No Mortality Signal With Stellarex Low-Dose Paclitaxel DCB: ILLUMENATE Pivotal 4-Year Outcomes

Background: Paclitaxel-coated balloons have shown safety and efficacy in the short- to intermediate-term; however, long-term data remain limited. Objectives: To report late safety and efficacy outcomes for a low-dose paclitaxel drug-coated balloon (DCB) compared with percutaneous transluminal angioplasty (PTA) in femoropopliteal lesions from a large randomized controlled trial (RCT). Methods: ILLUMENATE Pivotal is a multicenter, single-blind RCT conducted across 43 US and EU centers to examine the safety and efficacy of the Stellarex DCB for the treatment of femoropopliteal disease. Assessments were recorded for all active patients at 36 and 48 months. Vital status of patients formally exited from the study was also collected. Results: Primary patency through 36 months for patients treated with DCB was significantly higher compared with PTA (p=0.016). The primary safety endpoint through 36 months was 77.4% and 72.4%, respectively (p=0.377). Kaplan-Meier analysis indicated that a higher proportion of DCB subjects were event-free compared with PTA at all study visits. The rate of major adverse event (MAE) through 48 months was 32.9% in the DCB group and 37.9% in the PTA group (p=0.428). No differences in the rate of mortality were evident through 48 months of follow-up with 15.6% in the DCB group and 15.2% in the PTA group (p=0.929). Conclusions: Stellarex DCB was associated with significantly higher patency compared with PTA through 3 years with no mortality difference detected through 4 years. The data from the ILLUMENATE Pivotal RCT support the long-term safety and efficacy of the low-dose Stellarex DCB.

207. Ineffective Initial Antibiotics for Enteric Bacteremia: Does Every Hour Count with Rapid Diagnostics and Stewardship Intervention?

Background It has been a long-standing practice to administer broad-spectrum antibiotics early for sepsis as each hour delay is associated with increase in mortality. With increasing rates of antibiotic resistance fueled by unnecessary use of antibiotics, it is delicate to balance the benefits vs consequences of empiric carbapenem therapy. With rapid molecular blood culture diagnostics available, identification of extended-spectrum beta-lactamase (ESBL) producing bacteremia can occur within hours and therapy optimized with active stewardship intervention. With rapid diagnostics, does each hour of ineffective antibiotic therapy really count? Methods This multicenter, retrospective, cohort study compared adult inpatients with E. coli bacteremia from a urinary source who received initial effective (EA) vs ineffective antibiotics (IA). The primary outcome was clinical treatment success at day 4. Secondary endpoints included length of stay (LOS), infection-related mortality, incidence of C. difficile infection (CDI), and subgroup analysis of outcomes by ESBL (CTX-M type) vs non-ESBL. Associations with endpoints were assessed using Fisher’s Exact tests using R v. 4.0.3. Results Clinical treatment success at day 4 was higher in the EA (n = 488) vs IA (n = 119) groups (93.7% vs 86.6%, p = 0.01) and median LOS was shorter (5 [IQR 4-6] vs 5 [IQR 5-7] days, p < 0.01). There were no differences in infection-related mortality (3.1% vs 3.4%, p = 0.8), 30-day mortality (2.5% vs 2.5%, p > 0.9), or incidence of CDI (1.8% vs 0%, p = 0.3) in the EA vs IA groups, respectively. For patients on IA < 24 h vs > 24 h, there was no difference in clinical improvement at day 4 (86.7% vs 90.5%, p > 0.9) nor 30-day mortality (2.4% vs 4.8%, p = 0.4). Clinical treatment success at day 4 was higher among non-CTX-M (n = 476) vs CTX-M (n = 131) patients (93.9% vs 86.3%, p = 0.01) even among those that received initial EA (94.5% vs 83.3%, p = 0.02). Median LOS was also shorter in CTX-M vs non CTX-M (5 [IQR 4-6] vs 5 [IQR 4-8] days, p < 0.01). Conclusion There was no mortality difference among patients receiving initial EA vs IA for E. coli bacteremia with rapid molecular blood culture diagnostics with active stewardship. Therapy for patients on IE is rapidly corrected and stewardship programs can use this intervention to promote judicious use of carbapenems. Disclosures All Authors: No reported disclosures

Association between Serum Phosphate Levels and the Development of Aortic Stenosis in Patients Undergoing Hemodialysis

We aimed to investigate the factors associated with the development of aortic stenosis (AS) in patients undergoing hemodialysis (HD), and to elucidate the prognosis of HD patients with AS. Patients on HD that had also undergone echocardiography at Nagasaki Renal Center between July 2011 and June 2012 were included. Patients with AS at the time of inclusion were excluded. The diagnosis of AS was based on an annual routine or additional echocardiography. The patients were followed up until June 2021. The association between patient background and AS was also evaluated. Of the 302 patients (mean age, 67.4 ± 13.3 years; male, 58%; median dialysis history, 4.7 years), 60 developed AS and 10 underwent aortic valve replacement. A Cox proportional hazards model revealed that age (hazard ratio (HR), 1.07; 95% confidential interval (CI), 1.04–1.10; p < 0.001) and serum phosphate levels (HR, 1.40; 95%CI, 1.16–1.67, p < 0.001) were independent risk factors for developing AS. Incidentally, there was no significant mortality difference between patients with AS and those without (p = 0.53). Serum phosphate levels are a risk factor for developing AS and should be controlled. Annual echocardiography may contribute to the early detection of AS and improves the prognosis of patients undergoing HD.

The Correlation of Respiratory System Compliance and Mortality in COVID-19 Acute Respiratory Distress Syndrome: Do Phenotypes Really Exist?

Background: Recent literature suggests respiratory system compliance (Crs) based phenotypes exist among COVID-19 ARDS patients. We sought to determine whether these phenotypes exist and whether Crs predicts mortality. Methods: A retrospective observational cohort study of 111 COVID-19 ARDS patients admitted March 11-July 8, 2020. Crs was averaged for the first 72-hours of mechanical ventilation. Crs < 30ml/cmH2O was defined as poor Crs(phenotype-H) whereas Crs ≥ 30ml/cmH2O as preserved Crs(phenotype-L). Results: 111 COVID-19 ARDS patients were included, 40 phenotype-H and 71 phenotype-L. Both the mean PaO2/FiO2 ratio for the first 72-hours of mechanical ventilation and the PaO2/FiO2 ratio hospital nadir were lower in phenotype-H than L(115[IQR87] vs 165[87], p = 0.016), (63[32] vs 75[59], p = 0.026). There were no difference in characteristics, diagnostic studies, or complications between groups. Twenty-seven (67.5%) phenotype-H patients died vs 37(52.1%) phenotype-L(p = 0.115). Multivariable regression did not reveal a mortality difference between phenotypes; however, a 2-fold mortality increase was noted in Crs < 20 vs > 50ml/cmH2O when analyzing ordinal Crs groups. Moving up one group level (ex. Crs30-39.9ml/cmH2O to 40-49.9ml/cmH2O), was marginally associated with 14% lower risk of death(RR = 0.86, 95%CI 0.72, 1.01, p = 0.065). This attenuated(RR = 0.94, 95%CI 0.80, 1.11) when adjusting for pH nadir and PaO2/FiO2 ratio nadir. Conclusion: We identified a spectrum of Crs in COVID-19 ARDS similar to Crs distribution in non-COVID-19 ARDS. While we identified increasing mortality as Crs decreased, there was no specific threshold marking significantly different mortality based on phenotype. We therefore would not define COVID-19 ARDS patients by phenotypes-H or L and would not stray from traditional ARDS ventilator management strategies.

Prevention of Thromboembolic Events in COVID-19

Background: COVID-19 has developed into a global pandemic with respiratory compromise and systemic coagulopathy causing significant morbidity and mortality. Methods: A retrospective analysis was performed on all COVID-19 patients hospitalized between March and June 2020. Findings: Of 1265 COVID-19 positive hospitalized patients identified, 138 (10.9%) had a thromboembolism. Mortality rate in COVID-19 patients with thrombosis was 31.9%, significantly higher than COVID-19 patients who did not have thrombosis 10% (p<0.0001). The incidence of thrombosis was significantly less in those who received steroids at 14% as compared to other COVID-19 therapies: tocilizumab 25% (p=0.0031), hydroxychloroquine 42% (p<0.0001), and remdesivir 72% (p<0.0001). There was no difference in mortality in patients who had prophylactic enoxaparin 40.5% than therapeutic enoxaparin 51.7% (p= 0.3491). Adjusting for demographics, a logistics model showed no mortality difference in patients who had either dosing of anticoagulation (p=0.5810). The bleeding rate was 12.3%, significantly higher than reported bleeding rates for hospitalized nonCOVID-19 patients on anticoagulants at 7.2% (p<0.05). Interpretation: Our study shows the incidence of thrombosis in hospitalized COVID-19 patients was higher than the general population. The lowest incidence of thrombosis occurred in COVID-19 patients who received steroids. There was no mortality difference in patients who received prophylactic versus therapeutic anticoagulation prior to thrombosis, but there was a high incidence of bleeding events. Funding: No outside funding was used

Mortality risk for patients undergoing cancer treatment who acquire SARS-CoV-2: ASCO registry.

6509 Background: The ASCO Registry was created to analyze the impact of COVID-19 (COVID) on treatment (Tx) and outcomes of patients (pts) with cancer. Methods: The Registry includes pts with 1) a confirmed COVID diagnosis (Dx) and 2) clinically evident cancer receiving Tx/supportive care or resected cancer on adjuvant Tx <12 mos since surgery. Practices report data on cancer Dx and Tx at COVID Dx, COVID symptoms, comorbidities, cancer/COVID Tx, and survival. Kaplan-Meier estimation provided 30- and 90-day mortality rate estimates for pts with COVID Dx before or since 6/1/20 within pt subgroups with 95% confidence intervals (CI). Data submission cutoff for all practices was 10/24/20, except one that was 11/16/20. Results: This analysis reports on 453 pts with COVID Dx 3/5/20 to 10/22/20 who were on anticancer drug Tx for regional (9%) or metastatic (53%) solid tumors or hematologic cancers (38%) at COVID Dx. 38 practices entered data: health system-owned 51% of pts, privately-owned 25%, academic 24%. 53% of pts have ≥30 days follow-up or died ≤30 days from COVID Dx. Median age is 64 years; 53% of pts are female; 28% of pts are asymptomatic at COVID Dx. Multiple myeloma was most frequent cancer (17%). All-cause mortality rates (30 and 90 days) increased with pts’ age at COVID Dx [Table]. No mortality difference was seen based on sex, race, or comorbidities (hypertension, diabetes, pulmonary disease). Pts with COVID Dx before June 1 had worse survival than pts diagnosed on/after June 1. Pts with B-cell malignancies had higher mortality rates than pts with solid tumors. Conclusions: Severity of COVID illness and mortality were greater for patients with COVID Dx pre-June 1 than on/after June 1. Differences on/after June 1 may be attributed to improvements in COVID management, higher COVID testing rates, and more asymptomatic pts diagnosed. Variations in COVID-19 pt populations over time due to these changes should be considered when analyzing and interpreting pandemic data. Cancer pts with advanced age and B-cell cancers are at greatest risk of death but mortality rates for all groups (except those admitted to ICU) improved after 6/1/2020.[Table: see text]

Mortality rate and biomarker expression within COVID-19 patients who develop acute ischemic stroke: a systematic review and meta-analysis

Objective: To describe the mortality difference between acute ischemic stroke (AIS) and non-AIS groups within COVID-19 patients. Materials & methods: We included observational studies through September 2020 that categorized COVID-19 patients into two groups (with and without AIS). Results: Eight studies with a total sample size of 19,399 COVID-19 patients were included. The pooled risk difference showed that patients with COVID-19 who developed AIS had significantly higher mortality than those without AIS by a risk difference of 24% (95% CI: 0.10–0.39; p = 0.001). In two studies, the COVID-19+AIS group had significantly higher lymphocytes, procalcitonin and creatinine levels. Conclusion: Developing AIS significantly adds to the mortality of COVID-19. Timely interventions to manage those patients are strongly recommended.

Infants with pulmonary atresia intact ventricular septum who require balloon atrial septostomy have significantly higher 18-month mortality

Introduction: Many newborns with pulmonary atresia/intact ventricular septum require intervention to establish pulmonary flow and sufficient cardiac output. The resulting haemodynamic changes are not well characterised and may have unintended consequences. Methods: This is a 30-year (1988–2018) retrospective study of patients with pulmonary atresia intact ventricular septum. Results: Eighty-nine patients were included, and median follow-up was 8 years. Fifty-five per cent had coronary sinusoids and 27% had right ventricular-dependent coronary circulation. Most patients were managed with surgical aortopulmonary or modified Blalock–Taussig shunt (73%), and 12 patients underwent balloon atrial septostomy before surgical intervention. The remaining patients (27%) underwent only transcatheter interventions; 7 required an atrial septostomy and 17 required ductal stentings. All-cause mortality was 10%, most deaths (89%) occurred before 18 months of age. Of these early deaths, 87% required a balloon atrial septostomy and 85% had right ventricular-dependent coronary sinusoids. Eighteen-month mortality was significantly higher for patients who required a balloon atrial septostomy compared to those who did not (36% versus 1.4% p < 0.0001). Discussion: Patients with pulmonary atresia/intact ventricular septum who require balloon atrial septostomy in the newborn period have significantly higher 18-month mortality. Quantifying the mortality difference may help guide prognostication and expectation setting. Infants who had septostomy and a surgical shunt in the newborn period fared better than those who only underwent septostomy (even when accompanied by ductal stenting). For infants with right ventricular-dependent circulation, atrial septostomy should only be performed on an urgent or emergent basis and these patients should be considered for early surgical intervention and neonatal transplant.