One-year Outcomes after Discharge from Noncardiac Surgery and Association between Predischarge Complications and Death after Discharge: Analysis of the VISION Prospective Cohort Study.

BACKGROUND: In previous analyses, myocardial injury after noncardiac surgery, major bleeding, and sepsis were independently associated with most deaths in the 30 days after noncardiac surgery, but most of these deaths occurred during the index hospitalization for surgery. The authors set out to describe outcomes after discharge from hospital up to 1 yr after inpatient noncardiac surgery and associations between predischarge complications and postdischarge death up to 1 yr after surgery. METHODS: This study was an analysis of patients discharged after inpatient noncardiac surgery in a large international prospective cohort study across 28 centers from 2007 to 2013 of patients aged 45 yr or older followed to 1 yr after surgery. The study estimated (1) the cumulative postdischarge incidence of death and other outcomes up to a year after surgery and (2) the adjusted time-varying associations between postdischarge death and predischarge complications including myocardial injury after noncardiac surgery, major bleeding, sepsis, infection without sepsis, stroke, congestive heart failure, clinically important atrial fibrillation or flutter, amputation, venous thromboembolism, and acute kidney injury managed with dialysis. RESULTS: Among 38,898 patients discharged after surgery, the cumulative 1-yr incidence was 5.8% (95% CI, 5.5 to 6.0%) for all-cause death and 24.7% (95% CI, 24.2 to 25.1%) for all-cause hospital readmission. Predischarge complications were associated with 33.7% (95% CI, 27.2 to 40.2%) of deaths up to 30 days after discharge and 15.0% (95% CI, 12.0 to 17.9%) up to 1 yr. Most of the association with death was due to myocardial injury after noncardiac surgery (15.6% [95% CI, 9.3 to 21.9%] of deaths within 30 days, 6.4% [95% CI, 4.1 to 8.7%] within 1 yr), major bleeding (15.0% [95% CI, 8.3 to 21.7%] within 30 days, 4.7% [95% CI, 2.2 to 7.2%] within 1 yr), and sepsis (5.4% [95% CI, 2.2 to 8.6%] within 30 days, 2.1% [95% CI, 1.0 to 3.1%] within 1 yr). CONCLUSIONS: One in 18 patients 45 yr old or older discharged after inpatient noncardiac surgery died within 1 yr, and one quarter were readmitted to the hospital. The risk of death associated with predischarge perioperative complications persists for weeks to months after discharge.

Hypotension-Avoidance Versus Hypertension-Avoidance Strategies in Noncardiac Surgery : An International Randomized Controlled Trial.

BACKGROUND: Among patients having noncardiac surgery, perioperative hemodynamic abnormalities are associated with vascular complications. Uncertainty remains about what intraoperative blood pressure to target and how to manage long-term antihypertensive medications perioperatively. OBJECTIVE: To compare the effects of a hypotension-avoidance and a hypertension-avoidance strategy on major vascular complications after noncardiac surgery. DESIGN: Partial factorial randomized trial of 2 perioperative blood pressure management strategies (reported here) and tranexamic acid versus placebo. (ClinicalTrials.gov: NCT03505723). SETTING: 110 hospitals in 22 countries. PATIENTS: 7490 patients having noncardiac surgery who were at risk for vascular complications and were receiving 1 or more long-term antihypertensive medications. INTERVENTION: In the hypotension-avoidance strategy group, the intraoperative mean arterial pressure target was 80 mm Hg or greater; before and for 2 days after surgery, renin-angiotensin-aldosterone system inhibitors were withheld and the other long-term antihypertensive medications were administered only for systolic blood pressures 130 mm Hg or greater, following an algorithm. In the hypertension-avoidance strategy group, the intraoperative mean arterial pressure target was 60 mm Hg or greater; all antihypertensive medications were continued before and after surgery. MEASUREMENTS: The primary outcome was a composite of vascular death and nonfatal myocardial injury after noncardiac surgery, stroke, and cardiac arrest at 30 days. Outcome adjudicators were masked to treatment assignment. RESULTS: The primary outcome occurred in 520 of 3742 patients (13.9%) in the hypotension-avoidance group and in 524 of 3748 patients (14.0%) in the hypertension-avoidance group (hazard ratio, 0.99 [95% CI, 0.88 to 1.12]; P = 0.92). Results were consistent for patients who used 1 or more than 1 antihypertensive medication in the long term. LIMITATION: Adherence to the assigned strategies was suboptimal; however, results were consistent across different adherence levels. CONCLUSION: In patients having noncardiac surgery, our hypotension-avoidance and hypertension-avoidance strategies resulted in a similar incidence of major vascular complications. PRIMARY FUNDING SOURCE: Canadian Institutes of Health Research, National Health and Medical Research Council (Australia), and Research Grant Council of Hong Kong.

Tranexamic Acid in Patients Undergoing Noncardiac Surgery.

BACKGROUND: Perioperative bleeding is common in patients undergoing noncardiac surgery. Tranexamic acid is an antifibrinolytic drug that may safely decrease such bleeding. METHODS: We conducted a trial involving patients undergoing noncardiac surgery. Patients were randomly assigned to receive tranexamic acid (1-g intravenous bolus) or placebo at the start and end of surgery (reported here) and, with the use of a partial factorial design, a hypotension-avoidance or hypertension-avoidance strategy (not reported here). The primary efficacy outcome was life-threatening bleeding, major bleeding, or bleeding into a critical organ (composite bleeding outcome) at 30 days. The primary safety outcome was myocardial injury after noncardiac surgery, nonhemorrhagic stroke, peripheral arterial thrombosis, or symptomatic proximal venous thromboembolism (composite cardiovascular outcome) at 30 days. To establish the noninferiority of tranexamic acid to placebo for the composite cardiovascular outcome, the upper boundary of the one-sided 97.5% confidence interval for the hazard ratio had to be below 1.125, and the one-sided P value had to be less than 0.025. RESULTS: A total of 9535 patients underwent randomization. A composite bleeding outcome event occurred in 433 of 4757 patients (9.1%) in the tranexamic acid group and in 561 of 4778 patients (11.7%) in the placebo group (hazard ratio, 0.76; 95% confidence interval [CI], 0.67 to 0.87; absolute difference, -2.6 percentage points; 95% CI, -3.8 to -1.4; two-sided P<0.001 for superiority). A composite cardiovascular outcome event occurred in 649 of 4581 patients (14.2%) in the tranexamic acid group and in 639 of 4601 patients (13.9%) in the placebo group (hazard ratio, 1.02; 95% CI, 0.92 to 1.14; upper boundary of the one-sided 97.5% CI, 1.14; absolute difference, 0.3 percentage points; 95% CI, -1.1 to 1.7; one-sided P = 0.04 for noninferiority). CONCLUSIONS: Among patients undergoing noncardiac surgery, the incidence of the composite bleeding outcome was significantly lower with tranexamic acid than with placebo. Although the between-group difference in the composite cardiovascular outcome was small, the noninferiority of tranexamic acid was not established. (Funded by the Canadian Institutes of Health Research and others; POISE-3 ClinicalTrials.gov number, NCT03505723.).

High-Sensitivity Troponin I after Cardiac Surgery and 30-Day Mortality.

BACKGROUND: Consensus recommendations regarding the threshold levels of cardiac troponin elevations for the definition of perioperative myocardial infarction and clinically important periprocedural myocardial injury in patients undergoing cardiac surgery range widely (from >10 times to ≥70 times the upper reference limit for the assay). Limited evidence is available to support these recommendations. METHODS: We undertook an international prospective cohort study involving patients 18 years of age or older who underwent cardiac surgery. High-sensitivity cardiac troponin I measurements (upper reference limit, 26 ng per liter) were obtained 3 to 12 hours after surgery and on days 1, 2, and 3 after surgery. We performed Cox analyses using a regression spline that explored the relationship between peak troponin measurements and 30-day mortality, adjusting for scores on the European System for Cardiac Operative Risk Evaluation II (which estimates the risk of death after cardiac surgery on the basis of 18 variables, including age and sex). RESULTS: Of 13,862 patients included in the study, 296 (2.1%) died within 30 days after surgery. Among patients who underwent isolated coronary-artery bypass grafting or aortic-valve replacement or repair, the threshold troponin level, measured within 1 day after surgery, that was associated with an adjusted hazard ratio of more than 1.00 for death within 30 days was 5670 ng per liter (95% confidence interval [CI], 1045 to 8260), a level 218 times the upper reference limit. Among patients who underwent other cardiac surgery, the corresponding threshold troponin level was 12,981 ng per liter (95% CI, 2673 to 16,591), a level 499 times the upper reference limit. CONCLUSIONS: The levels of high-sensitivity troponin I after cardiac surgery that were associated with an increased risk of death within 30 days were substantially higher than levels currently recommended to define clinically important periprocedural myocardial injury. (Funded by the Canadian Institutes of Health Research and others; VISION Cardiac Surgery ClinicalTrials.gov number, NCT01842568.).

Rationale and design of the PeriOperative ISchemic Evaluation-3 (POISE-3): a randomized controlled trial evaluating tranexamic acid and a strategy to minimize hypotension in noncardiac surgery.

BACKGROUND: For patients undergoing noncardiac surgery, bleeding and hypotension are frequent and associated with increased mortality and cardiovascular complications. Tranexamic acid (TXA) is an antifibrinolytic agent with the potential to reduce surgical bleeding; however, there is uncertainty about its efficacy and safety in noncardiac surgery. Although usual perioperative care is commonly consistent with a hypertension-avoidance strategy (i.e., most patients continue their antihypertensive medications throughout the perioperative period and intraoperative mean arterial pressures of 60 mmHg are commonly accepted), a hypotension-avoidance strategy may improve perioperative outcomes. METHODS: The PeriOperative Ischemic Evaluation (POISE)-3 Trial is a large international randomized controlled trial designed to determine if TXA is superior to placebo for the composite outcome of life-threatening, major, and critical organ bleeding, and non-inferior to placebo for the occurrence of major arterial and venous thrombotic events, at 30 days after randomization. Using a partial factorial design, POISE-3 will additionally determine the effect of a hypotension-avoidance strategy versus a hypertension-avoidance strategy on the risk of major cardiovascular events, at 30 days after randomization. The target sample size is 10,000 participants. Patients ≥45 years of age undergoing noncardiac surgery, with or at risk of cardiovascular and bleeding complications, are randomized to receive a TXA 1 g intravenous bolus or matching placebo at the start and at the end of surgery. Patients, health care providers, data collectors, outcome adjudicators, and investigators are blinded to the treatment allocation. Patients on ≥ 1 chronic antihypertensive medication are also randomized to either of the two blood pressure management strategies, which differ in the management of patient antihypertensive medications on the morning of surgery and on the first 2 days after surgery, and in the target mean arterial pressure during surgery. Outcome adjudicators are blinded to the blood pressure treatment allocation. Patients are followed up at 30 days and 1 year after randomization. DISCUSSION: Bleeding and hypotension in noncardiac surgery are common and have a substantial impact on patient prognosis. The POISE-3 trial will evaluate two interventions to determine their impact on bleeding, cardiovascular complications, and mortality. TRIAL REGISTRATION: ClinicalTrials.gov NCT03505723. Registered on 23 April 2018.

Causes of cardiovascular and noncardiovascular death in the ISCHEMIA trial.

BACKGROUND: The International Study of Comparative Health Effectiveness with Medical and Invasive Approaches trial demonstrated no overall difference in the composite primary endpoint and the secondary endpoints of cardiovascular (CV) death/myocardial infarction or all-cause mortality between an initial invasive or conservative strategy among participants with chronic coronary disease and moderate or severe myocardial ischemia. Detailed cause-specific death analyses have not been reported. METHODS: We compared overall and cause-specific death rates by treatment group using Cox models with adjustment for pre-specified baseline covariates. Cause of death was adjudicated by an independent Clinical Events Committee as CV, non-CV, and undetermined. We evaluated the association of risk factors and treatment strategy with cause of death. RESULTS: Four-year cumulative incidence rates for CV death were similar between invasive and conservative strategies (2.6% vs 3.0%; hazard ratio [HR] 0.98; 95% CI [0.70-1.38]), but non-CV death rates were higher in the invasive strategy (3.3% vs 2.1%; HR 1.45 [1.00-2.09]). Overall, 13% of deaths were attributed to undetermined causes (38/289). Fewer undetermined deaths (0.6% vs 1.3%; HR 0.48 [0.24-0.95]) and more malignancy deaths (2.0% vs 0.8%; HR 2.11 [1.23-3.60]) occurred in the invasive strategy than in the conservative strategy. CONCLUSIONS: In International Study of Comparative Health Effectiveness with Medical and Invasive Approaches, all-cause and CV death rates were similar between treatment strategies. The observation of fewer undetermined deaths and more malignancy deaths in the invasive strategy remains unexplained. These findings should be interpreted with caution in the context of prior studies and the overall trial results.

Perioperative Troponin Screening Identifies Patients at Higher Risk for Major Cardiovascular Events in Noncardiac Surgery.

Myocardial injury after noncardiac surgery (MINS) includes patients with traditional myocardial infarction and those with ischemic myocardial injury after surgery. This study evaluated the prognostic value of MINS on major cardiovascular events and 30-day mortality, and determined independent preoperative predictors of MINS in patients after noncardiac surgery. This multicenter prospective cohort study was part of the VISION Study. The sample consisted of 2504 patients who underwent noncardiac surgery at 2 tertiary hospitals in Brazil between September 2008 and July 2012. Troponin Ts were measured 6-12 hours, and on days 1-3 after surgery. Cox regression analyses were performed to identify independent variables of major outcomes. A total of 314 (13%) patients were diagnosed with MINS, of which 26 (8%) died. Length-of-hospital stay of MINS patients was 3 times higher (18 ± 22 days vs 5.8 ± 11 days). In multivariate analysis, 30-day mortality was significantly higher among patients with MINS (hazard ratio [HR] 3.17 (95% confidence interval [CI] 1.56-6.41)), and major bleeding (HR 5.76 (95% CI 2.75-12.05)), sepsis (HR 5.08 (95% CI 2.25-11.46)), active cancer (HR 4.22 (95% CI 1.98-8.98)), and general surgery (HR 3.11 (95% CI 1.51-6.41)). Multivariable analysis indicated a higher chance of MINS in patients ≥75 years of age, history of diabetes mellitus, hypertension, heart failure, coronary disease, and end-stage renal failure. The incidence of MINS within 30 days after noncardiac surgery is related to higher mortality. Postoperative troponin monitoring in elder patients and with risk factors for atherosclerotic disease may help reduce postoperative cardiovascular events.

Association between complications and death within 30 days after noncardiac surgery.

BACKGROUND: Among adults undergoing contemporary noncardiac surgery, little is known about the frequency and timing of death and the associations between perioperative complications and mortality. We aimed to establish the frequency and timing of death and its association with perioperative complications. METHODS: We conducted a prospective cohort study of patients aged 45 years and older who underwent inpatient noncardiac surgery at 28 centres in 14 countries. We monitored patients for complications until 30 days after surgery and determined the relation between these complications and 30-day mortality using a Cox proportional hazards model. RESULTS: We included 40 004 patients. Of those, 715 patients (1.8%) died within 30 days of surgery. Five deaths (0.7%) occurred in the operating room, 500 deaths (69.9%) occurred after surgery during the index admission to hospital and 210 deaths (29.4%) occurred after discharge from the hospital. Eight complications were independently associated with 30-day mortality. The 3 complications with the largest attributable fractions (AF; i.e., potential proportion of deaths attributable to these complications) were major bleeding (6238 patients, 15.6%; adjusted hazard ratio [HR] 2.6, 95% confidence interval [CI] 2.2-3.1; AF 17.0%); myocardial injury after noncardiac surgery [MINS] (5191 patients, 13.0%; adjusted HR 2.2, 95% CI 1.9-2.6; AF 15.9%); and sepsis (1783 patients, 4.5%; adjusted HR 5.6, 95% CI 4.6-6.8; AF 12.0%). INTERPRETATION: Among adults undergoing noncardiac surgery, 99.3% of deaths occurred after the procedure and 44.9% of deaths were associated with 3 complications: major bleeding, MINS and sepsis. Given these findings, focusing on the prevention, early identification and management of these 3 complications holds promise for reducing perioperative mortality. Study registration: ClinicalTrials.gov, no. NCT00512109.

Efficacy of Anti-HER2 Agents in Combination With Adjuvant or Neoadjuvant Chemotherapy for Early and Locally Advanced HER2-Positive Breast Cancer Patients: A Network Meta-Analysis.

BACKGROUND: Several (neo)adjuvant treatments for patients with HER2-positive breast cancer have been compared in different randomized clinical trials. Since it is not feasible to conduct adequate pairwise comparative trials of all these therapeutic options, network meta-analysis offers an opportunity for more detailed inference for evidence-based therapy. METHODS: Phase II/III randomized clinical trials comparing two or more different (neo)adjuvant treatments for HER2-positive breast cancer patients were included. Relative treatment effects were pooled in two separate network meta-analyses for overall survival (OS) and disease-free survival (DFS). RESULTS: 17 clinical trials met our eligibility criteria. Two different networks of trials were created based on the availability of the outcomes: OS network (15 trials: 37,837 patients); and DFS network (17 trials: 40,992 patients). Two studies-the ExteNET and the NeoSphere trials-were included only in this DFS network because OS data have not yet been reported. The concept of the dual anti-HER2 blockade proved to be the best option in terms of OS and DFS. Chemotherapy (CT) plus trastuzumab (T) and lapatinib (L) and CT + T + Pertuzumab (P) are probably the best treatment options in terms of OS, with 62.47% and 22.06%, respectively. In the DFS network, CT + T + Neratinib (N) was the best treatment option with 50.55%, followed by CT + T + P (26.59%) and CT + T + L (20.62%). CONCLUSION: This network meta-analysis suggests that dual anti-HER2 blockade with trastuzumab plus either lapatinib or pertuzumab are probably the best treatment options in the (neo)adjuvant setting for HER2-positive breast cancer patients in terms of OS gain. Mature OS results are still expected for the Aphinity trial and for the sequential use of trastuzumab followed by neratinib, the treatment that showed the best performance in terms of DFS in our analysis.

Troponin T monitoring to detect myocardial injury after noncardiac surgery: a cost-consequence analysis.

BACKGROUND: Myocardial injury after noncardiac surgery (MINS) is a mostly asymptomatic condition that is strongly associated with 30-day mortality; however, it remains mostly undetected without systematic troponin T monitoring. We evaluated the cost and consequences of postoperative troponin T monitoring to detect MINS. METHODS: We conducted a model-based cost-consequence analysis to compare the impact of routine troponin T monitoring versus standard care (troponin T measurement triggered by ischemic symptoms) on the incidence of MINS detection. Model inputs were based on Canadian patients enrolled in the Vascular Events in Noncardiac Surgery Patients Cohort Evaluation (VISION) study, which enrolled patients aged 45 years or older undergoing inpatient noncardiac surgery. We conducted probability analyses with 10 000 iterations and extensive sensitivity analyses. RESULTS: The data were based on 6021 patients (48% men, mean age 65 [standard deviation 12] yr). The 30-day mortality rate for MINS was 9.6%. We determined the incremental cost to avoid missing a MINS event as $1632 (2015 Canadian dollars). The cost-effectiveness of troponin monitoring was higher in patient subgroups at higher risk for MINS, e.g., those aged 65 years or more, or with a history of atherosclerosis or diabetes ($1309). CONCLUSION: The costs associated with a troponin T monitoring program to detect MINS were moderate. Based on the estimated incremental cost per health gain, implementation of postoperative troponin T monitoring seems appealing, particularly in patients at high risk for MINS.

CONTEXTE: Les lésions myocardiques après chirurgie non cardiaque (CNC) sont majoritairement asymptomatiques et fortement associées au risque de mortalité dans les 30 jours; toutefois, dans la plupart des cas, elles ne sont pas détectées en l'absence d'une surveillance systématique de la troponine T. Nous avons évalué les coûts et les conséquences d'une telle surveillance pour détecter les lésions myocardiques après CNC. MÉTHODES: Nous avons mené une analyse coût-conséquence modélisée pour comparer la surveillance systématique de la troponine T aux soins habituels seuls (mesure de la troponine T seulement s'il y a présence de symptômes d'ischémie) sur la fréquence de détection de lésions myocardiques après CNC. Les données ayant servi à l'analyse provenaient des patients canadiens ayant participé à l'étude de cohorte VISION, qui visait à évaluer les complications vasculaires chez les patients de 45 ans et plus ayant subi une CNC. Nous avons mené des analyses de probabilité avec 10  000 itérations et des analyses de sensibilité approfondies. RÉSULTATS: Les données portaient sur 6021 patients (48 % du sexe masculin; âge moyen de 65 ans [écart-type de 12 ans]). Le taux de mortalité dans les 30 jours associé à une lésion myocardique après CNC était de 9,6 %. Nous avons déterminé que le coût marginal de la détection de la présence d'une lésion par surveillance de la troponine T était de 1632 $ (dollars canadiens en 2015). Le rapport coût-efficacité était plus bas pour les sous-groupes de patients à risque élevé de lésion myocardique après CNC, comme les patients de 65 ans et plus ou ceux ayant des antécédents d'athérosclérose ou de diabète (1309 $), que pour leurs pairs. CONCLUSION: Les coûts associés à un programme de surveillance de la troponine T pour détecter les lésions myocardiques après CNC étaient modérés. Le coût marginal estimé par gain de santé indique que la mise en œuvre de ce type de programme pourrait être une option intéressante, surtout pour les patients à risque élevé de lésion myocardique après CNC.

Effectiveness evaluation of mood disorder treatment algorithms in Brazilian public healthcare patients

Objective: To assess the effectiveness of three mood disorder treatment algorithms in a sample of patients seeking care in the Brazilian public healthcare system. Methods: A randomized pragmatic trial was conducted with an algorithm developed for treating episodes of major depressive disorder (MDD), bipolar depressive episodes and mixed episodes of bipolar disorder (BD). Results: The sample consisted of 259 subjects diagnosed with BD or MDD (DSM-IV-TR). After the onset of symptoms, the first treatment occurred ∼6 years and the use of mood stabilizers began ∼12 years. All proposed algorithms were effective, with response rates around 80%. The majority of the subjects took 20 weeks to obtain a therapeutic response. Conclusions: The algorithms were effective with the medications available through the Brazilian Unified Health System. Because therapeutic response was achieved in most subjects by 20 weeks, a follow-up period longer than 12 weeks may be required to confirm adequate response to treatment. Remission of symptoms is still the main desired outcome. Subjects who achieved remission recovered more rapidly and remained more stable over time. Clinical trial registration: NCT02901249, NCT02870283, NCT02918097

Effectiveness evaluation of mood disorder treatment algorithms in Brazilian public healthcare patients.

OBJECTIVE: To assess the effectiveness of three mood disorder treatment algorithms in a sample of patients seeking care in the Brazilian public healthcare system. METHODS: A randomized pragmatic trial was conducted with an algorithm developed for treating episodes of major depressive disorder (MDD), bipolar depressive episodes and mixed episodes of bipolar disorder (BD). RESULTS: The sample consisted of 259 subjects diagnosed with BD or MDD (DSM-IV-TR). After the onset of symptoms, the first treatment occurred ∼6 years and the use of mood stabilizers began ∼12 years. All proposed algorithms were effective, with response rates around 80%. The majority of the subjects took 20 weeks to obtain a therapeutic response. CONCLUSIONS: The algorithms were effective with the medications available through the Brazilian Unified Health System. Because therapeutic response was achieved in most subjects by 20 weeks, a follow-up period longer than 12 weeks may be required to confirm adequate response to treatment. Remission of symptoms is still the main desired outcome. Subjects who achieved remission recovered more rapidly and remained more stable over time. CLINICAL TRIAL REGISTRATION: NCT02901249, NCT02870283, NCT02918097.

Myocardial Injury After Noncardiac Surgery (MINS) in Vascular Surgical Patients: A Prospective Observational Cohort Study.

OBJECTIVE: To determine the prognostic relevance, clinical characteristics, and 30-day outcomes associated with myocardial injury after noncardiac surgery (MINS) in vascular surgical patients. BACKGROUND: MINS has been independently associated with 30-day mortality after noncardiac surgery. The characteristics and prognostic importance of MINS in vascular surgery patients are poorly described. METHODS: This was an international prospective cohort study of 15,102 noncardiac surgery patients 45 years or older, of whom 502 patients underwent vascular surgery. All patients had fourth-generation plasma troponin T (TnT) concentrations measured during the first 3 postoperative days. MINS was defined as a TnT of 0.03 ng/mL of higher secondary to ischemia. The objectives of the present study were to determine (i) if MINS is prognostically important in vascular surgical patients, (ii) the clinical characteristics of vascular surgery patients with and without MINS, (iii) the 30-day outcomes for vascular surgery patients with and without MINS, and (iv) the proportion of MINS that probably would have gone undetected without routine troponin monitoring. RESULTS: The incidence of MINS in the vascular surgery patients was 19.1% (95% confidence interval (CI), 15.7%-22.6%). 30-day all-cause mortality in the vascular cohort was 12.5% (95% CI 7.3%-20.6%) in patients with MINS compared with 1.5% (95% CI 0.7%-3.2%) in patients without MINS (P < 0.001). MINS was independently associated with 30-day mortality in vascular patients (odds ratio, 9.48; 95% CI, 3.46-25.96). The 30-day mortality was similar in MINS patients with (15.0%; 95% CI, 7.1-29.1) and without an ischemic feature (12.2%; 95% CI, 5.3-25.5, P = 0.76). The proportion of vascular surgery patients who suffered MINS without overt evidence of myocardial ischemia was 74.1% (95% CI, 63.6-82.4). CONCLUSIONS: Approximately 1 in 5 patients experienced MINS after vascular surgery. MINS was independently associated with 30-day mortality. The majority of patients with MINS were asymptomatic and would have gone undetected without routine postoperative troponin measurement.

Causes and Predictors of In-Hospital Mortality in Patients Admitted with or for Heart Failure at a Tertiary Hospital in Brazil / Causas e Preditores de Mortalidade Intra-Hospitalar em Pacientes que Internam com ou por Insuficiência Cardíaca em Hospital Terciário no Brasil

Abstract Background: Although heart failure (HF) has high morbidity and mortality, studies in Latin America on causes and predictors of in-hospital mortality are scarce. We also do not know the evolution of patients with compensated HF hospitalized for other reasons. Objective: To identify causes and predictors of in-hospital mortality in patients hospitalized for acute decompensated HF (ADHF), compared to those with HF and admitted to the hospital for non-HF related causes (NDHF). Methods: Historical cohort of patients hospitalized in a public tertiary hospital in Brazil with a diagnosis of HF identified by the Charlson Comorbidity Index (CCI). Results: A total of 2056 patients hospitalized between January 2009 and December 2010 (51% men, median age of 71 years, length of stay of 15 days) were evaluated. There were 17.6% of deaths during hospitalization, of which 58.4% were non-cardiovascular (63.6% NDHF vs 47.4% ADHF, p = 0.004). Infectious causes were responsible for most of the deaths and only 21.6% of the deaths were attributed to HF. The independent predictors of in-hospital mortality were similar between the groups and included: age, length of stay, elevated potassium, clinical comorbidities, and CCI. Renal insufficiency was the most relevant predictor in both groups. Conclusion: Patients hospitalized with HF have high in-hospital mortality, regardless of the primary reason for hospitalization. Few deaths are directly attributed to HF; Age, renal function and levels of serum potassium, length of stay, comorbid burden and CCI were independent predictors of in-hospital death in a Brazilian tertiary hospital.

Resumo Fundamento: Apesar da insuficiência cardíaca (IC) apresentar elevada morbimortalidade, são escassos os estudos na América Latina sobre causas e preditores de mortalidade intra-hospitalar. Desconhece-se, também, a evolução de pacientes com IC compensada hospitalizados por outros motivos. Objetivo: Identificar causas e preditores de mortalidade intra-hospitalar em pacientes que internam por IC aguda descompensada (ICAD), comparativamente aqueles que possuem IC e internam por outras condições (ICND). Métodos: Coorte histórica de pacientes internados em um hospital público terciário no Brasil com diagnóstico de IC identificados pelo escore de comorbidade de Charlson (ECCharlson). Resultados: Foram avaliados 2056 pacientes que internaram entre janeiro de 2009 e dezembro de 2010 (51% homens; idade mediana de 71 anos; tempo de permanência de 15 dias). Ocorreram 17,6% de óbitos durante a internação, dos quais 58,4% por causa não cardiovascular (63,6% ICND versus 47,4% ICAD, p = 0,004). As causas infecciosas foram responsáveis pela maior parte dos óbitos e apenas 21.6% das mortes foram atribuídas à IC. Os preditores independentes de mortalidade intra-hospitalar foram semelhantes entre os grupos e incluíram: idade, tempo de permanência, potássio elevado, comorbidades clínicas e ECCharlson. A insuficiência renal foi o preditor de maior relevância em ambos grupos. Conclusão: Pacientes internados com IC apresentam elevada mortalidade intra-hospitalar, independentemente do motivo primário de internação. Poucos óbitos são diretamente atribuídos à IC; Idade, alteração na função renal e níveis séricos de potássio, tempo de permanência, comorbidades e ECCharlson foram preditores independentes de morte intra-hospitalar em hospital terciário brasileiro. (Arq Bras Cardiol. 2017; [online].ahead print, PP.0-0)

Association of Postoperative High-Sensitivity Troponin Levels With Myocardial Injury and 30-Day Mortality Among Patients Undergoing Noncardiac Surgery.

IMPORTANCE: Little is known about the relationship between perioperative high-sensitivity troponin T (hsTnT) measurements and 30-day mortality and myocardial injury after noncardiac surgery (MINS). OBJECTIVE: To determine the association between perioperative hsTnT measurements and 30-day mortality and potential diagnostic criteria for MINS (ie, myocardial injury due to ischemia associated with 30-day mortality). DESIGN, SETTING, AND PARTICIPANTS: Prospective cohort study of patients aged 45 years or older who underwent inpatient noncardiac surgery and had a postoperative hsTnT measurement. Starting in October 2008, participants were recruited at 23 centers in 13 countries; follow-up finished in December 2013. EXPOSURES: Patients had hsTnT measurements 6 to 12 hours after surgery and daily for 3 days; 40.4% had a preoperative hsTnT measurement. MAIN OUTCOMES AND MEASURES: A modified Mazumdar approach (an iterative process) was used to determine if there were hsTnT thresholds associated with risk of death and had an adjusted hazard ratio (HR) of 3.0 or higher and a risk of 30-day mortality of 3% or higher. To determine potential diagnostic criteria for MINS, regression analyses ascertained if postoperative hsTnT elevations required an ischemic feature (eg, ischemic symptom or electrocardiography finding) to be associated with 30-day mortality. RESULTS: Among 21 842 participants, the mean age was 63.1 (SD, 10.7) years and 49.1% were female. Death within 30 days after surgery occurred in 266 patients (1.2%; 95% CI, 1.1%-1.4%). Multivariable analysis demonstrated that compared with the reference group (peak hsTnT <5 ng/L), peak postoperative hsTnT levels of 20 to less than 65 ng/L, 65 to less than 1000 ng/L, and 1000 ng/L or higher had 30-day mortality rates of 3.0% (123/4049; 95% CI, 2.6%-3.6%), 9.1% (102/1118; 95% CI, 7.6%-11.0%), and 29.6% (16/54; 95% CI, 19.1%-42.8%), with corresponding adjusted HRs of 23.63 (95% CI, 10.32-54.09), 70.34 (95% CI, 30.60-161.71), and 227.01 (95% CI, 87.35-589.92), respectively. An absolute hsTnT change of 5 ng/L or higher was associated with an increased risk of 30-day mortality (adjusted HR, 4.69; 95% CI, 3.52-6.25). An elevated postoperative hsTnT (ie, 20 to <65 ng/L with an absolute change ≥5 ng/L or hsTnT ≥65 ng/L) without an ischemic feature was associated with 30-day mortality (adjusted HR, 3.20; 95% CI, 2.37-4.32). Among the 3904 patients (17.9%; 95% CI, 17.4%-18.4%) with MINS, 3633 (93.1%; 95% CI, 92.2%-93.8%) did not experience an ischemic symptom. CONCLUSIONS AND RELEVANCE: Among patients undergoing noncardiac surgery, peak postoperative hsTnT during the first 3 days after surgery was significantly associated with 30-day mortality. Elevated postoperative hsTnT without an ischemic feature was also associated with 30-day mortality.

Periodontal disease and inflammatory blood cytokines in patients with stable coronary artery disease.

MATERIAL AND METHODS: This cross-sectional study included 91 patients with stable CAD who had been under optimized cardiovascular care. Blood levels of IL-1ß, IL-6, IL-8, IL-10, IFN-γ, and TNF-α were measured by Luminex technology. A full-mouth periodontal examination was conducted to record probing depth (PD) and clinical attachment (CA) loss. Multiple linear regression models, adjusting for gender, body mass index, oral hypoglycemic drugs, smoking, and occurre:nce of acute myocardial infarction were applied. RESULTS: CAD patients that experienced major events had higher concentrations of IFN-γ (median: 5.05 pg/mL vs. 3.01 pg/mL; p=0.01), IL-10 (median: 2.33 pg/mL vs. 1.01 pg/mL; p=0.03), and TNF-α (median: 9.17 pg/mL vs. 7.47 pg/mL; p=0.02). Higher numbers of teeth with at least 6 mm of CA loss (R2=0.07) and PD (R2=0.06) were significantly associated with higher IFN-γ log concentrations. Mean CA loss (R2=0.05) and PD (R2=0.06) were significantly related to IL-10 concentrations. Elevated concentrations of TNF-α were associated with higher mean CA loss (R2=0.07). CONCLUSION: Periodontal disease is associated with increased systemic inflammation in stable cardiovascular patients. These findings provide additional evidence supporting the idea that periodontal disease can be a prognostic factor in cardiovascular patients.

Periodontal disease and inflammatory blood cytokines in patients with stable coronary artery disease

ABSTRACT Periodontal disease has been associated with elevations of blood cytokines involved in atherosclerosis in systemically healthy individuals, but little is known about this association in stable cardiovascular patients. The aim of this study was to assess the association between periodontal disease (exposure) and blood cytokine levels (outcomes) in a target population of patients with stable coronary artery disease (CAD). Material and Methods This cross-sectional study included 91 patients with stable CAD who had been under optimized cardiovascular care. Blood levels of IL-1β, IL-6, IL-8, IL-10, IFN-γ, and TNF-α were measured by Luminex technology. A full-mouth periodontal examination was conducted to record probing depth (PD) and clinical attachment (CA) loss. Multiple linear regression models, adjusting for gender, body mass index, oral hypoglycemic drugs, smoking, and occurre:nce of acute myocardial infarction were applied. Results CAD patients that experienced major events had higher concentrations of IFN-γ (median: 5.05 pg/mL vs. 3.01 pg/mL; p=0.01), IL-10 (median: 2.33 pg/mL vs. 1.01 pg/mL; p=0.03), and TNF-α (median: 9.17 pg/mL vs. 7.47 pg/mL; p=0.02). Higher numbers of teeth with at least 6 mm of CA loss (R2=0.07) and PD (R2=0.06) were significantly associated with higher IFN-γ log concentrations. Mean CA loss (R2=0.05) and PD (R2=0.06) were significantly related to IL-10 concentrations. Elevated concentrations of TNF-α were associated with higher mean CA loss (R2=0.07). Conclusion Periodontal disease is associated with increased systemic inflammation in stable cardiovascular patients. These findings provide additional evidence supporting the idea that periodontal disease can be a prognostic factor in cardiovascular patients.

Impacto da Doença Periodontal no Perfil Lipídico de Pacientes com Doença Arterial Coronariana Crônica: uma Coorte Retrospectiva de 3 anos / Impact of Periodontal Disease in the Lipid Profile of Patients With Chronic Coronary Artery Disease: a 3-Year, Retrospective Cohort

Fundamento: A inflamação tem sido reconhecida como um importante fator de risco para as doenças cardiovasculares. A doença periodontal pode acarretar alterações de alguns marcadores plasmáticos envolvidos no processo aterogênico. Objetivo: Avaliar a associação entre a doença periodontal e os níveis lipídicos ao longo do tempo em pacientes com doença arterial coronariana crônica. Métodos: Este estudo de coorte retrospectivo incluiu uma amostra de pacientes cardiopatas crônicos recebendo atendimento em um ambulatório de atenção terciária de cardiopatia isquêmica. Dos 239 pacientes elegíveis, foram incluídos 80 que apresentavam dados retrospectivos de perfil lipídico entre 2009 e 2011. Foram realizados exames periodontais de todos os dentes presentes em 2011. Modelos múltiplos de equações de estimação generalizada foram aplicados para avaliar a associação entre parâmetros periodontais e alterações ao longo do tempo nos seguintes desfechos: triglicerídeos, colesterol total, LDL-colesterol e HDL-colesterol, com ajustes para idade, índice de massa corporal, fumo, uso de hipoglicemiante oral e tempo de acompanhamento. Resultados: Durante um tempo médio de acompanhamento de 713 dias, não houve mudanças significativas nas concentrações de triglicerídeos, colesterol total e LDL-colesterol. Um aumento significativo de 31,6% nos níveis de HDL-colesterol foi observado entre 2009 e 2011. Observamos uma associação negativa e significativa entre a média individual de perda de inserção periodontal e nível de HDL-colesterol, indicando que quanto maior a perda de inserção, mais baixos os níveis de HDL-colesterol ao longo do tempo. Conclusão: A doença periodontal destrutiva pode estar relacionada com um pior controle lipídico, particularmente relacionado a níveis de HDL-colesterol, em pacientes cardiopatas crônicos

Background: Inflammation has been recognized as an important risk factor for cardiovascular diseases. Periodontal disease may alter some plasma markers involved in the atherogenic process. Objective: To assess the association between periodontal disease and lipid levels over time in patients with chronic coronary artery disease.Methods: This retrospective cohort study included a sample of patients with chronic heart disease receiving care in an outpatient tertiary care for ischemic heart disease. Of 239 patients eligible for the study, we included 80 patients who had available retrospective data of lipid profile between 2009 and 2011. We performed periodontal examinations of all teeth present in 2011. Multiple models of generalized estimating equations were applied to assess the association between periodontal parameters and changes over time in the following outcomes: triglycerides, total cholesterol, LDL-cholesterol, and HDL-cholesterol levels adjusted for age, body mass index, smoking, use of oral hypoglycemic, and follow-up duration. Results: During a mean follow-up time of 713 days, there were no significant changes in the concentrations of triglycerides, total cholesterol, and LDL-cholesterol. A significant 31.6% increase in HDL-cholesterol levels was observed between 2009 and 2011. We observed a significant negative association between mean individual periodontal attachment loss and HDL- cholesterol levels, indicating that the greater the attachment loss, the lower the HDL-cholesterol level over time. Conclusion: Destructive periodontal disease may be related to a worse lipid control, specifically regarding HDL-cholesterol levels, in chronic cardiac patients

Cost-utility analysis of methylphenidate treatment for children and adolescents with ADHD in Brazil

Objective: To perform a cost-utility analysis on the treatment of attention deficit hyperactivity disorder (ADHD) with methylphenidate immediate-release (MPH-IR) in children and adolescents from Brazil. Method: A Markov model was constructed to compare MPH-IR vs. no treatment. A 24-week naturalistic study was conducted to collect transition probabilities and utility data. Effectiveness was expressed as quality-adjusted life-years (QALY), and costs reported in 2014 international dollars (I$). The perspective was the Brazilian Unified Health System as payer, and the time horizon was 6 years. Results: Of 171 patients, 73 provided information at baseline, and 56 at week 24. Considering the MPH-IR monthly cost of I$ 38, the incremental cost-effectiveness ratio (ICER) of treatment was I$ 9,103/QALY for children and I$ 11,883/QALY for adolescents. In two-way sensitivity analysis, considering one Gross National Product per capita (I$ 11,530) as willingness-to-pay, a cost of no-treatment lower than I$ 45/month would render MPH-IR a cost-saving strategy. Discussion: MPH-IR treatment of children and adolescents is cost-effective for ADHD patients from the Brazilian public health system perspective. Both patients and the healthcare system might benefit from such a strategy. Trial registration number: NCT01705613.