Faculty Bibliography

Pulmonary hypertension (PH), defined by a mean pulmonary artery pressure of >25mm Hg at rest, is strongly associated with morbidity and mortality in the perioperative period. The prevalence and outcomes of PH among patients referred for major noncardiac surgery in the United States are unknown. Patients ≥18 years of age hospitalized for noncardiac surgery were identified from Healthcare Cost and Utilization Project's National Inpatient Sample data from 2004 to 2014. Pulmonary hypertension was defined by International Classification of Diseases, Ninth Revision diagnosis codes. The primary outcome was perioperative major adverse cardiovascular events (MACCE), defined as in-hospital death, myocardial infarction, or ischemic stroke. Among 17,853,194 hospitalizations for major noncardiac surgery, 143,846 (0.81%) had PH. MACCE occurred in 8.3% of hospitalizations with any diagnosis of PH in comparison to 2.0% of those without PH (p <0.001), driven by an increased frequency of death (4.4% vs 1.1%, p <0.001) and nonfatal myocardial infarction (3.2% vs 0.6%, p <0.001). After adjusting for demographics, clinical covariates, and surgery type, PH remained independently associated with MACCE (aOR 1.43, 95% CI 1.40 to 1.46). In conclusion, PH is associated with perioperative major adverse cardiovascular events. Careful patient selection, recognition of perioperative risks, and appropriate intraoperative hemodynamic monitoring may improve perioperative cardiovascular outcomes.

Morbidity and mortality associated with cardiovascular disease can be significantly modified through lifestyle interventions, yet there is little emphasis on nutrition and lifestyle in medical education. Improving nutrition education for future physicians would likely lead to improved preparedness to counsel patients on lifestyle interventions. An online anonymous survey of medical residents, cardiology fellows, and faculty in Internal Medicine and Cardiology was conducted at New York University Langone Health assessing basic nutritional knowledge, self-reported attitudes and practices. A total of 248 physicians responded (26.7% response rate). Nutrition knowledge was fair, but few (13.5%) felt adequately trained to discuss nutrition with patients. A majority (78.4%) agreed that additional training in nutrition would allow them to provide better clinical care. Based on survey responses, a dedicated continuing medical education (CME) conference was developed to improve knowledge and lifestyle counseling skills of healthcare providers. In postconference evaluations, attendees reported improved knowledge of evidence-based lifestyle interventions. Most noted that they would prescribe a Mediterranean or plant-based diet and would make changes to their practice based on the conference. An annual CME conference on diet and lifestyle can effectively help interested providers overcome barriers to lifestyle change in clinical practice through improved nutrition knowledge.

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.

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.