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Introduction: Lower prevalence of atrial fibrillation (AF) despite a higher prevalence of risk factors in blacks compared to whites (AF paradox) has been reported. However, less information is available about recurrent ablation events in blacks compared to whites. Method(s): Demographic characteristics and one-year recurrent ablation events were analyzed in AF patients admitted to a community hospital from 2018 to 2021. Result(s): Recurrent AF ablation occurred in 3.7% (16/435) of the study population and was significantly higher in black compared to white patients [9/86 (10.5%) vs. 7/349 (2.0%), respectively, p=0.0001]. Black race and history of atrial flutter were predictors of recurrent AF ablation (p<0.05) within one year of initial ablation. Black patients were younger (p=0.03) with a significantly higher prevalence of hypertension, diabetes, cardiomyopathy/heart failure, thyroid disease, renal disease, sleep apnea, COVID-19, pacemaker/AICD placement, and history of Ventricular tachycardia (Table). Concomitant medications were similar between races besides higher use of antihypertensive medications in black patients (Table). Conclusion(s): In our community hospital setup, black patients with AF had a higher prevalence of comorbidities and significantly higher incidence of one-year recurrent ablation events despite similar therapy compared to white patients. These observations should be explored in a larger prospective study to understand the differential association of comorbidities in black AF patients and associated higher risk for recurrent events.
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Background: COVID-19 is associated with cytokine storm and hypercoagulability, indicating elevated risk for thrombotic events. Thromboelastography (TEG6s) assay has been used to demonstrate hypercoagulability in patients with COVID-19. Total Thrombus formation Analysis System (T-TAS) is a novel microfluidic assay that can be used to assess thrombogenicity in the presence of high shear as present in coronary arteries (PL chip) and 600/s shear stress indicating shear at large arteries (AR chip). Aim(s): To demonstrate the prothrombotic state in COVID-19 patients using a novel T-TAS assay and TEG6s. Method(s): Blood samples were collected from 111 patients with COVID-19 during hospitalization for TEG6s and T-TAS analysis, and from 155 healthy volunteers who were not on any antithrombotic agents for TEG6s analysis. Previously published normal ranges for T-TAS assays were used in the analysis. Result(s): 57% of COVID-19 patients were male and 65% were African American. All COVID-19 patients were on prophylaxis or full dose heparin during hospitalization. With the T-TAS AR chip, COVID-19 patients exhibited significantly shorter values in initial occlusion time (T10) and occlusion time and higher area under the curve (AUC) (p < 0.001 for all), indicating a prothrombotic state. There were no differences in PL chip parameters. In COVID-19 patients, TEG6s assay demonstrated reaction time within the normal range despite anticoagulant therapy, higher platelet-fibrin clot strength, fibrinogen clot strength and fibrinogen levels compared to healthy subjects (p < 0.001 for all). There were no differences in total platelet function parameters (PL chip) between COVID-19 patients and healthy subjects. Conclusion(s): Our data indicate that COVID-19 patients exhibit a prothrombotic state that can be assessed by a novel T-TAS assay and TEG6s. This study also indicated that prothrombotic state in COVID-19 patients may be driven by significantly higher fibrinogen levels in the presence of normal platelet function.
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Background: Hypercoagulability has been established in COVID-19 and has been linked to thrombotic risk. The existence of an antiphospholipid (aPL) syndrome in COVID-19 remains controversial. Aim(s): Determine if markers of aPL syndrome are elevated in COVID-19 and associated with hypercoagulability and in-hospital clinical events. Method(s): Blood, urine, clinical data, and outcomes were analyzed in patients hospitalized with COVID-19 (n = 100) enrolled in the IRB approved TARGET-COVID study and in healthy subjects (n = 131). aPL syndrome was assessed using using lupus anticoagulant assays (dRVVT and Hex LA, Precision BioLogic Inc.);aPL antibody (APA) profiling (IgA,IgM,IgG) against aB2GP1, anticardiolipin (aCL), and anti-phosphotidyl serine (aPS) assays (Corgenix). Hypercoagulability, and coagulation markers (D-Dimer, Factor-V, VIII, XII, and Prekalikrein) were assessed using thromboelastography (TEG-6s), ELISA, and standard coagulation assays, respectively. Result(s): Mean age was 59 +/- 19 years;predominately African American (65%), with a high prevalence of hypertension (74%), obesity (53%), and diabetes (45%). LA positivity was observed in 2%;and 32%, 23%, and 9% by aB2GP1, aCL, and aPS antibody testing, respectively (Figure 1). Hypercoagulability defined by platelet-fibrin clot strength (MA >= 68 mm) was observed in 62% of the total group and was not associated with LA or APA positivity. Patients had lower FV, FXII, PK activity vs. healthy subjects (p < 0.05 for all). D-dimer was higher in patients with aPL's vs. negative patients (p = 0.03) but was not associated with thrombotic events (21% vs. 16%). Patients with positive aPS antibodies had higher mortality than aPS negative, and aCL positive, and aB2GP1 positive patients (44% vs. 18%, 10%, 7%;p< 0.05) respectively. Conclusion(s): Based on LA assay, aPL syndrome is infrequent in COVID-19. However, there is a high prevalence of aPL antibodies that correlate with D-dimer with the greatest prevalence observed for aB2GP1. aPS positivity correlated with mortality and deserves further investigation as a biomarker of poor outcomes. (Figure Presented).
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Objective: To assess the relationship between serum 1,5-anhydroglucitol (1,5-AG), a marker of glycemic variability, and mortality in COVID-19 patients. Method: Data from 64 hospitalized COVID-19 patients were collected between June 2020-February 2021 at Sinai Hospital (Baltimore, MD), including 9 patients who died in the hospital. Medical history, demographic variables, and biochemical measurements were taken at time of admission. Baseline means for fasting blood glucose and 1,5-AG were 143.5 mg/dL (SD 68.9) and 14.7 ug/mL (SD 8.8), respectively. HbA1c available in 40 patients-mean value 6.9% (SD 2.3). Result: Multivariate logistic regression analysis showed that only 1,5-AG (n=64) was an independent predictor of mortality (AUC = 0.69, p value 0.017). Fasting glucose (n=64) and HbA1c (n=40) were not statsically significant with AUCs of 0.60 (p value 0.322) and 0.58 (p value 0.464), respectively. In an analysis of clinical variables, a combination of BMI and Age was predictive of mortality (AUC = 0.77, p value 0.004). Interestingly, when 1,5-AG was added to BMI and Age, the AUC increased to 0.94 (p value <0.0001). When fasting glucose was added to BMI and Age the AUC was 0.79 (p value 0.001). A cox regression analysis showed an OR (1,5-AG < 10 ug/mL) for mortality of 0.44 (95% CI 0.11, 1.85). Conclusion: 1,5-AG was an independent predictor of COVID-19 mortality. Fasting glucose and HbA1c showed no statistical significance to outcomes. The HbA1c findings confirm the results from other COVID-19 studies, but the finding that 1,5-AG outperformed fasting glucose in predicting mortality is new. 1,5-AG may provide important and unique information in the COVID-19 clinical setting. An algorithm of BMI, Age, and 1,5-AG may also be clinically useful.
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Background: Fasting hyperglycemia and diabetes are the independent predictors of morbidity and mortality in patients with COVID-19. Glycemic fluctuations may be independently associated with poor prognosis in adult patients hospitalized for COVID-19. Hypothesis: We hypothesize that 1,5-anhydroglucitol (1,5-AG), a marker of glycemic variability, is strongly associated with in-hospital mortality in patients with COVID-19. Methods: Medical history, demographic variables, and laboratory measurements were collected within 48 hours of hospitalization in COVID-19 patients (n=64), including 9 patients who died in the hospital. Serum 1,5AG was measured by an enzymatic colorimetric assay (GlycoMark, Precision Diabetes, Inc. Raleigh, NC). Multivariate regression analysis was performed to assess the relation between fasting glucose, hemoglobin (Hb)A1c and 1,5-AG and mortality. Results: Baseline mean ± SD for fasting blood glucose,1,5-AG and HbA1c (available in 40 patients) were 143 ± 69 mg/dL and 14.7 ± 8.8 ug/mL and 6.9±2.3%, respectively. Only 1,5-AG was an independent predictor of mortality (n=64, AUC = 0.69, p=0.017), but not fasting glucose (n=64, AUC =0.60, p=0.32) or HbA1c (n=40, AUC=0.58, p =0.46), respectively. With respect to clinical variables, a combination of BMI and Age was predictive of mortality (AUC = 0.77, p=0.004). Interestingly, when 1,5-AG was added to BMI and Age, the AUC increased to 0.94 (p <0.0001). When fasting glucose was added to BMI and Age the AUC was 0.79 (p =0.001). A cox regression analysis demonstrated that 1,5-AG < 10 ug/mL was associated with an odds ratio of 0.44 (95% CI =0.11-1.85) for mortality. Conclusions: This analysis demonstrated that 1,5-AG is a novel and independent predictor of COVID-19 mortality. 1,5-AG may provide important and unique information in the COVID-19 clinical setting. An algorithm of BMI, Age, and 1,5-AG can be used clinically to predict mortality. These findings warrant further investigation in larger studies specific for diabetic and non-diabetic populations.
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Introduction: Messenger RNA (mRNA) based vaccines (Pfizer/BioNTech and Moderna) have shown to be highly effective at providing immunity against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Aims: To study the duration of immunity, evolution of IgG antibody levels and IgG avidity (an index of antibody-antigen binding strength), and differences in immune responses between (mRNA) based vaccines. Methods: We performed a prospective study of 72 subjects without a history of SARS-CoV-2 who received both doses of either the Pfizer (n=55) or Moderna (n=17) mRNA vaccine. Anti-spike protein receptor binding domain (RBD) IgG antibody levels and IgG avidity indices were measured longitudinally using a qualitative finger stick MidaSpot™ rapid test at the point-of-care and a quantitative dry blood spot-based pGOLD™ laboratory test over ∼ 4 months post-vaccination. Results: On average, anti-RBD IgG antibody levels peaked at ∼2 weeks after second vaccination dose and declined thereafter, while antibody avidity increased suggesting antibody maturation (Figure). Moderna vaccine recipients exhibited higher side effect severity, higher peak anti-RBD IgG antibody levels and higher avidity up to the 90 days point, when compared to Pfizer vaccine recipients. Nevertheless, the differences in antibody and avidity levels diminished at ∼ 120 days post-vaccination, in line with the similar efficacy of the two vaccines. A qualitative MidaSpot finger stick rapid test detected 100% anti-SARS-CoV-2 RBD positivity for fully vaccinated subjects in both Pfizer and Moderna cohorts and turning negative greater than 90 days post-vaccination for 9% of subjects in the Pfizer cohort whose quantitative anti-IgG fell below the 25-percentile levels. Conclusions: Longitudinal quantitative measurements of anti-RBD antibody and avidity levels provide insight to immune responses and could aid the assessment of immunity and vaccine effectiveness.