Faculty Bibliography

BACKGROUND:Thrombosis is a prominent feature of the novel Coronavirus disease 2019 (COVID-19). The incidence of thrombosis during hospitalization for non-COVID-19 viral respiratory infections is uncertain. We evaluated the incidence of thrombosis in patients hospitalized with non-COVID-19 acute viral respiratory illnesses compared to COVID-19. METHODS:Adults age >18 years hospitalized with a non-COVID-19 viral respiratory illness between 2002-2014 were identified. The primary study outcome was a composite of venous and arterial thrombotic events, including myocardial infarction (MI), acute ischemic stroke, and venous thromboembolism, as defined by ICD-9 codes. The incidence of thrombosis in non-COVID-19 viral respiratory illnesses was compared to the recently published incidence of thrombosis in COVID-19 from 3,334 patients hospitalized in New York in 2020. RESULTS:Among 954,521 hospitalizations with viral pneumonia from 2002 to 2014 (mean age 62.3 years, 57.1% female), the combined incidence of arterial and venous thrombosis was 5.0%. Acute MI occurred in 2.8% of hospitalizations, VTE in 1.6%, ischemic stroke in 0.7%, and other systemic embolism in 0.1%. Patients with thrombosis had higher in-hospital mortality (14.9% vs. 3.3%, p<0.001) than those without thrombosis. The proportion of hospitalizations complicated by thrombosis was lower in patients with viral respiratory illness in 2002-2014 than in COVID-19 (median age 64; 39.6% female) in 2020 (5% vs. 16%; p<0.001) CONCLUSION: In a nationwide analysis of hospitalizations for viral pneumonias, thrombosis risk was lower than that observed in patients with COVID-19. Investigations into mechanisms of thrombosis and risk reduction strategies in COVID-19 and other viral respiratory infections are necessary. SHORT ABSTRACT/UNASSIGNED:We evaluated the incidence of thrombosis in patients hospitalized with non-COVID-19 acute viral respiratory illnesses nationwide from 2012 to 2014 and compared this to the incidence among patients hospitalized with COVID-19 at a large health system in New York. Non-COVID-19 viral respiratory illness was complicated by acute MI in 2.8% of hospitalizations, VTE in 1.6%, ischemic stroke in 0.7%, and other systemic embolism in 0.1%. The proportion of hospitalizations complicated by thrombosis was lower in patients with viral respiratory illness in 2002-2014 than in COVID-19 (5% vs. 16%; p<0.001).

BACKGROUND:Peripheral artery disease is common and associated with high mortality. There are limited data detailing causes of death among patients with peripheral artery disease. METHODS:EUCLID (Examining Use of Ticagrelor in Peripheral Artery Disease) was a randomized clinical trial that assigned patients with peripheral artery disease to clopidogrel or ticagrelor. We describe the causes of death in EUCLID using mortality end points adjudicated through a clinical events classification process. The association between baseline factors and cardiovascular death was evaluated by Cox proportional hazards modeling. The competing risk of noncardiovascular death was assessed by the cumulative incidence function for cardiovascular death and the Fine and Gray method to ascertain the association between baseline characteristics and cardiovascular mortality. RESULTS:A total of 1263 out of 13 885 (9.1%) patients died (median follow-up: 30 months). There were 706 patients (55.9%) with a cardiovascular cause of death and 522 (41.3%) with a noncardiovascular cause of death. The most common cause of cardiovascular death was sudden cardiac death (20.1%); while myocardial infarction (5.2%) and ischemic stroke (3.2%) were uncommon. The most common causes of noncardiovascular death were malignancies (17.9%) and infections (11.9%). The factor most associated with a higher risk of cardiovascular death was age per 5 year increase (HR, 1.26 [95% CI, 1.20-1.32]). Female sex was associated with a lower risk of cardiovascular death (HR, 0.68 [95% CI, 0.56-0.82]). To evaluate the effect of noncardiovascular death as a competing risk, we superimposed the cumulative incidence function curve with the Kaplan-Meier curve. These curves closely approximated each other. After accounting for the competing risk of noncardiovascular death, the magnitude and direction of the factors associated with cardiovascular death were minimally changed. CONCLUSIONS:Among patients with symptomatic peripheral artery disease, noncardiovascular causes of death reflected a high proportion (40%) of deaths. Accounting for noncardiovascular deaths as a competing risk, there was not a significant change in the risk estimation for cardiovascular death. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT01732822.

Objective: Whereas clopidogrel is effective at decreasing cardiovascular events in patients with peripheral artery disease, a substantial number of events continue to occur. This study investigated the variability in response to clopidogrel and its relationship with clinical outcomes.
Method(s): There were 300 patients enrolled in the Platelet Activity in Vascular Surgery and Cardiovascular Events (PACE) study before lower extremity revascularization, of whom 119 were receiving clopidogrel. Platelet aggregation was measured in response to adenosine diphosphate (ADP) 2M immediately before revascularization. Patients were observed longitudinally for a median follow-up of 18 months. The primary end point was major adverse limb events (MALEs), defined by major amputation or reoperation of the affected limb. Patients were stratified into groups according to the percentage ADP-induced aggregation at 300 seconds (<50% aggregation, normal responder; >=50% aggregation, poor responder).
Result(s): Overall, the median age was 70 years (62-76 years), and 39.5% were female. Thirty-six (30.3%) patients had a MALE event (15 major amputation and 25 major reoperation); 60 patients underwent open or hybrid operations, and 50 patients underwent endovascular procedures. The remaining nine patients had no interventions. Of the group of 119 patients, 97 patients were taking aspirin. Overall, median aggregation to ADP 2M was 22.5% (Q1-Q3, 10%-50%), and 27 patients (26%) were clopidogrel nonresponders. Baseline aggregation was higher in patients who went on to develop a MALE than in those without a MALE (43% vs 20%; P =.018). Patients with aggregation > median (22.5%) were more likely to experience a MALE than were patients with aggregation < median (69% vs 31%; hazard ratio [HR], 2.71; 95% confidence interval [CI], 1.23-5.98; P =.013). After multivariable adjustment for age, sex, race/ethnicity, body mass index, diabetes, coronary artery disease, and aspirin, aggregation > median was associated with MALEs (adjusted HR, 2.67; 95% CI, 1.18-6.01; P =.018). When stratified by established cutoffs for responsiveness to clopidogrel (50% aggregation), 27 (26%) patients were poor responders. Poor responders were more likely to experience MALEs than normal responders (59% vs 41%; HR, 2.33; 95% CI, 1.11-4.89; P =.026). After multivariable adjustment, poor responder status trended toward an increased risk of MALE compared with a normal responder (adjusted HR, 2.18; 95% CI, 1.00-4.78; P =.051).
Conclusion(s): Among patients undergoing lower extremity revascularization, poor response to clopidogrel is associated with increased risk for major adverse limb events. Preoperative screening to ensure therapeutic clopidogrel response should be considered in these patients.
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BACKGROUND:Patients with peripheral artery disease have a high risk of future cardiovascular disease events and mortality. Little is known about the changes in symptom classification over time in patients with peripheral artery disease and the association of changes in symptom classification with subsequent cardiovascular disease events. METHODS:In this analysis of the EUCLID trial (Examining Use of Ticagrelor in Peripheral Artery Disease), we examined the changes in Rutherford classification (RC) of patients over 12 months. We examined the baseline characteristics of patients by change in symptom classification at 12 months (improved=decreased RC, no change, or worsened=increased RC), and the association between changes in symptom classification (RC) at 12 months and subsequent cardiovascular disease events. RESULTS:<0.05 after 12 months postrandomization. CONCLUSIONS:Patients with comorbidities and prior history of cardiovascular disease events at baseline and within the first 12 months of the trial were more likely to have worsened symptom classification at 12 months. Worsening symptom classification over 12 months was associated subsequently with an increased risk of all-cause death, amputation, and a composite of cardiovascular death, myocardial infarction, or stroke. Graphic Abstract: A graphic abstract is available for this article.

Background There are limited data on health status instruments in patients with peripheral artery disease and cardiovascular and limb events. We evaluated the relationship between health status changes and cardiovascular and limb events. Methods and Results In an analysis of the EUCLID (Examining Use of Ticagrelor in Symptomatic Peripheral Artery Disease) trial, we examined the characteristics of 13 801 patients by tertile of health status instrument scores collected in the trial (EuroQol 5-Dimensions [EQ-5D], EQ visual analog scale [VAS], and peripheral artery questionnaire). We assessed the association between the baseline health status measurements and major adverse cardiovascular events, major adverse limb events, and lower-extremity revascularization procedures during trial follow-up and the association between 12-month health status change scores and subsequent end points during follow-up. There were 13 217 (95%) patients with EQ-5D scores, 13 533 (98%) with VAS scores, and 4431 (32%) with peripheral artery questionnaire scores. Patients in the lowest baseline EQ-5D tertile (0 to <0.69) were more likely to be female with severe claudication compared with the highest tertile (0.79-1.0; P<0.01). Patients in the lowest VAS (0-60) and peripheral artery questionnaire (0-49) tertiles had lower ankle-brachial indices compared with the highest tertiles (80-100 and 76-108, respectively; P<0.01). There was a significant association between baseline EQ-5D, VAS, and peripheral artery questionnaire scores and adjusted major adverse cardiovascular events, major adverse limb events, and lower-extremity revascularization (P<0.05). Improved EQ-5D and VAS scores over 12 months were associated with reduced risk of subsequent major adverse cardiovascular events or lower-extremity revascularization (all P<0.01). Conclusions Although health status instruments are rarely used in clinical practice, these measures are associated with outcomes, including major adverse cardiovascular events, major adverse limb events, and lower-extremity revascularization. Further research is needed to determine the relationship between changes in these instruments, revascularization, and outcomes.

OBJECTIVES/OBJECTIVE:The rate of thromboembolic events among patients with coronavirus disease 2019 is high; however, there is no robust method to identify those at greatest risk. We reviewed thromboelastography studies in critically ill patients with coronavirus disease 2019 to characterize their coagulation states. DESIGN/METHODS:Retrospective. SETTING/METHODS:Tertiary ICU in New York City. PATIENTS/METHODS:Sixty-four patients with coronavirus disease 2019 admitted to the ICU with thromboelastography performed. INTERVENTIONS/METHODS:None. MEASUREMENTS AND MAIN RESULTS/RESULTS:Fifty percent of patients had a clotting index in the hypercoagulable range (clotting index > 3) (median 3.05). Reaction time and K values were below the lower limit of normal in 43.8% of the population consistent with a hypercoagulable profile. The median α angle and maximum amplitude (75.8° and 72.8 mm, respectively) were in the hypercoagulable range. The α angle was above reference range in 70.3% of patients indicative of rapid clot formation. Maximum amplitude, a factor of fibrinogen and platelet count and function, and a measure of clot strength was above reference range in 60.1% of patients. Thirty-one percent had thromboembolic events; thromboelastography parameters did not correlate with events in our cohort. Those with D-dimer values greater than 2,000 were more likely to have shorter reaction times compared with those with D-dimer levels less than or equal to 2,000 (4.8 vs 5.6 min; p = 0.001). CONCLUSIONS:A large proportion of critically ill patients with coronavirus disease 2019 have hypercoagulable thromboelastography profiles with additional derangements related to fibrinogen and platelet function. As the majority of patients have an elevated thromboelastography maximum amplitude, a follow-up study evaluating platelet aggregation would be instructive.