. The risk factors for CVD are divided into two major classes: non-modifiable (age, gender, family history) and modifiable (including tobacco use, type 2 diabetes mellitus (T2DM), physical inactivity, unhealthy diet, abdominal obesity, high cholesterol, dyslipidemia, and stress). Because CVD is a major cause of mortality and morbidity, new and clinically useful biomarkers of cardiovascular risk are of essence. Since obesity is a risk factor for CVD, new ways to achieve weight loss are also important. In this thesis, the focus is on leptin, a metabolic hormone with a pivotal function in the balance of appetite and satiety, and inducing weight loss. The adipose tissue releases leptin, with plasma levels of leptin reflecting the total adipose mass. Since it is related to both fat mass and cardiovascular risk, and is pro-inflammatory, it has been studied as a potential link between obesity, inflammation, hypertension, and vascular function. In paper I, we aimed to see if repeated cold exposure increased metabolic rate and/or brown adipose tissue (BAT) volume in humans. Out of 28 recruited participants, we allocated 16 to expose themselves to cold for one hour every day for six weeks, while 12 were controls, instructed to avoid cold exposure. Through magnetic resonance imaging, we found that supra-clavicular BAT volume had increased in an on-treatment analysis of the cold exposure group. In paper II, we used baseline data from 720 participants in “Cardiovascular Risk factors In Patients with Diabetes—a Prospective study in Primary care” (CARDIPP), all of whom had T2DM and were 55-66 years old at recruitment. We followed patients for incidence of ischemic heart disease (IHD) mortality and morbidity for 4-7 years, using the national Swedish Cause of Death and Hospitalization Registries. Our study showed that serum leptin levels related positively to the hazard ratio in both men and women, and predicted IHD independently of age, HbA1c, BMI, systolic blood pressure, and LDL/HDL-cholesterol ratio. This supports the use of serum leptin in patients with T2DM to add independent prognostic information in terms of IHD. When adding pulse wave velocity (PWV) and intima-media thickness to the model as markers of arterial stiffness, the finding of increased risk of IHD related to leptin levels remained statistically significant in men, but not in women. In paper III, we aimed to discover novel associations between leptin and circulating proteins, to possibly link leptin with the development of CVD in patients with T2DM. Using proximity extension assay, we investigated associations between 88 plasma proteins in the CARDIPP population. We replicated the associations passing the significance threshold in patients with T2DM in an independent cohort and found that adipocyte fatty acid binding protein (A-FABP) was significantly associated with leptin in both cohorts, more so in men than women. A-FABP can be found in white adipocytes and macrophages, and some studies have identified it as a circulating biomarker for metabolic syndrome, T2DM, and cardiovascular events. Finally, in paper IV, we analyzed data from 1 658 men and 1 678 women aged 50 to 65 when included in “The Swedish CardioPulmonary bioImage Study” (SCAPIS), focusing on leptin and its possible correlation with PWV. In bivariate correlations, we found log transformed leptin, and inflammatory markers IL-6, IL-18, and CRP, were all correlated in both men and women. In a multivariable linear regression, log transformed leptin correlated positively with PWV, independently of home blood pressure, smoking, non-HDL, BMI, T2DM, and IL-6, IL-18, and CRP. This suggests it may be possible to use leptin as a marker for PWV and arterial stiffness. In conclusion, this thesis provides new insights into leptin and its potential associations with other circulating proteins, and its connection to cardiovascular disease and inflammation, both in patients with T2DM and in healthy subjects. It also provides more insight into brown adipose tissue.

Cardiovascular diseases have always been the leading cause of global morbidity and mortality. Aortic stenosis, which is a kind of cardiovascular disease has a high prevalence in elderlies that are 75 years and older. Currently, the only available treatment would be valve replacement surgery. Recently, a few studies have risen regarding the potential of extracellular vesicles to reduce the effects of aortic stenosis, hence allowing patients to opt for a non-life-threatening treatment in comparison to a surgical one. The goal within this study is to determine the pro-coagulability of extracellular vesicles (EVs) that were endogenously derived from human blood (patients and healthy individuals) and their effect on the coagulation cascade. This study was performed on cardiac spheroids that were formed through seeding human aortic endothelial cells in an ultra-low attachment 96-well plate for 96 hours. Spheroids were challenged with tumour necrosis factor-alpha (TNFα) for 24 hours prior to EVs incubation for 48 and 72 hours. The effects of EVs on these spheroids were observed in terms of their ability to induce tissue factor activity. There was no significant difference in the tissue factor activity between spheroids incubated with patient derived EVs or healthy individual derive EVs irrespective of TNFα challenge. To conclude, the results of this study were not significant to stipulate that extracellular vesicles are procoagulant. Hence, further research regarding their ability to reduce or rescue the effects of cardiovascular diseases needs to be performed.

Följande studie behandlar utvecklandet av automatiserade cellsegmenteringsmodeller med avsikt att identifiera gränser mellan celler i hjärtvävnad. Syftet är att möjliggöra analys av data genererad från multiplexed error-robust in situ hybridization (MERFISH). MERFISH är en spatial transcriptomics-teknik som till skillnad från exempelvis single-cell RNA sequencing (ScRNA-seq) och single molecule fluorescence in situ hybridization (smFISH), möjliggör profilering av hundratals RNA-sekvenser hos enskilda celler utan att förlora dess rumsliga kontext. I Kosuri laboratoriet på Salk Institute of Biological Studies i San Diego tillämpas MERFISH på mushjärtan. Syftet är att få en djupare insikt i hur celler är organiserade i friska hjärtan, och hur denna struktur ändras i och med åldring och sjukdom. Att extrahera meningsfull information från MERFISH medför dock en betydande utmaning - en exakt cellsegmentering. Studien bidrar följaktligen till utvecklandet av segmenteringsmodeller för att kringgå de utmaningar som står i vägen för all efterföljande analys. Då klassiska segmenteringsalgoritmer är otillräckliga för att segmentera den komplexa vävnad som hjärtat utgörs av, tillämpades några av dagens mest avancerade och framstående maskininlärningsalgoritmer inom fältet, kallade Cellpose och Omnipose. Givet den täta och heterogena hjärtvävnaden, som härstammar från en bred distribution av celltyper och geometrier, utvecklades två separata modeller; en för att täcka både mindre celler och kardiomyocyter skurna på tvärsnittet; och en för att enbart segmentera kardiomyocyter skurna i longitudinell riktning. Den förstnämnda modellen utvecklades och tränades i Cellpose, och uppnådde en träffsäkerhet på 91.2%. Modellen för longitudinella kardiomyocyter utvecklades istället både i Cellpose och Omnipose för att utvärdera vilket nätverk som är bäst lämpat för ändamålet. Ingen av nätverken lyckades uppnå en tillräckligt hög träffsäkerhet för att vara applicerbar, och är därmed i behov av fortsatt träning. Modellen genererad i Omnipose bedöms dock vara mest lovande, givet dess mer heltäckande segmentering. Ytterligare utvecklingsområden för framtiden innefattar segmentering av celler i fibros-täta regioner, samt att utveckla en 3D-segmentering av hela hjärtat för att uppnå en mer komplett MERFISH-analys. Sammanfattningsvis har de genererade segmenteringsmodellerna banat väg för möjliggörandet av en rigorös MERFISH-analys av hjärtat. Genom att avslöja några av de strukturella och funktionella orsakerna till hjärtsvikt på en cellulär nivå, kan vi således på sikt bidra till utvecklingen av mer effektiva terapeutiska strategier. The following study delves into the development of automated cell segmentation models, with the intention of identifying boundaries between cells in the cardiac tissue for analysing spatial transcriptomics data. Addressing the limitations of alternative techniques like single-cell RNA sequencing (ScRNA-seq) and single molecule fluorescence in situ hybridization (smFISH), the study underscores the innovative use of multiplexed error-robust fluorescence in situ hybridization (MERFISH) deployed by the Kosuri Lab at Salk Institute for Biological Studies. This advanced imaging-based technique allows for a single-cell transcriptome profiling of hundreds of different transcripts while retaining the spatial context of the tissue. The technique can accordingly reveal how the organization of cells within a healthy heart is altered during disease. However, the extraction of meaningful data from MERFISH poses a significant challenge - accurate cell segmentation. This thesis therefore presents the development of a robust model for cell boundary identification within cardiac tissue, leveraging some of the advanced supervised machine learning algorithms in the field, named Cellpose and Omnipose. Due to the dense and highly heterogeneous tissue- stemming from a wide distribution of cell types and shapes- two separate models had to be developed; one that covers the smaller cells and the cross-sectioned cardiomyocytes, and correspondingly one to cover the longitudinal cardiomyocytes. The cross-section model was successfully developed to achieve an accuracy of 91.2%, whereas the longitudinal model still needs further improvements before being implemented. The thesis acknowledges potential areas for improvement, emphasizing the need to further improve the segmentation of longitudinal cardiomyocytes, tackle the challenges with segmenting cells within fibrotic regions of the diseased heart, as well as achieving a precise 3D cell segmentation. Nonetheless, the generated models have paved the way towards enabling efficient downstream MERFISH analysis to ultimately understand the structural and functional dynamics of heart failure at a cellular level, aiding the development of more effective therapeutic strategies.

Myocardial infarction (MI) is one of the leading causes of mortality and disability worldwide. Emotional distress, such as anxiety and depression, are common among MI patients. The aim of this study was to investigate emotional reactions following MI and to explore how MI patients self-manage their emotional distress using the perspective of an explanatory behavioural model of depression and anxiety. Written testimonies from 92 MI patients starting an internet-based cognitive behavioural therapy (iCBT) were analysed using qualitative content analysis with a mixed deductive and inductive approach. Six themes were identified. The first three highlight the emotional reactions post-MI: Hypoarousal reactions and low mood; Hyperarousal reactions; and A changed sense of self and outlook on life. The following three themes describe strategies for managing emotional distress: Avoidance of potentially rewarding situations; Avoidance of heart relevant stimuli triggering anxiety; and Engaging in potentially positive activities and acceptance. The MI experience may trigger emotional reactions, with a particular emphasis on heart-focused anxiety, depression and a shift in the perception of one's identity. Patients tend to manage emotional distress through social withdrawal and experiential avoidance which likely maintains the distress. Applying a behavioural model to the management of emotional distress following MI is suited.

Background: The excess risk of cardiovascular disease associated with a wide array of infectious diseases is unknown. We quantified the short- and long-term risk of major cardiovascular events in people with severe infection and estimated the population-attributable fraction. Methods: We analyzed data from 331 683 UK Biobank participants without cardiovascular disease at baseline (2006-2010) and replicated our main findings in an independent population from 3 prospective cohort studies comprising 271 329 community-dwelling participants from Finland (baseline 1986-2005). Cardiovascular risk factors were measured at baseline. We diagnosed infectious diseases (the exposure) and incident major cardiovascular events after infections, defined as myocardial infarction, cardiac death, or fatal or nonfatal stroke (the outcome) from linkage of participants to hospital and death registers. We computed adjusted hazard ratios (HRs) and 95% CIs for infectious diseases as short- and long-term risk factors for incident major cardiovascular events. We also calculated population-attributable fractions for long-term risk. Results: In the UK Biobank (mean follow-up, 11.6 years), 54 434 participants were hospitalized for an infection, and 11 649 had an incident major cardiovascular event at follow-up. Relative to participants with no record of infectious disease, those who were hospitalized experienced increased risk of major cardiovascular events, largely irrespective of the type of infection. This association was strongest during the first month after infection (HR, 7.87 [95% CI, 6.36-9.73]), but remained elevated during the entire follow-up (HR, 1.47 [95% CI, 1.40-1.54]). The findings were similar in the replication cohort (HR, 7.64 [95% CI, 5.82-10.03] during the first month; HR, 1.41 [95% CI, 1.34-1.48] during mean follow-up of 19.2 years). After controlling for traditional cardiovascular risk factors, the population-attributable fraction for severe infections and major cardiovascular events was 4.4% in the UK Biobank and 6.1% in the replication cohort. Conclusions: Infections severe enough to require hospital treatment were associated with increased risks for major cardiovascular disease events immediately after hospitalization. A small excess risk was also observed in the long-term, but residual confounding cannot be excluded. CC BY 4.0Correspondence to: Pyry Sipilä, Clinicum, Department of Public Health, PO Box 20, FI-00014 University of Helsinki, Finland. Email pyry.sipila@helsinki.fiAcknowledgmentsThis research was conducted using data from the UK Biobank (https://www.ukbiobank.ac.uk/) via application 60565.Sources of FundingThis work was funded in whole, or in part, by grants from NordForsk (75021), Academy of Finland (329202 and 350426), Helsinki Institute of Life Science, Emil Aaltonen Foundation, Finnish Medical Foundation, Päivikki and Sakari Sohlberg Foundation, Finnish Foundation for Cardiovascular Research (a86898), US National Institute on Aging (R01AG056477, 1R56AG052519-01, and 1R01AG052519-01A1), UK Medical Research Council (MRC S011676/1, R024227/1, and MR/P023444/1), and Wellcome Trust (201440/Z/16/Z and 221854/Z/20/Z). The funders had no role in study design, data collection, analysis, or interpretation, or writing of the report or decision to submit it for publication.DisclosuresDr Sipilä reports grant support during the conduct of the study from NordForsk (75021), Academy of Finland (311492 and 329202), Helsinki Institute of Life Science, Emil Aaltonen Foundation, and Finnish Medical Foundation. Dr Lindbohm reports grant support during the conduct of the study from the Academy of Finland (339568) and Päivikki and Sakari Sohlberg Foundation. Dr Batty reports grant support from the UK Medical Research Council (MR/P023444/1) and US National Institute on Aging (1R56AG052519-01 and 1R01AG052519-01A1). Dr Vahtera reports grant support from the Academy of Finland (321409 and 329240) and NordForsk (75021). Dr Nyberg reports grant support from NordForsk (75021). Dr Warren-Gash reports support from Wellcome Fellowship (201440/Z/16/Z). Dr Kivimäki reports grant support during the conduct of the study from NordForsk (75021), UK Medical Research Council (MRC S011676/1 and R024227/1), US National Institute on Aging (R01AG056477), Academy of Finland (329202 and 350426), Finnish Foundation for Cardiovascular Research (a86898), Finnish Work Environment Fund (190424), and Wellcome Trust (221854/Z/20/Z). The other authors report no conflicts.

Background: Asymptomatic carotid stenosis is associated with increased risk of ischemic stroke. The management of asymptomatic carotid stenosis ranges from open surgical approaches, minimally invasive endovascular in-terventions, and medical therapeutics. However, the research synthesis comparing these interventions, as shown by the scattered and overlapping published meta-analysis, has been inconsistent and non-comprehensive. Methods: Using previously-employed methods, we searched for and compared published meta-analyses comparing carotid endarterectomy and carotid stenting. A comprehensive search was conducted for all rele-vant studies published until November 13th, 2021, using the following databases: PubMed/MEDLINE, Scopus, Web of Science, Cochrane Library, OVID, and Google Scholar. Results: Five meta-analysis studies were included in this review. In summary, clinical findings were: carotid endarterectomy reduced the rate of ischemic stroke and stroke-related mortality, but led to a higher rate of intraoperative cranial nerve injury. There was no significant difference between carotid endarterectomy and carotid stenting in ipsilateral stroke and myocardial infarction events. Conclusions: The clinical findings favor the carotid endarterectomy over the carotid stenting in terms of stroke incidence (overall and minor events) and stroke-related mortality rates. However, the carotid stenting was su-perior to the carotid endarterectomy in the events of cranial nerve injury during the intervention.

We aimed to explore the prevalence of atherosclerosis by using multi-view ultrasound examination of the carotid arteries and its association with clinical risk factors in a middle-aged population at low to intermediate risk of cardiovascular disease (CVD). Carotid vascular ultrasound was performed in 3532 participants in the VIPVIZA trial. Mean and maximal carotid intima media thickness (cIMT) at prespecified angles and plaque presence were examined on the left and right side. Associations between CVD risk factors and ultrasound variables were quantified by partial least squares (PLS) regression. A combined ultrasound variable was computed using weights of the first PLS component. Associations between CVD risk factors and the combined multi-view ultrasound variable, single cIMT and plaque measurements, respectively, were determined using linear regression modelling. The participants’ mean age was 55.7 years and 52.9% were women. Plaque prevalence was 51.1% in men and 39.0% in women. cIMT was higher in men than in women and in the left compared with the right carotid artery. The strongest association of CVD risk factors was observed with the combined multi-view ultrasound variable (R2 = 24%), compared with single cIMT variables (R2 = 14–18%) and plaque presence (R2 = 15%). The pattern was similar in both sexes. The association with CVD risk factors and the combined ultrasound variable was stronger in 40-year olds (R2 = 22%) compared with 50- or 60-year olds (R = 12%). CVD risk factors are stronger associated with a combined ultrasound variable than plaque presence or single cIMT measures suggesting that carotid multi-view ultrasonography better captures the focality of early atherosclerosis. Clinical Trial Registration: ClinicalTrials.gov, number NCT01849575. May 8, 2013.

Objectives: Reduced progression of atherosclerosis can decrease the risk of cardiovascular disease (CVD). This study aimed at evaluating the effect of a pictorial intervention showing atherosclerotic severity on the progression of carotid atherosclerosis. Methods: A prospective randomised open-label blinded end-point trial with participants aged 40–60 years enroled from a routine CVD prevention programme. The intervention group (n: 1575) and their treating physicians received an image based presentation of subclinical atherosclerotic severity measured by carotid ultrasound. The control group (n: 1579) did not receive any information about ultrasound results. Carotid ultrasound at baseline and at 3-year follow-up contained plaque detection and measurements of carotid intima media thickness (cIMT). The left, right and bilateral-mean-cIMT, plaque prevalence and total plaque area (TPA) at 3-year follow-up were compared between groups. Significance level was set to p = 0.01 to adjust for multiple comparisons. Results: The intervention group revealed reduced cIMT progression in the left-mean-cIMT of −0.011 mm (p = 0.001) compared with the control group. The intervention effect on cIMT progression was most prominent in individuals with increased cIMT and plaque prevalence at baseline (−0.021 mm, p = 0.005). There were no differences in progression between groups for the right-and bilateral-mean-cIMT (−0.005 mm, p = 0.223 and −0.005 mm, p = 0.036, respectively), nor any differences between groups for plaque prevalence or TPA (odds ratio 0.88, p = 0.09 and 0.89, p = 0.21, respectively). Conclusion: Pictorial presentation of subclinical atherosclerotic severity sent to both the individual and their treating physician resulted in significantly reduced left cIMT progression. Pictorial presentation has the potential to increase adherence in CVD prevention.

Background The study aimed to show the relationship between a large number of circulating metabolites and subsequent cardiovascular disease (CVD) and subclinical markers of CVD in the general population. Methods and Results In 2278 individuals free from CVD in the EpiHealth study (aged 45–75 years, mean age 61 years, 50% women), 790 annotated nonxenobiotic metabolites were measured by mass spectroscopy (Metabolon). The same metabolites were measured in the PIVUS (Prospective Investigation of Vasculature in Uppsala Seniors) study (n=603, all aged 80 years, 50% women), in which cardiac and carotid artery pathologies were evaluated by ultrasound. During a median follow‐up of 8.6 years, 107 individuals experienced a CVD (fatal or nonfatal myocardial infarction, stroke, or heart failure) in EpiHealth. Using a false discovery rate of 0.05 for age‐ and sex‐adjusted analyses and P P =0.0054). Thirty‐five of the 37 metabolites were related to subclinical markers of CVD evaluated in the PIVUS study. The metabolite 1‐carboxyethyltyrosine was associated with left atrial diameter as well as inversely related to both ejection fraction and the echogenicity of the carotid artery. Conclusions Several metabolites were discovered to be associated with future CVD, as well as with subclinical markers of CVD. A selection of metabolites improved discrimination when added on top of CVD risk factors.

BACKGROUND: Cardiac mechanics are influenced by loading conditions as well as sympathetic tone. Left atrial (LA) contractile function assessed by two-dimensional (2D) strain has been described in the setting of controlled preload alterations; however, studies show conflicting findings about change or direction of change. We hypothesized that the controlled preload reduction and the sympathetic nervous system activation that occurs during a standardized Valsalva manoeuvre would bring about a change in LA contraction strain.a METHODS: Healthy young adults of both sexes were recruited. Transthoracic echocardiographic ultrasound images were collected before and during a Valsalva manoeuvre. Standard imaging windows for LA strain assessment were used and the images were copied and stored for later offline analysis. These were assessed for adequate atrial wall visualization in 2D strain assessment. Paired comparisons were carried out using Student's T test. RESULT: Thirty-eight participants were included and there were 22 complete studies with paired pre- and during Valsalva manoeuvre. LA contraction strain at baseline was 10.5 ± 2.8% (standard deviation) and during the Valsalva manoeuvre 10.6 ± 4.6%, p = 0.86. CONCLUSION: The Valsalva manoeuvre, a combination of preload reduction and sympathetic nervous system activation, seems not to be associated with a change in LA contraction strain in healthy young individuals. LA contraction strain should be interpreted in the context of both atrial loading conditions and prevailing autonomic nervous system activity.

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 of life. However, some patients are not recovered at six months postoperatively, which could be explained by individual characteristics. To improve recovery outcomes, vascular nurses and other health care professionals should be aware of the possible recovery trajectories and factors associated with impaired recovery, and use them to anticipate and meet the patients’ individual care needs.

Ultrasonic echolucent carotid intima-media (IM) complex and accelerated progression of carotid intima mediathickness (cIMT) have both separately been shown to predict future cardiovascular events. The aim of this studywas to evaluate if the echogenicity of the IM-complex is associated with the 3-year progression of cIMT. B-modeultrasound images captured at baseline and 3-year follow-up in the ‘Visualization of asymptomatic atherosclerotic disease for optimum cardiovascular prevention’ (VIPVIZA) trial were included (n: 3154). The bilateral mean cIMT and IM-echogenicity by greyscale median (GSM) were measured in the common carotid artery. Associations between IM-GSM at baseline and the 3-year cIMT progression were investigated using linear regression models for the whole population and stratified by sex, age and VIPVIZA study group (intervention versus control). In addition, adjusted analyses for confounding factors were performed. Unadjusted analysis showed that decreased IM-GSM at baseline was associated with increased progression of cIMT (p < 0.001). Stratified by age, the association was significant among 40 (p < 0.001) and 60 years old (p < 0.001). The association was statistically significant in both sexes and on comparison of VIPVIZA study subgroups. Adjustments for confounding factors did not alter the estimated relationship between IM-GSM and cIMT progression. Echolucent carotid intima media at baseline associates with increased 3-year cIMT progression among an asymptomatic, middle-aged population. Echogenicity of the intima media may identify individuals at risk for accelerated vascular aging.

BackgroundWomen’s pregnancy history is associated with incident risk of coronary artery disease with some evidence also suggesting a relevance for prognosis following treatment.ObjectivesTo study the associations between maternal history of preterm delivery, a history of small for gestational age infant, parity and age at first delivery with clinical restenosis after percutaneous coronary intervention (PCI).MethodsIn this prospective cohort study, we included 6027 women<65 years undergoing their first PCI 2006–2017, merging clinical register data on PCI procedures in Sweden with comprehensive registry data on deliveries since 1973. We used proportional hazards regression to study the association between aspects of pregnancy history and clinical restenosis in per-segment analyses, and with target lesion revascularisation (TLR) in per-patient analyses. We adjusted models for procedural-related and patient-related predictors of restenosis.ResultsDuring 15 981 segment-years of follow-up, 343 (3.7%) events of clinical restenosis occurred. We found no strong evidence of associations between the studied aspects of pregnancy history and clinical restenosis following PCI. For example, the restenosis HR for a history of preterm delivery in the fully adjusted model was 1.09 (95% CI 0.77 to 1.55) and the TLR HR was 1.18 (95% CI 0.91 to 1.52).ConclusionRisk of restenosis following treatment with PCI did not differ by the studied aspects of pregnancy history, including preterm delivery, in young and middle-aged women. Larger studies are needed to obtain more precise estimates.

AimsThe aim was to describe the prevalence, characteristics, and outcome of patients with acute myocardial infarction (MI) developing left ventricular (LV) systolic dysfunction or pulmonary congestion by applying different criteria to define the population. Methods and resultsIn patients with MI included in the Swedish web-system for enhancement and development of evidence-based care in heart disease (SWEDEHEART) registry, four different sets of criteria were applied, creating four not mutually exclusive subsets of patients: patients with MI and ejection fraction (EF) < 50% and/or pulmonary congestion (subset 1); EF < 40% and/or pulmonary congestion (subset 2); EF < 40% and/or pulmonary congestion and at least one high-risk feature (subset 3, PARADISE-MI like); and EF < 50% and no diabetes mellitus (subset 4, DAPA-MI like). Subsets 1, 2, 3, and 4 constituted 31.6%, 15.0%, 12.8%, and 22.8% of all patients with MI (n = 87 177), respectively. The age and prevalence of different co-morbidities varied between subsets. For median age, 70 to 77, for diabetes mellitus, 22 to 33%; for chronic kidney disease, 22 to 38%, for prior MI, 17 to 21%, for atrial fibrillation, 7 to 14%, and for ST-elevations, 38 to 50%. The cumulative incidence of death or heart failure hospitalization at 3 years was 17.4% (95% CI: 17.1-17.7%) in all MIs; 26.9% (26.3-27.4%) in subset 1; 37.6% (36.7-38.5%) in subset 2; 41.8% (40.7-42.8%) in subset 3; and 22.6% (22.0-23.2%) in subset 4. ConclusionsDepending on the definition, LV systolic dysfunction or pulmonary congestion is present in 13-32% of all patients with MI and is associated with a two to three times higher risk of subsequent death or HF admission. There is a need to optimize management and improve outcomes for this high-risk population.