World Stroke Organization Brain & hEart globAl iniTiative Program.

INTRODUCTION: The World Stroke Organization (WSO) Brain & Heart Task Force developed the Brain & hEart globAl iniTiative (BEAT), a pilot feasibility implementation program to establish clinical collaborations between cardiologists and stroke physicians who work at large healthcare facilities. METHODS: The WSO BEAT pilot project focused on atrial fibrillation (AF) and patent foramen ovale (PFO) detection and management, and poststroke cardiovascular complications known as the stroke-heart syndrome. The program included 10 sites from 8 countries: Brazil, China, Egypt, Germany, Japan, Mexico, Romania, and the USA The primary composite feasibility outcome was the achievement of the following 3 implementation metrics (1) developing site-specific clinical pathways for the diagnosis and management of AF, PFO, and the stroke-heart syndrome; (2) establishing regular Neurocardiology rounds (e.g., monthly); and (3) incorporating a cardiologist to the stroke team. The secondary objectives were (1) to identify implementation challenges to guide a larger program and (2) to describe qualitative improvements. RESULTS: The WSO BEAT pilot feasibility program achieved the prespecified primary composite outcome in 9 of 10 (90%) sites. The most common challenges were the limited access to specific medications (e.g., direct oral anticoagulants) and diagnostic (e.g., prolonged cardiac monitoring) or therapeutic (e.g., PFO closure devices) technologies. The most relevant qualitative improvement was the achievement of a more homogeneous diagnostic and therapeutic approach. CONCLUSION: The WSO BEAT pilot program suggests that developing neurocardiology collaborations is feasible. The long-term sustainability of the WSO BEAT program and its impact on quality of stroke care and clinical outcomes needs to be tested in a larger and longer duration program.

Cardiovascular Safety of Azithromycin in Patients Hospitalized With COVID-19: A Prespecified Pooled Analysis of the COALITION I and COALITION II Randomized Clinical Trials.

The cardiovascular safety from azithromycin in the treatment of several infectious diseases has been challenged. In this prespecified pooled analysis of 2 multicenter randomized clinical trials, we aimed to assess whether the use of azithromycin might lead to corrected QT (QTc) interval prolongation or clinically relevant ventricular arrhythmias. In the COALITION COVID Brazil I trial, 667 patients admitted with moderate COVID-19 were randomly allocated to hydroxychloroquine, hydroxychloroquine plus azithromycin, or standard of care. In the COALITION COVID Brazil II trial, 447 patients with severe COVID-19 were randomly allocated to hydroxychloroquine alone versus hydroxychloroquine plus azithromycin. The principal end point for the present analysis was the composite of death, resuscitated cardiac arrest, or ventricular arrhythmias. The addition of azithromycin to hydroxychloroquine did not result in any prolongation of the QTc interval (425.8 ± 3.6 ms vs 427.9 ± 3.9 ms, respectively, mean difference -2.1 ms, 95% confidence interval -12.5 to 8.4 ms, p = 0.70). The combination of azithromycin plus hydroxychloroquine compared with hydroxychloroquine alone did not result in increased risk of the primary end point (proportion of patients with events at 15 days 17.2% vs 16.0%, respectively, hazard ratio 1.08, 95% confidence interval 0.78 to 1.49, p = 0.65). In conclusion, in patients hospitalized with COVID-19 already receiving standard-of-care management (including hydroxychloroquine), the addition of azithromycin did not result in the prolongation of the QTc interval or increase in cardiovascular adverse events. Because azithromycin is among the most commonly prescribed antimicrobial agents, our results may inform clinical practice. Clinical Trial Registration: NCT04322123, NCT04321278.

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.

Value-based Reimbursement as a Mechanism to Achieve Social and Financial Impact in the Healthcare System.

Value-based reimbursement strategies have been considered in the continuous search for establishing a sustainable healthcare system. For models that have been already implemented, success is demonstrated according to specific details of the patients' consumption profile based on their clinical condition and the risk balance among all the stakeholders. From fee-for-service to value-based bundled payment strategies, the manner in which accurate patient-level cost and outcome information are used varies, resulting in different risk agreements between stakeholders. A thorough understanding of value-based reimbursement agreements that views such agreements as a mechanism for risk management is critical to the task of ensuring that the healthcare system generates social impacts while ensuring financial sustainability. This perspective article focuses on a critical analysis of the impact of value-based reimbursement strategies on the healthcare system from a social and financial perspective. A critical analysis of the literature about value-based reimbursement was used to identify how these strategies impact healthcare systems. The literature analysis was followed by the conceptual description of value-based reimbursement agreements as mechanisms for achieving social and financial impacts on the healthcare system. There is no single successful path toward payment reform. Payment reform is used as a strategy to re-engineer the way in which the system is organized to provide care to patients, and its successful implementation leads to cultural, social, and financial changes. Stakeholders have reached consensus regarding the claim that the use of value reimbursement strategies and business models could increase efficiency and generate social impact by reducing healthcare inequity and improving population health. However, the successful implementation of such new strategies involves financial and social risks that require better management by all the stakeholders. The use of cutting-edge technologies are essential advances to manage these risks and must be paired with strong leadership focusing on the directive to improve population health and, consequently, value. Payment reform is used as a mechanism to re-engineer how the system is organized to deliver care to patients, and its successful implementation is expected to result in social and financial modifications to the healthcare system.

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.

Health-related quality of life outcomes in PARAGON-HF.

AIMS: Heart failure (HF) is associated with poor health-related quality of life (HRQL). Patients with HF with preserved ejection fraction (HFpEF) have similar HRQL impairment as those with reduced ejection fraction. This study describes the impact of sacubitril/valsartan on HRQL in patients with HFpEF enrolled in the PARAGON-HF trial. METHODS AND RESULTS: Patients completed the Kansas City Cardiomyopathy Questionnaire (KCCQ) and EuroQol (EQ-5D) at randomization, 4, 8 months, and annually thereafter. Changes in HRQL scores were evaluated using repeated measures models adjusted for treatment, baseline values and region. The pre-specified principal efficacy assessment was at 8 months at which time patients randomized to sacubitril/valsartan had borderline higher KCCQ clinical summary score (CSS) with least squares mean (LSM) adjusted difference of 1.0 (95% confidence interval [CI] 0.0, 2.1; p = 0.051). Including all visits up to 36 months, the LSM difference in KCCQ-CSS favoured sacubitril/valsartan with average adjusted difference of 1.1 (95% CI 0.1, 2.0; p = 0.034). Patients treated with sacubitril/valsartan had greater odds of clinically meaningful improvement (≥5-point increase) in KCCQ-CSS (odds ratio 1.31; 95% CI 1.06, 1.61) at 8 months. At 8 months, there was no significant difference in the EQ visual analogue scale between the treatment arms, but sacubitril/valsartan was associated with higher EQ-5D utility score (US-based) with LSM adjusted difference of 0.01 (95% CI 0.00, 0.02; p = 0.019). CONCLUSION: Compared with valsartan, sacubitril/valsartan had a borderline benefit on KCCQ-CSS at 8 months in patients with HFpEF. This benefit became more significant when data from all visits up to 36 months were included. This modest overall benefit was also supported by greater odds of patients reporting a clinically meaningful improvement in HRQL with sacubitril/valsartan.

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.

Transition of care of stable ischaemic heart disease patients from tertiary to primary care with telemedicine support: Randomized noninferiority clinical trial.

INTRODUCTION: Evidence of telehealth for chronic disease management is scarce and contradictory. OBJECTIVES: We aimed to evaluate the safety and efficacy of teleconsultations as support in the care transition of patients with stable coronary artery disease (CAD) from tertiary to primary care. METHODS: A randomized noninferiority clinical trial was undertaken in patients with CAD from a tertiary hospital in a middle-income country. Patients with functional angina class 1 or 2 and meeting discharge criteria were randomized to remain in the cardiology outpatient clinic for 12 months (control group, CG) or continue follow-up in a primary care unit with clinical support via telemedicine (intervention group, IG). The primary outcome was the maintenance of the functional angina class after 12 months. Secondary outcomes included control of risk factors and clinical outcomes. RESULTS: In total 271 patients (mean age, 66 years) were included; 81.1% and 91% of the IG and CG, respectively, maintained stable angina symptoms, thus noninferiority could not be shown between the groups. Regarding emergency room visits at 1 year, the IG (7.6%) was noninferior to the CG (6.0%) (absolute difference, 1.6%; noninferiority margin (NIM), -4.8% to 8.2%). For control of risk factors, 30.7% and 29.6% of the IG and CG, respectively, had blood pressure <130/80 mmHg (absolute difference, 1.1%; NIM, -10.5% to 12.8%), and 48.9% and 33.3% of diabetic patients in the IG and CG, respectively, had glycated haemoglobin <7% (absolute difference, 15.6%; NIM, -6.8% to 36%). CONCLUSIONS: In our study, the difference in the patients' angina functional class did not result in greater seeking of emergency care, supporting that discharge from the outpatient clinic with telemedicine is safe for patients with stable CAD treated at the tertiary level. The control of risk factors in these patients was noninferior to patients followed up in primary care. ClinicalTrials.gov (NCT02489565).

Dynamic changes in cardiovascular and systemic parameters prior to sudden cardiac death in heart failure with reduced ejection fraction: a PARADIGM-HF analysis.

AIMS: Prognostic models of sudden cardiac death (SCD) typically incorporate data at only a single time-point. We investigated independent predictors of SCD addressing the impact of integrating time-varying covariates to improve prediction assessment. METHODS AND RESULTS: We studied 8399 patients enrolled in the PARADIGM-HF trial and identified independent predictors of SCD (n = 561, 36% of total deaths) using time-updated multivariable-adjusted Cox models, classification and regression tree (CART), and logistic regression analysis. Compared with patients who were alive or died from non-sudden cardiovascular deaths, patients who suffered a SCD displayed a distinct temporal profile of New York Heart Association (NYHA) class, heart rate and levels of three biomarkers (albumin, uric acid and total bilirubin), with significant differences observed more than 1 year prior to the event (Pinteraction < 0.001). In multivariable models adjusted for baseline covariates, seven time-updated variables independently contributed to SCD risk (incremental likelihood chi-square = 46.2). CART analysis identified that baseline variables (implantable cardioverter-defibrillator use and N-terminal prohormone of B-type natriuretic peptide levels) and time-updated covariates (NYHA class, total bilirubin, and total cholesterol) improved risk stratification. CART-defined subgroup of highest risk had nearly an eightfold increment in SCD hazard (hazard ratio 7.7, 95% confidence interval 3.6-16.5; P < 0.001). Finally, changes over time in heart rate, NYHA class, blood urea nitrogen and albumin levels were associated with differential risk of sudden vs. non-sudden cardiovascular deaths (P < 0.05). CONCLUSIONS: Beyond single time-point assessments, distinct changes in multiple cardiac-specific and systemic variables improved SCD risk prediction and were helpful in differentiating mode of death in chronic heart failure.

Clinical characteristics and outcomes of patients hospitalized with COVID-19 in Brazil: Results from the Brazilian COVID-19 registry.

OBJECTIVES: To describe the clinical characteristics, laboratory results, imaging findings, and in-hospital outcomes of COVID-19 patients admitted to Brazilian hospitals. METHODS: A cohort study of laboratory-confirmed COVID-19 patients who were hospitalized from March 2020 to September 2020 in 25 hospitals. Data were collected from medical records using Research Electronic Data Capture (REDCap) tools. A multivariate Poisson regression model was used to assess the risk factors for in-hospital mortality. RESULTS: For a total of 2,054 patients (52.6% male; median age of 58 years), the in-hospital mortality was 22.0%; this rose to 47.6% for those treated in the intensive care unit (ICU). Hypertension (52.9%), diabetes (29.2%), and obesity (17.2%) were the most prevalent comorbidities. Overall, 32.5% required invasive mechanical ventilation, and 12.1% required kidney replacement therapy. Septic shock was observed in 15.0%, nosocomial infection in 13.1%, thromboembolism in 4.1%, and acute heart failure in 3.6%. Age >= 65 years, chronic kidney disease, hypertension, C-reactive protein ≥ 100mg/dL, platelet count < 100×109/L, oxygen saturation < 90%, the need for supplemental oxygen, and invasive mechanical ventilation at admission were independently associated with a higher risk of in-hospital mortality. The overall use of antimicrobials was 87.9%. CONCLUSIONS: This study reveals the characteristics and in-hospital outcomes of hospitalized patients with confirmed COVID-19 in Brazil. Certain easily assessed parameters at hospital admission were independently associated with a higher risk of death. The high frequency of antibiotic use points to an over-use of antimicrobials in COVID-19 patients.

Revisiting heart failure assessment based on objective measures in NYHA functional classes I and II.

OBJECTIVE: New York Heart Association (NYHA) functional class plays a central role in heart failure (HF) assessment but might be unreliable in mild presentations. We compared objective measures of HF functional evaluation between patients classified as NYHA I and II in the Rede Brasileira de Estudos em Insuficiência Cardíaca (ReBIC)-1 Trial. METHODS: The ReBIC-1 Trial included outpatients with stable HF with reduced ejection fraction. All patients had simultaneous protocol-defined assessment of NYHA class, 6 min walk test (6MWT), N-terminal pro-brain natriuretic peptide (NT-proBNP) levels and patient's self-perception of dyspnoea using a Visual Analogue Scale (VAS, range 0-100). RESULTS: Of 188 included patients with HF, 122 (65%) were classified as NYHA I and 66 (35%) as NYHA II at baseline. Although NYHA class I patients had lower dyspnoea VAS Scores (median 16 (IQR, 4-30) for class I vs 27.5 (11-49) for class II, p=0.001), overlap between classes was substantial (density overlap=60%). A similar profile was observed for NT-proBNP levels (620 pg/mL (248-1333) vs 778 (421-1737), p=0.015; overlap=78%) and for 6MWT distance (400 m (330-466) vs 351 m (286-408), p=0.028; overlap=64%). Among NYHA class I patients, 19%-34% had one marker of HF severity (VAS Score >30 points, 6MWT <300 m or NT-proBNP levels >1000 pg/mL) and 6%-10% had two of them. Temporal change in functional class was not accompanied by variation on dyspnoea VAS (p=0.14). CONCLUSIONS: Most patients classified as NYHA classes I and II had similar self-perception of their limitation, objective physical capabilities and levels of natriuretic peptides. These results suggest the NYHA classification poorly discriminates patients with mild HF.

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.

Diagnostic Accuracy of Perfusional Computed Tomography in Moderate Coronary Stenosis: Comparison With Fractional Flow Reserve.

Coronary computed tomography with myocardial perfusion imaging (CCTA-MPI) provides data on coronary anatomy and perfusion and may be useful in the assessment of ischemic coronary artery disease (CAD). Management of angiographically intermediate coronary lesions is challenging, and coronary fractional flow reserve (FFR) evaluation is recommended to assess whether these lesions are functionally significant. Our aim was to evaluate the diagnostic accuracy of CCTA-MPI in patients with stable CAD and at least 1 angiographically intermediate coronary lesion submitted to FFR. In this single-center prospective study, patients with stable CAD and at least 1 moderate coronary stenosis (50%-70% by visual estimation) were referred for CCTA-MPI (64-row multidetector) assessment before coronary FFR evaluation. Patients with severe coronary obstructions (≥70%) were excluded. The significance level adopted for all tests was 5%. Twenty-eight patients (mean age 60 ± SD years, 54% women) with 33 intermediate coronary obstructions were enrolled. Ten patients (30%) had functionally significant coronary obstructions characterized by FFR ≤0.8. The sensitivity, specificity, and accuracy of CCTA-MPI for the detection of functionally significant coronary obstructions were 30%, 100%, and 78.8%, respectively. CCTA-MPI positive predictive value was 100%, whereas negative predictive value was 76.7%. Correlation coefficient between tests was 0.48 (P = 0.005). On a novel approach to evaluate intermediate coronary lesions, accuracy of CCTA-MPI was 78.8%. The positive predictive value of an abnormal CCTA-MPI on this population was 100%, suggesting that CCTA-MPI may have a role in the assessment of patients with anatomically identified intermediate coronary lesions.

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.