Faculty Bibliography

BACKGROUND:Inferior vena cava thrombosis (IVCT), although rare, has a potential for significant morbidity and mortality. IVCT is often a result of IVC filter thrombosis, but it can also occur de novo. Although anticoagulation remains the standard of care, endovascular techniques to restore IVC patency have become key adjunctive therapies in recent years. This study examines a single-center experience with diagnosis and management of IVCT. METHODS:A retrospective Institutional Review Board-approved review of a single-center institutional database was screened to identify IVCT thrombosis using International Classification of Diseases code 453.2 over a 3-year period. Etiology of IVCT was separated into 2 groups: those with IVC thrombosis in the setting of prior IVC filter place and those in whom IVCT occurred de novo. Patient demographics, presenting characteristics, and management of IVCT were examined. Treatment options included expectant management with anticoagulation versus catheter-directed thrombolysis (CDT), mechanical thrombectomy, stenting, or a combination. For those who underwent intervention, technical success, defined as restoration of IVC patency, was assessed. RESULTS:Forty-one unique patients were identified with radiographically confirmed diagnosis of ICVT (mean age 61, range 25-91; 21 female, 51.2%). Eighteen (43.9%) patients presented with thrombosed IVC filter. Risk factors for venous thromboembolism included tobacco usage, current or prior smoking (n = 17, 41.5%), history of prior deep vein thrombosis (n = 25, 61.0%), malignancy (n = 17, 41.5%), use of hormonal supplements (n = 3, 7.3%), known thrombophilia (n = 4, 9.8%), and obesity (body mass index: mean 29, range 18.8-58.53). Eleven patients (26.8%) presented with pulmonary embolism (PE), and of those 63.6% had IVC filter thrombosis (n = 7). Risk of PE was not significantly different between those patients presenting with a thrombosed IVC filter compared to those with de novo IVCT (38.9% vs. 17.4%, P = 0.12) Management of IVCT included anticoagulation alone (n = 27, 65.9%), CDT (n = 5, 12.2%), mechanical thrombolysis (n = 10, 24.4%), and adjunctive IVC stent (n = 3, 7.3%). Among the 14 (34.1%) patients who had intervention for IVCT, patency was restored in 12 patients (85.7%). CONCLUSIONS:IVCT is a rare event and is associated with known risk factors for venous thromboembolism. PE can occur in roughly 25% of patients presenting with IVCT. Presence of a filter does not appear to confer an advantage in preventing PE when IVCT occurs. Although majority of IVCT is managed with anticoagulation alone, endovascular interventions, including lysis and stenting, can safely restore patency in most properly selected patients.

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.

Background: The mechanisms for increased cardiovascular risk in patients with Psoriasis (PsO) are unknown. Activated platelets adhere to damaged endothelium and secrete pro-inflammatory cytokines thus promoting atherosclerosis. The contribution of platelets to promote endothelial activation in PsO has not been established. Method(s): Patients with active PsO (n = 6, mean age 46 years, 50% male) were compared to age- and sex- matched controls. Result(s): Platelets were present in PsO lesional skin compared to non-lesional skin, and controls (Figure 1A). To investigate the clinical significance, isolated platelets from PsO and matched-controls demonstrated increased platelet adhesion to human aortic endothelial cells (HAECs) in both basal and activated (thrombin stimulated) states (Figure 1B). Platelets isolated from PsO subjects enhanced HAEC expression of pro-inflammatory transcripts IL-1B, IL-8 and COX-2 (Figure 1C) compared to controls. Next generation RNA sequencing of isolated platelets from PsO and controls revealed upregulation of transcripts indicative of platelet - endothelial interactions such as the pro-atherogenic mediators s100A8/A9 (p < 0.05). Conclusion(s): We describe for the first time platelet-endothelial interactions as a potential mechanism of early cardiovascular risk in patients with PsO. These findings have important clinical implications suggesting that targeting platelet specific pathways in PsO may reduce cardiovascular risk. [Figure presented]2019 American College of Cardiology Foundation. All rights reserved

Background: Perioperative stroke is associated with significant morbidity and mortality. Conventional cardiovascular risk scores have not been validated to predict acute stroke after non-cardiac surgery. Method(s): Patients undergoing non-cardiac surgery between 2009-2011 were identified from the United States National Surgical Quality Improvement Program (n=540,717). Established cardiovascular and perioperative risk models (CHADS, CHADS2VASC, RCRI, MICA and NSQIP ACS Surgical Risk Calculator [ACS-SRC]) were assessed to predict perioperative stroke. Receiver operating characteristic curves and c-statistics (AUC) were compared using Delong's test and likelihood ratios. Result(s): Stroke occurred in the perioperative period of 1,474 non-cardiac surgeries (0.2%). Patients with stroke were older, more frequently male, had lower body mass index, and were more likely to have undergone vascular surgery (p<0.001 all comparisons). The MICA risk score had the most favorable test characteristics in predicting perioperative stroke (AUC 0.83; Figure), and outperformed the more complex ACS-SRC model (AUC 0.81, p for comparison <0.001). In the subgroup of patients undergoing vascular surgery, the AUCs ranged from 0.59-0.67. Conclusion(s): The MICA surgical risk score provides excellent risk prediction for perioperative stroke in non-cardiac surgery. Stroke prediction in vascular surgery is suboptimal. Efforts to prevent perioperative stroke in high risk surgical patients are necessary. [Figure presented]2019 American College of Cardiology Foundation. All rights reserved

BACKGROUND:Systemic lupus erythematosus (SLE) is a complex autoimmune disease associated with an elevated risk for premature cardiovascular disease. Platelets express receptors contributing to inflammation and immunity including FcγRIIA, the low affinity receptor of the Fc portion of IgG antibodies. The variation at a single amino acid substitution, H131R, in the extracellular binding domain alters the affinity for IgG, which may account for individual variation in platelet activity and platelet mediated disease. OBJECTIVES/OBJECTIVE:This study was performed to investigate the association between FcγRIIA genotype, preclinical atherosclerosis, platelet reactivity, and vascular health. METHODS:FcγRIIA was genotyped in 80 SLE patients and 30 healthy controls. Carotid ultrasound plaque, soluble E-selectin, and platelet aggregability were evaluated in SLE and matched controls. RESULTS:Carotid plaque was significantly more prevalent in SLE patients carrying a variant allele compared to those who were homozygous ancestral (58% vs. 25%, P=0.04). In contrast, prevalent carotid plaque was not associated with genotype in controls. Consistently, SLE variant FcγRIIA carriers vs. ancestral had a significant increase in the levels of soluble E-selectin, which was not observed in controls. Monocyte and leukocyte-platelet aggregation and platelet aggregation in response to submaximal agonist stimulation were significantly elevated in SLE patients with the variant vs. ancestral genotype. CONCLUSIONS:Carotid ultrasound plaque, soluble E-selectin levels and platelet activity were more frequently prevalent in SLE patients carrying variant FcγRIIA. The interplay between FcγRIIA-mediated platelet activation and endothelial cells might represent a mechanism underlying the pathogenesis of cardiovascular disease in SLE patients.

Objective- Psoriasis is an inflammatory skin disease which heightens the risk of cardiovascular disease. This study directly investigated vascular endothelial health and systemically altered pathways in psoriasis and matched controls. Approach and Results- Twenty patients (mean age, 40 years; 50% male) with active psoriasis and 10 age-, sex-matched controls were recruited. To investigate systemically alerted pathways, a deep sequencing omics approach was applied, including unbiased blood transcriptomic and targeted proteomic analysis. Vascular endothelial health was assessed by transcriptomic profiling of endothelial cells obtained from the brachial veins of recruited participants. Blood transcriptomic profiling identified inflammasome signaling as the highest differentially expressed canonical pathway ( Z score 1.6; P=1×10^-7) including upregulation of CASP5 and interleukin ( IL) -1β. Proteomic panels revealed IL-6 as a top differentially expressed cytokine in psoriasis with pathway analysis highlighting IL-1β( Z score 3.7; P=1.02×10^-23) as an upstream activator of the observed upregulated proteins. Direct profiling of harvested brachial vein endothelial cells demonstrated inflammatory transcript (eg, IL-1β, CXCL10, VCAM-1, IL-8, CXCL1, Lymphotoxin beta, ICAM-1, COX-2, and CCL3) upregulation between psoriasis versus controls. A linear relationship was seen between differentially expressed endothelial inflammatory transcripts and psoriasis disease severity. IL-6 levels correlated with inflammatory endothelial cell transcripts and whole blood inflammasome-associated transcripts, including CASP5 and IL-1β. Conclusions- An unbiased sequencing approach demonstrated the inflammasome as the most differentially altered pathway in psoriasis versus controls. Inflammasome signaling correlated with psoriasis disease severity, circulating IL-6, and proinflammatory endothelial transcripts. These findings help better explain the heightened risk of cardiovascular disease in psoriasis. Clinical Trial Registration- URL: http://www.clinicaltrials.gov . Unique identifier: NCT03228017.

BACKGROUND:Real-world data on the clinical outcomes of heart failure (HF) across the spectrum of ejection fraction (EF) and the prognostic value of B-type natriuretic peptide (BNP) have not been well examined. HYPOTHESIS/OBJECTIVE:The real-world association between the clinical outcomes of HF and EF or BNP levels may differ across different EF or BNP values. METHODS:The Optum Integrated Claims-Clinical data (07/2009-09/2016) was used to identify adult patients with ≥1 HF diagnosis during a hospitalization or emergency room visit. Three EF cohorts were formed: reduced (rEF; EF<40%), mid-range (mrEF; EF 40%-49%), and preserved EF (pEF; EF≥50%). Stratifications by BNP levels were performed using median BNP as cutoff between high versus low BNP (H-BNP vs. L-BNP). RESULTS:In total, 7,005 HF patients with EF measurements (2,456 patients with both HF and BNP measurements) were identified. rEF patients had higher risk of stroke (HR=1.57, P=0.010) and AMI (HR=2.42, P<0.001) compared to pEF patients. H-BNP was associated with a significantly higher risk of mortality (P<0.001). rEF patients with H-BNP had a significantly higher risk of stroke than those with L-BNP. CONCLUSIONS:Patients with rEF had a significantly higher rate of stroke and AMI versus pEF patients, as did patients with H-BNP versus L-BNP. This study is the first to show the real-world association of EF and BNP (alone and in combination) with clinical outcomes, further supporting the recommendation to use these markers in clinical practice. These results may help guide future recommendations and improve the clinical management of HF.

Psoriasis is an inflammatory skin disease associated with increased cardiovascular risk and serves as a reliable model to study inflammatory atherogenesis. Because neutrophils are implicated in atherosclerosis development, this study reports that the interaction among low-density granulocytes, a subset of neutrophils, and platelets is associated with a noncalcified coronary plaque burden assessed by coronary computed tomography angiography. Because early atherosclerotic noncalcified burden can lead to fatal myocardial infarction, the low-density granulocyte-platelet interaction may play a crucial target for clinical intervention.

BACKGROUND:Coronary artery disease accelerates heart failure progression, leading to poor prognosis and a substantial increase in morbidity and mortality. This study was aimed to assess the impact of coronary artery disease on all-cause mortality, myocardial infarction (MI), and ischemic stroke (IS) among hospitalized newly-diagnosed heart failure (HF) patients with left ventricular systolic dysfunction (LVSD). METHODS:This retrospective cohort study included Medicare patients (aged ≥65 years) with ≥1 inpatient heart failure claim (index date = discharge date) during 01JAN2007-31DEC2013. Patients were required to have continuous enrollment for ≥1-year pre-index date (baseline: 1-year pre-index period) without a prior heart failure claim (in the 1 year pre-index prior to the index hospital admission); follow-up ran from the index date to death, disenrollment from the health plan, or the end of the study period, whichever occurred first. HF with LVSD patients, identified with diagnosis codes of systolic dysfunction (excluding baseline atrial fibrillation), were stratified based on prevalent coronary artery disease at baseline into coronary artery disease and non-coronary artery disease cohorts. Main outcomes were occurrence of major adverse cardiovascular events including all-cause mortality, myocardial infarction, and ischemic stroke. Propensity score matching (PSM) was used to balance patient characteristics. Kaplan-Meier curves of ACM and cumulative incidence distribution of MI/IS were presented. RESULTS:Of 22,230 HF with LVSD patients, 15,827 (71.2%) had coronary artery disease and were overall more likely to be younger (79.8 vs 80.9 years), male (49.6% vs. 35.6%), white (86.2% vs 81.4%), with more prevalent comorbidities including hypertension (80.7% vs 74.3%), hyperlipidemia (67.7% vs 46.7%), and diabetes (46.3% vs 35.8%) (all p < 0.0001). After propensity score matching, cohorts included 5792 patients each. The coronary artery disease cohort had significantly higher cumulative incidence of myocardial infarction and ischemic stroke at the end of 7-year follow-up vs non-coronary artery disease (myocardial infarction = 50.0% vs 18.0%; ischemic stroke = 23.3% vs 18.7%; all p < 0.0001). Follow-up all-cause mortality rates were similar between the two cohorts. CONCLUSIONS:HF with LVSD patients with coronary artery disease had significantly higher incidence of ischemic stroke and myocardial infarction, but similar all-cause mortality compared to those without coronary artery disease.