Topical Versus Intravenous Tranexamic Acid in Patients Undergoing Cardiac Surgery: The DEPOSITION Randomized Controlled Trial.

BACKGROUND: Although intravenous tranexamic acid is used in cardiac surgery to reduce bleeding and transfusion, topical tranexamic acid results in lower plasma concentrations compared to intravenous tranexamic acid, which may lower the risk of seizures. We aimed to determine whether topical tranexamic acid reduces the risk of in-hospital seizure without increasing the risk of transfusion among cardiac surgery patients. METHODS: We conducted a multicenter, double dummy, blinded, randomized controlled trial of patients recruited by convenience sampling in academic hospitals undergoing cardiac surgery with cardiopulmonary bypass. Between September 17, 2019, and November 28, 2023, a total of 3242 patients from 16 hospitals in 6 countries were randomly assigned (1:1 ratio) to receive either intravenous tranexamic acid (control) through surgery or topical tranexamic acid (treatment) at the end of surgery. The primary outcome was seizure, and the secondary outcome was red blood cell transfusion. After the last planned interim analysis-when 75% of anticipated participants had completed follow up-the Data and Safety Monitoring Board recommended to terminate the trial, and upon unblinding, the Operations Committee stopped the trial for safety. RESULTS: Among 3242 randomized patients (mean age, 66.0 years; 77.7% male), in-hospital seizure occurred in 4 of 1624 patients (0.2%) in the topical group and in 11 of 1628 patients (0.7%) in the intravenous group (absolute risk difference, -0.5%; 95% CI, -0.9 to 0.03; P = .07). Red blood cell transfusion occurred in 570 patients (35.1%) in the topical group and in 433 (26.8%) in the intravenous group (absolute risk difference, 8.3%; 95% CI, 5.2 to 11.5; P = .007). The absolute risk difference in transfusion of ≥4 units of red blood cells in the topical group compared to the intravenous group was 8.2% (95% CI, 3.4 to 12.9). CONCLUSIONS: Among patients having cardiac surgery, topical administration of tranexamic acid resulted in an 8.3% absolute increase in transfusion without reducing the incidence of seizure, compared to intravenous tranexamic acid.

Outcomes of Patients with a Mechanical Heart Valve and Poor Anticoagulation Control on Warfarin.

BACKGROUND: Patients with a mechanical heart valve (MHV) require oral anticoagulation. Poor anticoagulation control is thought to be associated with adverse outcomes, but data are limited. OBJECTIVE: To assess the risks of clinical outcomes in patients with a MHV and poor anticoagulation control on warfarin. PATIENTS/METHODS: We conducted a retrospective study of consecutive patients undergoing MHV implantation at a tertiary care center (2010-2019). Primary outcome was a composite of ischemic stroke, systemic embolism, or prosthetic valve thrombosis. Major bleeding and death were key secondary outcomes. We constructed multivariable regression models to assess the association between time in therapeutic range (TTR) on warfarin beyond 90 days after surgery with outcomes. RESULTS: We included 671 patients with a MHV (80.6% in aortic, 14.6% in mitral position; mean age 61 years, 30.3% female). Median follow-up was 4.9 years, mean TTR was 62.5% (14.5% TTR <40%, 24.6% TTR 40-60%, and 61.0% TTR >60%). Overall rates of the primary outcome, major bleeding, and death were 0.73, 1.41, and 1.44 per 100 patient-years. Corresponding rates for patients with TTR <40% were 1.31, 2.77, and 3.22 per 100 patient-years. In adjusted analyses, every 10% decrement in TTR was associated with a 31% increase in hazard for the primary outcome (hazard ratio [HR]: 1.31, 95% confidence interval [CI]: 1.13-1.52), 34% increase in major bleeding (HR: 1.34, 95% CI: 1.17-1.52), and 32% increase in death (HR: 1.32, 95% CI: 1.11-1.57). CONCLUSION: In contemporary patients with a MHV, poor anticoagulation control on warfarin was associated with increased risks of thrombotic events, bleeding, and death.

Oral Anticoagulation Use and Left Atrial Appendage Occlusion in LAAOS III.

BACKGROUND: LAAOS III (Left Atrial Appendage Occlusion Study III) showed that left atrial appendage (LAA) occlusion reduces the risk of ischemic stroke or systemic embolism in patients with atrial fibrillation undergoing cardiac surgery. This article examines the effect of LAA occlusion on stroke reduction according to variation in the use of oral anticoagulant (OAC) therapy. METHODS: Information regarding OAC use was collected at every follow-up visit. Adjusted proportional hazards modeling, including using landmarks of hospital discharge, 1 and 2 years after randomization, evaluated the effect of LAA occlusion on the risk of ischemic stroke or systemic embolism, according to OAC use. Adjusted proportional hazard modeling, with OAC use as a time-dependent covariate, was also performed to assess the effect of LAA occlusion, according to OAC use throughout the study. RESULTS: At hospital discharge, 3027 patients (63.5%) were receiving a vitamin K antagonist, and 879 (18.5%) were receiving a non-vitamin K antagonist oral anticoagulant (direct OAC), with no difference in OAC use between treatment arms. There were 2887 (60.5%) patients who received OACs at all follow-up visits, 1401 (29.4%) who received OAC at some visits, and 472 (9.9%) who never received OACs. The effect of LAA occlusion on the risk of ischemic stroke or systemic embolism was consistent after discharge across all 3 groups: hazard ratios of 0.70 (95% CI, 0.51-0.96), 0.63 (95% CI, 0.43-0.94), and 0.76 (95% CI, 0.32-1.79), respectively. An adjusted proportional hazards model with OAC use as a time-dependent covariate showed that the reduction in stroke or systemic embolism with LAA occlusion was similar whether patients were receiving OACs or not. CONCLUSIONS: The benefit of LAA occlusion was consistent whether patients were receiving OACs or not. LAA occlusion provides thromboembolism reduction in patients independent of OAC use.

Frailty and outcomes in heart failure patients from high-, middle-, and low-income countries.

BACKGROUND AND AIMS: There is little information on the incremental prognostic importance of frailty beyond conventional prognostic variables in heart failure (HF) populations from different country income levels. METHODS: A total of 3429 adults with HF (age 61 ± 14 years, 33% women) from 27 high-, middle- and low-income countries were prospectively studied. Baseline frailty was evaluated by the Fried index, incorporating handgrip strength, gait speed, physical activity, unintended weight loss, and self-reported exhaustion. Mean left ventricular ejection fraction was 39 ± 14% and 26% had New York Heart Association Class III/IV symptoms. Participants were followed for a median (25th to 75th percentile) of 3.1 (2.0-4.3) years. Cox proportional hazard models for death and HF hospitalization adjusted for country income level; age; sex; education; HF aetiology; left ventricular ejection fraction; diabetes; tobacco and alcohol use; New York Heart Association functional class; HF medication use; blood pressure; and haemoglobin, sodium, and creatinine concentrations were performed. The incremental discriminatory value of frailty over and above the MAGGIC risk score was evaluated by the area under the receiver-operating characteristic curve. RESULTS: At baseline, 18% of participants were robust, 61% pre-frail, and 21% frail. During follow-up, 565 (16%) participants died and 471 (14%) were hospitalized for HF. Respective adjusted hazard ratios (95% confidence interval) for death among the pre-frail and frail were 1.59 (1.12-2.26) and 2.92 (1.99-4.27). Respective adjusted hazard ratios (95% confidence interval) for HF hospitalization were 1.32 (0.93-1.87) and 1.97 (1.33-2.91). Findings were consistent among different country income levels and by most subgroups. Adding frailty to the MAGGIC risk score improved the discrimination of future death and HF hospitalization. CONCLUSIONS: Frailty confers substantial incremental prognostic information to prognostic variables for predicting death and HF hospitalization. The relationship between frailty and these outcomes is consistent across countries at all income levels.

Global Variations in Heart Failure Etiology, Management, and Outcomes.

Importance: Most epidemiological studies of heart failure (HF) have been conducted in high-income countries with limited comparable data from middle- or low-income countries. Objective: To examine differences in HF etiology, treatment, and outcomes between groups of countries at different levels of economic development. Design, Setting, and Participants: Multinational HF registry of 23 341 participants in 40 high-income, upper-middle-income, lower-middle-income, and low-income countries, followed up for a median period of 2.0 years. Main Outcomes and Measures: HF cause, HF medication use, hospitalization, and death. Results: Mean (SD) age of participants was 63.1 (14.9) years, and 9119 (39.1%) were female. The most common cause of HF was ischemic heart disease (38.1%) followed by hypertension (20.2%). The proportion of participants with HF with reduced ejection fraction taking the combination of a ß-blocker, renin-angiotensin system inhibitor, and mineralocorticoid receptor antagonist was highest in upper-middle-income (61.9%) and high-income countries (51.1%), and it was lowest in low-income (45.7%) and lower-middle-income countries (39.5%) (P < .001). The age- and sex- standardized mortality rate per 100 person-years was lowest in high-income countries (7.8 [95% CI, 7.5-8.2]), 9.3 (95% CI, 8.8-9.9) in upper-middle-income countries, 15.7 (95% CI, 15.0-16.4) in lower-middle-income countries, and it was highest in low-income countries (19.1 [95% CI, 17.6-20.7]). Hospitalization rates were more frequent than death rates in high-income countries (ratio = 3.8) and in upper-middle-income countries (ratio = 2.4), similar in lower-middle-income countries (ratio = 1.1), and less frequent in low-income countries (ratio = 0.6). The 30-day case-fatality rate after first hospital admission was lowest in high-income countries (6.7%), followed by upper-middle-income countries (9.7%), then lower-middle-income countries (21.1%), and highest in low-income countries (31.6%). The proportional risk of death within 30 days of a first hospital admission was 3- to 5-fold higher in lower-middle-income countries and low-income countries compared with high-income countries after adjusting for patient characteristics and use of long-term HF therapies. Conclusions and Relevance: This study of HF patients from 40 different countries and derived from 4 different economic levels demonstrated differences in HF etiologies, management, and outcomes. These data may be useful in planning approaches to improve HF prevention and treatment globally.

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.

Machine learning for detecting centre-level irregularities in randomized controlled trials: A pilot study.

Centralized statistical monitoring is sometimes employed as an alternative to onsite monitoring for randomized control trials. Current central monitoring methods have limitations, in that they are relatively resource intensive and do not necessarily generalize to studies where an irregularity pattern has not been observed before. Machine learning has been effective in detecting irregularities in industries such as finance and manufacturing, but to date none have been applied to clinical trials. We conducted a pilot study for the use of machine learning to identify center-level irregularities in data from multicenter clinical trials. We employed unsupervised machine learning methods, which do not rely on labelled data, and therefore allow for the automated discovery of previously unseen irregularity patterns while maintaining flexibility when applied to new data with different structures. This pilot study employs unsupervised machine learning to compute distance matrices between centres, which we used to produce centre-level continuous features. We then used a one-class support vector machine to learn the underlying distribution of each data set to identify data that was substantially different from these distributions. We evaluated our approach against current automatable centralized monitoring methods on two trials with known irregularities. While current approaches performed well on one trial (AUROC 0.752 for monitoring vs. 0.584 for machine learning), our techniques performed substantially better on the other (AUROC 0.140 for monitoring vs 0.728 for machine learning). The results of this pilot study suggest both the feasibility and the potential value of a machine learning-based approach to irregularity detection in RCTs.

Rivaroxaban in Rheumatic Heart Disease-Associated Atrial Fibrillation.

BACKGROUND: Testing of factor Xa inhibitors for the prevention of cardiovascular events in patients with rheumatic heart disease-associated atrial fibrillation has been limited. METHODS: We enrolled patients with atrial fibrillation and echocardiographically documented rheumatic heart disease who had any of the following: a CHA2DS2VASc score of at least 2 (on a scale from 0 to 9, with higher scores indicating a higher risk of stroke), a mitral-valve area of no more than 2 cm2, left atrial spontaneous echo contrast, or left atrial thrombus. Patients were randomly assigned to receive standard doses of rivaroxaban or dose-adjusted vitamin K antagonist. The primary efficacy outcome was a composite of stroke, systemic embolism, myocardial infarction, or death from vascular (cardiac or noncardiac) or unknown causes. We hypothesized that rivaroxaban therapy would be noninferior to vitamin K antagonist therapy. The primary safety outcome was major bleeding according to the International Society of Thrombosis and Hemostasis. RESULTS: Of 4565 enrolled patients, 4531 were included in the final analysis. The mean age of the patients was 50.5 years, and 72.3% were women. Permanent discontinuation of trial medication was more common with rivaroxaban than with vitamin K antagonist therapy at all visits. In the intention-to-treat analysis, 560 patients in the rivaroxaban group and 446 in the vitamin K antagonist group had a primary-outcome event. Survival curves were nonproportional. The restricted mean survival time was 1599 days in the rivaroxaban group and 1675 days in the vitamin K antagonist group (difference, -76 days; 95% confidence interval [CI], -121 to -31; P<0.001). A higher incidence of death occurred in the rivaroxaban group than in the vitamin K antagonist group (restricted mean survival time, 1608 days vs. 1680 days; difference, -72 days; 95% CI, -117 to -28). No significant between-group difference in the rate of major bleeding was noted. CONCLUSIONS: Among patients with rheumatic heart disease-associated atrial fibrillation, vitamin K antagonist therapy led to a lower rate of a composite of cardiovascular events or death than rivaroxaban therapy, without a higher rate of bleeding. (Funded by Bayer; INVICTUS ClinicalTrials.gov number, NCT02832544.).

Factors associated with health-related quality of life in heart failure in 23 000 patients from 40 countries: results of the G-CHF research programme.

AIMS: To examine clinical and social correlates of health-related quality of life (HRQL) in patients with heart failure (HF) from high- (HIC), upper middle- (UMIC), lower middle- (LMIC) and low-income (LIC) countries. METHODS AND RESULTS: Between 2017 and 2020, 23 292 patients with HF (32% inpatients, 61% men) from 40 countries were enrolled in the Global Congestive Heart Failure study. HRQL was recorded at baseline using the Kansas City Cardiomyopathy Questionnaire (KCCQ)-12. In a cross-sectional analysis, we compared age- and sex-adjusted mean KCCQ-12 summary scores (SS: 0-100, higher = better) between patients from different country income levels. We used multivariable linear regression examining correlations (estimated coefficients) of KCCQ-12-SS with sociodemographic, comorbidity, treatment and symptom covariates. The adjusted model (37 covariates) was informed by univariable findings, clinical importance and backward selection. Mean age was 63 years and 40% of patients were in New York Heart Association (NYHA) class III-IV. Average HRQL was 55 SD 27. It was 62.5 (95% confidence interval [CI] 62.0-63.1) in HIC, 56.8 (56.1-57.4) in UMIC, 48.6 (48.0-49.3) in LMIC, and 38.5 (37.3-39.7) in LICs (p < 0.0001). Strong correlates (estimated coefficient [95% CI]) of KCCQ-12-SS were NYHA class III versus class I/II (-12.1 [-12.8 to -11.4] and class IV versus class I/II (-16.5 [-17.7 to -15.3]), effort dyspnoea (-9.5 [-10.2 to -8.8]) and living in LIC versus HIC (-5.8 [-7.1 to -4.4]). Symptoms explained most of the KCCQ-12-SS variability (partial R2  = 0.32 of total adjusted R2  = 0.51), followed by sociodemographic factors (R2  = 0.12). Results were consistent in populations across income levels. CONCLUSION: The most important correlates of HRQL in HF patients relate to HF symptom severity, irrespective of country income level.

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.).

Prospective long-term follow-up of silicone-polyurethane-insulated implantable cardioverter-defibrillator leads.

BACKGROUND: St Jude Medical (now Abbott) Optim-insulated implantable cardioverter-defibrillator (ICD) leads were expected to overcome problems with insulation abrasion and externalized conductors in earlier models. Long-term follow-up is essential to the evaluation of lead performance. OBJECTIVE: To determine, in a prospective cohort of Optim-insulated ICD leads, the rates of all-cause mechanical failure and its subtypes (conductor fracture, insulation abrasion, externalized conductors, and other mechanical failures) and electrical dysfunction adjudicated as nonmechanical failure. METHODS: Abbott established 3 prospective registries, enrolling 11,155 leads among 10,872 patients beginning in 2006. There was standardized baseline documentation, 6-monthly follow-up, adverse events reporting, and documentation of lead revision or inactivation, study withdrawal, and death or transplant. The Population Health Institute (McMaster University) reviewed database functions, adjudicated all potential mechanical lead failures, and conducted independent data analyses. RESULTS: During a median follow-up of 4.6 years, there were 171 mechanical failures (1.53%, 95.4% freedom from failure by 12 years). There were no significant differences in survival among Durata DF4 and DF1 and Riata ST Optim leads. The year-to-year rate of failure of leads increased over time. There were 69 electrical dysfunctions (0.62%, 98.8% freedom from failure by 12 years) adjudicated as nonmechanical failure. CONCLUSION: During follow-up as long as 12 years (median 4.6 years), Optim-insulated leads had low rates of mechanical failure and electrical dysfunction. Independent analyses provide reliable data on the long-term outcomes essential to analyzing ICD lead performance.

An Insight of Clinical Evidence of Ayurveda Interventions in the Management of COVID-19 Patients.

BACKGROUND: Coronavirus disease 2019 (COVID-19) was caused by the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) and patients with COVID-19 may be treated with traditional medicine like Ayurveda alone or in combination with standard allopathic treatment, as Ayurveda is one of the oldest traditional medicinal systems followed by millions around the world. METHODS: The literature was searched in databases such as LitCOVID, Google Scholar, Science Direct, EBSCO, Scopus, Web of Science, EMBASE, and reference lists to identify articles relevant to the use of Ayurvedic medicines in the management of COVID-19. RESULTS: Several clinical studies have determined the efficacy of Ayurvedic medicines and formulations in the management of patients with COVID-19. CONCLUSION: The Ayurvedic medicines and formulations with antiviral, antioxidant, anti-inflammatory, and immunomodulatory properties could be used along with standard allopathic medicines to assist in the earlier detection of virus, speedy recovery of patients with COVID-19, faster discharge from hospitals, and the prevention of further deterioration.

Low Serum Testosterone in Men with Newly Diagnosed Androgen-Deprivation Therapy-Naïve Prostate Cancer and Its Relationship to Cardiovascular Risk Factors: A RADICAL-PC Substudy.

PURPOSE: Cardiovascular disease is a common cause of death in prostate cancer patients. Low testosterone is associated with increased cardiovascular risk in the general male population. We investigated the relationship between serum testosterone, cardiovascular disease and risk factors in androgen-deprivation therapy-naïve prostate cancer patients. MATERIALS AND METHODS: We performed a cross-sectional analysis of a subgroup of 1,326 androgen-deprivation therapy-naïve men from RADICAL-PC (Role of Androgen-Deprivation Therapy In CArdiovascular Disease-A Longitudinal Prostate Cancer study) in whom serum testosterone was measured at baseline. RADICAL-PC is a prospective multicenter cohort study of men (2,565) enrolled within 1 year of prostate cancer diagnosis, or within 6 months of commencing androgen-deprivation therapy for the first time. Cardiovascular risk factors, cancer characteristics and total serum testosterone were collected at baseline. Low testosterone was defined as total serum testosterone <11 nmol/L (<320 ng/dL). A Framingham cardiovascular risk score ≥15 was considered high risk for future cardiovascular events. We performed logistic regression to calculate odds ratios for the association between testosterone and cardiovascular risk. RESULTS: Among 1,326 participants (median age 67 years, range 45-93), 553 (42%) had low testosterone. Low testosterone was associated with existing cardiovascular disease, diabetes, elevated hemoglobin A1c, obesity, hypertriglyceridemia, low high-density lipoprotein cholesterol, hypertension and Framingham score >15. Among patients with low testosterone, the odds ratio for high cardiovascular risk was 1.33 (1.02-1.73) after adjusting for ethnicity, education, alcohol use, cancer characteristics, physical activity and body mass index. CONCLUSIONS: Among androgen-deprivation therapy-naïve prostate cancer patients, low testosterone is common and associated with increased cardiovascular risk factors.

Effect of Cognitive Reserve on the Association of Vascular Brain Injury With Cognition: Analysis of the PURE and CAHHM Studies.

BACKGROUND AND OBJECTIVES: To determine whether cognitive reserve attenuates the association of vascular brain injury with cognition. METHODS: Cross-sectional data were analyzed from 2 harmonized studies: the Canadian Alliance for Healthy Hearts and Healthy Minds (CAHHM) and the Prospective Urban and Rural Epidemiology (PURE) study. Markers of cognitive reserve were education, involvement in social activities, marital status, height, and leisure physical activity, which were combined into a composite score. Vascular brain injury was defined as nonlacunar brain infarcts or high white matter hyperintensity (WMH) burden on MRI. Cognition was assessed using the Montreal Cognitive Assessment Tool (MoCA) and the Digit Symbol Substitution Test (DSST). RESULTS: There were 10,916 participants age 35-81. Mean age was 58.8 years (range 35-81) and 55.8% were female. Education, moderate leisure physical activity, being in a marital partnership, being taller, and participating in social groups were each independently associated with higher cognition, as was the composite cognitive reserve score. Vascular brain injury was associated with lower cognition (ß -0.35 [95% confidence interval [CI] -0.53 to -0.17] for MoCA and ß -2.19 [95% CI -3.22 to -1.15] for DSST) but the association was not modified by the composite cognitive reserve variable (interaction p = 0.59 for MoCA and p = 0.72 for DSST). CONCLUSIONS: Both vascular brain injury and markers of cognitive reserve are associated with cognition. However, the effects were independent such that the adverse effects of covert vascular brain injury were not attenuated by higher cognitive reserve. To improve cognitive brain health, interventions to both prevent cerebrovascular disease and promote positive lifestyles are needed.

Clinical Profiles and Outcomes of Heart Failure in Five African Countries: Results from INTER-CHF Study.

Background: A wide knowledge gap exists on the clinical profiles and outcomes of heart failure (HF) in sub-Saharan Africa. Objectives: To determine the clinical profiles and outcomes of HF patients from five African countries. Methods: The INTERnational Congestive Heart Failure Study (INTER-CHF) is a prospective, multicenter cohort study. A total of 1,294 HF patients were consecutively recruited from Nigeria (383 patients), South Africa (169 patients), Sudan (501 patients), Uganda (151patients), and Mozambique (90 patients). HF was defined according to the Boston criteria for diagnosis. Cognitive function was assessed using the Montreal Cognitive Assessment (MoCA) score. Results: Of the 1294 patients, 51.4% were recruited as out-patients, 53.7% had HF with reduced ejection fraction (EF), 30.1% had HF with mid-range EF and 16.2% had HF with preserved EF (16.2%). The commonest etiologies of HF were hypertensive heart disease (35%) and ischemic heart disease (20%). The mean MoCA score was highest in Uganda (24.3 ± 1.1) and lowest in Sudan (13.6 ± 0.3). Prescriptions for guideline-recommended HF therapies were poor; only 1.2% of South African patients received an Implantable Cardioverter Defibrillator, and none of the patients received Cardiac Resynchronised Therapy. The composite outcome of death or HF hospitalization at one year among the patients was highest in Sudan (59.7%) and lowest in Mozambique (21.1%). Six variables were associated with higher mortality risk, while digoxin use (adjusted hazard ratio [aHR]: 0.69; 95% confidence interval [CI]: 0.49-0.97; p = 0.034) and 10mmHg unit increase in systolic blood pressure (aHR 0.86; 95%CI 0.81-0.93; p < 0.001) were associated with lower risk for mortality. Conclusions: This is the largest HF study in Africa that included in- and out-patients from the West, East, North, Central and South African sub-regions. Clinically relevant differences, including cognitive functional impairment, were found between the involved countries.

Association Between Perioperative Atrial Fibrillation and Long-term Risks of Stroke and Death in Noncardiac Surgery: Systematic Review and Meta-analysis.

BACKGROUND: Atrial fibrillation (AF) is frequently reported as a complication of noncardiac surgery. It is unknown whether new-onset perioperative AF is associated with an increased risk of stroke and death beyond the perioperative period. We performed a systematic review and meta-analysis to assess the long-term risks of stroke and mortality associated with new-onset perioperative AF after noncardiac surgery. METHODS: MEDLINE and EMBASE were searched from inception to March 2020 for studies reporting on the association between perioperative AF and the risk of stroke and death occurring beyond 30 days after noncardiac surgery. Reference screening, study selection, data extraction, and quality assessment were performed in duplicate. Data were pooled using inverse variance-weighted random-effects models and presented as risk ratios (RRs). RESULTS: From 7344 citations, we included 31 studies (3,529,493 patients). The weighted mean incidence of perioperative AF was 0.7%. During a mean follow-up of 28.1 ± 9.4 months, perioperative AF was associated with an increased risk of stroke (1.5 vs 0.9 strokes per 100 patient-years; RR: 2.9, 95% confidence interval [CI]: 2.1-3.9, I2 = 78%). Perioperative AF was also associated with a significantly higher risk of all-cause mortality (21.0 vs 7.6 deaths per 100 patient-years; RR: 1.8, 95% CI: 1.5-2.2, I2 = 94%). The pooled adjusted hazard ratios for stroke and all-cause mortality were 1.9 (95% CI: 1.6-2.2, I2 = 31%) and 1.5 (95% CI: 1.3-1.7, I2 = 20%), respectively. CONCLUSIONS: Patients who had perioperative AF after noncardiac surgery had a higher long-term risk of stroke and mortality compared with patients who did not. Whether this risk is modifiable with oral anticoagulation therapy should be investigated.

CONTEXTE: La fibrillation atriale (FA) est une arythmie fréquemment attribuée à une complication d'une chirurgie non cardiaque. On ne sait toutefois pas si l'apparition d'une FA périopératoire est associée à un risque accru d'accident vasculaire cérébral et de décès au-delà de la période périopératoire. Nous avons donc procédé à un examen et à une méta-analyse systématiques dans le but d'évaluer les risques à long terme d'accident vasculaire cérébral et de décès associés à l'apparition d'une FA périopératoire à la suite d'une chirurgie non cardiaque. MÉTHODOLOGIE: Des recherches ont été effectuées dans MEDLINE et EMBASE depuis leur création jusqu'à mars 2020 pour y relever les études signalant l'association entre la FA périopératoire et le risque d'accident vasculaire cérébral et de décès survenant au-delà de 30 jours à la suite d'une chirurgie non cardiaque. Le tri des références, la sélection des études, l'extraction des données et l'évaluation de la qualité ont été effectués en double. Les données ont été regroupées à l'aide de modèles à effets aléatoires pondérés par l'inverse de la variance et présentées sous forme de rapports de risques relatifs (RR). RÉSULTATS: Parmi 7 344 références, nous avons inclus 31 études (3 529 493 patients). L'incidence moyenne pondérée de FA périopératoire était de 0,7 %. Dans le cadre d'un suivi moyen de 28,1 ± 9,4 mois, la FA périopératoire était associée à un risque accru d'accident vasculaire cérébral (1,5 vs 0,9 accident vasculaire cérébral par 100 années-patients; RR de 2,9; intervalle de confiance [IC] à 95 %; de 2,1 à 3,9; I2 = 78 %). La FA périopératoire était également associée à un risque considérablement plus élevé de décès toutes causes confondues (21,0 vs 7,6 décès par 100 années-patients; RR de 1,8; IC à 95 %; de 1,5 à 2,2; I2 = 94 %). Les rapports de risques instantanés ajustés regroupés d'accident vasculaire cérébral et de décès toutes causes confondues étaient de 1,9 (IC à 95 %; de 1,6 à 2,2; I2 = 31 %) et de 1,5 (IC à 95 %; de 1,3 à 1,7; I2 = 20 %), respectivement. CONCLUSIONS: Les patients qui souffraient de FA périopératoire à la suite d'une chirurgie non cardiaque présentaient un risque accru à long terme d'accident vasculaire cérébral et de décès par rapport aux patients qui n'en souffraient pas. Il serait approprié d'examiner la possibilité de modifier ce risque par une anticoagulothérapie orale.

Left Atrial Appendage Occlusion during Cardiac Surgery to Prevent Stroke.

BACKGROUND: Surgical occlusion of the left atrial appendage has been hypothesized to prevent ischemic stroke in patients with atrial fibrillation, but this has not been proved. The procedure can be performed during cardiac surgery undertaken for other reasons. METHODS: We conducted a multicenter, randomized trial involving participants with atrial fibrillation and a CHA2DS2-VASc score of at least 2 (on a scale from 0 to 9, with higher scores indicating greater risk of stroke) who were scheduled to undergo cardiac surgery for another indication. The participants were randomly assigned to undergo or not undergo occlusion of the left atrial appendage during surgery; all the participants were expected to receive usual care, including oral anticoagulation, during follow-up. The primary outcome was the occurrence of ischemic stroke (including transient ischemic attack with positive neuroimaging) or systemic embolism. The participants, research personnel, and primary care physicians (other than the surgeons) were unaware of the trial-group assignments. RESULTS: The primary analysis population included 2379 participants in the occlusion group and 2391 in the no-occlusion group, with a mean age of 71 years and a mean CHA2DS2-VASc score of 4.2. The participants were followed for a mean of 3.8 years. A total of 92.1% of the participants received the assigned procedure, and at 3 years, 76.8% of the participants continued to receive oral anticoagulation. Stroke or systemic embolism occurred in 114 participants (4.8%) in the occlusion group and in 168 (7.0%) in the no-occlusion group (hazard ratio, 0.67; 95% confidence interval, 0.53 to 0.85; P = 0.001). The incidence of perioperative bleeding, heart failure, or death did not differ significantly between the trial groups. CONCLUSIONS: Among participants with atrial fibrillation who had undergone cardiac surgery, most of whom continued to receive ongoing antithrombotic therapy, the risk of ischemic stroke or systemic embolism was lower with concomitant left atrial appendage occlusion performed during the surgery than without it. (Funded by the Canadian Institutes of Health Research and others; LAAOS III ClinicalTrials.gov number, NCT01561651.).