Single or Combined Valve Surgery and Concomitant Right Coronary Artery Bypass through Right Anterior Minithoracotomy Approach.

BACKGROUND: Patients with combined valve and coronary artery disease are commonly performed by standard median sternotomy approach for coronary artery bypass grafting (CABG) and valve surgery. The purpose of this study is to describe our experience and show feasibility and safety of minimally invasive approach to single or combined valve pathology with single-vessel right coronary artery (RCA) disease, even if it is suitable to percutaneous coronary intervention. METHODS: This retrospective study comprised 28 consecutive patients who underwent single or combined valve surgery concomitant right CABG through right anterior minithoracotomy between February 2018 and December 2020. Preoperative evaluation, intraoperative, and postoperative outcomes were reviewed and analyzed. RESULTS: There were 12 men and 16 women. The mean age was 71.46 ± 6.82 years. Ten patients were in New York Heart Association class III or IV. The mean cardiopulmonary bypass and aortic cross-clamping times were 117.6 ± 21.3 and 98.1 ± 22.6 minutes, respectively. The mean time to extubation was 9.7 ± 5.6 hours, the mean intensive care unit stay was 37.4 ± 14.6 hours, and the mean hospital stay was 6.9 ± 3.2 days. There was one patient who underwent reoperation for bleeding. There were no instances of postoperative stroke, myocardial infarction, renal failure, or wound infection. The mean follow-up was 19 ± 2.4 months. CONCLUSION: Presence of RCA lesion is not a contraindication for minimally invasive approach in cases who underwent single or combined valve surgery. Combined valve surgery and right CABG via right anterior minithoracotomy are a safe and feasible option to standard median sternotomy surgery, even if RCA lesions seem suitable for stenting.

Multiple Valve Implantation Through a Minimally Invasive Approach: Comparison of Standard Median Sternotomy and Right Anterior Thoracotomy.

BACKGROUND: Following developments in the area of minimally invasive surgery and good, recently published surgical results, the areas in which minimally invasive surgery can be used are beginning to expand. This study aimed to describe experience and show the feasibility and safety of minimally invasive multiple valve implantation with right anterior minithoracotomy (RAT) and compare the outcomes with cases that underwent multiple valve surgery via a standard median sternotomy. METHODS: The study cohort comprised 52 patients with combined valvular disease who underwent aortic valve replacement and mitral valve replacement or repair, and/or tricuspid valve ring annuloplasty through median sternotomy (control group n=32) or minimally invasive surgery through a RAT (study group n=20) between January 2012 and December 2018 at the current centre. Preoperative evaluation included coronary catheterisation and multisliced computerised tomography in all patients. Postoperative clinical outcomes and haemodynamic performance of heart valves were reviewed. RESULTS: The mean age of patients was 72.6±7.1 years, and 50% were male. Seventeen (17) patients (32.6%) were in New York Heart Association functional class III or IV. Three (3) patients (7.6%) had third-degree atrioventricular block requiring permanent pacemaker implantation. Mean follow-up was 21±3.9 months (maximum 26 months). No major paravalvular leakage occurred, and there was no postoperative valve migration in either group. Non-valve-related deaths occurred in five patients during follow-up. CONCLUSION: This study showed that minimally invasive multiple valve implantation is a technically feasible and safe procedure with acceptable surgical outcomes and similar postoperative quality when compared with median sternotomy.

Percutaneous transapical approach and transcatheter closure for ventricular tachycardia ablation.

In patients with mechanical aortic and mitral valve prosthesis, left ventricular endocardial ablation via retrograde transaortic or antegrade transmitral approach carry high risk of catheter entrapment and death. In such cases, ablation can be performed via ventricular transseptal or transapical approach. Transapical approach, with the ease of catheter maneuverability and better endocardial contact, may be performed surgically or percutaneously. In this case report, we describe a patient with both aortic and mitral mechanical prosthesis who underwent ventricular tachycardia ablation via percutaneous transapical endocardial approach with the use of closure device.

Evaluation of the Role of Oxidative Stress in Degenerative Aortic Stenosis.

BACKGROUND AND AIM OF THE STUDY: Calcific and degenerative aortic diseases (CDADs) are a group of disorders that mostly affect the elderly population and may progress and warrant aortic valve replacement. It is believed that oxidative stress plays a role in the progression of the diseases. Several markers of oxidative stress were evaluated in a small cohort of patients with CDADs, and a control group with similar characteristics. METHODS: Thirty patients with aortic stenosis (AS) and 30 healthy subjects were included in the study. The activities of superoxide dismutase (SOD), glutathione peroxidase (GSH-Px) and catalase (CAT) in both groups were studied as markers of oxidative stress. All patients and control subjects were evaluated echocardiographically for CDAD, and enzyme levels monitored biochemically. RESULTS: The risk factors were similar in both groups, but levels of low-density lipoprotein (LDL) were higher in the CDAD group compared to controls (123.6 +/- 37.0 mg/dl versus 99.3 +/- 38.0 mg/dl, p < 0.01). The GSH-Px activity was significantly higher in the CDAD group than in controls (0.19 +/- 0.03 IU/ml versus 0.16 +/- 0.03 IU/ml, p < 0.01). A GSH-Px level > 0.18 IU/ml was found to be an indicator of CDAD, with a sensitivity of 70% and specificity of 73.3% on ROC analysis [AUC = 0.721, p < 0.05, 95% CI: 0.685 +/- 0.773]. SOD and CAT activities were similar in both groups (p > 0.05). CONCLUSION: The study results showed that the activity of GSH-Px, a marker of oxidative stress, is increased in patients with degenerative AS. The increase in GSH-Px activity may be a protective response to remove reactive oxygen derivatives (RODs) from the body.

Infective endocarditis related to a coronary artery fistula with an unusual localization and ectatic coronary arteries.

Coronary artery fistulas (CAF) are a rare cardiac anomaly that can be either congenital or acquired. CAFs have clinical significance because of complications such as dyspnea on exertion, congestive heart failure, and cardiac tamponade. The literature also contains case reports of CAF presenting as bacterial endocarditis. We describe a 31-year-old man who presented with native valve infective endocarditis related to an unusual form of a CAF between the circumflex coronary artery and left ventricle. He also had giant coronary arteries, which were imaged with computed tomography angiography and transesophageal echocardiography. The diameter of the circumflex coronary artery and left main coronary artery was measured as 19 mm. Surgical intervention for heart valves was performed because of vegetations resistant to continued antibiotic treatment. At the same time, the CAF was treated with surgery.

Measurement of Uncertainty in Prediction of No-Reflow Phenomenon after Primary Percutaneous Coronary Intervention Using Systemic Immune Inflammation Index: The Gray Zone Approach.

Systemic immune-inflammation index (SII), which is a good predictive marker for coronary artery disease, can be calculated by using platelet, neutrophil, and lymphocyte counts. The no-reflow occurrence can also be predicted using the SII. The aim of this study is to reveal the uncertainty of SII for diagnosing ST-elevation myocardial infarction (STEMI) patients who were admitted for primary percutaneous coronary intervention (PCI) for the no-reflow phenomenon. A total of 510 consecutive acute (STEMI) patients with primary PCI were reviewed and included retrospectively. For diagnostic tests which are not a gold standard, there is always an overlap between the results of patients with and without a certain disease. In the literature, for quantitative diagnostic tests where the diagnosis is not certain, two approaches have been proposed, named "grey zone" and "uncertain interval". The uncertain area of the SII, which is given the general term "gray zone" in this article, was constructed and its results were compared with the "grey zone" and "uncertain interval" approaches. The lower and upper limits of the gray zone were found to be 611.504-1790.827 and 1186.576-1565.088 for the grey zone and uncertain interval approaches, respectively. A higher number of patients inside the gray zone and higher performance outside the gray zone were found for the grey zone approach. One should be aware of the differences between the two approaches when making a decision. The patients who were in this gray zone should be observed carefully for detection of the no-reflow phenomenon.

GLP-1 Receptor Agonists and SGLT-2 Inhibitors in Patients With Versus Without Cardiovascular Disease: A Systematic Review, Meta-analysis, and Trial Sequential Analysis.

Glucagon-like peptide-1 receptor agonists (GLP1Ra) and sodium-glucose co-transporter-2 inhibitors (SGLT2i) reduce major adverse cardiovascular events (MACE). We assessed whether the effect differs in patients with and without cardiovascular (CV) disease, and rated the certainty of evidence by conducting a systematic review, meta-analysis, and trial sequential analysis of randomized controlled trials. Certainty of the evidence (CoE) was rated using the Grading of Recommendations, Assessment, Development, and Evaluation guidelines. The reduction in the risk of MACE was significant for both medications (high CoE), and the effect was similar in patients with and without CV disease (moderate CoE). GLP1Ra and SGLT2i reduced the risk of CV death (with high and moderate CoE, respectively), and the effects were consistent in the subgroups, but with very low CoE. While SGLT2i reduced the risk of fatal or non-fatal MI with a consistent effect in the subgroups, GLP1Ra reduced the risk of fatal or non-fatal stroke (with high CoE). In conclusion, GLP1Ra and SGLT2 inhibitors reduce the MACE to a similar extent in patients with and without CV disease, but have a differential effect on the reduction of fatal or non-fatal MI and stroke.

Relationship Between Work Mode, Time of Admission, and Mortality in St-Segment Elevation Myocardial Infarction: Results From the TURKMI Registry.

Treatment of acute myocardial infarction has evolved steadily. However, limited studies exist regarding the effect of all innovations on mortality. We aimed to investigate the effect of time of admission and work mode on 1-year outcomes in patients presenting with ST-segment elevation myocardial infarction (STEMI). Based on the TURKMI registry, we analyzed 735 STEMI patients recruited consecutively and prospectively from 50 PCI-capable cardiology clinics within a prespecified two-week period. Centers were categorized as "on-call" and "on-duty" according to their work mode. At 1-year follow-up, all-cause mortality and cardiovascular mortality were the primary outcomes. The secondary outcome was a composite of coronary revascularization, re-infarction/stroke, and recurrent angina. One-fifth of the participants (19.5%) were treated in the on-call group. All-cause mortality (7.9 vs 10.5%, aHR: 1.16, P = .650) and cardiovascular mortality rates (6.1 vs 9.1%, aHR: 1.35, P = .413) were similar between centers' modes of work. Likewise, both groups were equally likely to undergo coronary revascularization (P = .278), re-MI/stroke (P = .280), recurrent angina (P = .175), and the composite outcome of these components (P = .482). No significant difference was observed in primary outcomes between weekend and weekday admissions. In conclusion, we observed similar outcomes between the on-call and on-duty groups among STEMI patients.

Risk Factors, Use of Preventive Drugs, and Cardiovascular Events in Diabetes Mellitus: The PURE Türkiye Cohort.

BACKGROUND: The risk of cardiovascular disease is correlated with the frequency and control of associated risk factors in diabetes mellitus and may vary according to country. We evaluated risk factors for cardiovascular disease, cardiovascular events, and the use of preventive medications in patients with diabetes mellitus using the Prospective Urban and Rural Epidemiological Türkiye cohort. METHODS: Patients with diabetes mellitus versus without diabetes mellitus were compared for risk factors, cardioprotective drugs (angiotensin-converting enzyme inhibitors or angiotensin-II receptor antagonists, statins, and antiplatelets), and cardiovascular events. The primary outcome was major cardiovascular events (composite of cardiovascular death, myocardial infarction, stroke, or heart failure). RESULTS: Among 4041 participants, 549 (13.6%) had diabetes mellitus. The mean age (54.8 ± 8.4 vs. 49.3 ± 9.0 years, P <.001) and proportion of women (65.4% vs. 59.9%, P =.014) were higher in diabetics compared with non-diabetics. Hypertension, history of coronary heart disease, and use of statin, antiplatelets, and angiotensin-converting enzyme inhibitors or angiotensin-II receptor antagonists were more common in diabetics; however, the use of these medications at baseline was lower than optimal even in patients with diabetes mellitus and concomitant coronary heart disease (statin 31.2%, antiplatelets 46.9%, and angiotensin-converting enzyme inhibitors or angiotensin-II receptor antagonists 54.7%). During 11.5 years of follow-up, major cardiovascular events occurred in 288 (7.1%) patients, and the risk was higher in diabetics [hazard ratio (95% confidence interval) 1.71 (1.30-2.24); P <.001]. The increase in the risk of future events was comparable for those with diabetes mellitus alone without cardiovascular disease [hazard ratio 1.62 (1.20-2.20)] versus those with cardiovascular disease alone without diabetes mellitus [hazard ratio 1.31 (0.83-2.07)] and was additive in those with both conditions [hazard ratio 2.79 (1.65-4.69)]. The risk of major coronary events (myocardial infarction, angina, percutaneous, or surgical coronary intervention) was also higher in diabetes mellitus [hazard ratio 1.64 (1.26-2.15); P <.001]. CONCLUSION: Patients with diabetes mellitus have a higher risk of major cardiovascular events, and the risk is comparable to that observed in those with cardiovascular disease but no diabetes mellitus. The use of preventive medicines for cardiovascular diseases is disturbingly low in diabetics.

Intracoronary versus intravenous high-dose bolus plus maintenance administration of tirofiban in patients undergoing primary percutaneous coronary intervention for acute ST elevation myocardial infarction.

We aimed to examine whether intracoronary high-dose bolus of tirofiban plus maintenance would result in improved clinical outcome in STEMI patients undergoing primary PCI in this pilot trial. A total of 56 patients were enrolled to receive either intracoronary high-dose bolus plus maintenance (n = 34) or intravenous high-dose bolus plus maintenance (n = 22) of tirofiban. Pre and post intervention TIMI flow grades, myocardial blush grades, peak CKMB and troponin levels, time to peak CKMB and troponin, time to 50% ST resolution and major composite adverse cardiac event rates at 30 days were recorded. Although incidence of major adverse cardiac events was not different, post intervention TIMI flow and TIMI blush grades, peak CKMB and troponin levels, and time to peak CKMB and time to peak troponin were significantly different, favoring intracoronary strategy. In conclusion, this regimen improved myocardial reperfusion and coronary flow, and reduced myocardial necrosis, but failed to improve clinical outcomes at 30 days.

Effect of hypertension on coronary remodeling patterns in angiographically normal or minimally atherosclerotic coronary arteries: an intravascular ultrasound study.

Whether there is any particular role of hypertension in remodeling process has not been completely understood yet. The aim of this study was to assess the association between hypertension and remodeling patterns in normal or minimally atherosclerotic coronary arteries. Seventy-nine patients who were free of significant coronary atherosclerosis were divided into two groups according to the absence (n = 39) or presence (n = 40) of hypertension; and standard intravascular ultrasound examination was performed in 145 segments. To determine the remodeling pattern in early atherosclerotic process, patients were also analyzed according to the level of plaque burden at the lesion site after the analysis of remodeling patterns. Positive remodeling was more prevalent in the hypertensive group (52.5% vs. 12.8%; P < .001) whereas negative remodeling was more common in diabetic patients (53.6% vs. 27.4%; P = .03). Mean remodeling index was 1.04 for hypertensives and 0.96 for normotensives (P = .03). There were no correlations between remodeling patterns and other risk factors such as age, family history, and hypercholesterolemia. Early atherosclerotic lesions (< 30%) exhibited more negative remodeling characteristics while intermediate pattern was observed more frequently in patients with high plaque burden (P = .006 and .02, respectively). Positive remodeling showed no association in this context (P = .07). This study demonstrated that minimal atherosclerotic lesions in hypertensives had a tendency for compensatory arterial enlargement. Positive remodeling may result from local adaptive processes within vessel wall or hemodynamic effects of blood pressure itself.

Clinical Presentation and Outcomes in Real-Life Management of Elderly Patients Aged ≥75 Years Presenting with Acute Myocardial Infarction.

BACKGROUND: The aim of this study was to provide insight into the real-life clinical presentation and outcomes of the elderly presenting with acute myocardial infarction from the Turkish Myocardial Infarction registry database. METHODS: TURKMI was a nationwide, multicenter, observational, 15-day snapshot registry conducted to address the management of acute myocardial infarction patients admitted to percutaneous intervention-capable hospitals. The present analysis included the comparison of consecutively enrolled acute myocardial infarction patients aged ≥75 and <75 years. RESULTS: Of the overall 1930 patients, 362 patients were aged ≥75 years. Elderly patients were more likely to have hypertension and renal failure and less likely to have hypercholesterolemia. Elderly patients were admitted to hospitals almost 1 hour later mainly due to a late call to emergency medical service. At discharge, medical therapies were significantly less prescribed to the elderly. The proportion of patients undergoing coronary angiography was significantly lower in elderly (81.8% vs. 96.4%, P < .001). Both in-hospital and 1-year mortality were significantly higher in elderly patients (9.1% vs. 2.7% and 22.7% vs. 5.8%, P < .001 respectively). The adjusted risk of 1-year mortality was 4-fold in elderly (hazard ratio and 95% CI 4.0 [2.9-5.6], P < .001). In multivariate analysis, every 5-beat/min increase in heart rate increased mortality by 7%. Higher heart rate and use of antiplatelet agents on admission were predictors of mortality in elderly. CONCLUSION: In real-life settings, elderly patients presenting with acute myocardial infarction are prone to prolonged total ischemic time and are subjected to less-intensive medical treatment and interventional approaches. Besides age, the increased heart rate could be the major determinant of mortality.

Agreement between visually estimated left ventricular ejection fraction on echocardiography and quantitative measurements using cardiac magnetic resonance.

OBJECTIVE: Visual estimation of left ventricular ejection fraction (LVEF) is still used in routine clinical practice. However, most of the studies evaluating the agreement between the visually estimated LVEF (ve-LVEF) and quantitatively measured LVEF (qm-LVEF) either have not used appropriate statistical methods or gold standard imaging modality. In this study, we aimed to assess the agreement between the ve-LVEF and qm-LVEF using contemporary statistical methods and cardiac magnetic resonance imaging (CMRI). METHODS: In 54 subjects who underwent 1.5-T CMRI, echocardiographic images were recorded after the CMRI procedure on the same day. Two independent observers estimated ve-LVEFs on echocardiographic records in a random and blinded fashion, and qm-LVEF was obtained by CMRI. Agreement between the ve-LVEF and qm-LVEF values and intra/interobserver ve-LVEF estimations were assessed using intraclass correlation coefficient (ICC), Bland-Altman analysis, and kappa statistics. RESULTS: There was a high agreement between the ve-LVEF and qm-LVEF (ICC 0.93, 95% confidence interval 0.88-0.96). Bland-Altman analysis also demonstrated a good agreement between ve-LVEF and qm-LVEF with ve-LVEF, on average, being 0.6% lower than that obtained by CMRI (mean -0.6, limits of agreement -10.5 and +9.3). A good agreement was also observed for LVEF categories ≤35%, 36%-54%, and ≥55% (unweighted kappa 0.71, linearly weighted kappa 0.76); and LVEF of <55% and ≥55% (kappa 0.80). Intra/inter observer agreement was good for ve-LVEFs (ICC value 0.96 and 0.91, respectively). CONCLUSION: Visual approach for LVEF assessment may be used for rapid assessment of left ventricular systolic function in clinical practice, particularly in patients with good image quality.

Comparison of Biochemical Markers and Echocardiographic Parameters in the Diagnosis of Prosthetic Valve and Intracardiac Device Endocarditis.

BACKGROUND: The use of prosthetic valves and intracardiac devices has steadily increased in recent years. In this group of patients with prosthetic valves or intracardiac devices, infective endocarditis could not be easily diagnosed, and in general, infective endocar- ditis can be missed in many patients. The purpose of this study was to evaluate the diag- nostic performance of clinical, laboratory, and imaging parameters in a group of patients with pre-diagnosis of infective endocarditis. METHODS: Ninety-four patients diagnosed with prosthetic valve or intracardiac device endocarditis during 2008-2019 were included in the study. The patients' data were evalu-ated according to modified Duke criteria, and the data of the patients who were diag- nosed with and without a definitive infective endocarditis were compared accordingly. RESULTS: Values of procalcitonin (P < .001), leukocytes (P=.004), C-reactive protein (P < .001), sedimentation (P < .001), and maximal vegetation size (P = .012) were found to be significant in the diagnosis of IE. Criteria to determine definitive IE included a C-reactive protein level of 105 mg/dL or higher, 77% sensitivity, 75% specificity, 60% positive predic- tive value, and 87% negative predictive value. In particular, a C-reactive protein level of ≥105 mg/dL was found to positively indicate the diagnosis of definitive infective endocar- ditis by 10 times (odds ratio = 10; 95% CI: 3.6-27.8, P < .001). In a multiple logistic regression analysis, the C-reactive protein level was found to be the best independent predictor of definitive infective endocarditis in this population. CONCLUSION: In cases of prosthetic valve and intracardiac devices endocarditis where pre- diagnosis is difficult to confirm, measuring C-reactive protein levels is a reliable, strong, and simple parameter for definitive infective endocarditis diagnosis.

The Role of Non-Vitamin K Antagonist Oral Anticoagulants (NOACs) in Atrial Fibrillation: Treatment Management Based on Patient and Drug Characteristics.

Data from Turkey revealed that atrial fibrillation patient percentage under adequate anti- coagulation in Turkey is less than that in other countries due to multiple parameters such as treatment adherence problems, failure to follow guideline recommendations, negative perspective on the use of new drugs, drug costs, and payment conditions. The aim of this article is to provide physicians with a compiled resource that focuses on the differences between non-vitamin K antagonist oral anticoagulants and heterogeneity of atrial fibrilla- tion patients by reviewing the global and national data from a multidisciplinary perspective and provide guidance on the choice of non-vitamin K antagonist oral anticoagulants in atrial fibrillation patients. A gastroenterologist, 2 neurologists, and 11 cardiologists from university and training and research hospitals in Turkey who are experienced in atrial fibrillation and non-vitamin K antagonist oral anticoagulant treatments gathered in 3 separate meetings to identify the review topics and evaluate the outcomes of the systematic literature search. Based on the pharmacological characteristics, clinical studies, and real-world data compari- sons, it has been revealed that non-vitamin K antagonist oral anticoagulants are not similar. Thromboembolism and bleeding risks, renal and hepatic functions, coexisting conditions, and concomitant drug usage have been shown to affect the levels of benefits gained from non-vitamin K antagonist oral anticoagulant in atrial fibrillation patients. Although Turkish patients with atrial fibrillation have been observed to be younger, they are more likely to have coexisting cardiovascular conditions compared to the atrial fibrillation patients in other countries. Selection of an appropriate non-vitamin K antagonist oral anticoagulant in line with the available evidence and recent guidelines will provide substantial benefits to atrial fibrillation patients.

Lipid Modification to Reduce Cardiovascular Risk in Secondary Prevention Patients with Special Emphasis on PCSK9 Inhibitor Requirement: An Analysis Based on Delphi Panel Approach.

OBJECTIVE: The aim of this study is to analyze the low-density lipoprotein cholesterol-lowering therapies in secondary prevention patients by analyzing their plasma low-density lipoprotein cholesterol levels, current treatment, considering their inadequate response to medications (as defined in current guidelines), and the requirement for a protein convertase subtilisin/kexin type 9 inhibitor. METHODS: Delphi panel is used to seek expert consensus of experienced 12 cardiologists. A questionnaire consisting of 6 main questions is used to reflect the opinion of the expert panelists on the practices of low-density lipoprotein cholesterol-lowering therapies of patients with high and very high cardiovascular risk. Patients with atherosclerotic cardiovascular disease are covered in this present analysis. RESULTS: According to expert opinion data, 18.6% of the patient population with atherosclerotic cardiovascular disease is estimated to have experienced recurrent vascular events. The current treatment of the patient population is 39.7% on high dose, 36.9% on low/moderate dose of statin, 13.1% on maximum tolerated dose statin+ezetimibe, and 1.2% on maximum tolerated dose statin+ezetimibe+protein convertase subtilisin/kexin type 9 inhibitor. The percentage of atherosclerotic cardiovascular disease patients with inadequate treatment response is estimated to be 20.2% in those using "maximum tolerated dose statin+ezetimibe." The proportion of patients who will need to be treated with a protein convertase subtilisin/kexin type 9 inhibitor increases as their low-density lipoprotein cholesterol levels rises from 9.1% in 70-99 mg/dL to 50.8% in ≥160 mg/dL for these patients. CONCLUSION: According to expert opinion, although a substantial proportion of patients with secondary prevention have not achieved low-density lipoprotein cholesterol goals, the use of protein convertase subtilisin/kexin type 9 inhibitors is very low. Since the questionnaire subject to panel discussion did not include any question elaborating the issue, the discrepancy between the recommendation of the related guidelines and Turkish practice needs further studies for the explanation.

INTERBLEED: Design of an International Study of Risk Factors for Gastrointestinal Bleeding and Cardiovascular Events After Gastrointestinal Bleeding.

Background: Bleeding is the most common adverse event in those with cardiovascular (CV) disease receiving antithrombotic therapy, and it most commonly occurs in the gastrointestinal (GI) tract. Clinicians often dismiss bleeding as an adverse event that is reversible with effective antithrombotic therapy, but bleeding is associated with substantial morbidity and mortality, most likely mediated through an increased risk of CV events. Reducing the burden of bleeding requires knowledge of the potentially modifiable risk factors for bleeding and the potentially modifiable risk factors for adverse outcomes after bleeding. Methods: INTERBLEED is an international, multicentre, 2-component, observational study, with an incident case-control study examining the risk factors for GI bleeding, and a prospective cohort study of risk factors for CV events after GI bleeding. Cases either have CV disease and present to the hospital with GI bleeding or develop GI bleeding during hospitalization. Controls have CV disease, but no history of GI bleeding. We use a questionnaire to obtain detailed information on known and potential risk factors for GI bleeding and for CV events and outcomes after bleeding. We obtain CV and anthropometric measurements, perform functional and cognitive assessments, and follow participants at 3 months and 12 months. Results: As of April 1, 2022, the study is ongoing in 10 countries at 31 centres and has recruited 2407 cases and 1478 controls. Conclusions: Knowledge of risk factors for bleeding, and risk factors for CV events and functional decline after bleeding, will help develop strategies to prevent bleeding and subsequent complications.

Contexte: L'hémorragie est l'effet indésirable le plus fréquent chez les patients atteints de maladies cardiovasculaires (CV) qui reçoivent un traitement antithrombotique, et elle survient le plus souvent dans le tractus gastro-intestinal (GI). Les cliniciens considèrent souvent l'hémorragie comme une simple manifestation indésirable réversible par un traitement antithrombotique efficace, mais une morbidité et une mortalité considérables y sont associées, probablement en raison d'un risque accru d'événements CV. Une réduction du fardeau de l'hémorragie nécessite une connaissance des facteurs de risque potentiellement modifiables tant de l'hémorragie que des événements indésirables qui surviennent après l'hémorragie. Méthodologie: INTERBLEED est une étude internationale, observationnelle et multicentrique à deux volets; le premier volet est une étude cas-témoins incidents visant à examiner les facteurs de risque d'hémorragie GI, alors que le second volet est une étude de cohorte prospective visant à examiner les facteurs de risque d'événements CV après une hémorragie GI. Les cas sont des patients atteints de maladies CV qui consultent les services hospitaliers pour une hémorragie GI ou qui présentent une hémorragie GI en cours d'hospitalisation. Les témoins sont des patients atteints de maladies CV, mais sans antécédents d'hémorragie GI. Un questionnaire est utilisé pour obtenir des renseignements détaillés au sujet de facteurs de risque connus et potentiels d'hémorragie GI et d'événements CV et d'autres résultats de santé après une hémorragie. Des mesures cardiovasculaires et anthropométriques ainsi que des évaluations fonctionnelles et cognitives sont réalisées, et les participants sont revus après trois mois et 12 mois. Résultats: En date du 1er avril 2022, l'étude est en cours dans 10 pays et 31 établissements de santé; 2 407 cas et 1 478 témoins ont été recrutés. Conclusions: La connaissance des facteurs de risque d'hémorragie, ainsi que des facteurs de risque d'événements CV et de déclin fonctionnel à la suite d'une hémorragie, aidera à mettre en place des stratégies pour prévenir les hémorragies et les complications qui peuvent en découler.

Evaluation of acute infection-induced endothelial dysfunction and its potential mediators.

OBJECTIVES: Inflammation plays an important role in the pathophysiology of atherosclerosis. Some studies suggest a link between chronic infections, an inflammatory state, and endothelial dysfunction. However, data related to acute infections are scant. We have investigated: (i) the effect of acute infection on endothelial function; (ii) the role of potential mediators of endothelial dysfunction. METHODS: Forty patients 40 years old with acute infection (mean age 53.9 +/- 8.8 years), without coronary artery disease or its equivalents were enrolled. Endothelial function and blood levels of high sensitive C-reactive protein, interleukin-6, tumour necrosis factor-a, high-density lipoprotein cholesterol (HDL), low-density lipoprotein cholesterol (LDL), apolipoprotein-A1 (Apo-A1) and apolipoprotein-B100 (Apo-B100) were assessed in the acute infection phase and 1 month after recovery. Endothelial function was evaluated by brachial artery flow-mediated vasodilation (FMD). RESULTS: The intraclass correlation coefficients for intra- and interobserver agreement for FMD measurements were 0.98 (95% CI: 0.95-0.99) and 0.93 (95% CI: 0.83-0.97), respectively. FMD improved significantly 1 month after recovery (P < 0.001). Compared to the levels at 1 month, inflammatory markers, LDL cholesterol, LDL/HDL ratio, Apo-B100 and Apo-B100/Apo-A1 ratio were significantly higher. However, HDL and apo-A1 were significantly lower in the phase of acute infection. Change in FMD from baseline to 1 month after recovery correlated significantly only with the change in Apo-A1 (r = 0.35, P = 0.027). CONCLUSIONS: Acute infection causes transient endothelial dysfunction. It increases inflammatory markers and generates an atherogenic lipid profile. Among the parameters evaluated, only the change in Apo-A1 level was associated with acute infection-induced endothelial dysfunction.

An updated perspective and pooled analysis of cardiovascular outcome trials of GLP-1 receptor agonists and SGLT-2 inhibitors.

Glucagon-like peptide-1 (GLP-1) receptor agonists and sodium-glucose co-transporter-2 (SGLT-2) inhibitors reduce major cardiovascular (CV) events in patients with type 2 diabetes mellitus. In this review, we assessed the CV outcome trials of GLP-1 receptor agonists and SGLT-2 inhibitors in terms of their methodological properties and results, and also, using a meta-analytic approach, we calculated and interpreted the pooled analyses. A systematic PubMed search was conducted for CV outcome studies of GLP-1 receptor agonists and SGLT-2 inhibitors with the main outcome of three-point major adverse cardiovascular events (MACE), which is the composite of CV death, non-fatal myocardial infarction (MI), and non-fatal stroke. We pooled the results of each outcome for each group of medications using a fixed effect model. Also, the results of two studies of SGLT-2 inhibitors conducted in patients with heart failure were discussed briefly. We found 12 eligible studies, 7 with GLP-1 agonists (n=56,004) and 5 with SGLT-2 inhibitors (n=46,969). All of the drugs analyzed were non-inferior, and some superior, to placebo in terms of three-point MACE. Pooled analyses demonstrated that GLP-1 receptor agonists, especially those having structural homology for human GLP-1 receptor, and SGLT-2 inhibitors reduced the risk of three-point MACE (by 12% and 10%, respectively), CV mortality (12% and 15%), total mortality (12% and 13%), and to a lesser extent, fatal or non-fatal MI (8% and 9%). While GLP-1 receptor agonists reduced the risk of ischemic stroke by 15%, SGLT-2 inhibitors decreased the risk of hospitalization for heart failure by 32%. GLP-1 agonists and SGLT-2 inhibitors reduced the risk of MACE in patients with type 2 diabetes with established CV disease or those with high risk for CV disease. Also, SGLT-2 inhibitors reduced the risk of hospitalization for heart failure independent of the diabetes status.