Attainment of LDL-Cholesterol Goals in Patients with Previous Myocardial Infarction: A Real-World Cross-Sectional Analysis. / Atingimento das Metas de Colesterol LDL em Pacientes com Histórico de Infarto Agudo do Miocárdio: Estudo Transversal do Mundo Real.

BACKGROUND: The European Society of Cardiology guidelines recommend an LDL-cholesterol (LDL-C) < 55 mg/dL for patients with established cardiovascular disease. While the Friedewald equation to estimate LDL-C is still widely used, the newer Martin-Hopkins equation has shown greater accuracy. OBJECTIVES: We aimed to assess: A) the proportion of patients reaching LDL-C goal and the therapies used in a tertiary center; B) the impact of using the Martin-Hopkins method instead of Friedewald's on the proportion of controlled patients. METHODS: A single-center cross-sectional study including consecutive post-myocardial infarction patients followed by 20 cardiologists in a tertiary hospital. Data was collected retrospectively from clinical appointments that took place after April 2022. For each patient, the LDL-C levels and attainment of goals were estimated from an ambulatory lipid profile using both Friedewald and Martin-Hopkins equations. A two-tailed p-value of < 0.05 was considered statistically significant for all tests. RESULTS: Overall, 400 patients were included (aged 67 ± 13 years, 77% male). Using Friedewald's equation, the median LDL-C under therapy was 64 (50-81) mg/dL, and 31% had LDL-C within goals. High-intensity statins were used in 64% of patients, 37% were on ezetimibe, and 0.5% were under PCSK9 inhibitors. Combination therapy of high-intensity statin + ezetimibe was used in 102 patients (26%). Applying the Martin-Hopkins method would reclassify a total of 31 patients (7.8%). Among those deemed controlled by Friedewald's equation, 27 (21.6%) would have a Martin-Hopkins' LDL-C above goals. CONCLUSIONS: Less than one-third of post-myocardial infarction patients had LDL-C within the goal. Applying the Martin-Hopkins equation would reclassify one-fifth of presumably controlled patients into the non-controlled group.

FUNDAMENTO: As diretrizes da Sociedade Europeia de Cardiologia recomendam um nível de colesterol LDL (LDL-C) < 55 mg/dL para pacientes com doença cardiovascular estabelecida. Embora a fórmula de Friedewald ainda seja amplamente utilizada para estimar o LDL-C, a fórmula mais recente de Martin-Hopkins mostrou maior precisão. OBJETIVOS: Nosso objetivo foi avaliar: A) a proporção de pacientes que atingiram a meta de LDL-C e as terapias utilizadas em um centro terciário; B) o impacto da utilização do método de Martin-Hopkins em vez do método de Friedewald na proporção de pacientes controlados. MÉTODOS: Estudo transversal monocêntrico, incluindo pacientes consecutivos pós-infarto do miocárdio, acompanhados por 20 cardiologistas, em um hospital terciário. Os dados foram coletados retrospectivamente de consultas clínicas realizadas após abril de 2022. Para cada paciente, os níveis de LDL-C e o atingimento das metas foram estimados a partir de um perfil lipídico ambulatorial, utilizando as fórmulas de Friedewald e Martin-Hopkins. Um valor-p bicaudal < 0,05 foi considerado estatisticamente significativo para todos os testes. RESULTADOS: Foram incluídos 400 pacientes (com 67 ± 13 anos, 77% do sexo masculino). Utilizando a fórmula de Friedewald, a mediana de LDL-C sob terapia foi de 64 (50-81) mg/dL, e 31% tinham LDL-C dentro da meta. Estatinas de alta intensidade foram usadas em 64% dos pacientes, 37% estavam em uso de ezetimiba e 0,5% estavam em uso de inibidores de PCSK9. A terapia combinada de estatina de alta intensidade + ezetimiba foi utilizada em 102 pacientes (26%). A aplicação do método de Martin-Hopkins reclassificaria um total de 31 pacientes (7,8%). Entre aqueles considerados controlados pela fórmula de Friedewald, 27 (21,6%) teriam LDL-C estimado por Martin-Hopkins acima da meta. CONCLUSÕES: Menos de um terço dos pacientes pós-infarto do miocárdio apresentaram LDL-C dentro da meta. A aplicação da fórmula de Martin-Hopkins reclassificaria um quinto dos pacientes presumivelmente controlados no grupo de pacientes não controlados.

Factor XI Inhibitors: A New Horizon in Anticoagulation Therapy.

Anticoagulation therapy has undergone significant evolution, marked by the emergence of direct oral anticoagulants with distinct advantages. Despite these advancements, challenges persist in managing residual thrombotic and bleeding risks, particularly among vulnerable populations. The pursuit of alternative drugs has honed in on factor XI/XIa inhibitors. This comprehensive review delves into several key aspects regarding this new target: (i) the role of factor XI in the coagulation cascade; (ii) the genetic evidence and pathophysiologic rationale supporting factor XI inhibition as a therapeutic target; (iii) an exploration of the various types of factor XI/XIa inhibitors currently under investigation; (iv) potential applications of these medications, spanning thromboprophylaxis after orthopedic surgery, stroke prevention in atrial fibrillation, secondary prevention after acute coronary syndrome, non-cardioembolic stroke, thromboprophylaxis after foreign material implantation, end-stage renal disease, and patients with cancer; and (v) an overview of ongoing studies, recent findings, and the future trajectory of research into these drugs.

Atingimento das Metas de Colesterol LDL em Pacientes com Histórico de Infarto Agudo do Miocárdio: Estudo Transversal do Mundo Real / Attainment of LDL-Cholesterol Goals in Patients with Previous Myocardial Infarction: A Real-World Cross-Sectional Analysis

Resumo Fundamento: As diretrizes da Sociedade Europeia de Cardiologia recomendam um nível de colesterol LDL (LDL-C) < 55 mg/dL para pacientes com doença cardiovascular estabelecida. Embora a fórmula de Friedewald ainda seja amplamente utilizada para estimar o LDL-C, a fórmula mais recente de Martin-Hopkins mostrou maior precisão. Objetivos: Nosso objetivo foi avaliar: A) a proporção de pacientes que atingiram a meta de LDL-C e as terapias utilizadas em um centro terciário; B) o impacto da utilização do método de Martin-Hopkins em vez do método de Friedewald na proporção de pacientes controlados. Métodos: Estudo transversal monocêntrico, incluindo pacientes consecutivos pós-infarto do miocárdio, acompanhados por 20 cardiologistas, em um hospital terciário. Os dados foram coletados retrospectivamente de consultas clínicas realizadas após abril de 2022. Para cada paciente, os níveis de LDL-C e o atingimento das metas foram estimados a partir de um perfil lipídico ambulatorial, utilizando as fórmulas de Friedewald e Martin-Hopkins. Um valor-p bicaudal < 0,05 foi considerado estatisticamente significativo para todos os testes. Resultados: Foram incluídos 400 pacientes (com 67 ± 13 anos, 77% do sexo masculino). Utilizando a fórmula de Friedewald, a mediana de LDL-C sob terapia foi de 64 (50-81) mg/dL, e 31% tinham LDL-C dentro da meta. Estatinas de alta intensidade foram usadas em 64% dos pacientes, 37% estavam em uso de ezetimiba e 0,5% estavam em uso de inibidores de PCSK9. A terapia combinada de estatina de alta intensidade + ezetimiba foi utilizada em 102 pacientes (26%). A aplicação do método de Martin-Hopkins reclassificaria um total de 31 pacientes (7,8%). Entre aqueles considerados controlados pela fórmula de Friedewald, 27 (21,6%) teriam LDL-C estimado por Martin-Hopkins acima da meta. Conclusões: Menos de um terço dos pacientes pós-infarto do miocárdio apresentaram LDL-C dentro da meta. A aplicação da fórmula de Martin-Hopkins reclassificaria um quinto dos pacientes presumivelmente controlados no grupo de pacientes não controlados.

Abstract Background: The European Society of Cardiology guidelines recommend an LDL-cholesterol (LDL-C) < 55 mg/dL for patients with established cardiovascular disease. While the Friedewald equation to estimate LDL-C is still widely used, the newer Martin-Hopkins equation has shown greater accuracy. Objectives: We aimed to assess: A) the proportion of patients reaching LDL-C goal and the therapies used in a tertiary center; B) the impact of using the Martin-Hopkins method instead of Friedewald's on the proportion of controlled patients. Methods: A single-center cross-sectional study including consecutive post-myocardial infarction patients followed by 20 cardiologists in a tertiary hospital. Data was collected retrospectively from clinical appointments that took place after April 2022. For each patient, the LDL-C levels and attainment of goals were estimated from an ambulatory lipid profile using both Friedewald and Martin-Hopkins equations. A two-tailed p-value of < 0.05 was considered statistically significant for all tests. Results: Overall, 400 patients were included (aged 67 ± 13 years, 77% male). Using Friedewald's equation, the median LDL-C under therapy was 64 (50-81) mg/dL, and 31% had LDL-C within goals. High-intensity statins were used in 64% of patients, 37% were on ezetimibe, and 0.5% were under PCSK9 inhibitors. Combination therapy of high-intensity statin + ezetimibe was used in 102 patients (26%). Applying the Martin-Hopkins method would reclassify a total of 31 patients (7.8%). Among those deemed controlled by Friedewald's equation, 27 (21.6%) would have a Martin-Hopkins' LDL-C above goals. Conclusions: Less than one-third of post-myocardial infarction patients had LDL-C within the goal. Applying the Martin-Hopkins equation would reclassify one-fifth of presumably controlled patients into the non-controlled group.

Association Between the Magnitude of Glycemic Control and Body Weight Loss With GLP-1 Receptor Agonists and Risk of Atherosclerotic Cardiovascular Disease: A Systematic Review and Meta-analyses of Randomized Diabetes Cardiovascular Outcomes Trials.

PURPOSE: Reduction of major atherosclerotic cardiovascular events (MACE) has not been consistent among different glucagon-like peptide-1 receptor agonists (GLP-1 RAs) in patients with type 2 diabetes mellitus (T2DM). The aim of this study was to assess the association between the magnitude of glycemic control, body weight loss, and reductions in systolic blood pressure (SBP) and low-density lipoprotein cholesterol (LDL-C) achieved through GLP-1 RA therapy and MACE. METHODS: Electronic databases (MEDLINE, CENTRAL, SCOPUS) were searched through March 2023. Studies were eligible if they were cardiovascular outcome trials (CVOTs) comparing GLP-1 RAs versus placebo in T2DM patients. The outcome of interest was 3-point MACE - cardiovascular death, myocardial infarction, or stroke. Random-effects meta-regression analyses evaluated the associations between reductions of HbA1c, body weight, SBP and LDL-C and reduction of MACE. RESULTS: Overall, 8 CVOTs were included (60079 patients, 30693 with GLP-1 RAs). Reductions of HbA1C were associated with the reduction of 3P-MACE (Log RR -0.290 [95% CI -0.515;-0.064], p = 0.012), with an estimated RR reduction of 25% for each 1% absolute reduction in HbA1C levels. Body weight loss was associated with the reduction of 3P-MACE (Log RR -0.068 [95% CI -0.135;-0.001], p = 0.047), with an estimated RR reduction of 7% for each 1 kg reduction in body weight. Reductions of SBP (Log RR -0.058 [95% CI -0.192;0.076], p = 0.396) and LDL-C (Log RR -0.602 [95% CI -4.157;2.953], p = 0.740) were not associated with the reduction of 3P-MACE. CONCLUSIONS: In T2DM patients, more potent GLP-1 RAs in reducing HbA1c and body weight were associated with greater reductions of MACE.

Parameters of the mitral apparatus in patients with ischemic and nonischemic dilated cardiomyopathy.

The mitral valve apparatus is a complex structure consisting of several coordinating components: the annulus, two leaflets, the chordae tendineae, and the papillary muscles. Due to the intricate interplay between the mitral valve and the left ventricle, a disease of the latter may influence the normal function of the former. As a consequence, valve insufficiency may arise despite the absence of organic valve disease. This is designated as functional or secondary mitral regurgitation, and it arises from a series of distortions to the valve components. This narrative review describes the normal anatomy and the pathophysiology behind the mitral valve changes in ischemic and non-ischemic dilated cardiomyopathies. It also explains the value of a complete multiparametric assessment of this structure. Not only must an assessment include quantitative measures of regurgitation, but also various anatomical parameters from the mitral apparatus and left ventricle, since they carry prognostic value and are predictors of mitral valve repair success and durability.

Influence of Age on the Diagnostic Value of Coronary Artery Calcium Score for Ruling Out Obstructive Coronary Disease in Symptomatic Patients.

Concerns have been raised about the added diagnostic value of coronary artery calcium score (CACS) of 0 for reducing the likelihood of obstructive coronary artery disease (CAD) in younger patients. Our study aimed to assess the influence of age on the value of CAC = 0 in symptomatic patients who underwent coronary computed tomography angiography (CCTA). We conducted a 2-center retrospective study assessing symptomatic patients with suspected CAD who underwent CACS and CCTA. Pretest probability was calculated according to the Juarez-Orozco method and obstructive CAD was defined as ≥50% luminal stenosis. The diagnostic likelihood ratios and negative predictive values were used to assess the diagnostic value of a CACS of 0 to rule out obstructive CAD. A total of 2,043 patients (mean age 60 ± 11 years, 60% women, 48.5% CACS of 0) were analyzed. The pretest probability of obstructive CAD increased with age, whereas the proportion of patients with a CACS of 0 decreased with age. The added diagnostic value of a CACS of 0 was lower in younger patients (negative likelihood ratios ranging from 0.36 for <50 years to 0.10 for ≥70 years). However, the prevalence of obstructive CAD in patients with a CACS of 0 was low in all age groups. In a cohort of symptomatic patients who underwent CCTA for suspected CAD, the added diagnostic value of a CACS of 0 decreases significantly at younger ages. However, it is offset by their lower pretest probabilities, yielding high negative predictive values independently of age.

Effectiveness and Safety of P2Y12 Inhibitor Pretreatment for Primary PCI in STEMI: Systematic Review and Meta-analysis.

ABSTRACT: Dual antiplatelet therapy with aspirin and P2Y12 inhibitors in patients with ST-segment elevation myocardial infarction (STEMI) has been shown to be associated with better outcomes. Yet, there is uncertainty regarding the optimal timing for its initiation. We performed a systematic review and meta-analysis of evidence on pretreatment with P2Y12 inhibitors in combination with aspirin in patients with STEMI undergoing primary percutaneous coronary intervention (PCI). We performed a systematic search of electronic databases PubMed, CENTRAL, and Scopus until April 2022. Studies were eligible if they compared P2Y12 inhibitor upstream administration with downstream use in patients with STEMI submitted to PCI. Studies with patients receiving fibrinolysis or medical therapy only were excluded. Outcomes were assessed at the shortest follow-up available. Of 2491 articles, 3 RCT and 16 non-RCT studies were included, with a total of 79,300 patients (66.1% pretreated, 66.0% treated with clopidogrel). Pretreatment was associated with reduction in definite stent thrombosis (odds ratio [OR] 0.61 [0.38-0.98]), all-cause death (OR 0.77 [0.60-0.97]), and cardiogenic shock (OR 0.60 [0.48-0.75]). It was also associated with a lower incidence of thrombolysis in myocardial infarction flow <3 pre-PCI (OR 0.78 [0.67-0.92]). However, incidence of recurrent MI was not significantly reduced (OR 0.93 [0.57-1.52]). Regarding safety, pretreatment was not associated with a higher risk of major bleeding events (OR 0.83 [0.75-0.92]). Pretreatment with dual antiplatelet therapy, including a P2Y12 inhibitor, was associated with better pre-PCI coronary perfusion, lower incidence of definite stent thrombosis, cardiogenic shock, and, possibly, all-cause mortality with no sign of potential harm encountered.

Upstream anticoagulation in patients with ST-segment elevation myocardial infarction: a systematic review and meta-analysis.

BACKGROUND AND AIM: Parenteral anticoagulation is recommended for all patients presenting with ST-segment elevation myocardial infarction (STEMI) during primary percutaneous coronary intervention (PPCI). Whether upstream anticoagulation improves clinical outcomes is not well established. We conducted a systematic review and meta-analysis of contemporary evidence on parenteral anticoagulation timing for STEMI patients. METHODS: We performed a systematic search of electronic databases (PubMed, CENTRAL, and Scopus) until December 2022. Studies were eligible if they (a) compared upstream anticoagulation with administration at the catheterization laboratory and (b) enrolled patients with STEMI undergoing PPCI. Efficacy outcomes included in-hospital or 30-day mortality, in-hospital cardiogenic shock (CS), and TIMI flow grade pre- and post-PPCI. Safety outcome was defined as in-hospital or 30-day major bleeding. RESULTS: Overall, seven studies were included (all observational), with a total of 69,403 patients. Upstream anticoagulation was associated with a significant reduction in the incidence of in-hospital or 30-day all-cause mortality (OR 0.61; 95% CI 0.45-0.81; p < 0.001) and in-hospital CS (OR 0.68; 95% CI 0.58-0.81; p < 0.001) and with an increase in spontaneous reperfusion (pre-PPCI TIMI > 0: OR 1.46; 95% CI 1.35-1.57; p < 0.001). Pretreatment was not associated with an increase in major bleeding (OR 1.02; 95% CI 0.70-1.48; p = 0.930). CONCLUSIONS: Upstream anticoagulation was associated with a significantly lower risk of 30-day all-cause mortality, incidence of in-hospital CS, and improved reperfusion of the infarct-related artery (IRA). These findings were not accompanied by an increased risk of major bleeding, suggesting an overall clinical benefit of early anticoagulation in STEMI. These results require confirmation in a dedicated randomized clinical trial.

Extracorporeal cardiopulmonary resuscitation for refractory out-of-hospital cardiac arrest: a systematic review and meta-analysis of randomized clinical trials.

INTRODUCTION: Extracorporeal cardiopulmonary resuscitation (ECPR) is currently recommended as a rescue therapy for selected patients in refractory out-of-hospital cardiac arrest (OHCA). However, there is conflicting evidence regarding its effect on survival and neurological outcomes. We conducted a systematic review and meta-analysis of randomized clinical trials (RCTs) to evaluate whether ECPR is superior to standard CPR in refractory OHCA. METHODS: We performed a systematic search of electronic databases (PubMed, CENTRAL, and Scopus) until March 2023. Studies were eligible if they a) were RCTs, and b) compared ECPR vs. standard CPR for OHCA. Outcomes were defined as survival with a favorable neurological status (cerebral performance category 1 or 2) at both the shortest follow-up and at 6 months, and in-hospital mortality. Meta-analyses using a random-effects model were undertaken. RESULTS: Three RCTs, with a total of four hundred and eighteen patients, were included. Compared with standard CPR, ECPR was associated with a non-statistically significant higher rate of survival with a favorable neurological outcome at the shortest follow-up (26.4% vs. 17.2%; RR 1.47 [95% CI 0.91-2.40], P = 0.12) and at 6 months (28.3% vs. 18.6%; RR 1.48 [95% CI 0.88-2.49], P = 0.14). The mean absolute rate of in-hospital mortality was not significantly lower in the ECPR group (RR 0.89 [95% CI 0.74-1.07], P = 0.23). CONCLUSION: ECPR was not associated with a significant improvement in survival with favorable neurologic outcomes in refractory OHCA patients. Nevertheless, these results constitute the rationale for a well-conducted, large-scale RCT, aiming to clarify the effectiveness of ECPR compared to standard CPR.

Implications of three different testing strategies in the diagnostic approach to patients with stable chest pain and low pretest probability of obstructive coronary artery disease.

INTRODUCTION: The clinical implications of a widespread adoption of guideline recommendations for patients with stable chest pain and low pretest probability (PTP) of obstructive coronary artery disease (CAD) remain unclear. We aimed to assess the results of three different testing strategies in this subgroup of patients: A) defer testing; B) perform coronary artery calcium score (CACS), withholding further testing if CACS â€‹= â€‹0 and proceeding to coronary computed tomography angiography (CCTA) if CACS>0; C) perform CCTA in all. METHODS: Two-center cross-sectional study assessing 1328 symptomatic patients undergoing CACS and CCTA for suspected CAD. PTP was calculated based on age, sex and symptom typicality. Obstructive CAD was defined as any luminal stenosis ≥50% on CCTA. RESULTS: The prevalence of obstructive CAD was 8.6% (n â€‹= â€‹114). In the 786 patients (56.8%) with CACS â€‹= â€‹0, 8.5% (n â€‹= â€‹67) had some degree of CAD [1.9% (n â€‹= â€‹15) obstructive, and 6.6% (n â€‹= â€‹52) nonobstructive]. Among those with CACS>0 (n â€‹= â€‹542), 18.3% (n â€‹= â€‹99) had obstructive CAD. The number of patients needed to scan (NNS) to identify one patient with obstructive CAD was 13 for strategy B vs. A, and 91 for strategy C vs. B. CONCLUSIONS: Using CACS as gatekeeper would decrease CCTA use by more than 50%, at the cost of missing obstructive CAD in one in 100 patients. These findings may help inform decisions on testing, which will ultimately depend on the willingness to accept some diagnostic uncertainty.

Acute kidney injury patterns in acute heart failure: The prognostic value of worsening renal function and its timing.

INTRODUCTION: Acute decompensated heart failure (ADHF) admissions are frequently complicated by different patterns of serum creatinine (SCr) elevation. We aimed to assess the prognostic impact of worsening renal function (WRF) based on the timing of its occurrence. METHODS: This was a retrospective cohort of patients admitted for ADHF. Standard WRF was defined as an increase in SCr of ≥0.3 mg/dl during hospitalization. WRF timing was classified as early (within 48 hours of admission) or late (>48 hours). Acute kidney injury (AKI) at admission was defined as a rise in SCr of ≥0.3 mg/dl from outpatient baseline measurement to first measurement at admission. The primary endpoint was a composite of all-cause mortality or hospitalization for cardiovascular events at one-year follow-up. RESULTS: Overall, 249 patients were included (mean age 77±11 years, 62% with preserved left ventricular ejection fraction). Early WRF occurred in 49 patients (19.7%) and was associated with a higher risk of the primary outcome (HR 2.49; 95% CI 1.66-3.73), whereas late WRF was not (p=0.411). After stratification for the presence of early WRF and/or AKI at admission, only patients with early WRF but no AKI at admission and patients with both AKI at admission and early WRF showed a higher risk of the primary outcome after multivariate Cox regression. CONCLUSION: Early WRF was associated with a higher risk of the primary outcome. The timing of WRF seems to be an important factor to take into account when considering the prognostic impact of creatinine variations during hospitalization for ADHF.

Predicting obstructive coronary artery disease in heart failure with reduced ejection fraction: A practical clinical score.

INTRODUCTION AND OBJECTIVES: Obstructive coronary artery disease (CAD) remains the most common etiology of heart failure with reduced ejection fraction (HFrEF). However, there is controversy whether invasive coronary angiography (ICA) should be used initially to exclude CAD in patients presenting with new-onset HFrEF of unknown etiology. Our study aimed to develop a clinical score to quantify the risk of obstructive CAD in these patients. METHODS: We performed a cross-sectional observational study of 452 consecutive patients presenting with new-onset HFrEF of unknown etiology undergoing elective ICA in one academic center, between January 2005 and December 2019. Independent predictors for obstructive CAD were identified. A risk score was developed using multivariate logistic regression of designated variables. The accuracy and discriminative power of the predictive model were assessed. RESULTS: A total of 109 patients (24.1%) presented obstructive CAD. Six independent predictors were identified and included in the score: male gender (2 points), diabetes (1 point), dyslipidemia (1 point), smoking (1 point), peripheral arterial disease (1 point), and regional wall motion abnormalities (3 points). Patients with a score ≤3 had less than 15% predicted probability of obstructive CAD. Our score showed good discriminative power (C-statistic 0.872; 95% CI 0.834-0.909: p<0.001) and calibration (p=0.333 from the goodness-of-fit test). CONCLUSIONS: A simple clinical score showed the ability to predict the risk of obstructive CAD in patients presenting with new-onset HFrEF of unknown etiology and may guide the clinician in selecting the most appropriate diagnostic modality for the assessment of obstructive CAD.

Secondary mitral regurgitation: Maintaining coherence with the American Society of Echocardiography grading guidelines, which proportionality concept best predicts prognosis in the real world?

INTRODUCTION: Proportionality of secondary mitral regurgitation (sMR) may be a key factor in deciding whether a patient may benefit from mitral intervention. The aim of this study was to evaluate the prognostic value of two different concepts of proportionality and assess their ability to improve MR stratification proposed by the American Society of Echocardiography (ASE) guidelines. METHODS: We conducted a retrospective analysis in patients with reduced left ventricular ejection fraction (LVEF) (<50%) and at least mild sMR. Proportionality status was calculated using formulas proposed by a) Grayburn et al. - disproportionate sMR defined as EROALVEDV >0.14; b) Lopes et al. - disproportionate sMR whenever measured EROA>theoretical EROA (determined as 50%×LVEF×LVEDVMitralVTI). Primary endpoint was all-cause mortality. RESULTS: A total of 572 patients (69±12 years; 76% male) were included. Mean LVEF was 33±9%, with a median left ventricular end-diastolic volume of 174 mL [136;220] and a median effective regurgitant orifice area of 14 mm2 [8;22]. During mean follow-up of 4.1±2.7 years, there were 254 deaths. There was considerable disagreement (p<0.001) between both formulas: of 96 patients with disproportionate sMR according to Lopes' criteria, 46 (48%) were considered proportionate according to Grayburn's; and of 62 patients with disproportionate sMR according to Grayburn's, 12 (19%) were considered proportionate according to Lopes' formula. In multivariate analysis, only Lopes' definition of disproportionate sMR maintained independent prognostic value (hazard ratio 1.5; 95% confidence interval 1.07-2.1, p=0.018) and improved the risk stratification of ASE sMR classification. CONCLUSION: Of the two formulas available to define disproportionate sMR, Lopes' model emerged as the only one with independent prognostic value while improving the risk stratification proposed by the ASE guidelines.

Achieving higher efficacy without compromising safety with factor XI inhibitors versus low molecular weight heparin for the prevention of venous thromboembolism in major orthopedic surgery-Systematic review and meta-analysis.

BACKGROUND: In recent years, many important advances have been seen in anticoagulation therapy. However, bleeding risk is still a major concern. Factor XI (FXI) inhibition has emerged as a potential advantageous target to minimize this risk. OBJECTIVES: We conducted a systematic review and meta-analysis of current evidence on FXI inhibitors for thromboprophylaxis in major orthopedic surgery. METHODS: We performed a systematic search of electronic databases (PubMed, CENTRAL, and Scopus) until May of 2022. Studies were considered eligible if they were randomized controlled trials (RCTs) evaluating FXI inhibitors in thromboprophylaxis versus low molecular weight heparin (LMWH). For analysis purposes, we considered efficacy (venous thromboembolism [VTE], symptomatic VTE) and safety (major and clinically relevant non-major [CRNM] bleeding events, major bleeding events, blood transfusion necessities, adverse events, major adverse events) outcomes. RESULTS: Overall, four RCTs were included, with a total of 2269 patients, 372 VTE events, and 50 major or CRNM bleeding events. Regarding efficacy outcomes, FXI inhibitors were associated with a significant reduction in the incidence of VTE events (odds ratio [OR] 0.50; 95% confidence interval [CI: 0.36, 0.69]). Concerning safety outcomes, FXI inhibitors significantly reduced major or CRNM bleeding events (OR 0.41; 95% CI [0.22, 0.75]). It was also associated with a lower percentage of patients needing a blood transfusion, despite not meeting statistical significance (OR 0.69; 95% CI [0.32, 1.48]). Incidence of adverse events and major adverse events were similar between groups. CONCLUSION: Factor XI inhibitors showed a significant reduction in the incidence of VTE and bleeding events among patients submitted to major orthopedic surgery.

Dapagliflozin in a Real-World Chronic Heart Failure Population: How Many Are Actually Eligible?

BACKGROUND: In patients with heart failure (HF) and reduced ejection fraction (HFrEF) with or without type 2 diabetes mellitus, the sodium-glucose cotransporter 2 inhibitor (SGLT2i) dapagliflozin was recently shown to reduce the risk of worsening HF or death from cardiovascular causes in the dapagliflozin in patients with heart failure and reduced ejection fraction (DAPA-HF) trial. Our goal was to investigate how many patients in a real-world setting would be eligible for dapagliflozin according to the DAPA-HF enrolment criteria. METHODS: This is a single-center retrospective study enrolling consecutive, unselected patients followed up in an HF clinic from 2013 to 2019. Key DAPA-HF inclusion criteria (i.e., left ventricular ejection fraction [LVEF] ≤40% and NT-proBNP ≥600 pg/mL [or ≥900 pg/mL if atrial fibrillation]) and exclusion criteria (estimated glomerular filtration rate [eGFR] <30 mL/kg/1.73 m2 and systolic blood pressure [SBP] <95 mm Hg) were considered. RESULTS: Overall, 479 patients (age 76 ± 13 years; 50.5% male; 78.9% hypertensive; 45.1% with an eGFR <60 mL/min/1.73 m2; 36.5% with TD2M; and 33.5% with ischaemic HF) were assessed. The median SBP was 128.5 (112.0-146.0) mm Hg, mean eGFR was 50.8 ± 23.7 mL/min/1.73 m2, and median NT-proBNP was 2,183 (IQR 1,010-5,310) pg/mL. Overall, 155 (32.4%) patients had LVEF ≤40%. According to the DAPA-HF trial key criteria, 90 patients (18.8%) would be eligible for dapagliflozin. The remainder would be excluded due to LVEF >40% (67.6%), eGFR <30 mL/min/1.73 m2 (19.4%), NT-proBNP below the cutoff (16.7%), and/or SBP <95 mm Hg (6.5%). If we center the analysis to those with LVEF ≤40%, 58.1% would be eligible for dapagliflozin. The remainder would be excluded due to an eGFR <30 mL/min/1.73 m2 (20%), NT-proBNP below the cutoff (16.1%), and/or SBP <95 mm Hg (8.4%). CONCLUSION: Roughly half of our real-world HFrEF cohort would be eligible for dapagliflozin according to the key criteria of the DAPA-HF trial. The main reason for non-eligibility was an eGFR <30 mL/min/1.73 m2. However, two-thirds of patients had LVEF >40%. These findings show that dapagliflozin is a promising complementary new drug in the therapeutic armamentarium of most patients with HFrEF, while highlighting the urgent need for disease-modifying drugs in mid-range and preserved LVEF and the need to assess the efficacy and safety of SLGT2i in advanced kidney disease patients. The results of ongoing SGLT2i trials in these LVEF subgroups are eagerly awaited.