Faculty Bibliography

BACKGROUND:Myocardial injury after non-cardiac surgery (MINS) is a common post-operative cardiovascular complication and is associated with short and long-term mortality. The objective of this study was to describe the contemporary management of patients with and without MINS after total joint and spine orthopedic surgery at a large urban health system in the United States. METHODS:Adults admitted for total joint and major spine surgery from January 2013 through December 2015 with ≥1 cardiac troponin (cTn) measurement during their hospitalization were identified. MINS was defined by a peak cTn above the 99th percentile of the upper reference limit. Demographics, medical comorbidities, and admission and discharge medications were reviewed for all patients. RESULTS:A total of 2561 patients underwent 2798 orthopedic surgeries, and 236 cases of MINS were identified. Patients with MINS were older (71.9 ± 10.9 vs. 67.0 ± 10.0, p < 0.001) and more likely to have cardiovascular risk factors, including hypertension, chronic kidney disease, prior stroke, coronary artery disease, prior MI, and a history of heart failure. Among patients with MINS, only 112 (47.5%) were discharged on a combination of aspirin and statin. Patients with MINS were more likely to be prescribed a statin (154 [65.3%] vs. 1463 [57.1%], p = 0.018), beta-blocker (147 [62.3%] vs. 1194 [46.6%], p < 0.001), and oral anticoagulation (65 [27.5%] vs. 436 [17.0%], p < 0.001) than patients without MINS. CONCLUSIONS:The proportion of patients with MINS who were prescribed medical therapy for atherosclerotic cardiovascular disease was low. Additional efforts to determine optimal management of MINS are warranted.

Importance/UNASSIGNED:Patients with peripheral artery disease (PAD) are at high risk for myocardial infarction (MI). Objective/UNASSIGNED:To characterize the incidence and types of MI in a PAD population, identify factors associated with MI, and determine the association of MI with cardiovascular mortality and acute limb ischemia. Design, Setting, and Participants/UNASSIGNED:The Study Comparing Cardiovascular Effects of Ticagrelor and Clopidogrel in Patients With Peripheral Artery Disease (EUCLID) was a double-blind randomized clinical trial conducted at 811 sites in 28 countries that randomized 13 885 patients with symptomatic PAD to monotherapy with ticagrelor or clopidogrel. Participants had an ankle-brachial index (ABI) of 0.80 or less or previous lower extremity revascularization. Median follow-up was 30 months. For these analyses, patients were evaluated for MI occurrence during follow-up irrespective of treatment. Data were analyzed from June 2017 to September 2018. Main Outcomes and Measures/UNASSIGNED:An adjudication clinical events committee classified MI as type 1 (spontaneous), type 2 (secondary), type 3 (sudden cardiac death), type 4a (less than 48 hours after percutaneous coronary intervention), type 4b (definite stent thrombosis), or type 5 (less than 72 hours after coronary artery bypass graft). A multivariate regression model was developed by stepwise selection to identify factors associated with MI, and a time-dependent multivariate Cox regression analysis was performed to determine the association of MI with cardiovascular death and acute limb ischemia requiring hospitalization. Results/UNASSIGNED:Of the 13 885 patients included in this analysis, 9997 (72.0%) were male, and the median (interquartile range) age was 66 (60-73) years. Myocardial infarction occurred in 683 patients (4.9%; 2.4 events per 100 patient-years) during a median follow-up of 30 months. Patients experiencing MI were older (median [interquartile range] age, 69 [62-75] vs 66 [60-72] years), more likely to have diabetes (349 of 683 [51.1%] vs 4996 of 13 202 [37.8%]) or a previous lower extremity revascularization (466 of 683 [68.2%] vs 7409 of 13 202 [56.1%]), and had a lower ABI (if included by ABI) compared with censored patients. Of the 683 patients with MI during follow-up, the most common MI type was type 1 (405 [59.3%]), followed by type 2 (236 [34.6%]), type 4a (14 [2.0%]), type 3 (12 [1.8%]), type 4b (11 [1.6%]), and type 5 (5 [0.7%]). Postrandomization MI was independently associated with cardiovascular death (adjusted hazard ratio, 9.0; 95% CI, 7.3-11.2; P < .001) and acute limb ischemia requiring hospitalization (adjusted hazard ratio, 2.5; 95% CI, 1.3-5.0; P = .008). Conclusions and Relevance/UNASSIGNED:Approximately 5% of patients with symptomatic PAD had an MI during a median follow-up of 30 months. Type 1 MI (spontaneous) was the most common MI type; however, one-third of MIs were type 2 MI (secondary). More research is needed to identify therapies to reduce the risk of MI in patients with PAD and to improve management of type 2 MI. Trial Registration/UNASSIGNED:ClinicalTrials.gov Identifier: NCT01732822.

Chronic inflammation drives many obesity-associated conditions, including atherosclerosis. GlycA, a marker of systemic inflammation with lower intraindividual variability than hsCRP, is independently associated with incident cardiovascular events and mortality. Although GlycA is elevated in obesity, correlations with anthropometric measures are modest and the effect of weight loss on GlycA is untested. Obese (BMI 44.6±6.6kg/m² ), non-diabetic women (33.7±8.2 years) undergoing Roux-en-Y gastric bypass (n=23) or sleeve gastrectomy (n=31) were prospectively studied at baseline, 6 and 12 months post-procedure. Women with normal BMI (n=14) served as controls. Bariatric surgery significantly reduced GlycA by 6 months (451±47umol/L vs 383±50umol/L; p<0.001) with further reduction at 12 months (348±41umol/L; p<0.001) and no difference between procedures. At 12 months, despite 41% of surgical subjects maintaining BMI >30kg/m² , GlycA levels did not differ between surgical and control subjects (p=0.13). Increased HDL particle size was strongly associated with reduced GlycA (r=-0.49; p<0.001) and was found to mediate up to 43% of its weight-loss-associated fall. This is the first study to demonstrate that surgical weight loss markedly reduces levels of GlycA.

Background/UNASSIGNED:Perioperative cardiovascular outcomes of transplant surgery are not well defined. We evaluated the incidence of perioperative major cardiovascular and cerebrovascular events (MACCE) after non-cardiac transplant surgery from a large database of hospital admissions from the United States. Methods/UNASSIGNED:Patients ≥18 years of age undergoing non-cardiac solid organ transplant surgery from 2004 to 2014 were identified from the Healthcare Cost and Utilization Project's (HCUP) National Inpatient Sample (NIS). The primary outcome was perioperative MACCE, defined as in-hospital death, myocardial infarction (MI), or ischemic stroke. Results/UNASSIGNED:A total of 49,978 hospitalizations for transplant surgery were identified. Renal (67.3%), liver (21.6%), and lung (6.7%) transplantation were the most common surgeries. Perioperative MACCE occurred in 1,539 transplant surgeries (3.1%). Recipients of organ transplantation were more likely to have perioperative MACCE in comparison to non-transplant, non-cardiac surgery (3.1% vs. 2.0%, p < 0.001; adjusted OR [aOR] 1.29, 95% CI 1.22-1.36). MACCE after transplant surgery were driven by increased mortality (1.7% vs. 1.1%, p < 0.001; aOR 1.15, 95% CI 1.07-1.23) and MI (1.2% vs. 0.6%, p < 0.001; aOR 2.26, 95% CI 2.09-2.46) versus non-transplant surgery, with lower rates of stroke (0.3% vs. 0.5%, p < 0.001; aOR 0.56, 95% CI 0.47-0.65). Among patients hospitalized for renal, liver, and lung transplantation, MACCE occurred in 1.7%, 5.6%, and 7.5%, respectively, with no difference in the frequency of MI by surgery type. Conclusions/UNASSIGNED:Cardiovascular outcomes of transplant surgery vary by surgical subtype and are largely driven by increased perioperative death and MI. Efforts to reduce cardiovascular risks of non-cardiac organ transplant surgery are necessary.

BACKGROUND:Heart failure (HF) is associated with an incremental risk of ischemic stroke, but limited real-world data exist in Patients with HF without atrial fibrillation (AF). OBJECTIVES/OBJECTIVE:This study quantified the incremental risk of ischemic stroke among newly diagnosed patients with HF and without AF. METHODS:Adult patients with an HF-related claim and ≥18 months of enrollment before their index HF (i.e., baseline period) were identified in Truven Health Analytics MarketScan Databases (01/2010-04/2015). Patients without an AF diagnosis during the baseline period and without an ischemic stroke within 14 days of the index date were propensity score matched 1:1 to individuals with neither HF nor AF and observed for ischemic stroke. A similar analysis was performed for the overall HF population (regardless of AF status). Incidence rates (calculated using Poisson regression models) were compared using incidence rate ratios (IRRs) between HF and non-HF cohorts; Kaplan-Meier analyses with log-rank tests were used to compare incidence rates over time. RESULTS:A total of 66,414 patients with HF were identified of which 52,005 did not have AF. Patients with HF without AF had significantly higher rates of ischemic stroke than patients without HF without AF during follow-up (IRR=1.91 [95%CI: 1.75-2.09], p<0.001). Ischemic stroke rates remained significantly higher for patients with HF over time among individuals without AF (p<0.001 for log-rank test at 12, 24, and 36 months).Similar results were found for the overall HF population. CONCLUSIONS:Even in the absence of AF, Patients with HF are at heightened risk of ischemic stroke compared to patients without HF.

Objective: To determine whether monocyte-platelet aggregates (MPA) correlate with aortic aneurysm (AA) prevalence and severity. BACKGROUND: Inflammation and intraluminal thrombus are key hallmarks of complex AA. While monocytes fuel inflammation in AA, the contribution of platelets is unknown. We hypothesized that increased platelet activity yields to MPA that drive AA development and indicate disease severity.
Method(s): Blood was collected from 49 symptomatic patients admitted for aneurysm repair procedures (8 thoracic and 41 abdominal) and 36 matched controls. All subjects were on aspirin monotherapy. Platelet responsiveness to agonists was characterized by light transmission aggregometry. Flow cytometry analysis allowed leukocytes (CD45+)/monocytes (CD14+)-platelet (CD61+) aggregates (LPA/MPA) measurements in the blood and profiled MPA in post-surgical aneurysm tissues.
Result(s): Platelet aggregation in response to ADP (57% vs. 35% aggregation, p<0.001) and arachidonic acid (24% vs. 16% aggregation, p=0.03), was increased in patients with AA versus controls. LPA (17.7 vs 6.2% CD61+ leukocytes, p=0.002) and MPA (18.0 vs 7.2% CD61+ Monocytes, p=0.008) were robustly increased in AA vs controls. MPA but not LPA was strongly and positively associated with AA size (p<0.0001). To delve into the role of MPA in situ in AA sac, platelets and tissue macrophage activation was characterized. Compared to the non-diseased part of the aorta, diseased section had significantly higher platelet infiltration (7.0% vs 1.2% CD61+ cells, p=0.006) and interaction with CD68+ tissue macrophages (8.3% vs. 0.7%, CD61+ macrophages p=0.03). Notably, macrophages highly expressed the adhesion protein, ICAM-1, in the diseased part (39.6 vs 3.3% in the non-diseased section, p<0.001) which further increased to 69.4% (p=0.01) when macrophages were in contact with platelets.
Conclusion(s): Our data highlights MPA as a novel mediator valuable to predict AA prevalence and severity

Patients surviving an acute coronary syndrome (ACS) remain at increased risk of ischemic events long term. This paper reviews current evidence and guidelines for oral antiplatelet therapy for secondary prevention following ACS, with respect to decreased risk of ischemic events versus bleeding risk according to individual patient characteristics and risk factors. Specifically, data are reviewed from clinical studies of clopidogrel, prasugrel, ticagrelor and vorapaxar, as well as the results of systematic reviews and meta-analyses looking at the benefits and risks of oral antiplatelet therapy, and the relative merits of shorter versus longer duration of dual antiplatelet therapy, in different patient groups.