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Background: Iron deficiency (ID) is associated with adverse prognosis in patients with heart failure. This study aims to investigate the relationship between ID and expression of genes involved in iron metabolism in human myocardium and skeletal muscle, focusing on Transferrin 1 receptor (TfR1), the main pathway of cellular iron uptake. Methods: Patients undergoing elective CABG were assessed prior to surgery with echocardiography and serum iron parameters. Core needle biopsies were collected from the left and right ventricle (LV, RV), the right atrium and intercostal skeletal muscle (SM). Gene expression analyses were done by mRNA sequencing. Results: Of 69 patients (median age 69 years, 91% men), 28% had ID. 26% had HFrEF, 25% had HFpEF phys-iology according to echocardiographic findings and NT-proBNP levels, and 49% had normal LV function. The expression of TfR1 was increased in patients with ID compared to patients without ID in ventricular tissue (p = 0.04) and in intercostal SM (p = 0.01). The increase in TfR1 expression in LV and RV was more pronounced when analysing patients with absolute ID (S-Ferritin

Background: Obesity is associated with unfavorable outcomes for infectious diseases. Most researches exploring the association between nutritional status and dengue severity have focused on pediatric populations, with only few studies assessing adult patients. Methods: Adult patients with laboratory-confirmed dengue admitted to a tertiary hospital in southern Taiwan between 2014 and 2015 were enrolled retrospectively. Demographics, comorbidities, clinical presentation, laboratory findings, and outcomes were obtained from caserecord forms. Patients were categorized into obese group and nonobese group. The obese group comprised patients with a body mass index of >= 27.5 kg/m(2). Results: A total of 1417 hospitalized patients with dengue were evaluated. The mean age was 57.9 years (range: 18e92 years). The obese and nonobese groups comprised 333 (23.5%) and 1084 (76.5%) patients, respectively. The obese group included more patients with hypertension (85%, p < 0.001), diabetes mellitus (33%, p < 0.001), and congestive heart failure ( 6.3%, p Z 0.049). Multivariate analysis revealed that the obese group had more petechiae (AOR: 1.353, 95% CI: 1.025e1.786, p Z 0.033), more dyspnea (AOR: 1.380, 95% CI: 1.015e1.876, p Z 0.040), and more severe hepatitis (AOR: 2.061, 95% CI: 1.050e4.048, p Z 0.036). The obese group also had higher peak hematocrit values (44.1%, p < 0.001) and lower nadir platelet count (45.3 x 10(3)/mL, p Z 0.049) than the nonobese group. Conclusion: In adult patients with dengue, obese group had more petechiae, dyspnea, severe hepatitis, lower nadir of platelet count, and higher peak hematocrit level. We observed no difference in severe dengue or mortality between obese and nonobese group.

Previous studies have demonstrated superior patency of no-touch as compared to conventional saphenous vein grafts in coronary artery bypass grafting. We aimed to compare mid-term clinical outcomes of both techniques in a large cohort of routine patients. We identified all patients undergoing non-emergent primary coronary artery bypass grafting with either no-touch or conventional saphenous vein grafts at our institution between 2000 and 2020. Propensity score matching was used to create adjusted cohorts based on 5,288 eligible patients. The primary outcome was the combined endpoint of all-cause mortality and repeat revascularization. Secondary outcomes were individual rates of all-cause mortality and repeat revascularization, surgical complications, and short-term mortality. Propensity score matching resulted in cohorts of no-touch (n=923) and conventional (n=923) saphenous vein grafted patients with comparable baseline characteristics. Mean follow-up time was significantly shorter for the no-touch compared to the conventional cohort (4.9 ± 2.3 versus 8.3 ± 2.6 years, p< 0.001). Up to seven-year follow-up, neither the rate of the primary composite endpoint nor death differed significantly between the cohorts. The rate of repeat revascularization was significantly higher in patients in the no-touch cohort (12.9% versus 9.3% at seven-year follow-up, p=0.022. Post-hoc analysis of percutaneous coronary intervention during follow-up revealed comparable rates of saphenous vein graft failure (no-touch 42/923 (4.6%) versus conventional 32/923 (3.5%), p=0.286). In this large propensity score matched registry study, coronary artery bypass with no-touch compared to conventional saphenous vein grafting did neither enhance mid-term survival nor reduce the rate of repeat revascularization.

Hypertensive disorders of pregnancy (HDP) are the most common causes of maternal and perinatal morbidity and mortality. They are responsible for 16% of maternal deaths in high-income countries and approximately 25% in low- and middle-income countries. The impact of HDP can be lifelong as they are a recognized risk factor for future cardiovascular disease. During pregnancy, the cardiovascular system undergoes significant adaptive changes that ensure adequate uteroplacental blood flow and exchange of oxygen and nutrients to nurture and accommodate the developing fetus. Failure to achieve normal cardiovascular adaptation is associated with the development of HDP. Hemodynamic alterations in women with a history of HDP can persist for years and predispose to long-term cardiovascular morbidity and mortality. Therefore, pregnancy and the postpartum period are an opportunity to identify women with underlying, often unrecognized, cardiovascular risk factors. It is important to develop strategies with lifestyle and therapeutic interventions to reduce the risk of future cardiovascular disease in those who have a history of HDP.

Objectives: Various vascular grafts are used in coronary artery bypass graft (CABG) surgeries, however, the most commonly used one is the saphenous vein graft (SVG). Various studies conducted on this topic have found a relationship between uric acid to HDL-C (UHR) and cardiovascular diseases. In this current study, we aimed to investigate the predictive importance of UHR value in predicting long-term SVG disease in patients who underwent CABG surgery. Methods: Patients who had a history of CABG surgery at least one year prior, had stable angina pectoris, and underwent coronary angiography between January 01, 2016 and January 01, 2020, were included in the study retrospectively. Patients with open saphenous veins were defined as Group 1, and patients who had 50% or more stenosis in at least one SVG after coronary angiography, were defined as Group 2. Results: The median age of the 204 patients included in Group 1 and 292 patients in Group 2 were 65 (38-77) years and 66 (45-79) years, respectively (p = 0.251). The two groups were similar in terms of gender, hypertension, chronic obstructive pulmonary disease rates, history of cerebrovascular events, ejection fraction, body mass index, and current medical treatments. In univariate analysis, SVG disease was found to significantly correlate with diabeter mellitus (odds ratio [OR]: 1.644, 95% confidence interval [CI]: 1.190-1.985, p = 0.008), current smoking (OR: 0.875, 95% CI: 0.669-0.940, p = 0.030), number of patients with target artery diameter < 1.5 mm (OR: 1.945, 95% CI: 1.221-2.398, p < 0.001), age of SVG (OR: 2.960, 95% CI: 1.980-4.168, p < 0.001), uric acid (OR: 1.241, 95% CI: 1.078-1.592, p = 0.004), triglyceride (OR: 0.780, 95% CI: 0.569-0.935, p = 0.044) and UHR (OR: 1.894, 95% CI: 1.384-2.896, p < 0.001). Conclusions: In this study, we showed that we can predict saphenous vein graft occlusion with serum UHR value.

OBJECTIVE: Maximal oxygen consumption at an exercise test (VO2 -max) is a commonly used marker of physical fitness. In the present study, we aimed to find independent clinical predictors of VO2 -max by use of multiple measurements of cardiac, respiratory and vascular variables collected while resting. METHODS: In the Prospective study of Obesity, Energy and Metabolism (POEM), 420 subjects aged 50 years were investigated regarding endothelial function, arterial compliance, heart rate variability, arterial blood flow and atherosclerosis, left ventricular structure and function, lung function, multiple blood pressure measurements, life style habits, body composition and in addition a maximal bicycle exercise test with gas exchange (VO2 and VCO2 ). RESULTS: When VO2 -max (indexed for lean mass) was used as dependent variable and the 84 hemodynamic or metabolic variables were used as independent variables in separate sex-adjusted models, 15 variables showed associations with p

Objectives Measurement of high-sensitivity (hs) cardiac troponin (cTn) T and I is widely studied for cardiac assessment of stable populations. Recent data suggest clinical and prognostic discrepancies between both hs-cTn. We aimed at reviewing published studies with respect to underlying causes and clinical implications. Content We summarized current evidence on release and clearance mechanisms of cTnT and I, and on preanalytical and assay-related issues potentially portending to differences in measured concentrations. We also performed a systematic review of outcome studies comparing both hs-cTn in the general population, patients with congestive heart failure, stable coronary artery disease and atrial fibrillation. Summary and outlook For the interpretation of concentrations of hs-cTnT, stronger association with renal dysfunction compared to hs-cTnI should be considered. Hs-cTnT also appears to be a stronger indicator of general cardiovascular morbidity and all-cause mortality. Hs-cTnI concentrations tend to be more sensitive to coronary artery disease and ischemic outcomes. These findings apparently reflect variations in the mechanisms of cardiac affections resulting in cTn release. Whether these differences are of clinically relevance remains to be elucidated. However, having the option of choosing between either hs-cTn might represent an option for framing individualized cardiac assessment in the future.

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: Differences in adverse cardiac remodeling between patients who have bicuspid (BAV) and tricuspid aortic valve (TAV) with severe isolated aortic stenosis (AS) and its prognostic impact after surgical aortic valve replacement remains unclear. We sought to investigate differences in preoperative diastolic and systolic function in patients with BAV and TAV who have severe isolated AS and the incidence of postoperative heart failure hospitalization and mortality. Methods: Two hundred seventy-one patients with BAV (n=152) or TAV (n=119) and severe isolated AS without coronary artery disease or other valvular heart disease, scheduled for surgical aortic valve replacement, were prospectively included. Comprehensive preoperative echocardiographic assessment of left ventricular (LV) diastolic and systolic function was performed. The heart failure events were registered during a mean prospective follow-up of 1260 days versus 1441 days for patients with BAV or TAV, respectively. Results: Patients with BAV had a more pronounced LV hypertrophy with significantly higher indexed LV mass ([LVMi] 134 g/m 2 versus 104 g/m 2 , P P P P P =0.007), and a higher prevalence of preoperative levosimendan treatment ( P P P =0.004). Survival was not different between patients with BAV and TAV (log-rank P =0.165). Conclusions: Although they were significantly younger, patients with BAV who had isolated severe AS had worse preoperative LV function and an increased risk of postoperative heart failure hospitalization compared with patients who had TAV. Our findings suggest that patients who have BAV with AS might benefit from closer surveillance and possibly earlier intervention.

Aims: Unmet needs exist in the diagnosis and treatment of heart failure (HF) in the elderly population. Our aim was to analyse and compare data of diagnostics and management of very elderly patients (aged ≥85 years) compared with younger patients (aged 18–84 years) with HF in Sweden. Methods: Incidence of ≥2 HF diagnosis (ICD-10) was identified from primary/secondary care in Uppsala and Västerbotten during 2010–2015 via electronic medical records linked to data from national health registers. Analyses investigated the diagnosis, treatment patterns, hospitalizations and outpatient visits, and mortality. Results: Of 8702 patients, 27.7% were ≥85 years old, women (60.2%); most patients (80.7%) had unknown left ventricular ejection fraction; key co-morbidities comprised anaemia, dementia, and cerebrovascular disease. More very elderly patients received cardiovascular disease (CVD)-related management after diagnosis in primary care (13.6% vs. 6.5%; P < 0.0001), but fewer patients underwent echocardiography (19.3% vs. 42.9%; P < 0.0001). Within 1 year of diagnosis, very elderly patients were less likely to be hospitalized (all-cause admissions per patient: 1.9 vs. 2.3; P < 0.0001; CVD-related admissions per patient: 1.8 vs. 2.1; P = 0.0004) or prescribed an angiotensin-converting enzyme inhibitor/angiotensin receptor blocker (ACEI/ARB) plus a β-blocker (45.2% vs. 56.9%; P < 0.0001) or an ACEI/ARB plus a β-blocker plus a mineralocorticoid receptor antagonist (15.4% vs. 31.7%; P < 0.0001). One-year mortality was high in patients ≥85 years old, 30.5% (CI: 28.3-32.7%) out of 1797 patients. Conclusions: Despite the large number of very elderly patients with newly diagnosed HF in Sweden, poor diagnostic work-up and subsequent treatment highlight the inequality of care in this vulnerable population.

Background: There are no evidence-based recommendations on the optimal time point to initiate non–vitamin K antagonist oral anticoagulants (NOACs) after acute ischemic stroke in patients with atrial fibrillation. We aimed to investigate the efficacy and safety of early versus delayed initiation of NOAC in these patients. Methods: TIMING (Timing of Oral Anticoagulant Therapy in Acute Ischemic Stroke With Atrial Fibrillation) was a registry-based, randomized, noninferiority, open-label, blinded end-point study at 34 stroke units using the Swedish Stroke Register for enrollment and follow-up. Within 72 hours from stroke onset, patients were randomized to early (≤4 days) or delayed (5–10 days) NOAC initiation, with choice of NOAC at the investigators’ discretion. The primary outcome was the composite of recurrent ischemic stroke, symptomatic intracerebral hemorrhage, or all-cause mortality at 90 days. The prespecified noninferiority margin was 3%. Secondary outcomes included the individual components of the primary outcome. Results: Between April 2, 2017, and December 30, 2020, 888 patients were randomized to either early (n=450) or delayed (n=438) initiation of NOAC. No patient was lost to 90-day follow-up. Mean age was 78.3 years (SD, 9.9 years); 46.2% were women; 49.1% had previously known atrial fibrillation; and 17.5% prior stroke. The primary outcome occurred in 31 patients (6.89%) assigned to early initiation and in 38 patients (8.68%) assigned to delayed NOAC initiation (absolute risk difference, −1.79% [95% CI, −5.31% to 1.74%]; P noninferiority =0.004). Ischemic stroke rates were 3.11% and 4.57% (risk difference, −1.46% [95% CI, −3.98% to 1.07%]) and all-cause mortality rates were 4.67% and 5.71% (risk difference, −1.04% [95% CI, −3.96% to 1.88%]) in the early and delayed groups, respectively. No patient in either group experienced symptomatic intracerebral hemorrhage. Conclusions: Early initiation was noninferior to delayed start of NOAC after acute ischemic stroke in patients with atrial fibrillation. Numerically lower rates of ischemic stroke and death and the absence of symptomatic intracerebral hemorrhages implied that the early start of NOAC was safe and should be considered for acute secondary stroke prevention in patients eligible for NOAC treatment. Registration: URL: http://www.clinicaltrials.gov ; Unique identifier: NCT02961348.

Background: After acute coronary syndrome (ACS), patients with a previous myocardial infarction (MI) may be at particularly high risk for major adverse cardiovascular events (MACE) and death. We studied the effects of the PCSK9 inhibitor alirocumab in patients with recent ACS according to previous history of MI..Methods: The ODYSSEY OUTCOMES trial compared alirocumab with placebo, beginning 1 to 12 months after ACS with median 2.8-year follow-up. The primary MACE outcome comprised death from coronary heart disease, nonfatal MI, fatal or nonfatal ischemic stroke, and hospitalization for unstable angina. Of 18,924 patients, 3633 (19.2%) had previous MI. Results: Patients with previous MI were older, more likely male, with more cardiovascular risk factors and previous events. With placebo, 4-year risks of MACE and death were higher among those with vs without previous MI (20.5% vs 8.9%, P < 0.001; 7.4% vs 3.4%, P < 0.001, respectively). Alirocumab reduced the risk of events regardless of the presence or absence of a history of MI (MACE, adjusted hazard ratio [aHR] 0.90, 95% confidence interval [CI], 0.78-1.05 vs 0.82, 0.73-0.92; P-interaction = 0.34; death, aHR 0.84; 95% CI, 0.64-1.08 vs 0.87, 0.72-1.05; P-interaction = 0.81). Estimated absolute risk reductions with alirocumab were numerically greater with vs without previous MI (MACE, 1.91% vs 1.42%; death, 1.35% vs 0.41%). Conclusions: A previous history of MI places patients with recent ACS at high risk for recurrent MACE and death. Alirocumab reduced the relative risks of these events consistently in patients with or without previous MI but with numerically greater absolute benefit in the former subgroup. (ODYSSEY OUTCOMES: NCT01663402)

Background: Women have a worse prognosis after ST-segment elevation myocardial infarction (STEMI) than men. The prognostic role of thrombus burden (TB) in influencing the sex-related differences in clinical outcomes after STEMI has not been clearly investigated. Objectives: The aim of this study was to assess the sex-related differences in TB and its clinical implications in patients with STEMI. Methods: Individual patient data from the 3 major randomized clinical trials of manual thrombus aspiration were analyzed, encompassing a total of 19,047 patients with STEMI, of whom 13,885 (76.1%) were men and 4,371 (23.9%) were women. The primary outcome of interest was 1-year cardiovascular (CV) death. The secondary outcomes of interest were recurrent myocardial infarction, heart failure, all-cause mortality, stroke, stent thrombosis (ST), and target vessel revascularization at 1 year. Results: Patients with high TB (HTB) had worse 1-year outcomes compared with those presenting with low TB (adjusted HR for CV death: 1.52; 95% CI: 1.10-2.12; P = 0.01). In unadjusted analyses, female sex was associated with an increased risk for 1-year CV death regardless of TB. After adjustment, the risk for 1-year CV death was higher only in women with HTB (HR: 1.23; 95% CI: 1.18-1.28; P < 0.001), who also had an increased risk for all-cause death and ST than men. Conclusions: In patients with STEMI, angiographic evidence of HTB negatively affected prognosis. Among patients with HTB, women had an excess risk for ST, CV, and all-cause mortality than men. Further investigations are warranted to better understand the pathophysiological mechanisms leading to excess mortality in women with STEMI and HTB.

Objectives: Atrial fibrillation (AF) may cause thromboembolism and cardiac morbidity and mortality. Patients with cardiovascular diseases are at risk for developing AF. In this study, the relationship between inflammation markers and AF was examined. Methods: Among 689 people followed up in the cardiology outpatient clinic for reasons such as hypertension, coronary artery disease, and rheumatic valve disease, 88 patients with AF and 601 patients without AF were compared. The blood parameters of the AF group were examined during the period when AF developed in the patients. Hemogram and biochemistry parameters of AF and non-AF groups were compared. Results: C-reactive protein to albumin ratio (CAR), neutrophil count to albumin ratio, neutrophil count to lymphocyte count ratio, and monocyte count to lymphocyte count ratio were significantly higher in the AF group than in the non-AF group (p < 0.001, p < 0.001, p = 0.001, and p < 0.001; respectively). According to the Receiver Operating Characteristics analysis, it was found that the CAR value of cut-off: 0.0533 could diagnose AF with 74% sensitivity (AUC: 0.789, CI 95%: 0.726-0.853, p < 0.001). Albumin value of cut-off: 3.75 was found to be able to diagnose AF with 82% specificity (AUC: 0.772, CI 95%: 0.707-0.836, p < 0.001). Conclusions: AF is an arrhythmia that should be recognized early due to the complications it causes, and the CAR value can be used in the diagnosis of AF in individuals with cardiac disease.

Objectives: Platelet-lymphocyte ratio (PLR) combines the predictive risk of platelet and lymphocyte counts into a single risk index. PLR has been studied as a predictive marker in a variety of cardiovascular diseases. However, our understanding of the link between PLR and coronary artery disease (CAD) remains limited. The present study aimed to evaluate the relationship between PLR and intensity of coronary atherosclerosis in patients with suspected CAD. Methods: In this retrospective study, we included 221 patients undergoing dual-source 64-slice coronary computed tomography angiography (CCTA). Total and different types of leukocyte counts were measured with an automatic blood counter. Based on a modified version of the American Heart Association's categorisation, the coronary artery tree was divided into 16 segments. To assess the extent of coronary atherosclerosis, the number of affected coronary segments was counted. Coronary artery plaques were classified into three categories: (1) calcified plaque, (2) non-calcified plaque, and (3) mixed plaque. Results: After multivariable backward stepwise regression analysis, PLR remained as an independent predictor for both the presence and extent of coronary atherosclerosis (OR=2.38, 95% CI: 1.27-4.47 and OR=1.66, 95% CI: 1.10-2.51, respectively). There was no significant relationship between PLR and plaque morphology. Conclusions: Higher PLR was associated with the intensity of coronary atherosclerosis detected by CCTA. Further research is necessary to determine the optimal approach to using PLR in medical practice.

Cardiovascular diseases are among the leading causes of death worldwide. Atherosclerotic cardiovascular diseases consist of a broad spectrum of diseases such as coronary artery disease, carotid artery disease, peripheral artery diseases, cerebral vascular diseases and visceral artery diseases. Although atherosclerosis occurs over time due to age; hypertension, hyperlipidemia, smoking, and diabetes mellitus are important factors that play a role in the emergence of atherosclerosis. Diabetes mellitus has an active role in the development of atherosclerotic cardiovascular disease. It is expected that there will be a significant increase in the incidence of diabetes-related cardiovascular diseases in the future. In this review, it is aimed to review the coexistence of diabetes with different cardiovascular diseases and its menanisms.

Objectives: We planned our survey study to evaluate the opinion of cardiologists about the class II recommendations on levels of evidence in the current European Society of Cardiology Guidelines (ESC). Our aim is to determine which diagnosis or treatment option most prefer by cardiologist when guidelines do not make clear recommendations. Methods: The survey was conducted on September 2020 with the participation of cardiologists (n = 102). Our survey covers ESC's guidelines published in 2018-2020 on diagnosis and treatment strategies in coronary artery disease, diabetes, heart valve disease, arrhythmia, dyslipidemia and heart failure. Our survey consisting of 40 questions was shared with the cardiologists via e-mail. Results: Participants answered all of the survey questions. The majority of the participants (79.41%) did not consider the addition of a second long-term antithrombotic medication in addition to aspirin for secondary prevention in diabetes mellitus (DM) and coronary artery disease (CAD) patients who are not at high risk of bleeding. The lowest low density lipoprotein (LDL) value achieved by the participant physicians with treatment in their practices was < 40 mg/dl in 32 (31.37%) participants . One of the striking results of the survey was that 51.96% of the participants stated that it was not possible to measure the lipoprotein a (Lp(a)) level in the center where they were carrying out their practices, and 34.31% did not consider the Lp(a) level in the treatment of dyslipidemia in terms of directing the treatment. As for patients with asymptomatic Wolff-Parkinson-White (WPW) syndrome, 58.82% of the participants considered catheter ablation therapy. Conclusions: Although there were different opinions on some recommendations, the participants were mostly in agreement. We think that these survey results, which were mostly based on expert opinions, may contribute to the guidelines to be published in the future with the increase of survey studies on these issues.

Aims Repeated risk assessments and treatment patterns over long time are sparsely studied in chronic thromboembolic pulmonary hypertension (CTEPH); thus, we aimed to investigate changes in risk status and treatment patterns in incident patients with CTEPH over a 5 year period. Methods and results Descriptive and explorative study including 311 patients diagnosed with CTEPH 2008-2019 from the Swedish pulmonary hypertension registry, stratified by pulmonary endarterectomy surgery (PEA). Risk and PH-specific treatment were assessed in surgically treated (PEA) and medically treated (non-PEA) patients at diagnosis and up to 5 years follow-up. Data are presented as median (Q1-Q3), count or per cent. Prior to surgery, 63% in the PEA-group [n = 98, age 64 (51-71) years, 37% female] used PH-specific treatment and 20,69, and 10% were assessed as low, intermediate or high risk, respectively. After 1 year post-surgery, 34% had no PH-specific treatment or follow-up visit registered despite being alive at 5 years. Of patients with a 5 year visit (n = 23), 46% were at low and 54% at intermediate risk, while 91% used PH-specific treatment. In the non-PEA group [n = 213, age 72 (65-77) years, 56% female], 28% were assessed as low, 61% as intermediate and 11% as high risk. All patients at high risk versus 50% at low risk used PH-specific treatment. The 1 year mortality was 6%, while the risk was unchanged in 57% of the patients; 14% improved from intermediate to low risk, and 1% from high to low risk. At 5 years, 27% had a registered visit and 28% had died. Of patients with a 5 year visit (n = 58), 38% were at low, 59% at intermediate and 1% at high risk, and 86% used PH-specific treatment. Conclusions Risk status assessed pre-surgery did not foresee long-term post-PEA risk and pre-surgery PH-specific treatment did not foresee long-term post-PEA treatment. Medically treated CTEPH patients tend to remain at the same risk over time, suggesting a need for improved treatment strategies in this group. Funding Agencies|Swedish Association of Local Authorities and Regions; Actelion Pharmaceuticals; Janssen Pharmaceutical Company of Johnson & Johnson, Allschwil, Switzerland

Background: We investigated eligibility for dapagliflozin and empagliflozin in a real-world heart failure (HF) cohort based on selection criteria of DAPA-HF (Dapagliflozin and Prevention of Adverse Outcomes in Heart Failure), DELIVER (Dapagliflozin Evaluation to Improve the Lives of Patients with Preserved Ejection Fraction Heart Failure), and EMPEROR (Empagliflozin Outcome Trial in Patients with Chronic Heart Failure with Reduced Ejection Fraction and Empagliflozin Outcome Trial in Patients with Chronic Heart Failure with APreserved Ejection Methods and Results: Selection criteria were applied to the Swedish HF registry outpatient population according to 3 scenarios: (i) a "trial scenario" applying all selection criteria; (ii) a "pragmatic scenario" applying the most clinically relevant criteria; and (iii) a "label scenario" following the regulatory agencies labels. Of the 49,317 patients, 55% had an ejection fraction of less than 40% and were assessed for eligibility based on DAPA-HF and EMPEROR-Reduced, 45% had ejection fraction of 40% or greater and were assessed based on EMPEROR-Preserved and DELIVER. Eligibility using trial, pragmatic, and label scenarios was 35%, 61%, and 80% for DAPA-HF; 31%, 55%, and 81% for EMPEROR-Reduced; 30%, 61%, and 74% for DELIVER; and 32%, 59%, and 75% for EMPEROR-Preserved, respectively. The main selection criteria limiting eligibility were HF duration and N-terminal pro-B type natriuretic peptide levels. Eligible patients had more severe HF, more comorbidities, higher use of HF treatments and higher mortality and morbidity. Clinical Highlights: Large clinical trials for the approval of new drugs in heart failure often apply numerous selection criteria, limiting the generalizability of trial findings to real-world populations. We assessed eligibility for dapagliflozin and empagliflozin according to trial criteria, the more practical criteria usually applied in daily practice for treatment selection, and the criteria mandated by regulatory agencies, in a real-word heart failure population. Our results from the Swedish Heart Failure Registry show that a great number of patients with heart failure might be candidates for these therapies, which have been shown to significantly decrease morbidity and mortality; therefore, their use should be implemented in clinical practice. Lay summary: When strictly applying selection criteria used in clinical trials, only one-third of a real-world heart failure population is eligible for treatment with empagliflozin and dapagliflozin. Adopting approaches that consider the most meaningful criteria, that is, those most clinically relevant or those mandated by regulatory agencies, significantly broadened eligibility. These results might contribute to future trial design taking into consideration the characteristics of real-world populations, feasibility, and potential cost benefits. Conclusions: In a real-world HF setting, eligibility for sodium glucose co-transporter-2 inhibi-tors was similar whether selection criteria from DAPA-HF or EMPEROR-Reduced were applied in HFrEF, or EMPEROR-Preserved or DELIVER in HFpEF. These data might help stakeholders assessing the consequences of future trial eligibility. (J Cardiac Fail 2022;28:1050-1062) Funding Agencies|AstraZeneca; Boehringer Ingelheim

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

Data are scarce on long-term outcomes after ischemic stroke (IS) or transient ischemic attack (TIA). In this prospective cohort study, we examined the cumulative incidence of major adverse cardiovascular events (MACE) after IS and TIA using a competing risk model and factors associated with new events using a Cox-proportional hazard regression model. All patients discharged alive from Östersund Hospital with IS or TIA between 2010 and 2013 (n = 1535) were followed until 31 December 2017. The primary endpoint was a composite of IS, type 1 acute myocardial infarction (AMI), and cardiovascular (CV) death. Secondary endpoints were the individual components of the primary endpoint, in all patients and separated in IS and TIA subgroups. The cumulative incidence of MACE (median follow-up: 4.4 years) was 12.8% (95% CI: 11.2–14.6) within 1 year after discharge and 35.6% (95% CI: 31.8–39.4) by the end of follow-up. The risk of MACE and CV death was significantly increased in IS compared to TIA (p-values

A substantial proportion of patients with infective endocarditis (IE) are subjected to heart valve surgery. Microbiological findings on valves are important both for diagnostics and for tailored antibiotic therapy, post-operatively. The aims of this study were to describe microbiological findings on surgically removed valves and to examine the diagnostic benefits of 16S-rDNA PCR and sequencing (16S-analysis). Adult patients who were subjected to heart valve surgery for IE between 2012 and 2021 at Skåne University Hospital, Lund, where a 16S-analysis had been performed on the valve, constituted the study population. Data were gathered from medical records, and the results from blood cultures, valve cultures, and 16S-analyses of valves were compared. A diagnostic benefit was defined as providing an agent in blood culture negative endocarditis, providing a new agent in episodes with positive blood cultures, or confirming one of the findings in episodes with a discrepancy between blood and valve cultures. 279 episodes in 272 patients were included in the final analysis. Blood cultures were positive in 259 episodes (94%), valve cultures in 60 episodes (22%), and 16S-analyses in 227 episodes (81%). Concordance between the blood cultures and the 16S-analysis was found in 214 episodes (77%). The 16S-analyses provided a diagnostic benefit in 25 (9.0%) of the episodes. In blood culture negative endocarditis, the 16S-analyses had a diagnostic benefit in 15 (75%) of the episodes. A 16S-analysis should be routinely performed on surgically removed valves in blood culture negative endocarditis. In patients with positive blood cultures, 16S-analysis may also be considered, as a diagnostic benefit was provided in some patients.IMPORTANCE This work demonstrates that it can be of importance to perform both cultures and analysis using 16S-rDNA PCR and sequencing of valves excised from patients undergoing surgery for infective endocarditis. 16S-analysis may help both to establish a microbiological etiology in cases of blood culture negative endocarditis and to provide help in situations where there are discrepancies between valve and blood cultures. In addition, our results show a high degree of concordance between blood cultures and 16S-analyses, indicating that the latter has a high sensitivity and specificity for the etiological diagnosis of endocarditis in patients who were subjected to heart valve surgery.

Background: Coronavirus disease 2019 (COVID-19) mRNA vaccines are associated with an increased risk of myocarditis using hospital discharge diagnoses as an outcome. The validity of these register-based diagnoses is uncertain. Methods: Patient records for subjects < 40 years of age and a diagnosis of myocarditis in the Swedish National Patient Register were manually reviewed. Brighton Collaboration diagnosis criteria for myocarditis were applied based on patient history, clinical examination, laboratory data, electrocardiograms, echocardiography, magnetic resonance imaging and myocardial biopsy. Poisson regression was used to estimate incidence rate ratios, comparing the register-based outcome variable to validated outcomes. Interrater reliability was assessed by a blinded re-evaluation. Results: Overall, 95.6% (327/342) of cases registered as myocarditis were confirmed (definite, probable or possible myocarditis according to Brighton Collaboration diagnosis criteria, positive predictive value 0.96 [95% CI 0.93–0.98]). Of the 4.4% (15/342) cases reclassified as no myocarditis or as insufficient information, two cases had been exposed to the COVID-19 vaccine no more than 28 days before the myocarditis diagnosis, two cases were exposed >28 days before admission and 11 cases were unexposed to the vaccine. The reclassification had only minor impact on incidence rate ratios for myocarditis following COVID-19 vaccination. In total, 51 cases were sampled for a blinded re-evaluation. Of the 30 randomly sampled cases initially classified as either definite or probably myocarditis, none were re-classified after re-evaluation. Of the in all 15 cases initially classified as no myocarditis or insufficient information, 7 were after re-evaluation re-classified as probable or possible myocarditis. This re-classification was mostly due to substantial variability in electrocardiogram interpretation. Conclusion: This validation of register-based diagnoses of myocarditis by manual patient record review confirmed the register diagnosis in 96% of cases and had high interrater reliability. Reclassification had only a minor impact on the incidence rate ratios for myocarditis following COVID-19 vaccination.

Despite poor prognosis, patients with type 2 myocardial infarction (MI) tend to be underdiagnosed and undertreated compared to those with type 1 MI. Whether this discrepancy has improved over time is uncertain. We conducted a registry-based cohort study investigating type 2 MI patients managed at Swedish coronary care units (n = 14,833) during 2010–2022. Multivariable-adjusted changes (first three vs last three calendar years of the observation period) were assessed regarding diagnostic examinations (echocardiography, coronary assessment), provision of cardioprotective medications (betablockers, renin–angiotensin–aldosterone-system inhibitors, statins) and 1-year all-cause mortality. Compared to type 1 MI patients (n = 184,329), those with type 2 MI less often had diagnostic examinations and cardioprotective medications. Increases in the use of echocardiography (OR 1.08 [95% confidence interval 1.06–1.09]) and coronary assessment (OR 1.06 [95% confidence interval 1.04–1.08]) were smaller compared to type 1 MI (pinteraction

Objective: Postoperative delirium (POD) is common after cardiac surgery. We have previously identified plasma sodium concentration and the volume of infused fluids during surgery as possible risk factors. Both are linked to the selection and composition of the pump prime used for cardiopulmonary bypass (CPB). Present study aims to examine whether hyperosmolality increases the risk for POD. Design: Patients ≥65 years (n = 195) scheduled for cardiac surgery were prospectively enrolled into this double blinded randomised clinical trial. Study group received a pump prime containing mannitol and ringer-acetate (966 mOsmol) (n = 98) vs. ringer-acetate (388 mOsmol) (n = 97) in the control group. Postoperative delirium was defined according to DSM-5 criteria based on a test-battery pre- and postoperatively (days 1–3). Plasma osmolality was measured on five occasions and coordinated with the POD assessments. The primary outcome was the POD incidence related to hyperosmolality as the secondary outcome. Results: The incidence of POD was 36% in the study group and 34% in the control group, without intergroup difference (p=.59). The plasma osmolality was significantly higher in the study group, both on days 1 and 3 and after CPB (p

OBJECTIVES Coronary artery bypass grafting for advanced coronary artery disease is a well-established procedure with excellent long-term results. The issue of saphenous vein graft (SVG) performance and its relation to clinical symptoms and thereby the potential for improvement by using superior grafts are still not fully understood. We aim to estimate the contribution of late SVG failure to the long-term outcome. METHODS A study population operated between 1997 and 2020, with an internal thoracic artery with a single distal anastomosis and 1, 2 or 3 distal SVG anastomoses, was isolated from the Swedish Web System for Enhancement and Development of Evidence-Based Care in Heart Disease Evaluated According to Recommended Therapies registry. Data regarding postoperative clinically driven coronary angiography and status of bypass grafts were collected. RESULTS The study population consisted of 44 951 patients. Clinically driven angiography occurred in 10.1% (9.5–10.8), 7.9% (7.6–8.3) and 7.1% (6.7–7.5), respectively, of patients within 3 years and 23.6% (22.6–24.5), 20.0% (19.5–20.6) and 17.5% (16.9–18.2), respectively, of patients within 10 years after surgery. Excluding the first 3 postoperative years, no failed SVGs were found in >75%, 60% and 45%, respectively, of cases when an angiography was performed in the first 10 years after surgery. CONCLUSIONS The results suggest that the risk of symptomatic graft failure due to vein graft disease during the first 10 years after surgery is in the range of 1–2% for every grafted coronary vessel and provide an estimate for the upper limit of the improvements in results that could be achieved by replacing SVGs with superior grafts.

Objectives: The aim of this study was to assess the safety and efficacy of single Judkins left (JL) catheter to view right and left coronary artery in right transradial coronary angiography. Methods: A total of 266 patients underwent coronary angiography from the right radial artery were studied prospectively. Patients with ad-hoc percutaneous coronary intervention (PCI), peripheral angiography, ventriculography or aortography procedures (67 patients) were excluded from the study. Coronary angiography was performed with the JL catheter as single catheter group in 171 of the remaining 199 patients, and with the Judkins right and left catheters as the control group in the other 28 patients. Complications, procedure success, procedure time and fluoroscopy time were evaluated between the two groups. Results: Procedure success were 93% (159/171) in patients with a single catheter group and 96.4% (27/28) in patients with two catheter (Judkins right and left) group (control group) (p = 0.49). Complications (spasm) are the same between the two groups (8 of 171 [4.7%] patients in study group and 1 of 28 [3.6%] patients in control group, p = 0.79). Fluroscopy time in single JL catheter group was significantly higher (6.20 ± 4.97 min vs 3.76 ± 2.78 min, p = 0.01). Conclusions: Single JL catheter using to view right and left coronary artery in right transradial coronary angiography was safe and effective. In our study, the success rate of getting left and right coronary artery images with a single JL catheter as high as 93%. However, insisting on imaging with a single catheter extends the duration of fluoroscopy time.

Introduction: Studies have indicated that men have a higher overall risk of VTE than women. In previous studies, we have noted that risk factors for VTE, such as alcohol consumption and physical activity, can differ between sexes. The aim of the present study was to estimate the incidence of first-ever VTE and the association of traditional cardiovascular risk factors with VTE risk in men and women separately. Materials and methods: Inhabitants of Västerbotten County in northern Sweden, who had participated in a health examination between 1985 and 2014 were included. The mean age at inclusion was 46.3 years (range 26–65 years). All first-ever VTE events experienced by the participants from the health examination to September 5, 2014 were identified and validated. Results: A total of 1110 men and 944 women had an objectively verified first-ever VTE event. The incidence of VTE was 1.54 (95% CI 1.45–1.63) per 1000 years of follow-up for men and 1.22 (95% CI 1.14–1.30) for women. Higher age, weight and body mass index were associated with increased risk of VTE in both sexes. Men with hypertension had a lower risk of VTE, HR 0.75 (95% CI 0.65–0.87) and men with more than secondary school education had a higher risk of VTE. Taller women had an increased risk of VTE. Conclusions: In the studied age group, we found that men had a higher incidence of first-ever VTE than women. Notably, we also found that hypertension was associated with lower risk of VTE in men but not in women.

Infective endocarditis (IE) is a serious infection of the inner surface of heart, resulting from minor lesions in the endocardium. The damage induces a healing reaction, which leads to recruitment of fibrin and immune cells. This sterile healing vegetation can be colonized during temporary bacteremia, inducing IE. We have previously established a novel in vitro IE model using a simulated IE vegetation (IEV) model produced from whole venous blood, on which we achieved stable bacterial colonization after 24 h. The bacteria were organized in biofilm aggregates and displayed increased tolerance toward antibiotics. In this current study, we aimed at further characterizing the time course of biofilm formation and the impact on antibiotic tolerance development. We found that a Staphylococcus aureus reference strain, as well as three clinical IE isolates formed biofilms on the IEV after 6 h. When treatment was initiated immediately after infection, the antibiotic effect was significantly higher than when treatment was started after the biofilm was allowed to mature. We could follow the biofilm development microscopically by visualizing growing bacterial aggregates on the IEV. The findings indicate that mature, antibiotic-tolerant biofilms can be formed in our model already after 6 h, accelerating the screening for optimal treatment strategies for IE.

Purpose: This review intends to illustrate basic principles on how to apply the Fourth Universal Definition of Myocardial Infarction (UDMI) for the diagnosis of peri-procedural myocardial infarction (MI) after percutaneous coronary interventions (PCI) in clinical practice. Methods and Results: Review of routine case-based events. Increases in cardiac troponin (cTn) concentrations are common after elective PCI in patients with chronic coronary syndrome (CCS). Peri-procedural PCI-related MI (type 4a MI) in CCS patients should be diagnosed in cases of major peri-procedural acute myocardial injury indicated by an increase in cTn concentrations of >5-times the 99th percentile upper reference limit (URL) together with evidence of new peri-procedural myocardial ischaemia as demonstrated by electrocardiography (ECG), imaging, or flow-limiting peri-procedural complications in coronary angiography. Measurement of cTn baseline concentrations before elective PCI is useful. In patients presenting with acute MI undergoing PCI, peri-procedural increases in cTn concentrations are usually due to their index presentation and not PCI-related, apart from obvious major peri-procedural complications, such as persistent occlusion of a large side branch or no-reflow after stent implantation. Conclusion: The distinction between type 4a MI, PCI-related acute myocardial injury, and chronic myocardial injury can be challenging in individuals undergoing PCI. Careful integration of all available clinical data is essential for correct classification.

Aims Use of implantable cardioverter-defibrillators (ICD) for primary prevention of sudden cardiac death (SCD) in heart failure with reduced ejection fraction (HFrEF) is limited. We aimed to investigate barriers to ICD use in HFrEF while considering the predicted risk of mortality and SCD. Method and results Patients from the SwedeHF registered in 2011-2018 and with an indication for primary prevention ICD were analysed. The Seattle Proportional Risk and Seattle Heart Failure Models were used to predict the proportional SCD and all-cause mortality risk, respectively. A multivariable logistic regression model was fitted to identify independent predictors of ICD use/non-use; Cox regression models to evaluate the interaction between predicted SCD/mortality risk and ICD use for mortality. Of 13 475 patients, only 15.5% had an ICD. Those with higher predicted proportional SCD risk (>45%) had an similar to 80% higher likelihood to have an ICD. Other predictors of non-use were follow-up in primary versus specialty care, higher comorbidity burden and lower socioeconomic status. ICD use was associated with lower mortality only in patients with higher predicted SCD and lower mortality risk (34% and 37% relative risk reduction for 3-year all-cause and cardiovascular mortality, respectively). In this subgroup of patients, underuse of ICD was 81.8%. Conclusion In a contemporary registry, only 15.5% of patients with an indication for primary prevention ICD received the device. While a high predicted proportional SCD risk was appropriately linked to ICD use, the lack of specialized follow-up, higher comorbidity burden, and lower socioeconomic status were major unjustified impediments to implementation. Our findings suggest areas for improving ICD use for primary prevention of SCD in clinical practice. Funding Agencies|Boston Scientific; EU/EFPIA Innovative Medicines Initiative 2 Joint Undertaking BigData@Heart grant [116074]

Objective Patients hospitalized with acute coronary syndrome (ACS) in Sweden routinely undergo an echocardiographic examination with assessment of left ventricular ejection fraction (LVEF). LVEF is a measurement widely used for outcome prediction and treatment guidance. The obtained LVEF is categorized as normal (> 50%) or mildly, moderately, or severely impaired (40–49, 30–39, and Methods A random sample of 130 patients from three hospitals were included. LVEF re-evaluation was performed by two independent reviewers using the modified biplane Simpson method and their mean LVEF was compared to the LVEF reported to SWEDEHEART. Agreement between reported and re-evaluated LVEF was assessed using Gwet’s AC2 statistics. Results Analysis showed good agreement between reported and re-evaluated LVEF (AC2: 0.76 [95% CI 0.69–0.84]). The LVEF re-evaluations were in agreement with the registry reported LVEF categorization in 86 (66.0%) of the cases. In 33 (25.4%) of the cases the SWEDEHEART-reported LVEF was lower than re-evaluated LVEF. The opposite relation was found in 11 (8.5%) of the cases (p Conclusion Independent validation of SWEDEHEART-reported LVEF shows an overall good agreement with the re-evaluated LVEF. However, a tendency towards underestimation of LVEF was observed, with the largest discrepancy between re-evaluated LVEF and registry LVEF in subjects with subnormal LV-function in whom the reported assessment of LVEF should be interpreted more cautiously. Graphical abstract

Aims: One of the bothersome symptoms that heart failure (HF) patients can experience is thirst. There are limited data on the association between thirst and fluid intake and clinical variables. Therefore, the aim of this study was to describe severe thirst in stable HF patients and assess factors related to severe thirst, including actual fluid intake and sodium intake. Methods and results: The study had a cross-sectional design. Stable HF patients from two HF clinics in the Netherlands were included and assessed thirst by a visual analogue scale ranging from 0 to 100. They also completed questionnaires on thirst distress, self-care behaviour, and HF symptoms. A 3 day food diary was completed to assess actual fluid intake and sodium intake. Finally, patients collected urine for 24 h. Patients were divided into severe and low thirst based on thirst score and thirst distress. T-tests, Mann-Whitney tests, and chi(2) tests were conducted to assess differences between both groups. Multivariable logistic regression analysis was performed to assess factors associated with severe thirst. A total of 100 patients were included (40% female, mean age 72 +/- 12) of which 68 completed the food diary. The mean thirst score was 28 +/- 25, and 25% experienced severe thirst. The majority of patients (94%) were prescribed a fluid restriction, 37% had a restriction between 1500 and 2000 mL, and 32% a restriction of 1500 mL. Severe thirst in the total group with 100 patients was associated with a higher dose of loop diuretics [odds ratio (OR) 3.25; 95% confidence interval (CI) 1.01-10.45; P = 0.048] and a higher urine output over 24 h (OR 1.002; 95% CI 1.00-1.003; P = 0.010). In the group of patients who completed the food diary (N = 68), severe thirst was associated with a higher sodium intake (OR 1.002; 95% CI 1.001-1.003; P = 0.003), a higher dose of loop diuretics (OR 22.69; 95% CI 2.78-185.04; P = 0.004), and more fatigue (OR 11.2; 95% CI 1.54-82.12; P = 0.017). Conclusions: A quarter of all stable HF patients experienced severe thirst. A higher dose of loop diuretics was associated with more thirst; therefore, it might be important to review the dose of loop diuretics critically and try to decrease it in order to relieve severe thirst. Because all patients were prescribed a fluid restriction, a reconsideration of this restriction is also suggested.

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.

Objectives: Total circulatory arrest (TCA) technique is a method used in cardiac surgery accompanied by cardiopulmonary bypass (CPB). It has been shown that Tulbaghia violacea extract increases antioxidant capacity, regulates blood pressure, decreases lipid peroxide, and reduces atherosclerosis. In this experimental study, we aimed to investigate the effect of T. violacea extract administration on serum oxidative stress parameters (Total antioxidant status [TAS], total oxidant status [TOS] and oxidative stress index [OSI] and deoxyribonucleic acid [DNA] damage level with 8-Hydroxy-2-Deoxyguanosine [8-OHdG]) and histopathological changes in the heart and other organs in rats with deep circulatory arrest model.Methods: In this study, 48 Wistar Albino adult rats, 24 female and 24 male, obtained from Harran University Experimental Animals Research Center were used. The average weight of female rats was 250-300 g, and the average weight of male rats was 450-500 g. These rats were randomly divided into four groups. 6 male and 6 female rats were used in each group (Group 1 = Sham, Group 2 = Injury, Group 3 = Treatment and Injury, Group 4 = Treatment).Results: As a result of this experimental study, the changes in the biochemical 8-OHdG, TOS, OSI and TAS levels of the groups were found to be statistically significant (p < 0.001). In the subgroup analyzes of the data, 8-OHdG level, which is an oxidative DNA damage marker in Group 2 was higher than the Group 1, Group 3 and Group 4 and there was a statistically significant difference (p < 0.001, p = 0.027 and p < 0.001; respectively). The TOS level of the injury group was higher than Group 1, Group 3 and Group 4 and there was a statistically significant difference (p < 0.001, p = 0.003 and p < 0.001; respectively).Conclusions: As a result of our study, we revealed that T. violacea extract has a protective effect on organ and tissue damage in the TCA model.

Background/Aim: The anatomic location of the heart in the mediastinal space may change and significant electrophysiological changes may appear after pneumonectomy, lobectomy, and segmentectomy. The aim of the present study was to perform a comprehensive investigation of electrocardiographic alterations after lung resection.Methods: In this retrospective cohort study, sixty-six patients (9 females, 57 males) who had lung resections were enrolled. Electrocardiograms of preoperative (24 hours before operation) and postoperative periods (after operation 7 (2) days) were analyzed. Result: Postoperative mean Pmin and QRS duration levels were lower than the respective preoperative values. In comparison with preoperative values, postoperative mean P dispersion, QTmax, QTmin, QT mean, QTd, QTc, QTc dispersion, JT, JTc, mean Tpe/QTmean, mean Tpe/QTc ratio (%), and mean Tpe/JT ratio (%) levels were found to be significantly higher. Postoperative mean pulse, mean Pmax, mean PR interval, mean RR, and mean Tpe/JTc ratio were not significantly different when compared with preoperative levels.Conclusion: Alterations in electrocardiography parameters reflecting the electrophysiology of the heart since heart position basically changes after lung resection may appear.

Aims To conduct a health economic evaluation of ticagrelor in patients with type 2 diabetes and coronary artery disease (CAD) from a multinational payer perspective. Cost–effectiveness and cost–utility of ticagrelor were evaluated in the overall effect of Ticagrelor on Health Outcomes in Diabetes Mellitus Patients Intervention Study (THEMIS) trial population and in the predefined patient group with prior percutaneous coronary intervention. Methods and results A Markov model was developed to extrapolate patient outcomes over a lifetime horizon. The primary outcome was incremental cost–effectiveness ratios (ICERs), which were compared with conventional willingness-to-pay thresholds [€47 000/quality-adjusted life-year (QALY) in Sweden and €30 000/QALY in other countries]. Treatment with ticagrelor resulted in QALY gains of up to 0.045 in the overall population and 0.099 in patients with percutaneous coronary intervention (PCI). Increased costs and benefits translated to ICERs ranged between €27 894 and €42 252/QALY across Sweden, Germany, Italy, and Spain in the overall population. In patients with prior PCI, estimated ICERs improved to €18 449, €20 632, €20 233, and €13 228/QALY in Sweden, Germany, Italy, and Spain, respectively, driven by higher event rates and treatment benefit. Conclusion Based on THEMIS results, ticagrelor plus aspirin compared with aspirin alone may be cost–effective in some European countries in patients with T2DM and CAD and no prior myocardial infarction (MI) or stroke. Additionally, ticagrelor is likely to be cost–effective across European countries in patients with a history of PCI.

Background: Heart failure (HF) is a highly prevalent disorder for which disease mechanisms are incompletely understood. The discovery of disease-associated proteins with causal genetic evidence provides an opportunity to identify new therapeutic targets. Methods: We investigated the observational and causal associations of 90 cardiovascular proteins, which were measured using affinity-based proteomic assays. First, we estimated the associations of 90 cardiovascular proteins with incident heart failure by means of a fixed-effect meta-analysis of 4 population-based studies, composed of a total of 3019 participants with 732 HF events. The causal effects of HF-associated proteins were then investigated by Mendelian randomization, using cis -protein quantitative loci genetic instruments identified from genomewide association studies in more than 30 000 individuals. To improve the precision of causal estimates, we implemented an Mendelian randomization model that accounted for linkage disequilibrium between instruments and tested the robustness of causal estimates through a multiverse sensitivity analysis that included up to 120 combinations of instrument selection parameters and Mendelian randomization models per protein. The druggability of candidate proteins was surveyed, and mechanism of action and potential on-target side effects were explored with cross-trait Mendelian randomization analysis. Results: Forty-four of ninety proteins were positively associated with risk of incident HF ( P –4 ). Among these, 8 proteins had evidence of a causal association with HF that was robust to multiverse sensitivity analysis: higher CSF-1 (macrophage colony-stimulating factor 1), Gal-3 (galectin-3) and KIM-1 (kidney injury molecule 1) were positively associated with risk of HF, whereas higher ADM (adrenomedullin), CHI3L1 (chitinase-3-like protein 1), CTSL1 (cathepsin L1), FGF-23 (fibroblast growth factor 23), and MMP-12 (matrix metalloproteinase-12) were protective. Therapeutics targeting ADM and Gal-3 are currently under evaluation in clinical trials, and all the remaining proteins were considered druggable, except KIM-1. Conclusions: We identified 44 circulating proteins that were associated with incident HF, of which 8 showed evidence of a causal relationship and 7 were druggable, including adrenomedullin, which represents a particularly promising drug target. Our approach demonstrates a tractable roadmap for the triangulation of population genomic and proteomic data for the prioritization of therapeutic targets for complex human diseases.

The definition of a new case is a vital step in incidence studies in both epidemiology and pharmacoepidemiology, although with significant differences in methodology between the fields. We define and apply a framework for two different types of new cases of drug use, first-ever and recurrent, and show how the associated misclassifications related to length of run-in period can be expressed by the positive predictive value (PPV). In the study, we consider individual-level dispensations of statins 2006-2019 for 1,017,058 individuals with at least one dispensation in 2019 in Sweden. The incidence proportion for statins for both sexes of all ages in Sweden 2019 varied from 17.4/1000 with a run-in of 8 months, 9.45/1000 with 5 years and 8.4/1000 with 10 years. The PPV was 49% with 8 months and 89% for 5 years using 10 years as gold standard. We conclude that the interpretation of incidence and thus the selection of an appropriate run-in period, in pharmacoepidemiology, depends on whether first-ever use, recurrent treatment or both together (new cases) is the focus of the research question studied. At least five different misclassifications can be introduced depending on how incidence is defined. Funding Agencies|NEPI foundation [SE802400-2589]

Standardized data definitions are essential for monitoring and benchmarking the quality of care and patient outcomes in observational studies and randomized controlled trials. There are no contemporary pan-European data standards for the acute coronary syndrome (ACS) and percutaneous coronary intervention (PCI). The European Unified Registries for Heart Care Evaluation and Randomised Trials (EuroHeart) project of the European Society of Cardiology (ESC) aimed to develop such data standards for ACS and PCI. Following a systematic review of the literature on ACS and PCI data standards and evaluation of contemporary ACS and PCI registries, we undertook a modified Delphi process involving clinical and registry experts from 11 European countries, as well as representatives from relevant ESC Associations, including the European Association of Percutaneous Cardiovascular Interventions (EAPCI) and Acute CardioVascular Care (ACVC). This resulted in final sets of 68 and 84 ‘mandatory’ variables and several catalogues of optional variables for ACS and PCI, respectively. Data definitions were provided for these variables, which have been programmed as the basis for continuous registration of individual patient data in the online EuroHeart IT platform. By means of a structured process and the interaction with major stakeholders, internationally harmonized data standards for ACS and PCI have been developed. In the context of the EuroHeart project, this will facilitate country-level quality of care improvement, international observational research, registry-based randomized trials, and post-marketing surveillance of devices and pharmacotherapies.

Background Despite improvements in the treatment and prevention of cardiovascular disease since the 1960s, the incidence of cardiovascular diseases among young people has remained the same for many years. This study aimed to compare the clinical and psychosocial attributes of young persons affected by myocardial infarction under the age of 50 years compared to middle-aged myocardial infarction patients 51–65 years old. Methods Data from patients with a documented STEMI or NSTEMI elevated acute myocardial infarction in the age groups up to 65 years, were collected from cardiology clinics at three hospitals in southeast Sweden. The Stressheart study comprised a total of 213 acute myocardial infarction patients, of which n = 33 (15.5%) were under 50 years of age and n = 180 (84.5%) were middle-aged, (51–65 years). These acute myocardial infarction patients filled in a questionnaire at discharge from the hospital and further information through documentation of data in their medical records. Results Blood pressure was significantly higher in young compared to middle-aged patients. For diastolic blood pressure (p = 0.003), systolic blood pressure (p = 0.028), and mean arterial pressure (p = 0.005). Young AMI patients had a higher (p = 0.030) body mass index (BMI) than the middle-aged. Young AMI patients were reported to be more stressed (p = 0.042), had more frequently experienced a serious life event the previous year (p = 0.029), and felt less energetic (p = 0.044) than middle-aged AMI patients. Conclusions This study revealed that persons under the age of 50 affected by acute myocardial infarction exhibit traditional cardiovascular risk factors like high blood pressure, and higher BMI, and were more exposed to some psychosocial risk factors. The risk profile of young persons under age 50 affected by AMI was in these respects more exaugurated than for middle-aged persons with AMI. This study underlines the importance of the early discovery of those at increased risk and encourages preventative actions to focus on both clinical and psychosocial risk factors.

Background Effectiveness estimates from observational studies on ticagrelor use in routine clinical care are conflicting, with some contrary to the results of the pivotal randomized controlled trial of ticagrelor in acute coronary syndrome. The aim of this study was to estimate the effect of implementing and using ticagrelor in routine clinical care in patients with myocardial infarction using a natural experimental approach. Methods and Results This is a retrospective cohort study including patients hospitalized for myocardial infarction in Sweden between 2009 and 2015. The study exploited differences in the timing and speed of ticagrelor implementation between treatment centers as a source of random treatment assignment. The effect of implementing and using ticagrelor was estimated based on the admitting center's likelihood of treating patients with ticagrelor, measured as the proportion of patients treated in the 90 days before patient admission. The main outcome was 12‐month mortality. The study included 109 955 patients, of whom 30 773 were treated with ticagrelor. Being admitted to a treatment center with higher past ticagrelor use was associated with a reduction in 12‐month mortality (2.5 percentage points for 100% versus 0% past use [95% CI, 0.2–4.8]). The results are in line with the findings from the ticagrelor pivotal trial. Conclusions Using a natural experiment, this study finds that the implementation and use of ticagrelor in routine clinical care has reduced 12‐month mortality in patients admitted to the hospital with myocardial infarction in Sweden and supports the external validity of randomized evidence on ticagrelor effectiveness.

Evidence suggests potential links between circadian rhythm and atrial fibrillation (AF). However, whether circadian disruption can predict the onset of AF in the general population remains largely unknown. We aim to investigate the association of accelerometer-measured circadian rest-activity rhythm (CRAR, the most prominent circadian rhythm in humans) with the risk of AF, and examine joint associations and potential interactions of CRAR and genetic susceptibility with AF incidence. We include 62,927 white British participants of UK Biobank without AF at baseline. CRAR characteristics, including amplitude (strength), acrophase (timing of peak activity), pseudo-F (robustness), and mesor (height), are derived by applying an extended cosine model. Genetic risk is assessed with polygenic risk scores. The outcome is the incidence of AF. During a median follow-up of 6.16 years, 1920 participants developed AF. Low amplitude [hazard ratio (HR): 1.41, 95% confidence interval (CI): 1.25–1.58], delayed acrophase (HR: 1.24, 95% CI: 1.10–1.39), and low mesor (HR: 1.36, 95% CI: 1.21–1.52), but not low pseudo-F, are significantly associated with a higher risk of AF. No significant interactions between CRAR characteristics and genetic risk are observed. Joint association analyses reveal that participants with unfavourable CRAR characteristics and high genetic risk yield the highest risk of incident AF. These associations are robust after controlling for multiple testing and in a series of sensitivity analyses. Accelerometer-measured CRAR abnormalities, characterized by decreased strength and height, and later timing of peak activity of circadian rhythm, are associated with a higher risk of AF in the general population.

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.

Background Decisions in the management of aortic stenosis are based on the peak pressure drop, captured by Doppler echocardiography, whereas gold standard catheterization measurements assess the net pressure drop but are limited by associated risks. The relationship between these two measurements, peak and net pressure drop, is dictated by the pressure recovery along the ascending aorta which is mainly caused by turbulence energy dissipation. Currently, pressure recovery is considered to occur within the first 40–50 mm distally from the aortic valve, albeit there is inconsistency across interventionist centers on where/how to position the catheter to capture the net pressure drop. Methods We developed a non-invasive method to assess the pressure recovery distance based on blood flow momentum via 4D Flow cardiovascular magnetic resonance (CMR). Multi-center acquisitions included physical flow phantoms with different stenotic valve configurations to validate this method, first against reference measurements and then against turbulent energy dissipation (respectively n = 8 and n = 28 acquisitions) and to investigate the relationship between peak and net pressure drops. Finally, we explored the potential errors of cardiac catheterisation pressure recordings as a result of neglecting the pressure recovery distance in a clinical bicuspid aortic valve (BAV) cohort of n = 32 patients. Results In-vitro assessment of pressure recovery distance based on flow momentum achieved an average error of 1.8 ± 8.4 mm when compared to reference pressure sensors in the first phantom workbench. The momentum pressure recovery distance and the turbulent energy dissipation distance showed no statistical difference (mean difference of 2.8 ± 5.4 mm, R2 = 0.93) in the second phantom workbench. A linear correlation was observed between peak and net pressure drops, however, with strong dependences on the valvular morphology. Finally, in the BAV cohort the pressure recovery distance was 78.8 ± 34.3 mm from vena contracta, which is significantly longer than currently accepted in clinical practise (40–50 mm), and 37.5% of patients displayed a pressure recovery distance beyond the end of the ascending aorta. Conclusion The non-invasive assessment of the distance to pressure recovery is possible by tracking momentum via 4D Flow CMR. Recovery is not always complete at the ascending aorta, and catheterised recordings will overestimate the net pressure drop in those situations. There is a need to re-evaluate the methods that characterise the haemodynamic burden caused by aortic stenosis as currently clinically accepted pressure recovery distance is an underestimation.

Aims: Atrial fibrillation (AF) is becoming increasingly common. Traditional cardiovascular risk factors (CVRF) do not explain all AF cases. Blood-based biomarkers reflecting cardiac injury such as high-sensitivity troponin I (hsTnI) may help close this gap. Methods: We investigated the predictive ability of hsTnI for incident AF in 45,298 participants (median age 51.4 years, 45.0% men) across European community cohorts in comparison to CVRF and established biomarkers (C-reactive protein, N-terminal pro B-type natriuretic peptide). Results: During a median follow-up of 7.7 years, 1734 (3.8%) participants developed AF. Those in the highest hsTnI quarter (≥4.2 ng/L) had a 3.91-fold (95% confidence interval (CI) 3.30, 4.63; p

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