ABSTRACT
INTRODUCTION: Coronavirus disease 2019 (COVID-19) can be associated with coagulopathy and a high incidence of thromboembolic events. These events were associated with worse clinical outcomes, especially in critically ill patients. Our study investigated the safety of full dose anticoagulation (AC), in ventilated, predominantly Black patients with COVID-19 infection. METHODS: This is a retrospective observational study based on a chart review of patients admitted to the University Hospital of Brooklyn in New York City from March 23rd through April 23rd, 2020. Inclusion criteria included age ≥ 18 years, confirmed COVID-19 infection, and need for mechanical ventilation. The variables collected included demographics, comorbidities, laboratory results, type of anticoagulation, and Sepsis- Induced Coagulopathy (SIC) score RESULTS: A total of 48 hospitalized patients met the inclusion criteria. 41 (85.4%) were Black, 26 (54%) were males, 22 (46%) were females, and the average age was 68 years. Average days on mechanical ventilation was 13.6 days. D-Dimer was elevated in all patients, with an average of 5.8 mcg/ml. Almost all patients (47/48) had elevated SIC score, defined as SIC score of 2 or above. AC agent used was Heparin in 13 patients (27.1%), low molecular weight heparin (LMWH) in 12 (25%), direct oral anticoagulants (DOAC) in 8 (16.7%), and multiple AC agents in 15 (31.3%). AC was stopped because of major bleed in 5 patients. Overall mortality was 62.5%. AC discontinuation was not associated with increased overall mortality (Pearson Chi-Square= 0.228;p=0.633) CONCLUSIONS: Our study showed that full dose anticoagulation was administered in high risk ICU patients with COVID-19 infection, and significantly elevated D-Dimer level and SIC score. Most patients received heparin or LMWH, or a combination of heparin products with transition to DOAC. However only 5 patients had a major bleed, that was not a significant contributor to overall mortality. Based on our results, administration of full dose anticoagulation in ventilated predominantly black patients with COVID-19 infection, was overall safe and well tolerated.
ABSTRACT
Background: The novel coronavirus disease-2019 (COVID-19) caused by the severe acute respiratory syndrome coronavirus-2 (SARS CoV-2) has been a major cause of morbidity and mortality around the world. Thirteen million cases have been diagnosed with approximately 570,000 deaths worldwide. COVID-19 is associated with ischemia, myocarditis and eventual resulting arrhythmia. Cases may present as acute thrombotic occlusion, stress cardiomyopathy, or coronary spasm. Hydroxychloroquine (HCQ) was temporarily approved by FDA for COVID-19 treatment. In this study, we planned to characterize the risk and degree of QTc prolongation in largely African-American population in central Brooklyn, who were hospitalized with COVID-19 infection in association with inpatient administration of HCQ and azithromycin. One of the major adverse drug effects of HCQ and chloroquine is the potential prolongation of corrected QT interval (QTc). Methods: In our retrospective study, we included patients, both males and females, 18 years of age and older who were admitted at SUNY Downstate Medical Center, Brooklyn, New York, for COVID-19 infection and were treated with hydroxychloroquine. Native baseline RR, QRS, and QT intervals were measured before administering the first dose of hydroxychloroquine and within 24 h of administration. The RR interval was measured as a distance between the peak of the R-wave and the peak of the previous R-wave in the same lead in milliseconds and converted to a heart rate by equation, 60,000/RR. For correction of the QT, we used common formulas: QTc = QT/√RR [Bazett formula], QTc = QT/∛RR [Fridericia formula], QTc = QT + 0.154 (1-RR) [Framingham formula], QTc = QT + 1.75 (heart rate-60) [Hodges formula]. QTc interval prolongation was defined based on the following rules: Male Rules: 1) Baseline <450 ms, and post HCQ >450 ms;2) >15% increase over baseline post HCQ;and 3) baseline >450 ms and <500 ms, and post is >500 ms;Female Rules: 1) Baseline <470 ms, and post HCQ >470 ms;2) >15% increase over baseline post HCQ;and 3) baseline >470 ms and <500 ms, and post is >500 ms. Statistics: Means were compared using independent sample t-tests;paired sample t-tests and proportions were compared using Chi square analysis. QT correction formulas were compared using 1-way ANOVA and post hoc analysis was done with Tukey correction. Binary univariate and multivariate regression were performed to determine risk factor predictors for QTc prolongation. Results: We screened 444 consecutive patients with COVID-19 who were admitted to our hospital between March 10 and April 15, 2020, a total of 247 were excluded from this study because they met the exclusion criteria. Thus, 197 patients were included in the analysis. The mean baseline QTc interval calculated using the Bazett, Hodges, Frederica, Framingham methods were 451.0 ± 34.3, 425.1 ± 28.9, 417.2 ± 34.0, and 413.9 ± 31 ms, respectively. Of the 4 correction methods, 35.5% of all patients met the criteria for prolongation using the Bazett method. Of all patients included in the study 125 (63.5%) were male and 72 (36.5%) were female. Subjects were predominantly African American ancestry, 179 (90.9%). The mean age of all patients was 66.1 ± 13.3 years. The most common comorbidities were hypertension (74.6%), diabetes (55.3%), and hyperlipidemia (37.5%). Of all study participants, 91.7% received concomitant azithromycin;31% of patients were on home beta-blocker therapy, while 27.9% were on home calcium-channel blockers. Of baseline electrocardiograms, 87.8% were sinus rhythm. Total number of patients meeting prolongation criteria was less using the Hodges, Frederica, and Framingham methods. Mean QTc values in both genders are presented in (Tables 1, 2, 3, and 4). All 4 methods showed statistically significant increases in QTc. Bazett had the relatively largest difference between pre- and post-therapy QT interval with a mean difference of 14.48 ms. The increase was present in both men and women. The mean difference across sexes was largest using the Bazett method 16.43, bu this was not statistically significant. Univariate analysis across all methods found that the concomitant use of azithromycin was not a significant predictor in QT prolongation across the Bazett, Hodges, Frederica, and Framingham methods. However, the presence of coronary artery disease was a statistically significant predictor for QT prolongation. The presence of congestive heart failure was also a predictor using the Hodges and Framingham methods. (Table 5, 6, 7, and 8) (Figure 1) [Formula presented] ANOVA analysis across all subjects showed a significant difference between the four methods. There were significant differences between Bazett and 3 methods. The largest difference was between Bazett and Framingham, by 37.12 s. There was also a smaller difference between the Hodge and Framingham methods. The significant difference between the Bazzett method and the others also persisted across both men and women. The difference between Hodges and Bazzett was only significant in men (Table 9, 10, and 11). QT prolongation irrespective of the method used for correction did not predict mortality. [Formula presented] [Formula presented] [Formula presented] [Formula presented] [Formula presented] [Formula presented] [Formula presented] [Formula presented] [Formula presented] [Formula presented] [Formula presented] Conclusion: It was notable that the longest QTc prolongation seen in this study was only 14.48 ms, using the Bazett formula. With other formulas, this prolongation was significantly smaller and so was the proportion of patients meeting QTc prolongation criteria. Not surprisingly, the Bazett formula again overestimated extend of QT prolongation. We can only speculate that the differences are perhaps related to the fact that our population was nearly exclusively African American. Common channels variation has been well documented to be a factor in QT prolongation, including drug-inducted QT prolongation. In the African-American ethnic subgroup, Ser1103Tyr-SCN5A is seen in approximately 8 % of population and can certainly explain our data. Furthermore, frequency of CAD and CHF was slightly higher than reported in other studies and both entities were associated with QT prolongation on our population. Reassuringly, the presence of QT prolongation was not found to be a predictor of mortality in our cohort. Categories Other: COVID-19 Lectures