Clinical Characteristics,Management Strategies and Outcomes of Acute Myocardial Infarction Patients With Prior Coronary Artery Bypass Grafting

ObjectiveTo investigate the management strategies, temporal trends, and clinical outcomes of patients with a history of coronary artery bypass graft (CABG) surgery and presenting with acute myocardial infarction (MI).Patients and MethodsWe undertook a retrospective cohort study using the National Inpatient Sample database from the United States (January 2004–September 2015), identified all inpatient MI admissions (7,250,768 records) and stratified according to history of CABG (group 1, CABG-naive [94%]; group 2, prior CABG [6%]).ResultsPatients in group 2 were older, less likely to be female, had more comorbidities, and were more likely to present with non-ST-elevation myocardial infarction compared with group 1. More patients underwent coronary angiography (68% vs 48%) and percutaneous coronary intervention (PCI) (44% vs 26%) in group 1 compared with group 2. Following multivariable logistic regression analyses, the adjusted odd ratio (OR) of in-hospital major adverse cardiovascular and cerebrovascular events (OR, 0.98; 95% CI, 0.95 to 1.005; P=.11), all-cause mortality (OR, 1; 95% CI, 0.98 to 1.04; P=.6) and major bleeding (OR, 0.99; 95% CI, 0.94 to 1.03; P=.54) were similar to group 1. Lower adjusted odds of in-hospital major adverse cardiovascular and cerebrovascular events (OR, 0.64; 95% CI, 0.57 to 0.72; P<.001), all-cause mortality (OR, 0.45; 95% CI, 0.38 to 0.53; P<.001), and acute ischemic stroke (OR, 0.71; 95% CI, 0.59 to 0.86; P<.001) were observed in group 2 patients who underwent PCI compared with those managed medically without any increased risk of major bleeding (OR, 1.08; 95% CI, 0.94 to 1.23; P=.26).ConclusionsIn this national cohort, MI patients with prior-CABG had a higher risk profile, but similar in-hospital adverse outcomes compared with CABG-naive patients. Prior-CABG patients who received PCI had better in-hospital clinical outcomes compared to those who received medical management.     

Prognostic Value of Cardiac Magnetic Resonance Imaging in Acute Coronary Syndrome Patients With Troponin Elevation and Nonobstructive Coronary Arteries

ObjectiveTo define the diagnostic yield of cardiac magnetic resonance (CMR) in differentiating the underlying causes of myocardial infarction with nonobstructive coronary arteries (MINOCA) and to determine the long-term prognostic implications of such diagnoses.MethodsCardiac magnetic resonance evaluation was performed in 227 patients (mean age, 56.4±14.9 years; 120 [53%] female) with a “working diagnosis” of MINOCA as defined by presentation with a troponin-positive acute coronary syndrome (troponin I >0.04 μg/L) and nonobstructed coronary arteries between January 1, 2007, and February 28, 2013. Follow-up was performed to assess the primary composite end point of myocardial infarction, heart failure, and all-cause mortality.ResultsCardiac magnetic resonance identified nonstructural cardiomyopathies in 97 (43%) patients, myocardial infarction in 55 (24%) patients, structural cardiomyopathies in 27 (12%) patients, and pulmonary embolism in 1 patient. No CMR abnormalities were identified in the remaining patients. Kaplan-Meier analysis demonstrated the ability of a CMR diagnosis to predict the risk of the primary composite end point (P=.005) at 5-year follow-up. Worse outcomes were seen among patients with “true” MINOCA and a normal CMR image compared with those with CMR-confirmed myocardial infarction (P=.02). Use of antiplatelets (78% [37/45] vs 95% [52/55]; P=.01), beta blockers (56% [25/45] vs 82% [45/55]; P=.004), and statins (64% [29/45] vs 85% [47/55]; P=.01) was significantly lower in patients with true MINOCA with normal CMR imaging compared with those with CMR-confirmed myocardial infarction.ConclusionsCardiac magnetic resonance carries a high diagnostic yield in patients with MINOCA and predicts long-term prognosis. Patients with MINOCA with normal CMR imaging had an increased rate of major adverse cardiac events and lower use of guideline-recommended myocardial infarction therapy compared with those with CMR-confirmed myocardial infarction.     

Bleeding in Patients With Gastrointestinal Cancer Compared With Nongastrointestinal Cancer Treated With Apixaban,Rivaroxaban, or Enoxaparin for Acute Venous Thromboembolism

ObjectiveTo compare the bleeding risk in patients with gastrointestinal (GI) cancer with that in patients with non-GI cancer treated with anticoagulation for acute cancer-associated venous thromboembolism (Ca-VTE).Patients and MethodsConsecutive patients with Ca-VTE seen at the Mayo Thrombophilia Clinic between March 1, 2013, and April 20, 2020, were observed prospectively to assess major bleeding and clinically relevant nonmajor bleeding (CRNMB).ResultsIn the group of 1392 patients with Ca-VTE, 499 (35.8%) had GI cancer including 272 with luminal GI cancer (lower GI, 208; upper GI, 64), 176 with pancreatic cancer, and 51 with hepatobiliary cancer. The rate of major bleeding and CRNMB in patients with GI cancer was similar to that in 893 (64.2%) patients with non-GI cancer treated with apixaban, rivaroxaban, or enoxaparin. Apixaban had a higher rate of major bleeding in luminal GI cancer compared with the non-GI cancer group (15.59 vs 3.26 per 100 person-years; P=.004) and compared with enoxaparin in patients with luminal GI cancer (15.59 vs 3.17; P=.04). Apixaban had a lower rate of CRNMB compared with rivaroxaban in patients with GI cancer (3.83 vs 9.40 per 100 person-years; P=.03). Patients treated with rivaroxaban in the luminal GI cancer group had a major bleeding rate similar to that of patients with non-GI cancer (2.04 vs 4.91 per 100 person-years; P=.37).ConclusionApixaban has a higher rate of major bleeding in patients with luminal GI cancer compared with patients with non-GI cancer and compared with enoxaparin in patients with luminal GI cancer. Rivaroxaban shows no increased risk of major bleeding in patients with GI cancer or luminal GI cancer compared with patients with non-GI cancer.Trial RegistrationClinicalTrials.gov identifier: NCT03504007.     

Robotic Mitral Valve Repair: Indication for Surgery Does Not Influence Early Outcomes

ObjectiveTo evaluate the outcomes of robotic mitral valve repair (MVr) by primary indication per American Heart Association guidelines for surgery: class I vs class IIa.Patients and MethodsFrom January 1, 2008, through September 30, 2016, 603 patients underwent robotic MVr for severe primary mitral regurgitation. Medical records of 576 consenting patients were retrospectively reviewed to determine the primary indication for surgery. Patients were stratified into class I or class IIa, and preoperative, intraoperative, and postoperative variables were compared.ResultsOf 516 patients, 428 (83%) had class I indication and 88 (17%) had class IIa indication for surgery. Preoperatively, no significant differences were observed between both cohorts. Importantly, a significantly higher number of patients with class I indication underwent MVr for bileaflet prolapse (172 of 428 [40%] vs 21 of 88 [25%]; P=.03). Early MVr outcomes indicated recurrent mitral regurgitation (moderate or greater) in only 12 of 576 (2%), and no significant differences were observed between classes (P=.23). Apart from parameters for ventricular size, all other intraoperative and postoperative variables were comparable between both cohorts.ConclusionComparable outcomes were indicated across all classes of indications for MVr surgery. These results continue to support the use of this surgical technique, even in less sick patients. Early referral along with more extensive robotic MVr experience will likely result in further improvements in long-term outcomes.     

Women Are Less Likely to Survive AMI Presenting With Out-of-Hospital Cardiac Arrest: A Nationwide Study

ObjectiveTo assess the impact of patient’s sex on outcomes and management of acute myocardial infarction (AMI) patients presenting with out-of-hospital cardiac arrest (OHCA).Patients and MethodsWe conducted a population-based retrospective cohort study in AMI patients admitted with OHCA between 2010 and 2017 from the Myocardial Ischaemia National Audit Project (MINAP) registry. We used multivariable logistic regression models to evaluate the role of sex as a predictor of clinical outcomes and treatment strategy.ResultsOf 16,278 patients, women constituted almost one-quarter of the population (n=3710 [22.7%]). Women were older (median age 69 [IQR, 57-79] years vs 63 [IQR, 54-72] years, P<.001), experienced longer call-to-hospital-arrival time (median, 1.2 hours vs 1.1 hours; P=.008), were less likely to present with shockable rhythm (86.8% vs 91.5%, P<.001), and less likely to receive dual antiplatelet therapy (73.8% vs 78.6%, P<.001), beta blockers (64.7% vs 72.3%, P<.001), angiotensin-converting enzyme inhibitors (49.0% vs 55.3%, P<.001), coronary angiography (73.7% vs 83.3%, P<.001), and percutaneous coronary intervention (37.5% vs. 40.7%, p 0.004). After adjusting for patient characteristics and management, women had significantly higher odds of in-hospital death compared with men (odds ratio [OR], 1.3; 95% CI, 1.1 to 1.5) and lower odds of receiving coronary angiography (OR, 0.67; 95% CI, 0.59 to 0.75) and coronary artery bypass graft (OR, 0.28; 95% CI, 0.19 to 0.40).ConclusionWomen were less likely to survive following OHCA secondary to AMI. Hospital protocols that minimize physician bias and improve women-physician communication are needed to close this gap.     

Physician Identification Badges: A Multispecialty Quality Improvement Study to Address Professional Misidentification and Bias

ObjectiveTo evaluate whether providing resident physicians with “DOCTOR” role identification badges would impact perceptions of bias in the workforce and alter misidentification rates.Participants and MethodsBetween October 2019 and December 2019, we surveyed 341 resident physicians in the anesthesiology, dermatology, internal medicine, neurologic surgery, otorhinolaryngology, and urology departments at Mayo Clinic in Rochester, Minnesota, before and after an 8-week intervention of providing “DOCTOR” role identification badges. Differences between paired preintervention and postintervention survey answers were measured, with a focus on the frequency of experiencing perceived bias and role misidentification (significance level, α=.01). Free-text comments were also compared.ResultsOf the 159 residents who returned both the before and after surveys (survey response rate, 46.6% [159 of 341]), 128 (80.5%) wore the “DOCTOR” badge. After the intervention, residents who wore the badges were statistically significantly less likely to report role misidentification at least once a week from patients, nonphysician team members, and other physicians (50.8% [65] preintervention vs 10.2% [13] postintervention; 35.9% [46] vs 8.6% [11]; 18.0% [23] vs 3.9% [5], respectively; all P<.001). The 66 female residents reported statistically significantly fewer episodes of gender bias (65.2% [43] vs 31.8% [21]; P<.001). The 13 residents who identified as underrepresented in medicine reported statistically significantly less misidentification from patients (84.6% [11] vs 23.1% [3]; P=.008); although not a statistically significant difference, the 13 residents identifying as underrepresented in medicine also reported less misidentification with nonphysician team members (46.2% [6] vs 15.4% [2]; P=.13).ConclusionResidents reported decreased role misidentification after use of a role identification badge, most prominently improved among women. Decreasing workplace bias is essential in efforts to improve both diversity and inclusion efforts in training programs.     

Efficacy of Prolonged Antibiotic Therapy for Renal Cyst Infections in Polycystic Kidney Disease

ObjectiveTo determine the impact of antibiotic therapy (ATBT) on outcomes of renal cyst infection (CyI) in patients with polycystic kidney disease.Patients and MethodsWe undertook a single-center retrospective study of CyI in autosomal dominant polycystic kidney disease (January 1, 2000, through December 31, 2018). Cyst infections were classified as definite (microbiologically proven), probable (radiologic signs), or possible (clinical or biologic signs only). We studied the determinants of ATBT failure (persistence of infection beyond 72 hours of microbiologically adequate initial ATBT, with requirement for ATBT change, cyst drainage, or nephrectomy) and recurrences (>14 days after the end of ATBT).ResultsAmong 90 patients, 139 CyIs (11 definite, 74 probable, 54 possible) were compiled. Cultures were positive in 106 of 139 (76%) episodes, with Escherichia coli found in 89 of 106 (84%). Treatment failures and recurrences within 1 year of follow-up were more frequent in definite/probable CyI (20/85 [34%] and 16/85 [19%]) than in possible CyI (2/54 [4%] and 4/54 [7%]; P<.01 and P=.08, respectively). Male sex (odds ratio [OR], 7.79; 95% CI, 1.72 to 46.68; P<.01), peak C-reactive protein level above 250 mg/L (OR, 7.29; 95% CI, 1.78 to 35.74; P<.01; to convert C-reactive protein values to nmol/L, multiply by 9.524), and cyst wall thickening (OR, 7.70; 95% CI, 1.77 to 43.47; P=.01) but not the modalities of initial ATBT were independently associated with higher risk of failure. In a Cox proportional hazards model, kidney transplant recipients exhibited higher risk of recurrence (hazard ratio, 3.76; 95% CI, 1.06 to 13.37; P=.04), whereas a total duration of ATBT of 28 days or longer was protective (hazard ratio, 0.02; 95% CI, 0.00 to 0.16; P<.001), with an inverse correlation between duration and recurrence (81% for treatment <21 days, 47% for 21 to 27 days, 2% for ≥28 days; P<.0001).ConclusionInitial first-line ATBT had no significant effect on renal CyI treatment failure. Treatment duration of 28 days and longer reduced recurrences.     

Arthritis Prediction of Advanced Hepatic Fibrosis in HFE Hemochromatosis

ObjectiveTo evaluate whether arthritis predicts the likelihood of advanced hepatic fibrosis in HFE hemochromatosis.Patients and MethodsWe conducted a retrospective, cross-sectional analysis of 112 well-characterized patients with HFE hemochromatosis and liver biopsy–validated fibrosis staging recruited between January 1, 1983, and December 31, 2013. Complete clinical, biochemical, hematologic, and noninvasive serum biochemical indices (aspartate aminotransferase to platelet ratio index [APRI] and fibrosis 4 index [FIB4]) were available. Scheuer fibrosis stages 3 and 4, APRI greater than 0.44, or FIB4 greater than 1.1 were used to define advanced hepatic fibrosis. Comparisons between groups were performed using categorical analysis, unpaired or paired t test.ResultsMale (n=76) and female (n=36) patients were similar in age. Nineteen patients had advanced hepatic fibrosis, and 47 had hemochromatosis arthritis. Arthritis was significantly associated with the presence of advanced hepatic fibrosis as determined by liver biopsy (sensitivity, 84%, [95% CI, 62% to 95%]; negative predictive value, 95% [95% CI, 87% to 99%]; relative risk, 7.4 [95% CI, 2.5 to 23]; P<.001), APRI (sensitivity, 75% [95% CI, 55% to 88%]; negative predictive value, 91% [95% CI, 81% to 96%]; relative risk, 4.5 [95% CI, 2.0 to 10.2]; P<.001), or FIB4 (sensitivity, 61% [95% CI, 41% to 78%]; negative predictive value, 67% [95% CI, 68% to 90%]; relative risk, 2.2 [95% CI, 1.1 to 4.6]; P=.03). Mean cell volume values were significantly higher pretreatment in patients with F3-4 fibrosis (96.7±1.1 fL) compared with F0-2 fibrosis (93.4±0.5 fL; P=.004) and declined following treatment (F3-4, 93.2±0.9 fL, P=.01; F0-2, 91.7±0.6 fL, P=.01).ConclusionAdvanced hepatic fibrosis is strongly associated with arthritis in HFE hemochromatosis. The absence of arthritis predicts a low likelihood of advanced hepatic fibrosis, supporting its use as a clinical marker for advanced hepatic fibrosis in HFE hemochromatosis.     

Implementation of a Comprehensive Patient Blood Management Program for Hospitalized Patients at a Large United States Medical Center

ObjectiveTo assess changes in inpatient transfusion utilization and patient outcomes with implementation of a comprehensive patient blood management (PBM) program at a large US medical center.Patients and MethodsThis is an observational study of graduated PBM implementation for hospitalized adults (age ≥18 years) from January 1, 2010, through December 31, 2017, at two integrated hospital campuses at a major academic US medical center. Allogeneic transfusion utilization and clinical outcomes were assessed over time through segmented regression with multivariable adjustment comparing observed outcomes against projected outcomes in the absence of PBM activities.ResultsIn total, 400,998 admissions were included. Total allogeneic transfusions per 1000 admissions decreased from 607 to 405 over the study time frame, corresponding to an absolute risk reduction for transfusion of 6.0% (95% confidence interval [CI]: 3.6%, 8.3%; P<.001) and a 22% (95% CI: 6%, 37%; P=.006) decrease in the rate of transfusions over projected. The risk of transfusion decreased for all blood components except cryoprecipitate. Transfusion reductions were experienced for all major surgery types except liver transplantation, which remained stable over time. Hospital length of stay (multiplicative increase in geometric mean 0.85 [95% CI: 0.81, 0.89]; P<.001) and incident in-hospital adverse events (absolute risk reduction: 1.5% [95% CI: 0.1%, 3.0%]; P=.04) were lower than projected at the end of the study time frame.ConclusionPatient blood management implementation for hospitalized patients in a large academic center was associated with substantial reductions in transfusion utilization and improved clinical outcomes. Broad-scale implementation of PBM in US hospitals is feasible without signal for patient harm.     

Proton Pump Inhibitors and In-Hospital Gastrointestinal Bleeding in Patients With Acute Coronary Syndrome Receiving Dual Antiplatelet Therapy

ObjectiveTo evaluate the association between proton pump inhibitor (PPI) use and in-hospital gastrointestinal (GI) bleeding in patients with acute coronary syndrome (ACS) taking dual antiplatelet therapy (DAPT).Patients and MethodsThis study is based on the Improving Care for Cardiovascular Disease in China-ACS project, an ongoing collaborative registry and quality improvement project of the American Heart Association and the Chinese Society of Cardiology. A total of 25,567 patients with ACS taking DAPT from 172 hospitals from July 1, 2017, through December 31, 2018, were included. Multivariable Cox regression and propensity score–matched analyses were used to evaluate the association between PPI use and in-hospital GI bleeding.ResultsOf these patients with ACS, 63.9% (n=16,332) were prescribed PPIs within 24 hours of admission. Patients using PPIs had a higher rate of GI bleeding compared with those not using PPIs (1.0% vs 0.5%; P<.001). In the multivariable Cox regression analysis, early PPI use was associated with a 58% higher risk of GI bleeding (hazard ratio, 1.58; 95% CI, 1.15 to 2.18; P=.005). Further propensity score matching attenuated the association but still showed that patients using PPIs had a higher rate of GI bleeding (0.8% vs 0.6%; P=.04).ConclusionIn China, PPIs are widely used within 24 hours of admission in patients with ACS taking DAPT. An increased risk of GI bleeding is observed in inpatients with early PPI use. Randomized trials on early use of PPIs in patients with ACS receiving DAPT are warranted.Trial Registrationclinicaltrials.gov Identifier: NCT02306616.     

Clinical Presentation,Management, and Outcomes of Cardiovascular Implantable Electronic Device Infections Due to Gram-Negative Versus Gram-Positive Bacteria

ObjectiveTo describe and compare the clinical presentation, management, and outcomes of cardiovascular implantable electronic device (CIED) infections due to gram-negative bacteria (GNB) and CIED infections due to gram-positive bacteria (GPB).Patients and MethodsWe retrospectively reviewed all CIED infection cases at Mayo Clinic from January 1, 1992, through December 31, 2015. Cases were classified based on positive microbiology data from extracted devices or blood cultures.ResultsOf the 623 CIED infections during the study period, 31 (5.0%) were caused by GNB and 323 (51.8%) by GPB. Patients in the GNB group were more likely to present with local inflammatory findings at the pocket site (90.3% vs 72.4%; P=.03). All patients with bacteremia due to GNB had concomitant pocket infection compared with those with GPB (100% vs 33.9%; P=.002). After extraction, 41.9% of patients in the GNB group were managed with oral antibiotics vs 2.4% in the GPB group (P<.001). There were no statistically significant differences in infection relapse/recurrence or 1-year survival rates between the 2 groups.ConclusionCompared with CIED infections caused by GPB, those due to GNB are more likely to present with pocket infection. Device-related GNB bacteremia almost always originates from the generator pocket. After extraction, oral antibiotic drug therapy may be a reasonable option in select cases of pocket infections due to GNB. No difference in outcomes was observed between the 2 groups.     

Newer P2Y12 Inhibitors vs Clopidogrel in Acute Myocardial Infarction With Cardiac Arrest or Cardiogenic Shock: A Systematic Review and Meta-analysis

ObjectiveTo evaluate the outcomes, safety, and efficacy of dual antiplatelet therapy (DAPT) with newer P2Y₁₂ inhibitors compared with clopidogrel in patients with acute myocardial infarction (AMI) complicated by cardiac arrest (CA) or cardiogenic shock (CS).Patients and MethodsMEDLINE, EMBASE, and the Cochrane Library were queried systematically from inception to January 2021 for comparative studies of adults (≥18 years) with AMI-CA/CS receiving DAPT with newer P2Y₁₂ inhibitors as opposed to clopidogrel. We compared outcomes (30-day or in-hospital and 1-year all-cause mortality, major bleeding, and definite stent thrombosis) of newer P2Y₁₂ inhibitors and clopidogrel in patients with AMI-CA/CS.ResultsEight studies (1 randomized trial and 7 cohort studies) comprising 1100 patients (695 [63.2%] receiving clopidogrel and 405 [36.8%] receiving ticagrelor or prasugrel) were included. The population was mostly male (68.5%-86.7%). Risk of bias was low for these studies, with between-study heterogeneity and subgroup differences not statistically significant. Compared with the clopidogrel cohort, the newer P2Y₁₂ cohort had lower rates of early mortality (odds ratio [OR], 0.60; 95% CI, 0.45 to 0.81; P=.001) (7 studies) and 1-year mortality (OR, 0.51; 95% CI, 0.36 to 0.71; P<.001) (3 studies). We did not find a significant difference in major bleeding (OR, 1.21; 95% CI, 0.71 to 2.06; P=.48) (6 studies) or definite stent thrombosis (OR, 2.01; 95% CI, 0.63 to 6.45; P=.24) (7 studies).ConclusionIn patients with AMI-CA/CS receiving DAPT, compared with clopidogrel, newer P2Y₁₂ inhibitors were associated with lower rates of early and 1-year mortality. Data on major bleeding and stent thrombosis were inconclusive.     

Tricuspid Regurgitation Impact on Outcomes (TRIO): A Simple Clinical Risk Score

ObjectiveTo determine which clinical variables infer the highest risk for mortality in patients with notable tricuspid regurgitation (TR) and to develop a clinical assessment tool (the Tricuspid Regurgitation Impact on Outcomes [TRIO] score).Patients and MethodsA single-center retrospective cohort of 13,608 patients with undifferentiated moderate to severe TR at the time of index echocardiography between January 1, 2005, and December 31, 2016, was included. Baseline demographic and clinical data were obtained. Patients were randomly assigned to a training (N=10,205) and a validation (N=3403) cohort. Median follow-up was 6.5 years (interquartile range, 0.8 to 11.0 years). Variables associated with mortality were identified by Cox proportional hazards methods. A geographically distinct cohort of 7138 patients was used for further validation. The primary end point was all-cause mortality over 10 years.ResultsThe 5-year probability of death was 53% for moderate TR, 63% for moderate-severe TR (hazard ratio [HR], 1.24 [95% CI, 1.17 to 1.31]; P<.001 vs moderate), and 71% for severe TR (HR, 1.55 [95% CI, 1.47 to 1.64]; P<.001 vs moderate). Factors associated with all-cause mortality on multivariate analysis included age 70 years or older, male sex, creatinine level greater than 2 mg/dL, congestive heart failure, chronic lung disease, aspartate aminotransferase level of 40 U/L or greater, heart rate of 90 beats/min or greater, and severe TR. Variables were assigned 1 or 2 points (HR, >1.5) and added to compute the TRIO score. The score was associated with all-cause mortality (C statistic = 0.67) and was able to separate patients into risk categories. Findings were similar in the second, independent and geographically distinct cohort.ConclusionThe TRIO score is a simple clinical tool for risk assessment in patients with notable TR. Future prospective studies to validate its use are warranted.     

Effect of the Renin-Angiotensin System Inhibitors on Inflammatory Markers: A Systematic Review and Meta-analysis of Randomized Controlled Trials

ObjectiveTo synthesize more conclusive evidence on the anti-inflammatory effects of angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs).MethodsPubMed, Scopus, and Embase were searched from inception until March 1, 2021. We included randomized controlled trials (RCTs) that assessed the effect of ACEIs or ARBs, compared with placebo, on any of the following markers: C-reactive protein (CRP), interleukin 6 (IL-6), or tumor necrosis factor α (TNF-α). Mean changes in the levels of these markers were pooled as a weighted mean difference (WMD) with a 95% CI.ResultsThirty-two RCTs (n=3489 patients) were included in the final analysis. Overall pooled analysis suggested that ACEIs significantly reduced plasma levels of CRP (WMD, ?0.54 [95% CI, ?0.88 to ?0.21]; P=.002; I²=96%), IL-6 (WMD, ?0.84 [95% CI, ?1.03 to ?0.64]; P<.001; I²=0%), and TNF-α (WMD, ?12.75 [95% CI, ?17.20 to ?8.29]; P<.001; I²=99%). Moreover, ARBs showed a significant reduction only in IL-6 (WMD, ?1.34 [95% CI, ?2.65 to ?0.04]; P=.04; I²=85%) and did not significantly affect CRP (P=.15) or TNF-α (P=.97) levels. The lowering effect of ACEIs on CRP levels remained significant with enalapril (P=.006) and perindopril (P=.01) as well as with a treatment duration of less than 24 weeks (WMD, -0.67 [95% CI, ?1.07 to -0.27]; P=.001; I²=94%) and in patients with coronary artery disease (WMD, ?0.75 [95% CI, ?1.17 to ?0.33]; P<.001; I²=96%).ConclusionBased on this meta-analysis, ACEIs showed a beneficial lowering effect on CRP, IL-6, and TNF-α, whereas ARBs were effective as a class in reduction of IL-6 only.     

Prevalence and Natural History of Mitral Annulus Calcification and Related Valve Dysfunction

ObjectiveTo evaluate the prevalence and natural history of mitral annulus calcification (MAC) and associated mitral valve dysfunction (MVD) in patients undergoing clinically indicated echocardiography.MethodsA retrospective review was conducted of all adults who underwent echocardiography in 2015. Mitral valve dysfunction was defined as mitral regurgitation or mitral stenosis (MS) of moderate or greater severity. All-cause mortality during 3.0 (0.4 to 4.2) years of follow-up was compared between groups stratified according to the presence of MAC or MVD.ResultsOf 24,414 evaluated patients, 5502 (23%) had MAC. Patients with MAC were older (75±10 years vs 60±16 years; P<.001) and more frequently had MVD (MS: 6.6% vs 0.5% [P<.001]; mitral regurgitation without MS: 9.5% vs 6.1% [P<.001]). Associated with MS in patients with MAC were aortic valve dysfunction, female sex, chest irradiation, renal dysfunction, and coronary artery disease. Kaplan-Meier 1-year survival was 76% in MAC+/MVD+, 87% in MAC+/MVD?, 86% in MAC?/MVD+, and 92% in MAC?/MVD?. Adjusted for age, diabetes, renal dysfunction, cancer, chest irradiation, ejection fraction below 50%, aortic stenosis, tricuspid regurgitation, and pulmonary hypertension, MAC was associated with higher mortality during follow-up (adjusted hazard ratio, 1.40; 95% CI, 1.31 to 1.49; P<.001); MVD was associated with even higher mortality in patients with MAC (adjusted hazard ratio, 1.79; 95% CI, 1.58 to 2.01; P<.001). There was no significant interaction between MAC and MVD for mortality (P=.10).ConclusionIn a large cohort of adults undergoing echocardiography, the prevalence of MAC was 23%. Mitral valve dysfunction was more than twice as prevalent in patients with MAC. Adjusted mortality was increased in patients with MAC and worse with both MAC and MVD.     

Direct Oral Anticoagulants Compared With Dalteparin for Treatment of Cancer-Associated Thrombosis: A Living,Interactive Systematic Review and Network Meta-analysis

ObjectiveTo maintain living, interactive evidence (LIvE) on the benefits and harms of different treatment options in adults with cancer-associated thrombosis (CAT).MethodsWe have used a novel LIvE synthesis framework to maintain this living, interactive systematic review since September 19, 2018. Randomized controlled trials evaluating the efficacy and safety of direct oral anticoagulants (DOACs) compared with low-molecular-weight heparin for CAT are included in this analysis. Details of LIvE synthesis framework are available at the website https://cat.network-meta-analysis.com.ResultsThe results are constantly updated as new information becomes available (https://cat.network-meta-analysis.com/CAT.html). The living, interactive systematic review currently includes 4 randomized controlled trials (N=2894). Direct comparisons show that DOACs significantly decrease recurrent venous thromboembolism (VTE) events compared with dalteparin (odds ratio [OR], 0.59; 95% CI, 0.41 to 0.86; I², 25%) without significantly increasing major bleeding (OR, 1.34; 95% CI, 0.83 to 2.18; I², 28%). Mixed treatment comparisons show that apixaban (OR, 0.41; 95% credible interval [CrI], 0.16 to 0.95) and rivaroxaban (OR, 0.58; 95% CrI, 0.37 to 0.90) significantly decrease VTE recurrent events compared with dalteparin. Edoxaban significantly increases major bleeding compared with dalteparin (OR, 1.73; 95% CrI, 1.04 to 3.16), and rivaroxaban significantly increases clinically relevant nonmajor bleeding compared with dalteparin and other DOACs. There are no significant differences between DOACs in terms of VTE recurrences and major bleeding.ConclusionDOACs should be considered a standard of care for the treatment of CAT except in patients with a high risk of bleeding. Current evidence favors the use of apixaban for the treatment of CAT among other DOACs.RegistrationOpen Science Framework (https://osf.io/dth86).     

Macrovascular Thrombotic Events in a Mayo Clinic Enterprise-Wide Sample of Hospitalized COVID-19–Positive Compared With COVID-19–Negative Patients

ObjectiveTo determine the difference in the rate of thromboembolic complications between hospitalized coronavirus disease 2019 (COVID-19)–positive compared with COVID-19–negative patients.Patients and MethodsAdult patients hospitalized from January 1, 2020, through May 8, 2020, who had COVID-19 testing by polymerase chain reaction assay were identified through electronic health records across multiple hospitals in the Mayo Clinic enterprise. Thrombotic outcomes (venous and arterial) were identified from the hospital problem list.ResultsWe identified 3790 hospitalized patients with COVID-19 testing across 19 hospitals, 102 of whom had positive test results. The median age was lower in the COVID-positive patients (62 vs 67 years; P=.03). The median duration of hospitalization was longer in COVID-positive patients (8.5 vs 4 days; P<.001) and more required intensive care unit care (56.9% [58 of 102] vs 26.8% [987 of 3688]; P<.001). Comorbidities, including atrial fibrillation/flutter, heart failure, chronic kidney disease, and malignancy, were observed less frequently with COVID-positive admissions. Any venous thromboembolism was identified in 2.9% of COVID-positive patients (3 of 102) and 4.6% of COVID-negative patients (168 of 3688). The frequency of venous and arterial events was not different between the groups. The unadjusted odds ratio (OR) for COVID-positive–patients for any venous thromboembolism was 0.63 (95% CI, 0.19 to 2.02). A multivariable logistic regression model evaluated death within 30 days of hospital discharge; neither COVID positivity (adjusted OR, 1.12; 95% CI, 0.54 to 2.34) nor thromboembolism (adjusted OR, 0.90; 95% CI, 0.60 to 1.32) was associated with death.ConclusionEarly experience in patients with COVID-19 across multiple academic and regional hospitals representing different US regions demonstrates a lower than previously reported incidence of thrombotic events. This incidence was not higher than a contemporary COVID-negative hospitalized comparator.     

Sex Differences in Management and Outcomes Among Patients With High-Risk Pulmonary Embolism: A Nationwide Analysis

ObjectiveTo examine the sex differences in management and outcomes among patients with high-risk acute pulmonary embolism (PE).Patients and MethodsThe Nationwide Readmissions Database was used to identify hospitalizations with high-risk PE from January 1, 2016, to December 31, 2018. Differences in use of advanced therapies, in-hospital mortality, and bleeding events were compared between men and women.ResultsA total of 125,901 weighted hospitalizations with high-risk PE were identified during the study period; 46.3% were women (n=58,253). Women were older and had a higher prevalence of several comorbidities and risk factors of PE such as morbid obesity, diabetes mellitus, chronic pulmonary disease, heart failure, and metastatic cancer. Systemic thrombolysis and catheter-directed interventions were more commonly used among women; however, mechanical circulatory support was less frequently used. In-hospital mortality was higher among women in the unadjusted analysis (30.7% vs 27.8%, P<.001) and after propensity score matching (odds ratio [OR], 1.16; 95% confidence interval [CI], 1.08 to 1.25; P<.001), whereas the rates of intracranial hemorrhage and non–intracranial hemorrhage were not different. On multivariate regression analysis, female sex (OR, 1.18; 95% CI, 1.15 to 1.21; P<.001) was independently associated with increased odds of in-hospital mortality.ConclusionIn this contemporary observational cohort of patients admitted with high-risk PE, women had higher rates of in-hospital mortality despite receiving advanced therapies more frequently, whereas the rate of major bleeding events was not different from men. Efforts are needed to minimize the excess mortality observed among women.     

Effectiveness and Safety of Clopidogrel vs Aspirin in Elderly Patients With Ischemic Stroke

ObjectiveTo evaluate the risks of recurrent stroke and major bleeding events with clopidogrel and aspirin use among patients aged 80 years or older.Patients and MethodsThis retrospective cohort study was conducted using the Full Population Data of the Health and Welfare Database in Taiwan. Patients aged 80 years or older who received monotherapy with clopidogrel or aspirin following hospitalization for primary acute ischemic stroke between January 1, 2009, and December 31, 2018, were included. Inverse probability of treatment weighting was used to balance measured covariates between clopidogrel and aspirin users. Measured outcomes included recurrent acute ischemic stroke, acute myocardial infarction, composite cardiovascular events (recurrent stroke or acute myocardial infarction), intracranial hemorrhage, major gastrointestinal tract bleeding, and composite major bleeding events (intracranial hemorrhage or major gastrointestinal tract bleeding).ResultsA total of 15,045 patients were included in the study, 1979 of whom used clopidogrel and 13,066 who used aspirin following hospitalization for primary acute ischemic stroke. Clopidogrel use was associated with significantly lower risk of recurrent acute ischemic stroke (hazard ratio [HR], 0.89; 95% CI, 0.83 to 0.96; P=.002), composite cardiovascular events (HR, 0.88; 95% CI, 0.82 to 0.95; P<.001), intracranial hemorrhage (HR, 0.71; 95% CI, 0.56 to 0.90; P=.005), and composite major bleeding events (HR, 0.89; 95% CI, 0.80 to 0.99; P=.04) compared with aspirin use.ConclusionIn patients aged 80 years or older with primary acute ischemic stroke, clopidogrel users had lower risks of recurrent stroke and the composite cardiovascular events compared with aspirin users. Clopidogrel users also had lower risks of intracranial hemorrhage and the composite major bleeding events compared with aspirin users.     

Readmissions Among Patients Admitted With Acute Decompensated Heart Failure Based on Income Quartiles

ObjectiveTo determine the impact of socioeconomic status using median household income within the patient's community on rate of readmission among patients with heart failure (HF).Patients and MethodsWe derived a study cohort of patients who were admitted from January 1, 2013, through December 31, 2014, with congestive HF from the Healthcare Cost and Utilization Project National Readmission Database. Patients were stratified into quartiles according to the estimated median household income of residents in the patient's ZIP Code (quartile 1, lowest; quartile 4, highest). The primary outcome was 30-day readmission. We used univariate and multivariate models to compare patients with respect to baseline characteristics, income quartiles, and 30-day readmission.ResultsAbout 20% (110,152 of 546,841) of patients with an index HF admission were readmitted within the first 30 days. Patients in the lowest income quartile had a higher readmission rate compared with those in the highest income quartile (21.1% [35,422 of 167,625] vs 19.5% [20,771 of 106,353]; P<.001). Patients within the lowest income group had higher odds of readmission for cardiovascular causes compared with the highest income group (50.6% [17,923 of 35,422] vs 48.8% [10,136 of 20,771; P<.001). Readmissions within the lowest income group accounted for 30% of all rehospitalization-related costs at $715 million. Multivariate analysis confirmed a higher rate of 30-day readmission among patients in the lowest income group compared with those in the highest group (adjusted odds ratio, 1.11; 95% CI, 1.08-1.13).ConclusionOur study shows that patients in communities with the lowest quartile of income have a higher rate of readmission following the index HF admission with high associated costs. Readmission reporting and reimbursement adjustments should account for these socioeconomic inequalities.