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Background: Clinical trials suggest that therapeutic-dose heparin may prevent critical illness and vascular complications due to COVID-19, but knowledge gaps exist regarding the efficacy of therapeutic heparin including its comparative effect relative to intermediate-dose anticoagulation. Objectives: The authors performed 2 complementary secondary analyses of a completed randomized clinical trial: 1) a prespecified per-protocol analysis; and 2) an exploratory dose-based analysis to compare the effect of therapeutic-dose heparin with low- and intermediate-dose heparin. Methods: Patients who received initial anticoagulation dosed consistently with randomization were included. The primary outcome was organ support-free days (OSFDs), a combination of in-hospital death and days free of organ support through day 21. Results: Among 2,860 participants, 1,761 (92.8%) noncritically ill and 857 (89.1%) critically ill patients were treated per-protocol. Among noncritically ill per-protocol patients, the posterior probability that therapeutic-dose heparin improved OSFDs as compared with usual care was 99.3% (median adjusted OR: 1.36; 95% credible interval [CrI]: 1.07-1.74). Therapeutic heparin had a high posterior probability of efficacy relative to both low- (94.6%; adjusted OR: 1.26; 95% CrI: 0.95-1.64) and intermediate- (99.8%; adjusted OR: 1.80; 95% CrI: 1.22-2.62) dose thromboprophylaxis. Among critically ill per-protocol patients, the posterior probability that therapeutic heparin improved outcomes was low. Conclusions: Among noncritically ill patients hospitalized for COVID-19 who were randomized to and initially received therapeutic-dose anticoagulation, heparin, compared with usual care, was associated with improved OSFDs, a combination of in-hospital death and days free of organ support. Therapeutic heparin appeared superior to both low- and intermediate-dose thromboprophylaxis.
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This study shows that we can use synthetic cohorts created from medical risk calculators to gain insights into how risk estimations, clinical reasoning, data-driven subgrouping, and the confidence in risk calculator scores are connected. When prediction variables aren't evenly distributed in these synthetic cohorts, they can be used to group similar cases together, revealing new insights about how cohorts behave. We also found that the confidence in predictions made by these calculators can vary depending on patient characteristics. This suggests that it might be beneficial to include a "normalized confidence" score in future versions of these calculators for healthcare professionals. We plan to explore this idea further in our upcoming research.
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Modelos Teóricos , Medición de Riesgo , Humanos , Estudios de Cohortes , Medición de Riesgo/métodosRESUMEN
The Cox proportional hazards model is one of the most popular statistical tools to model time to event outcomes without the need for specifying the hazards or survival time distributions. The Cox model requires that the ratio of the hazards of the occurrence of the outcome for any 2 individuals remains constant during the entire follow-up. Studies comparing coronary revascularisation strategies, however, might be prone to violations of proportionality by the crossing of the hazard functions over time. Early increases in the risk of cardiovascular outcomes are commonly observed when comparing coronary artery bypass grafting vs percutaneous coronary intervention, whereas decreased risk might be observed later during the follow-up. The same is valid for comparisons between invasive vs conservative coronary revascularisation strategies. In these situations, the statistical power of the Cox model is reduced, and hazard ratios might not be an informative summary measure of treatment effect. In this article, we discuss methods to identify and account for nonproportionality. We illustrate the use of these methods in a case study based on reconstructed data from a coronary revascularisation clinical trial. And finally, we review the cardiovascular literature to estimate how the proportionality assumption has been reported in coronary revascularisation studies recently.
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Enfermedad de la Arteria Coronaria , Intervención Coronaria Percutánea , Humanos , Resultado del Tratamiento , Puente de Arteria Coronaria , Intervención Coronaria Percutánea/métodos , Modelos de Riesgos Proporcionales , Corazón , Enfermedad de la Arteria Coronaria/cirugíaRESUMEN
BACKGROUND: Previous studies have failed to show a cardioprotective benefit of beta-blockers in patients with stable coronary artery disease (CAD). OBJECTIVES: This study sought to determine the association between beta-blockers and cardiovascular events in patients with stable CAD using a new user design. METHODS: All patients aged >66 years undergoing elective coronary angiography in Ontario, Canada, from 2009 to 2019 with diagnosed obstructive CAD were included. Exclusion criteria included heart failure or a recent myocardial infarction, as well as having a beta-blocker prescription claim in the previous year. Beta-blocker use was defined as having at least 1 beta-blocker prescription claim in the 90 days preceding or after the index coronary angiography. The main outcome was a composite of all-cause mortality and hospitalization for heart failure or myocardial infarction. Inverse probability of treatment weighting using the propensity score was used to account for confounding. RESULTS: This study included 28,039 patients (mean age: 73.0 ± 5.6 years; 66.2% male), and 12,695 of those (45.3%) were newly prescribed beta-blockers. The 5-year risks of the primary outcome were 14.3% in the beta-blocker group and 16.1% in the no beta-blocker group (absolute risk reduction: -1.8%; 95% CI: -2.8 to -0.8; HR: 0.92; 95% CI: 0.86-0.98; P = 0.006). This result was driven by reductions in myocardial infarction hospitalization (cause-specific HR: 0.87; 95% CI: 0.77-0.99; P = 0.031), whereas no differences were observed in all-cause death or heart failure hospitalization. CONCLUSIONS: In patients with angiographically documented stable CAD without heart failure or a recent myocardial infarction, beta-blockers were associated with a small but significant reduction in cardiovascular events at 5 years.
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Sistema Cardiovascular , Enfermedad de la Arteria Coronaria , Insuficiencia Cardíaca , Infarto del Miocardio , Isquemia Miocárdica , Humanos , Masculino , Anciano , Femenino , Isquemia Miocárdica/tratamiento farmacológico , Enfermedad de la Arteria Coronaria/complicaciones , Enfermedad de la Arteria Coronaria/tratamiento farmacológico , Insuficiencia Cardíaca/tratamiento farmacológico , Infarto del Miocardio/tratamiento farmacológico , Ontario/epidemiologíaRESUMEN
IMPORTANCE: Overactivation of the renin-angiotensin system (RAS) may contribute to poor clinical outcomes in patients with COVID-19. Objective: To determine whether angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) initiation improves outcomes in patients hospitalized for COVID-19. DESIGN, SETTING, AND PARTICIPANTS: In an ongoing, adaptive platform randomized clinical trial, 721 critically ill and 58 non-critically ill hospitalized adults were randomized to receive an RAS inhibitor or control between March 16, 2021, and February 25, 2022, at 69 sites in 7 countries (final follow-up on June 1, 2022). INTERVENTIONS: Patients were randomized to receive open-label initiation of an ACE inhibitor (n = 257), ARB (n = 248), ARB in combination with DMX-200 (a chemokine receptor-2 inhibitor; n = 10), or no RAS inhibitor (control; n = 264) for up to 10 days. MAIN OUTCOMES AND MEASURES: The primary outcome was organ support-free days, a composite of hospital survival and days alive without cardiovascular or respiratory organ support through 21 days. The primary analysis was a bayesian cumulative logistic model. Odds ratios (ORs) greater than 1 represent improved outcomes. RESULTS: On February 25, 2022, enrollment was discontinued due to safety concerns. Among 679 critically ill patients with available primary outcome data, the median age was 56 years and 239 participants (35.2%) were women. Median (IQR) organ support-free days among critically ill patients was 10 (-1 to 16) in the ACE inhibitor group (n = 231), 8 (-1 to 17) in the ARB group (n = 217), and 12 (0 to 17) in the control group (n = 231) (median adjusted odds ratios of 0.77 [95% bayesian credible interval, 0.58-1.06] for improvement for ACE inhibitor and 0.76 [95% credible interval, 0.56-1.05] for ARB compared with control). The posterior probabilities that ACE inhibitors and ARBs worsened organ support-free days compared with control were 94.9% and 95.4%, respectively. Hospital survival occurred in 166 of 231 critically ill participants (71.9%) in the ACE inhibitor group, 152 of 217 (70.0%) in the ARB group, and 182 of 231 (78.8%) in the control group (posterior probabilities that ACE inhibitor and ARB worsened hospital survival compared with control were 95.3% and 98.1%, respectively). CONCLUSIONS AND RELEVANCE: In this trial, among critically ill adults with COVID-19, initiation of an ACE inhibitor or ARB did not improve, and likely worsened, clinical outcomes. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02735707.
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Antagonistas de Receptores de Angiotensina , Inhibidores de la Enzima Convertidora de Angiotensina , Tratamiento Farmacológico de COVID-19 , COVID-19 , Sistema Renina-Angiotensina , Femenino , Humanos , Masculino , Persona de Mediana Edad , Antagonistas de Receptores de Angiotensina/farmacología , Antagonistas de Receptores de Angiotensina/uso terapéutico , Inhibidores de la Enzima Convertidora de Angiotensina/farmacología , Inhibidores de la Enzima Convertidora de Angiotensina/uso terapéutico , Teorema de Bayes , COVID-19/terapia , Sistema Renina-Angiotensina/efectos de los fármacos , Hospitalización , Tratamiento Farmacológico de COVID-19/métodos , Enfermedad Crítica , Receptores de Quimiocina/antagonistas & inhibidoresRESUMEN
BACKGROUND: Prior studies of therapeutic-dose anticoagulation in patients with COVID-19 have reported conflicting results. OBJECTIVES: We sought to determine the safety and effectiveness of therapeutic-dose anticoagulation in noncritically ill patients with COVID-19. METHODS: Patients hospitalized with COVID-19 not requiring intensive care unit treatment were randomized to prophylactic-dose enoxaparin, therapeutic-dose enoxaparin, or therapeutic-dose apixaban. The primary outcome was the 30-day composite of all-cause mortality, requirement for intensive care unit-level of care, systemic thromboembolism, or ischemic stroke assessed in the combined therapeutic-dose groups compared with the prophylactic-dose group. RESULTS: Between August 26, 2020, and September 19, 2022, 3,398 noncritically ill patients hospitalized with COVID-19 were randomized to prophylactic-dose enoxaparin (n = 1,141), therapeutic-dose enoxaparin (n = 1,136), or therapeutic-dose apixaban (n = 1,121) at 76 centers in 10 countries. The 30-day primary outcome occurred in 13.2% of patients in the prophylactic-dose group and 11.3% of patients in the combined therapeutic-dose groups (HR: 0.85; 95% CI: 0.69-1.04; P = 0.11). All-cause mortality occurred in 7.0% of patients treated with prophylactic-dose enoxaparin and 4.9% of patients treated with therapeutic-dose anticoagulation (HR: 0.70; 95% CI: 0.52-0.93; P = 0.01), and intubation was required in 8.4% vs 6.4% of patients, respectively (HR: 0.75; 95% CI: 0.58-0.98; P = 0.03). Results were similar in the 2 therapeutic-dose groups, and major bleeding in all 3 groups was infrequent. CONCLUSIONS: Among noncritically ill patients hospitalized with COVID-19, the 30-day primary composite outcome was not significantly reduced with therapeutic-dose anticoagulation compared with prophylactic-dose anticoagulation. However, fewer patients who were treated with therapeutic-dose anticoagulation required intubation and fewer died (FREEDOM COVID [FREEDOM COVID Anticoagulation Strategy]; NCT04512079).
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COVID-19 , Tromboembolia , Humanos , Enoxaparina/uso terapéutico , Anticoagulantes/efectos adversos , Coagulación Sanguínea , Tromboembolia/prevención & control , Tromboembolia/inducido químicamenteRESUMEN
BACKGROUND: The ISCHEMIA trial showed similar cardiovascular outcomes of an initial conservative strategy as compared with invasive management in patients with stable ischemic heart disease without left main stenosis. We aim to assess the feasibility of predicting significant left main stenosis using extensive clinical, laboratory and non-invasive tests data. METHODS: All adult patients who had stress testing prior to undergoing an elective coronary angiography for stable ischemic heart disease in Ontario, Canada, between April 2010 and March 2019, were included. Candidate predictors included comprehensive demographics, comorbidities, laboratory tests, and cardiac stress test data. The outcome was stenosis of 50% or greater in the left main coronary artery. A traditional model (logistic regression) and a machine learning algorithm (boosted trees) were used to build prediction models. RESULTS: Among 150,423 patients included (mean age: 64.2 ± 10.6 years; 64.1% males), there were 9,225 (6.1%) with left main stenosis. The final logistic regression model included 24 predictors and 3 interactions, had an optimism-adjusted c-statistic of 0.72 and adequate calibration (optimism-adjusted Integrated Calibration Index 0.0044). These results were consistent in subgroups of males and females, diabetes and non-diabetes, and extent of ischemia. The boosted tree algorithm had similar accuracy, also resulting in a c-statistic of 0.72 and adequate calibration (Integrated Calibration Index 0.0054). CONCLUSIONS: In this large population-based study of patients with stable ischemic heart disease using extensive clinical data, only modest prediction of left main coronary artery disease was possible with traditional and machine learning modelling techniques.
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Enfermedad de la Arteria Coronaria , Estenosis Coronaria , Isquemia Miocárdica , Masculino , Adulto , Femenino , Humanos , Persona de Mediana Edad , Anciano , Constricción Patológica , Modelos Logísticos , Isquemia Miocárdica/diagnóstico , Isquemia Miocárdica/epidemiología , Angiografía Coronaria/métodos , Ontario/epidemiología , Estenosis Coronaria/diagnósticoRESUMEN
Background: Appropriate selection of patients with stable coronary artery disease (CAD) for coronary angiography is dependent on the pretest probability of obstructive CAD; however, little is known about the potential differences in CAD by race and ethnic groups. Objectives: The purpose of this study was to evaluate the association of race and ethnicity with coronary obstruction in stable CAD. Methods: We evaluated first coronary angiography for CAD evaluation between 2012 and 2019 in Ontario, Canada. Race and ethnicity were identified by physicians. The main outcome was the rate of obstructive CAD (left main stenosis ≥50% or major epicardial vessel stenosis ≥70%). Multivariable logistic regression analyses evaluated the independent association of race and ethnicity with CAD. Results: Among 71,199 CAD patients, 14.0% were South Asian (SA), 4.4% were East Asian (EA), and 58,131 were White patients. SA patients were the youngest at 60.9 years vs 62.4 years for EA patients and 65.1 years for White patients but were most likely to have obstructive CAD (46.9%) (EA 43.0% and White patients 37.9%). SA patients had the highest prevalence of 3-vessel CAD at 13.4% (vs 12.5% in EA and 7.7% in White patients). The adjusted odds ratio was 67% higher (1.67; 95% CI: 1.59 to 1.75) for having obstructive CAD in SA patients than that in White patients. EA patients also had significantly increased adjusted odds of obstructive CAD compared with White patients (1.40; 95% CI: 1.29-1.52). Conclusions: SA patients were younger at presentation but had the highest adjusted odds of obstructive CAD. Incorporation of race and ethnicity information may improve risk-prediction tools for detection of coronary obstruction.
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INTRODUCTION: Coronary atherosclerotic burden and SYNTAX Score (SS) are predictors of cardiovascular events. OBJECTIVES: To investigate the value of SYNTAX scores (SS, SYNTAX Score II (SSII) and residual SYNTAX Score (rSS)) for predicting cardiovascular events in patients with coronary artery disease (CAD). DESIGN: Retrospective cohort study. SETTING: Single tertiary centre. PARTICIPANTS: Medicine, Angioplasty or Surgery Study database patients with stable multivessel CAD and preserved ejection fraction. INTERVENTIONS: Patients with CAD undergoing coronary artery bypass graft (CABG), percutaneous coronary intervention (PCI) or medical treatment (MT) alone from January 2002 to December 2015. PRIMARY AND SECONDARY OUTCOMES: Primary: 5-year all-cause mortality. Secondary: composite of all-cause death, myocardial infarction, stroke and subsequent coronary revascularisation at 5 years. RESULTS: A total of 1719 patients underwent PCI (n=573), CABG (n=572) or MT (n=574) alone. The SS was not considered an independent predictor of 5-year mortality in the PCI (low, intermediate and high SS at 6.5%, 6.8% and 4.3%, respectively, p=0.745), CABG (low, intermediate and high SS at 5.7%, 8.0% and 12.1%, respectively, p=0.194) and MT (low, intermediate and high SS at 6.8%, 6.9% and 6.5%, respectively, p=0.993) cohorts. The SSII (low, intermediate and high SSII at 3.6% vs 7.9% vs 10.5%, respectively, p<0.001) was associated with a higher mortality risk in the overall population. Within each treatment strategy, SSII was associated with a significant 5-year mortality rate, especially in CABG patients with higher SSII (low, intermediate and high SSII at 1.8%, 9.7% and 10.0%, respectively, p=0.004) and in MT patients with high SSII (low, intermediate and high SSII at 5.0%, 4.7% and 10.8%, respectively, p=0.031). SSII demonstrated a better predictive accuracy for mortality compared with SS and rSS (c-index=0.62). CONCLUSIONS: Coronary atherosclerotic burden alone was not associated with significantly increased risk of all-cause mortality. The SSII better discriminates the risk of death. TRIAL REGISTRATION NUMBER: ISRCTN66068876.
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Enfermedad de la Arteria Coronaria , Infarto del Miocardio , Intervención Coronaria Percutánea , Puente de Arteria Coronaria/efectos adversos , Humanos , Infarto del Miocardio/etiología , Intervención Coronaria Percutánea/efectos adversos , Estudios Retrospectivos , Resultado del TratamientoRESUMEN
Clinical, laboratory, and autopsy findings support an association between coronavirus disease-2019 (COVID-19) and thromboembolic disease. Acute COVID-19 infection is characterized by mononuclear cell reactivity and pan-endothelialitis, contributing to a high incidence of thrombosis in large and small blood vessels, both arterial and venous. Observational studies and randomized trials have investigated whether full-dose anticoagulation may improve outcomes compared with prophylactic dose heparin. Although no benefit for therapeutic heparin has been found in patients who are critically ill hospitalized with COVID-19, some studies support a possible role for therapeutic anticoagulation in patients not yet requiring intensive care unit support. We summarize the pathology, rationale, and current evidence for use of anticoagulation in patients with COVID-19 and describe the main design elements of the ongoing FREEDOM COVID-19 Anticoagulation trial, in which 3,600 hospitalized patients with COVID-19 not requiring intensive care unit level of care are being randomized to prophylactic-dose enoxaparin vs therapeutic-dose enoxaparin vs therapeutic-dose apixaban. (FREEDOM COVID-19 Anticoagulation Strategy [FREEDOM COVID]; NCT04512079).
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Anticoagulantes/uso terapéutico , COVID-19/complicaciones , Tromboembolia/prevención & control , Trombosis/prevención & control , COVID-19/terapia , Cuidados Críticos , Enoxaparina/uso terapéutico , Hospitalización , Humanos , Pirazoles/uso terapéutico , Piridonas/uso terapéutico , Tromboembolia/virología , Trombosis/virologíaRESUMEN
BACKGROUND AND AIMS: Chronic kidney disease (CKD) confers a high risk for poor cardiovascular outcomes. We conducted a systematic review and meta-analysis to estimate the effects of revascularization as the initial management strategy compared with medical therapy among patients with CKD and coronary artery disease. METHODS: A Medline/PubMed literature research was conducted to identify randomized studies comparing early coronary revascularization with optimal medical therapy or medical therapy alone in patients with CKD (estimated glomerular filtration rate <60 mL/min/1.73 m2 or maintenance dialysis). The primary outcome was myocardial infarction. The secondary outcomes were all-cause mortality or progression to kidney failure. The risk ratio (RR) was estimated using a random-effects model. RESULTS: Eleven randomized trials were included (3422 patients). Revascularization was associated with lower incidence of myocardial infarction compared with medical therapy in patients with CKD: RR 0.71 (95% confidence interval [CI] 0.54-0.94; p=0.02). This result was mainly driven from a significantly lower incidence of myocardial infarction with early revascularization among patients with stable coronary artery disease: RR 0.59; 95% CI 0.37-0.93. A similar incidence of all-cause mortality was observed with both treatment strategies: RR 0.88 (95% CI 0.72-1.08; p=0.22). A trend towards lower incidence of all-cause mortality was observed with revascularization in the subgroup of patients presenting with NSTE-ACS: RR 0.73 (95% CI 0.51-1.04; p=0.08) but not among patients with stable coronary disease. There was no difference in progression to kidney failure between the two strategies. CONCLUSIONS: Coronary revascularization may be superior to medical therapy among patients with CKD and coronary disease.
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Enfermedad de la Arteria Coronaria , Infarto del Miocardio , Intervención Coronaria Percutánea , Insuficiencia Renal Crónica , Infarto del Miocardio con Elevación del ST , Humanos , Infarto del Miocardio/epidemiología , Infarto del Miocardio/etiología , Infarto del Miocardio/terapia , Revascularización Miocárdica , Intervención Coronaria Percutánea/efectos adversos , Insuficiencia Renal Crónica/complicaciones , Insuficiencia Renal Crónica/epidemiología , Infarto del Miocardio con Elevación del ST/terapia , Resultado del TratamientoRESUMEN
PURPOSE OF REVIEW: To review the current evidence for coronary revascularization in patients with diabetes mellitus (DM) in the setting of an acute coronary syndrome (ACS). RECENT FINDINGS: In patients with DM and stable multivessel ischemic heart disease, coronary artery bypass graft surgery (CABG) has been observed to be superior to percutaneous coronary intervention (PCI) in long-term follow-up, leading to lower rates of all-cause mortality, myocardial infarction, and repeat revascularization. In the ACS setting, PCI remains the most frequently performed procedure. In patients with an ST-segment-elevation myocardial infarction (STEMI), primary PCI should be the revascularization method of choice, whenever feasible. Controversy still exists regarding when and how to deal with possible residual lesions. In the non-ST-segment-elevation (NSTE) ACS setting, although there are no data from randomized controlled trials (RCTs), recent observational data and sub-analyses of randomized studies have suggested that CABG may be the preferred approach for patients with DM and multivessel coronary disease. There is a paucity of RCTs evaluating revascularization strategies (PCI and CABG) in patients with DM and ACS. CABG may be a viable strategy, leading to improved outcomes, especially following NSTE-ACS.
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Síndrome Coronario Agudo , Enfermedad de la Arteria Coronaria , Diabetes Mellitus , Infarto del Miocardio , Intervención Coronaria Percutánea , Síndrome Coronario Agudo/cirugía , Puente de Arteria Coronaria/métodos , Enfermedad de la Arteria Coronaria/cirugía , Humanos , Infarto del Miocardio/cirugía , Resultado del TratamientoRESUMEN
OBJECTIVE: Understanding cardiorenal pathophysiology in heart failure (HF) is of clinical importance. We sought to characterize the renal hemodynamic function and the transrenal gradient of the renin-angiotensin-aldosterone system (RAAS) markers in patients with HF and in controls without HF. METHODS: In this post hoc analysis, the glomerular filtration rate (GFRinulin), effective renal plasma flow (ERPFPAH) and transrenal gradients (arterial-renal vein) of angiotensin converting enzyme (ACE), aldosterone, and plasma renin activity (PRA) were measured in 47 patients with HF and in 24 controls. Gomez equations were used to derive afferent (RA) and efferent (RE) arteriolar resistances. Transrenal RAAS gradients were also collected in patients treated with intravenous dobutamine (HF, nâ¯=â¯11; non-HF, nâ¯=â¯11) or nitroprusside (HF, nâ¯=â¯18; non-HF, nâ¯=â¯5). RESULTS: The concentrations of PRA, aldosterone and ACE were higher in the renal vein vs the artery in patients with HF vs patients without HF (P < 0.01). In patients with HF, a greater ACE gradient was associated with greater renal vascular resistance (râ¯=â¯0.42; P 0.007) and greater arteriolar resistances (RA: râ¯=â¯0.39; Pâ¯=â¯0.012; RE: râ¯=â¯0.48; Pâ¯=â¯0.002). Similarly, a greater aldosterone gradient was associated with lower GFR (râ¯=â¯-0.51; Pâ¯=â¯0.0007) and renal blood flow (RBF), râ¯=â¯-0.32; Pâ¯=â¯0.042) whereas greater PRA gradient with lower ERPF (râ¯=â¯-0.33; Pâ¯=â¯0.040), GFR (râ¯=â¯-0.36; Pâ¯=â¯0.024), and RBF (râ¯=â¯-0.33; Pâ¯=â¯0.036). Dobutamine and nitroprusside treatment decreased the transrenal gradient of ACE (Pâ¯=â¯0.012, P < 0.0001, respectively), aldosterone (Pâ¯=â¯0.005, Pâ¯=â¯0.030) and PRA (Pâ¯=â¯0.014, Pâ¯=â¯0.002) in patients with HF only. CONCLUSIONS: A larger transrenal RAAS marker gradient in patients with HF suggests a renal origin for neurohormonal activation associated with a vasoconstrictive renal profile.
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Insuficiencia Cardíaca , Sistema Renina-Angiotensina , Aldosterona/uso terapéutico , Biomarcadores , Dobutamina/uso terapéutico , Insuficiencia Cardíaca/diagnóstico , Insuficiencia Cardíaca/tratamiento farmacológico , Hemodinámica , Humanos , Nitroprusiato/uso terapéutico , Renina/uso terapéuticoRESUMEN
BACKGROUND: Warfarin is the only oral anticoagulant approved for use following mechanical valve surgery (MeVS). Patients may experience prolonged hospital length of stay (LOS) following MeVS awaiting an appropriate warfarin effect. We aimed to determine whether an association exists between time to achieve the first therapeutic international normalized ratio (INR) and LOS following MeVS. MATERIALS AND METHODS: Retrospective single center cohort study. We included consecutive adult patients undergoing elective MeVS from 2013 to 2018. Landmark analyses and multivariable regression with time-updated INR were used to estimate the association between time to therapeutic INR (TTI) and LOS. RESULTS: Among 384 patients (median age: 51 years, interquartile range [IQR]: 41-57; 58.3% male), the median TTI was 4 days (IQR: 2-5). Thirty seven percent of patients were discharged with a subtherapeutic INR, many on bridging anticoagulation or with an INR close to target. Those achieving therapeutic INR had an increased rate of hospital discharge (adjusted hazard ratio: 2.17; 95% confidence interval: 1.71-2.76; p < .0001). Attainment of a therapeutic INR anytime between postoperative Days 4 and 13 was significantly associated with a shorter LOS. CONCLUSIONS: Prolonged time to achieve a therapeutic INR was independently associated with prolonged LOS. Future strategies aimed at improving attainment of therapeutic INR following MeVS may reduce hospital LOS.
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Anticoagulantes , Válvulas Cardíacas , Adulto , Estudios de Cohortes , Femenino , Humanos , Relación Normalizada Internacional , Tiempo de Internación , Masculino , Persona de Mediana Edad , Estudios RetrospectivosRESUMEN
BACKGROUND: Advanced age is associated with both left bundle branch block (LBBB) and hypertension and the usefulness of ECG criteria to detect left ventricular hypertrophy (LVH) in patients with LBBB is still unclear. The diagnostic performance and clinical applicability of ECG-based LVH criteria in patients with LBBB defined by stricter ECG criteria is unknown. The aim of this study was to compare diagnostic accuracy and clinical utility of ECG criteria in patients with advanced age and strict LBBB criteria. METHODS: Retrospective single-center study conducted from Jan/2017 to Mar/2018. Patients undergoing both ECG and echocardiogram examinations were included. Ten criteria for ECG-based LVH were compared using LVH defined by the echocardiogram as the gold standard. Sensitivity, specificity, predictive values, likelihood ratios, AUC, and the Brier score were used to compare diagnostic performance and a decision curve analysis was performed. RESULTS: From 4621 screened patients, 68 were included, median age was 78.4 years, (IQR 73.3-83.4), 73.5% with hypertension. All ECG criteria failed to provide accurate discrimination of LVH with AUC range between 0.54 and 0.67, and no ECG criteria had a balanced tradeoff between sensitivity and specificity. No ECG criteria consistently improved the net benefit compared to the strategy of performing routine echocardiogram in all patients in the decision curve analysis within the 10-60% probability threshold range. CONCLUSION: ECG-based criteria for LVH in patients with advanced age and true LBBB lack diagnostic accuracy or clinical usefulness and should not be routinely assessed.
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Bloqueo de Rama/diagnóstico , Electrocardiografía , Hipertrofia Ventricular Izquierda/diagnóstico , Anciano , Anciano de 80 o más Años , Bloqueo de Rama/complicaciones , Ecocardiografía , Femenino , Humanos , Hipertensión/complicaciones , Hipertrofia Ventricular Izquierda/complicaciones , Masculino , Estudios Retrospectivos , Sensibilidad y EspecificidadRESUMEN
BACKGROUND: Thrombosis and inflammation may contribute to morbidity and mortality among patients with coronavirus disease 2019 (Covid-19). We hypothesized that therapeutic-dose anticoagulation would improve outcomes in critically ill patients with Covid-19. METHODS: In an open-label, adaptive, multiplatform, randomized clinical trial, critically ill patients with severe Covid-19 were randomly assigned to a pragmatically defined regimen of either therapeutic-dose anticoagulation with heparin or pharmacologic thromboprophylaxis in accordance with local usual care. The primary outcome was organ support-free days, evaluated on an ordinal scale that combined in-hospital death (assigned a value of -1) and the number of days free of cardiovascular or respiratory organ support up to day 21 among patients who survived to hospital discharge. RESULTS: The trial was stopped when the prespecified criterion for futility was met for therapeutic-dose anticoagulation. Data on the primary outcome were available for 1098 patients (534 assigned to therapeutic-dose anticoagulation and 564 assigned to usual-care thromboprophylaxis). The median value for organ support-free days was 1 (interquartile range, -1 to 16) among the patients assigned to therapeutic-dose anticoagulation and was 4 (interquartile range, -1 to 16) among the patients assigned to usual-care thromboprophylaxis (adjusted proportional odds ratio, 0.83; 95% credible interval, 0.67 to 1.03; posterior probability of futility [defined as an odds ratio <1.2], 99.9%). The percentage of patients who survived to hospital discharge was similar in the two groups (62.7% and 64.5%, respectively; adjusted odds ratio, 0.84; 95% credible interval, 0.64 to 1.11). Major bleeding occurred in 3.8% of the patients assigned to therapeutic-dose anticoagulation and in 2.3% of those assigned to usual-care pharmacologic thromboprophylaxis. CONCLUSIONS: In critically ill patients with Covid-19, an initial strategy of therapeutic-dose anticoagulation with heparin did not result in a greater probability of survival to hospital discharge or a greater number of days free of cardiovascular or respiratory organ support than did usual-care pharmacologic thromboprophylaxis. (REMAP-CAP, ACTIV-4a, and ATTACC ClinicalTrials.gov numbers, NCT02735707, NCT04505774, NCT04359277, and NCT04372589.).
Asunto(s)
Anticoagulantes/administración & dosificación , Tratamiento Farmacológico de COVID-19 , Heparina/administración & dosificación , Trombosis/prevención & control , Anciano , Anticoagulantes/efectos adversos , Anticoagulantes/uso terapéutico , COVID-19/mortalidad , Enfermedad Crítica , Femenino , Hemorragia/inducido químicamente , Heparina/efectos adversos , Heparina/uso terapéutico , Mortalidad Hospitalaria , Humanos , Modelos Logísticos , Masculino , Persona de Mediana Edad , Oportunidad Relativa , Respiración Artificial , Insuficiencia del TratamientoRESUMEN
PURPOSE: We aimed to determine the association between sepsis and long-term cardiovascular events. METHODS: We conducted a systematic review of observational studies evaluating post-sepsis cardiovascular outcomes in adult sepsis survivors. MEDLINE, Embase, and the Cochrane Controlled Trials Register and Database of Systematic Reviews were searched from inception until April 21st, 2021. Two reviewers independently extracted individual study data and evaluated risk of bias. Random-effects models estimated the pooled crude cumulative incidence and adjusted hazard ratios (aHRs) of cardiovascular events compared to either non-septic hospital survivors or population controls. Primary outcomes included myocardial infarction, stroke, and congestive heart failure; outcomes were analysed at maximum reported follow-up (from 30 days to beyond 5 years post-discharge). RESULTS: Of 12,649 screened citations, 27 studies (25 cohort studies, 2 case-crossover studies) were included with a median of 4,289 (IQR 502-68,125) sepsis survivors and 18,399 (IQR 4,028-83,506) controls per study. The pooled cumulative incidence of myocardial infarction, stroke, and heart failure in sepsis survivors ranged from 3 to 9% at longest reported follow-up. Sepsis was associated with a higher long-term risk of myocardial infarction (aHR 1.77 [95% CI 1.26 to 2.48]; low certainty), stroke (aHR 1.67 [95% CI 1.37 to 2.05]; low certainty), and congestive heart failure (aHR 1.65 [95% CI 1.46 to 1.86]; very low certainty) compared to non-sepsis controls. CONCLUSIONS: Surviving sepsis may be associated with a long-term, excess hazard of late cardiovascular events which may persist for at least 5 years following hospital discharge.