Empagliflozin's role in reducing ventricular repolarization heterogeneity: insights into cardiovascular mortality decline from the EMPATHY-HEART trial.

BACKGROUND: The incidence of myocardial infarction (MI) and sudden cardiac death (SCD) is significantly higher in individuals with Type 2 Diabetes Mellitus (T2DM) than in the general population. Strategies for the prevention of fatal arrhythmias are often insufficient, highlighting the need for additional non-invasive diagnostic tools. The T-wave heterogeneity (TWH) index measures variations in ventricular repolarization and has emerged as a promising predictor for severe ventricular arrhythmias. Although the EMPA-REG trial reported reduced cardiovascular mortality with empagliflozin, the underlying mechanisms remain unclear. This study investigates the potential of empagliflozin in mitigating cardiac electrical instability in patients with T2DM and coronary heart disease (CHD) by examining changes in TWH. METHODS: Participants were adult outpatients with T2DM and CHD who exhibited TWH > 80 µV at baseline. They received a 25 mg daily dose of empagliflozin and were evaluated clinically including electrocardiogram (ECG) measurements at baseline and after 4 weeks. TWH was computed from leads V4, V5, and V6 using a validated technique. The primary study outcome was a significant (p < 0.05) change in TWH following empagliflozin administration. RESULTS: An initial review of 6,000 medical records pinpointed 800 patients for TWH evaluation. Of these, 412 exhibited TWH above 80 µV, with 97 completing clinical assessments and 90 meeting the criteria for high cardiovascular risk enrollment. Empagliflozin adherence exceeded 80%, resulting in notable reductions in blood pressure without affecting heart rate. Side effects were generally mild, with 13.3% experiencing Level 1 hypoglycemia, alongside infrequent urinary and genital infections. The treatment consistently reduced mean TWH from 116 to 103 µV (p = 0.01). CONCLUSIONS: The EMPATHY-HEART trial preliminarily suggests that empagliflozin decreases heterogeneity in ventricular repolarization among patients with T2DM and CHD. This reduction in TWH may provide insight into the mechanism behind the decreased cardiovascular mortality observed in previous trials, potentially offering a therapeutic pathway to mitigate the risk of severe arrhythmias in this population. TRIAL REGISTRATION: NCT: 04117763.

Long-term outcomes of perioperative myocardial infarction/injury after non-cardiac surgery.

AIMS: Perioperative myocardial infarction/injury (PMI) following non-cardiac surgery is a frequent cardiac complication. Better understanding of the underlying aetiologies and outcomes is urgently needed. METHODS AND RESULTS: Aetiologies of PMIs detected within an active surveillance and response programme were centrally adjudicated by two independent physicians based on all information obtained during clinically indicated PMI work-up including cardiac imaging among consecutive high-risk patients undergoing major non-cardiac surgery in a prospective multicentre study. PMI aetiologies were hierarchically classified into 'extra-cardiac' if caused by a primarily extra-cardiac disease such as severe sepsis or pulmonary embolism; and 'cardiac', further subtyped into type 1 myocardial infarction (T1MI), tachyarrhythmia, acute heart failure (AHF), or likely type 2 myocardial infarction (lT2MI). Major adverse cardiac events (MACEs) including acute myocardial infarction, AHF (both only from day 3 to avoid inclusion bias), life-threatening arrhythmia, and cardiovascular death as well as all-cause death were assessed during 1-year follow-up. Among 7754 patients (age 45-98 years, 45% women), PMI occurred in 1016 (13.1%). At least one MACE occurred in 684/7754 patients (8.8%) and 818/7754 patients died (10.5%) within 1 year. Outcomes differed starkly according to aetiology: in patients with extra-cardiac PMI, T1MI, tachyarrhythmia, AHF, and lT2MI 51%, 41%, 57%, 64%, and 25% had MACE, and 38%, 27%, 40%, 49%, and 17% patients died within 1 year, respectively, compared to 7% and 9% in patients without PMI. These associations persisted in multivariable analysis. CONCLUSION: At 1 year, most PMI aetiologies have unacceptably high rates of MACE and all-cause death, highlighting the urgent need for more intensive treatments. STUDY REGISTRATION: https://clinicaltrials.gov/ct2/show/NCT02573532.

Effects of dabigatran versus warfarin on 2-year cognitive outcomes in old patients with atrial fibrillation: results from the GIRAF randomized clinical trial.

BACKGROUND: Observational studies support a role for oral anticoagulation to reduce the risk of dementia in atrial fibrillation patients, but conclusive data are lacking. Since dabigatran offers a more stable anticoagulation, we hypothesized it would reduce cognitive decline when compared to warfarin in old patients with atrial fibrillation. METHODS: The GIRAF trial was a 24-month, randomized, parallel-group, controlled, open-label, hypothesis generating trial. The trial was done in six centers including a geriatric care unit, secondary and tertiary care cardiology hospitals in São Paulo, Brazil. We included patients aged ≥ 70 years and CHA2DS2-VASc score > 1. The primary endpoint was the absolute difference in cognitive performance at 2 years. Patients were assigned 1:1 to take dabigatran (110 or 150 mg twice daily) or warfarin, controlled by INR and followed for 24 months. Patients were evaluated at baseline and at 2 years with a comprehensive and thorough cognitive evaluation protocol of tests for different cognitive domains including the Montreal Cognitive Assessment (MoCA), Mini-Mental State Exam (MMSE), a composite neuropsychological test battery (NTB), and computer-generated tests (CGNT). RESULTS: Between 2014 and 2019, 5523 participants were screened and 200 were assigned to dabigatran (N = 99) or warfarin (N = 101) treatment. After adjustment for age, log of years of education, and raw baseline score, the difference between the mean change from baseline in the dabigatran group minus warfarin group was - 0.12 for MMSE (95% confidence interval [CI] - 0.88 to 0.63; P = 0.75), 0.05 (95% CI - 0.07 to 0.18; P = 0.40) for NTB, - 0.15 (95% CI - 0.30 to 0.01; P = 0.06) for CGNT, and - 0.96 (95% CI - 1.80 to 0.13; P = 0.02) for MoCA, with higher values suggesting less cognitive decline in the warfarin group. CONCLUSIONS: For elderly patients with atrial fibrillation, and without cognitive compromise at baseline that did not have stroke and were adequately treated with warfarin (TTR of 70%) or dabigatran for 2 years, there was no statistical difference at 5% significance level in any of the cognitive outcomes after adjusting for multiple comparisons. TRIAL REGISTRATION: Cognitive Impairment Related to Atrial Fibrillation Prevention Trial (GIRAF), NCT01994265 .

Empagliflozin Inhibits Proximal Tubule NHE3 Activity, Preserves GFR, and Restores Euvolemia in Nondiabetic Rats with Induced Heart Failure.

BACKGROUND: SGLT2 inhibitors reduce the risk of heart failure (HF) mortality and morbidity, regardless of the presence or absence of diabetes, but the mechanisms underlying this benefit remain unclear. Experiments with nondiabetic HF rats tested the hypothesis that the SGLT2 inhibitor empagliflozin (EMPA) inhibits proximal tubule (PT) NHE3 activity and improves renal salt and water handling. METHODS: Male Wistar rats were subjected to myocardial infarction or sham operation. After 4 weeks, rats that developed HF and sham rats were treated with EMPA or untreated for an additional 4 weeks. Immunoblotting and quantitative RT-PCR evaluated SGLT2 and NHE3 expression. Stationary in vivo microperfusion measured PT NHE3 activity. RESULTS: EMPA-treated HF rats displayed lower serum B-type natriuretic peptide levels and lower right ventricle and lung weight to tibia length than untreated HF rats. Upon saline challenge, the diuretic and natriuretic responses of EMPA-treated HF rats were similar to those of sham rats and were higher than those of untreated HF rats. Additionally, EMPA treatment prevented GFR decline and renal atrophy in HF rats. PT NHE3 activity was higher in HF rats than in sham rats, whereas treatment with EMPA markedly reduced NHE3 activity. Unexpectedly, SGLT2 protein and mRNA abundance were upregulated in the PT of HF rats. CONCLUSIONS: Prevention of HF progression by EMPA is associated with reduced PT NHE3 activity, restoration of euvolemia, and preservation of renal mass. Moreover, dysregulation of PT SGLT2 may be involved in the pathophysiology of nondiabetic HF.

Patients with COVID-19 who experience a myocardial infarction have complex coronary morphology and high in-hospital mortality: Primary results of a nationwide angiographic study.

OBJECTIVES: We aimed to explore angiographic patterns and in-hospital outcomes of patients with concomitant coronavirus disease-19 (COVID-19) and myocardial infarction (MI). BACKGROUND: Patients with COVID-19 may experience MI during the course of the viral infection. However, this association is currently poorly understood. METHODS: This is a multicenter prospective study of consecutive patients with concomitant COVID-19 and MI who underwent coronary angiography. Quantitative and qualitative coronary angiography were analyzed by two observers in an independent core lab. RESULTS: A total of 152 patients were included, of whom 142 (93.4%) had COVID-19 diagnosis confirmation. The median time between symptom onset and hospital admission was 5 (1-10) days. A total of 83 (54.6%) patients presented with ST-elevation MI. The median angiographic Syntax score was 16 (9.0-25.3) and 69.0% had multi-vessel disease. At least one complex lesion was found in 73.0% of patients, 51.3% had a thrombus containing lesion, and 57.9% had myocardial blush grades 0/1. The overall in-hospital mortality was 23.7%. ST-segment elevation MI presentation and baseline myocardial blush grades 0 or 1 were independently associated with a higher risk of death (HR 2.75, 95%CI 1.30-5.80 and HR 3.73, 95%CI 1.61-8.61, respectively). CONCLUSIONS: Patients who have a MI in the context of ongoing COVID-19 mostly present complex coronary morphologies, implying a background of prior atherosclerotic disease superimposed on a thrombotic milieu. The in-hospital prognosis is poor with a markedly high mortality, prompting further investigation to better clarify this newly described condition.

Evolocumab treatment in patients with HIV and hypercholesterolemia/mixed dyslipidemia: BEIJERINCK study design and baseline characteristics.

BACKGROUND: People living with human immunodeficiency virus (PLHIV) are at higher risk of atherosclerotic cardiovascular disease (ASCVD) due to traditional and HIV- or antiretroviral treatment (ART)-related risk factors. The use of high-intensity statin therapy is often limited by comorbidities and drug-drug interactions with ART. Herein, we present the design and baseline characteristics of the BEIJERINCK study, which will assess the safety and efficacy of evolocumab in PLHIV and hypercholesterolemia/mixed dyslipidemia. METHODS: Randomized, double-blind, placebo-controlled, multinational trial that investigates monthly subcutaneous evolocumab 420 mg versus placebo in PLHIV with hypercholesterolemia/mixed dyslipidemia who are treated with maximally-tolerated statin therapy. The primary outcome is the baseline to week 24 percent change in low density lipoprotein cholesterol (LDL-C). Secondary outcomes include achievement of LDL-C < 70 mg/dL and percent change in other plasma lipid and lipoprotein levels. Safety will also be examined. RESULTS: This study enrolled and dosed 464 patients who had a mean age of 56.4 years and were mostly male (82.5%). Mean duration with HIV was 17.4 years, and, by design, HIV viral load at screening was ≤50 copies/mL. ASCVD was documented in 35.6% of patients. Mean LDL-C of enrolled patients at baseline was 133.3 mg/dL. Statin use was prevalent (79.3% overall) with 74.6% receiving moderate or high-intensity statins. In total, 20.7% of patients did not receive statins due to intolerance/contraindications. CONCLUSIONS: The BEIJERINCK study is the first clinical trial to examine the lipid-lowering efficacy and safety of a fully human PCSK9 monoclonal antibody inhibitor in a moderate/high cardiovascular risk population of PLHIV.

Troponin I as a mortality marker after lung resection surgery - a prospective cohort study.

BACKGROUND: Cardiovascular complications associated with thoracic surgery increase morbidity, mortality, and treatment costs. Elevated cardiac troponin level represents a predictor of complications after non-cardiac surgeries, but its role after thoracic surgeries remains undetermined. The objective of this study was to analyze the relationship between troponin I elevation and morbidity and mortality after one year in patients undergoing lung resection surgery. METHODS: This prospective cohort study evaluated 151 consecutive patients subjected to elective lung resection procedures using conventional and video-assisted thoracoscopic techniques at a University Hospital in Brazil, from July 2012 to November 2015. Preoperative risk stratification was performed using the scores obtained by the American College of Physicians (ACP) and the Society of Cardiology of the state of São Paulo (EMAPO) scoring systems. Troponin I levels were measured in the immediate postoperative period (POi) and on the first and second postoperative days. RESULTS: Most patients had a low risk for complications according to the ACP (96.7%) and EMAPO (82.8%) scores. Approximately 49% of the patients exhibited increased troponin I (≥0.16 ng/ml), at least once, and 22 (14.6%) died in one year. Multivariate analysis showed that the elevation of troponin I, on the first postoperative day, correlated with a 12-fold increase in mortality risk within one year (HR 12.02, 95% CI: 1.82-79.5; p = 0.01). CONCLUSIONS: In patients undergoing lung resection surgery, with a low risk of complications according to the preoperative evaluation scores, an increase in troponin I levels above 0.16 ng/ml in the first postoperative period correlated with an increase in mortality within one year.

Cardiovascular and psychopathological factors among non-sexually compulsive, sexually compulsive, and hypersexual individuals in Sao Paulo, Brazil.

We decided to explore the frequency of cardiovascular risk factors, according to three levels of severity of compulsive sexual behavior (CSB), namely, non-sexually compulsive (1), sexually compulsive (2), and sexually compulsive, and hypersexual (3). We also investigated the impact of a psychiatric co-morbidity on the Framingham heart risk score (FRS). 94 non-sexually compulsive, 57 sexually compulsive, and 60 hypersexual individuals underwent psychiatric interview, blood collection, self-responsiveness, and anthropometric measurement. The analyses were repeated with individuals aged up to 44 and aged more than 44 years old. Regarding the total sample, we observed significant association among those sexually compulsive, and hypersexual participants with presenting the HIV serologic status, and a greater proportion of psychiatric conditions as much as the severity of CSB increases. Individuals with substance-related disorder predicted higher Framingham scores. The analyses with people aged more than 44 years old presented some different results, such as association among presenting low FRS and the sexually compulsive participants, and sexual compulsivity predicted lower scores of the Framingham. The study points out to the relevance of comprehensive psychiatric examination of whom presenting CSB and opens an avenue forward investigation of the effect of high rates of sexual activity on cardiovascular risk.

Comparison of high-sensitivity cardiac troponin I and T for the prediction of cardiac complications after non-cardiac surgery.

BACKGROUND: We aimed to directly compare preoperative high-sensitivity cardiac troponin (hs-cTn) I and T concentration for the prediction of major cardiac complications after non-cardiac surgery. METHODS: We measured hs-cTnI and hs-cTnT preoperatively in a blinded fashion in 1022 patients undergoing non-cardiac surgery. The primary endpoint was a composite of major cardiac complications including cardiac death, cardiac arrest, myocardial infarction, clinically relevant arrhythmias, and acute heart failure within 30 days. We hypothesized that the type of surgery may impact on the predictive accuracy of hs-cTnI/T and stratified all analyses according to the type of surgery. RESULTS: Major cardiac complications occurred in 108 (11%) patients, 58/243 (24%) patients undergoing vascular surgery and 50/779 (6%, P < .001) patients undergoing non-vascular surgery. Using regulatory-approved 99th percentile cut-off concentrations, preoperative hs-cTnI elevations were less than one-fifth as common as preoperative hs-cTnT elevations (P < .001). Among patients undergoing vascular surgery, preoperative hs-cTnI concentrations, but not hs-cTnT, was an independent predictor of cardiac complications (adjusted odds ratio (aOR) 1.5, 95% confidence interval (95% CI) 1.0-2.1). The area under the receiver-operating characteristics curve (AUC) was 0.67 (95% CI, 0.59-0.75) for hs-cTnI versus 0.59 (95% CI 0.51-0.67, P = .012) for hs-cTnT. In contrast, among patients undergoing non-vascular surgery both preoperative hs-cTnI and hs-cTnT were independent predictors of the primary endpoint (aOR 1.6, 95% CI 1.3-2.0, and aOR 3.0, 95% CI 2.0-4.6, respectively) and showed higher predictive accuracy (AUC 0.77, 95% CI, 0.71-0.83, and 0.79, 95% CI 0.73-0.85, P = ns). CONCLUSIONS: Preoperative hs-cTnI and hs-cTnT concentrations predict major cardiac complications after non-vascular surgery, while, in patients undergoing vascular surgery, hs-cTnI may have better accuracy.

Effects of clomiphene citrate on male obesity-associated hypogonadism: a randomized, double-blind, placebo-controlled study.

BACKGROUND: Obesity causes secondary hypogonadism (HG) in men. Standard testosterone (T) replacement therapy improves metabolic parameters but leads to infertility. OBJECTIVE: To evaluate clomiphene citrate (CC) treatment of adult men with male obesity-associated secondary hypogonadism (MOSH). DESIGN: Single-center, randomized, double-blind, placebo-controlled trial. PARTICIPANTS: Seventy-eight men aged 36.5 ± 7.8 years with a body mass index (BMI) > 30 kg/m2, total testosterone (TT) ≤ 300 ng/dL, and symptoms in the ADAM questionnaire. INTERVENTION: Random allocation to receive 50 mg CC or placebo (PLB) for 12 weeks. OUTCOMES: (1) Clinical features: ADAM and sexual behavior questionnaires; (2) hormonal profile: serum TT, free T, estradiol (E2), luteinizing hormone (LH), follicle-stimulating hormone (FSH), and sex hormone-binding globulin (SHBG); (3) body composition: BMI, waist circumference, and bioelectric impedance analysis; (4) metabolic profile: blood pressure, fasting blood glucose, HbA1c, insulin, HOMA-IR, and lipid profile; (5) endothelial function: flow-mediated dilation of the brachial artery, quantitative assessment of endothelial progenitor cells and serum sICAM-1, sVCAM-1, and selectin-sE levels; (6) safety aspects: hematocrit, serum prostate-specific antigen, International Prostate Symptom Score, and self-reported adverse effects. RESULTS: There was an improvement in one sexual complaint (weaker erections; P < 0.001); increases (P < 0.001) in TT, free T, E2, LH, FSH, and SHBG; and improvements in lean mass (P < 0.001), fat-free mass (P = 0.004), and muscle mass (P < 0.001) in the CC group. CC reduced HDL (P < 0.001). No statistically significant differences were seen in endothelial function. CONCLUSIONS: CC appeared to effectively improve the hormonal profile and body composition. CC may be an alternative treatment for MOSH in adult men.

Hypertension, mitral valve disease, atrial fibrillation and low education level predict delirium and worst outcome after cardiac surgery in older adults.

BACKGROUND: Delirium is a common complication after cardiac surgery in older adult patients. However, risk factors and the influence of delirium on patient outcomes are not well established. We aimed to determine the incidence, predisposing and triggering factors of delirium following cardiac surgery. METHODS: One hundred seventy-three consecutive patients aged ≥60 years were studied. Patients' characteristics and two cognitive function assessment tests were recorded preoperatively. Perioperative variables were blood transfusion, orotracheal intubation time (OIT), renal dysfunction, and hypoxemia. Delirium was assessed using the Confusion Assessment Method for the Intensive Care Unit. The composite outcome consisted of death, infection, and perioperative myocardial infarction until hospital discharge or 30 days after surgery, and for up to 18 months. RESULTS: One hundred six patients (61.27%) were men and the age was 69.5 ± 5.8 years. EuroSCORE II index was 4.06 ± 3.86. Hypertension was present in 75.14%, diabetes in 39.88%, and 30.06% were illiterate. Delirium occurred in 59 patients (34.1%). Education level (OR 0.81, 0.71-0.92), hypertension (OR 2.73, 1.16-6.40), and mitral valve disease (OR 2.93, 1.32-6.50) were independent predisposing factors for delirium, and atrial fibrillation after surgery (OR 2.49, 1.20-5.20) represented the potential triggering factor. Delirium (OR 2.35, 1.20-4.58) and OIT ≥ 900 min (OR 2.50; 1.30-4.80) were independently associated with the composite outcome. CONCLUSIONS: In older adult patients submitted to cardiac surgery, delirium is a frequent complication that is associated with worst outcome. Independent risk factors for delirium included education level, hypertension, mitral valve disease, and atrial fibrillation after cardiac surgery.

Prediction of major cardiac events after vascular surgery.

OBJECTIVE: Predicting cardiac events is essential to provide patients with the best medical care and to assess the risk-benefit ratio of surgical procedures. The aim of our study was to evaluate the performance of the Revised Cardiac Risk Index (Lee) and the Vascular Study Group of New England Cardiac Risk Index (VSG) scores for the prediction of major cardiac events in unselected patients undergoing arterial surgery and to determine whether the inclusion of additional risk factors improved their accuracy. METHODS: The study prospectively enrolled 954 consecutive patients undergoing arterial vascular surgery, and the Lee and VSG scores were calculated. Receiver operating characteristic curves for each cardiac risk score were constructed and the areas under the curve (AUCs) compared. Two logistic regression models were done to determine new variables related to the occurrence of major cardiac events (myocardial infarction, heart failure, arrhythmias, and cardiac arrest). RESULTS: Cardiac events occurred in 120 (12.6%) patients. Both scores underestimated the rate of cardiac events across all risk strata. The VSG score had AUC of 0.63 (95% confidence interval [CI], 0.58-0.68), which was higher than the AUC of the Lee score (0.58; 95% CI, 0.52-0.63; P = .03). Addition of preoperative anemia significantly improved the accuracy of the Lee score to an AUC of 0.61 (95% CI, 0.58-0.67; P = .002) but not that of the VSG score. CONCLUSIONS: The Lee and VSG scores have low accuracy and underestimate the risk of major perioperative cardiac events in unselected patients undergoing vascular surgery. The Lee score's accuracy can be increased by adding preoperative anemia. Underestimation of major cardiac complications may lead to incorrect risk-benefit assessments regarding the planned operation.

CTHRSSVVC Peptide as a Possible Early Molecular Imaging Target for Atherosclerosis.

The purpose of our work was to select phages displaying peptides capable of binding to vascular markers present in human atheroma, and validate their capacity to target the vascular markers in vitro and in low-density lipoprotein receptor knockout (LDLr(-/-)) mouse model of atherosclerosis. By peptide fingerprinting on human atherosclerotic tissues, we selected and isolated four different peptides sequences, which bind to atherosclerotic lesions and share significant similarity to known human proteins with prominent roles in atherosclerosis. The CTHRSSVVC-phage peptide displayed the strongest reactivity with human carotid atherosclerotic lesions (p < 0.05), when compared to tissues from normal carotid arteries. This peptide sequence shares similarity to a sequence present in the fifth scavenger receptor cysteine-rich (SRCR) domain of CD163, which appeared to bind to CD163, and subsequently, was internalized by macrophages. Moreover, the CTHRSSVVC-phage targets atherosclerotic lesions of a low-density lipoprotein receptor knockout (LDLr(-/-)) mouse model of atherosclerosis in vivo to High-Fat diet group versus Control group. Tetraazacyclododecane-1,4,7,10-tetraacetic acid-CTHRSSVVC peptide (DOTA-CTHRSSVVC) was synthesized and labeled with (111)InCl3 in >95% yield as determined by high performance liquid chromatography (HPLC), to validate the binding of the peptide in atherosclerotic plaque specimens. The results supported our hypothesis that CTHRSSVVC peptide has a remarkable sequence for the development of theranostics approaches in the treatment of atherosclerosis and other diseases.

Prognostic value of perioperative high sensitivity troponin in patients undergoing hip and knee arthroplasty.

The authors conducted a prospective observational study to investigate the prognostic value of high-sensitivity Troponin I (hs-TnI) in the short- and long-term periods after orthopedic surgery, including Total Hip and Knee Arthroplasty (THA and TKA, respectively), in a tertiary orthopedic center in Brazil. Perioperative Myocardial Injury (PMI) was defined as an absolute increase in hs-TnI of ≥ 26 ng/L above preoperative values. The primary endpoint was all-cause mortality assessed at 30 days and 18 months after surgery. The secondary endpoint consisted of a composite outcome: cardiovascular death, acute myocardial infarction, angina requiring revascularization, and/or stroke. The authors compared Relative Risks (RR) of all-cause mortality and composite outcomes in patients with or without PMI at 30 days and 18 months. A Cox proportional hazards model for long-term outcomes was calculated and adjusted for age > 70 years, gender, and Revised Cardiac Risk Index (RCRI) class ≥ 2. PMI occurred in 3.4 % of all surgeries. At 30-days, 6.6 % of patients with PMI had died versus none without PMI. At 18 months, 20.0 % of PMI versus 4.7 % without PMI had died (RR = 5.0; 95 % Confidence Interval [95 % CI 1.3-19.3]). Based on composite outcomes in short and long-term periods, the RRs were 16.2 (95 % CI 2.7-96.5) and 7.7 (95 % CI 2.2-26.6), respectively. PMI was associated with all-cause mortality after 18 months and increased risk for a composite outcome (Hazard Ratio [HR = 3.97], 95 % CI 1.13-13.89 and HR = 5.80, 95 % CI 1.93-17.45, respectively). Patients with PMI who underwent THA or TKA presented worse short- and long-term prognoses compared to those without PMI.

Aspirin responsiveness safely lowers perioperative cardiovascular risk.

INTRODUCTION: Vascular surgeries are related to high cardiac morbidity and mortality, and the maintenance of aspirin in the perioperative period has a protective effect. The purpose of this study was to evaluate the association between preoperative platelet aggregability and perioperative cardiovascular (CV) events. METHODS: A preoperative platelet aggregation test was performed on an impedance aggregometer in response to collagen and to arachidonic acid (AA) for 191 vascular surgery patients under chronic use of aspirin. We analyzed the following CV events: acute myocardial infarction, unstable angina, isolated troponin elevation, acute ischemic stroke, reoperation, and cardiac death. Hemorrhagic events were also evaluated and classified according to the Thrombolysis In Myocardial Infarction criteria. RESULTS: The incidence of CV events was 22% (n = 42). Higher platelet response to AA was associated with CV events, so that patients in the fourth quartile (higher than 11Ω) had almost twice the incidence of CV events when compared with the three lower quartiles: 35% vs 19%; P = .025. The independent predictors of CV events were hemodynamic instability during anesthesia (odds ratio [OR], 4.12; 95% confidence interval [CI], 1.87-9.06; P < .001), dyslipidemia (OR, 3.9; 95% CI, 1.32-11.51; P = .014), preoperative anemia (OR, 2.64; 95% CI, 1.19-5.85; P = .017), and AA platelet aggregability in the upper quartile (OR, 2.48; 95% CI, 1.07-5.76; P = .034). Platelet aggregability was not associated with hemorrhagic events, even when we compared the lowest quartile of AA platelet aggregability (0-1.00 Ω) with the three upper quartiles (>1.00 Ω; OR, 0.77; 95% CI, 0.43-1.37; P = .377). CONCLUSIONS: The degree of aspirin effect on platelet aggregability maybe important in the management of perioperative CV morbidity, without increment in the bleeding toll.

Impact of the period of the day on all-cause mortality and major cardiovascular complications after arterial vascular surgeries.

BACKGROUND: Conflicting results are reported about daytime variation on mortality and cardiac outcomes after non-cardiac surgeries. In this cohort study, we evaluate whether the period of the day in which surgeries are performed may influence all-cause mortality and cardiovascular outcomes in patients undergoing non-cardiac arterial vascular procedures. METHODS: 1,267 patients who underwent non-cardiac arterial vascular surgeries between 2012 and 2018 were prospectively included in our cohort and categorized into two groups: morning (7 a.m. to 12 a.m., 79%) and afternoon/night (12:01 p.m. to 6:59 a.m. in the next day, 21%) surgeries. Primary endpoint was all-cause mortality within 30 days and one year. Secondary endpoints were the incidence of perioperative myocardial injury/infarction (PMI), and the incidence of major adverse cardiac events (MACE, including acute myocardial infarction, acute heart failure, arrhythmias, cardiovascular death) at hospital discharge. RESULTS: After adjusting for confounders in the multivariable Cox proportional regression, all-cause mortality rates at 30 days and one year were higher among those who underwent surgery in the afternoon/night (aHR 1.6 [95%CI 1.1-2.3], P = 0.015 and aHR 1.7 [95%CI 1.3-2.2], P < 0.001, respectively). Afternoon/night patients had higher incidence of PMI (aHR 1.4 [95%CI 1.1-1.7], P < 0.001). There was no significant difference in the incidence of MACE (aHR 1.3 [95%CI 0.9-1.7], P = 0.074). CONCLUSIONS: In patients undergoing arterial vascular surgery, being operated in the afternoon/night was independently associated with increased all-cause mortality rates and incidence of perioperative myocardial injury/infarction.

Proteomics of high-density lipoprotein subfractions and subclinical atherosclerosis in type 1 diabetes mellitus: a case-control study.

BACKGROUND: Subclinical atherosclerosis is frequently observed in type 1 diabetes (T1D) although the mechanisms and markers involved in the evolution to established cardiovascular disease are not well known. High-density lipoprotein cholesterol in T1D is normal or even high, and changes in its functionality and proteomics are considered. Our aim was to evaluate the proteomics of HDL subfractions in T1D and control subjects and its association with clinical variables, subclinical atherosclerosis markers and HDL functionality. METHODS: A total of 50 individuals with T1D and 30 matched controls were included. Carotid-femoral pulse wave velocity (PWV), flow-mediated vasodilation (FMD), cardiovascular autonomic neuropathy (CAN), and ten-year cardiovascular risk (ASCVDR) were determined. Proteomics (parallel reaction monitoring) was determined in isolated HDL2 and HDL3 that were also utilized to measure cholesterol efflux from macrophages. RESULTS: Among 45 quantified proteins, 13 in HDL2 and 33 in HDL3 were differentially expressed in T1D and control subjects. Six proteins related to lipid metabolism, one to inflammatory acute phase, one to complement system and one to antioxidant response were more abundant in HDL2, while 14 lipid metabolism, three acute-phase, three antioxidants and one transport in HDL3 of T1D subjects. Three proteins (lipid metabolism, transport, and unknown function) were more abundant in HDL2; and ten (lipid metabolism, transport, protease inhibition), more abundant in HDL3 of controls. Individuals with T1D had higher PWV and ten-year ASCVDR, and lower FMD, Cholesterol efflux from macrophages was similar between T1D and controls. Proteins in HDL2 and HDL3, especially related to lipid metabolism, correlated with PWV, CAN, cholesterol efflux, HDLc, hypertension, glycemic control, ten-year ASCVDR, and statins use. CONCLUSION: HDL proteomics can be predictive of subclinical atherosclerosis in type 1 diabetes. Proteins that are not involved in reverse cholesterol transport may be associated with the protective role of HDL.

Acute heart failure after non-cardiac surgery: incidence, phenotypes, determinants and outcomes.

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.

Treatment with methotrexate inhibits atherogenesis in cholesterol-fed rabbits.

A decrease in the number of cardiovascular events in patients with rheumatoid arthritis or psoriasis treated with methotrexate (MTX) has been observed in the literature. The aim of this study was to test whether MTX could promote anti-inflammatory effects and reduce the atherosclerotic lesions in rabbits with atherosclerosis induced by cholesterol feeding. Twenty male New Zealand rabbits were fed a 1% cholesterol diet for 60 days. Starting from day 30 of cholesterol feeding, 10 animals were treated with 4 weekly intravenous injections of MTX (4 mg/kg) and 10 with 4 weekly saline solution injections for 30 days. MTX reduced the size of the lesion areas of cholesterol-fed animals by 75% and intima-media ratio 2-fold. The drug inhibited macrophage migration into the intima by 50% and the presence of apoptotic cells by 84% but did not inhibit the intimal proliferation of smooth muscle cells. MTX treatment also diminished the positive staining area of metalloproteinase 9 in the intima, which is probably beneficial. In the tumor necrosis factor-α-treated human umbilical vein endothelial cell line, incubation with MTX led to downregulation of 5 pro-inflammatory genes, TNF-α, VAP-1, IL-1ß, CXCL2, and TLR2, and upregulation of the anti-inflammatory TGF-ß1 gene, thus showing endothelium-protective properties. In conclusion, MTX showed direct in vivo anti-atherosclerotic action and may have potential in the treatment of this disorder.