Carnicelli, Anthony

Abstract Background Direct oral anticoagulation (DOACs) prevent stroke in patients with atrial fibrillation (AF) and have a superior safety profile compared with vitamin K antagonists (VKA). Yet, better definition of incidence and risk factors for major bleeding associated with DOACs in clinical practice may be important given emerging stroke prevention technologies, both pharmacologic and nonpharmacologic. Purpose To describe the incidence of and risk factors for major bleeding in individuals with AF on DOAC therapy. Methods We reviewed electronic health record data for two patient cohorts with AF prescribed DOACs: (1) Duke University Health System (DUHS) (2010–2018) and (2) Sites within the Patient-Centered Clinical Research Network (PCORnet) (2015–2019) which had ≥6 years assimilated data from both inpatient and outpatient encounters (7 sites). In each cohort, we assessed the 5-year incidence of major bleeding events defined as hospitalization for intracranial hemorrhage, or hospitalization for gastro-intestinal bleeding or procedure to control bleeding accompanied by transfusion within ±7 days or death within 30 days. Multivariable Fine-Gray proportional hazards modeling in each cohort was performed to evaluate independent risk factors for major bleeding on DOAC therapy. Results The cohorts included 10,625 patients (DUHS) and 58,321 patients (PCORnet) with AF. Major bleeding events occurred within 5 years of diagnosis in 639 (7.9%) of DUHS patients and 2568 (6.6%) of PCORnet patients (Table 1). The DUHS model predicted time to first major bleeding event with a C-index of 0.756 (95% CI 0.737, 0.775) and the PCORNet model had a c-index of 0.745 (0.736, 0.755) (Table 2). Independent factors associated with major bleeding consistent across both models (p<0.001 in PCORnet for all unless noted) were higher CHA2DS2-VASc scores, lower eGFR, anemia (HR per 1-point increase in hemoglobin up to 12 g/dL 0.79 [0.76, 0.82]), prior major bleeding (HR 2.70 [2.22, 3.30]), cancer (HR 1.23 [1.12, 1.36]), recent cardiac surgery (HR 0.70 [0.51, 0.97]; p=0.030), alcohol use (HR 1.56 [1.29, 1.88]), aspirin use (HR 1.44 [1.32, 1.57]), and selective serotonin reuptake inhibitor use (HR 1.30 [1.19, 1.42]). Conclusions Across a large and geographically diverse contemporary population, risk of bleeding on DOAC for stroke prevention in AF remains a frequent and important clinical problem. There is an unmet need for stroke prevention therapies with improved safety profiles. We identified risk factors for major bleeding events on DOAC therapy, some of which are not represented in traditional risk scores, which may inform shared decision making for stroke prevention. Funding Acknowledgement Type of funding sources: Private company. Main funding source(s): Bayer Pharmaceuticals

OBJECTIVES: Cardiogenic shock presents with variable severity. Categorizing cardiogenic shock into clinical stages may improve risk stratification and patient selection for therapies. We sought to determine whether a structured implementation of the 2019 Society for Cardiovascular Angiography and Interventions clinical cardiogenic shock staging criteria that is ascertainable in clinical registries discriminates mortality in a contemporary population with or at-risk for cardiogenic shock. DESIGN: We developed a pragmatic application of the Society for Cardiovascular Angiography and Interventions cardiogenic shock staging criteria—A (at-risk), B (beginning), C (classic cardiogenic shock), D (deteriorating), or E (extremis)—and examined outcomes by stage. SETTING: The Critical Care Cardiology Trials Network is an investigator-initiated multicenter research collaboration coordinated by the TIMI Study Group (Boston, MA). Consecutive admissions with or at-risk for cardiogenic shock during two annual 2-month collection periods (2017–2019) were analyzed. PATIENTS: Patients with or at-risk for cardiogenic shock. MEASUREMENTS AND MAIN RESULTS: Of 8,240 CICU admissions reviewed, 1,991 (24%) had or were at-risk for cardiogenic shock. Distributions across the five stages were as follows: A: 33%; B: 7%; C: 16%; D: 23%; and E: 21%. Overall in-hospital mortality among patients with established cardiogenic shock was 39%; however, mortality varied from only 15.8% to 32.1% to 62.5% across stages C, D, and E (Cochran-Armitage p trend < 0.0001). The Society for Cardiovascular Angiography and Interventions stages improved mortality prediction beyond the Sequential Organ Failure Assessment and Intra-Aortic Balloon Pumpin Cardiogenic Shock II scores. CONCLUSIONS: Although overall mortality in cardiogenic shock remains high, it varies considerably based on clinical stage, identifying stage C as relatively lower risk. We demonstrate a pragmatic adaptation of the Society for Cardiovascular Angiography and Interventions cardiogenic shock stages that effectively stratifies mortality risk and could be leveraged for future clinical research.

Background Several studies have shown improved outcomes in closed compared with open medical and surgical intensive care units. However, very little is known about the ideal organizational structure in the modern cardiac intensive care unit (CICU). Methods and Results We retrospectively reviewed consecutive unique admissions (n=3996) to our tertiary care CICU from September 2013 to October 2017. The aim of our study was to assess for differences in clinical outcomes between an open compared with a closed CICU. We used multivariable logistic regression adjusting for demographics, comorbidities, and severity of illness. The primary outcome was in‐hospital mortality. We identified 2226 patients in the open unit and 1770 in the closed CICU. The unadjusted in‐hospital mortality in the open compared with closed unit was 9.6% and 8.9%, respectively ( P =0.42). After multivariable adjustment, admission to the closed unit was associated with a lower in‐hospital mortality (odds ratio [OR], 0.69; 95% CI: 0.53–0.90, P =0.007) and CICU mortality (OR, 0.70; 95% CI, 0.52–0.94, P =0.02). In subgroup analysis, admissions for cardiac arrest (OR, 0.42; 95% CI, 0.20–0.88, P =0.02) and respiratory insufficiency (OR, 0.43; 95% CI, 0.22–0.82, P =0.01) were also associated with a lower in‐hospital mortality in the closed unit. We did not find a difference in CICU length of stay or total hospital charges ( P >0.05). Conclusions We found an association between lower in‐hospital and CICU mortality after the transition to a closed CICU. These results may help guide the ongoing redesign in other tertiary care CICUs.

Background: Temporary mechanical circulatory support (MCS) devices provide hemodynamic assistance for shock refractory to pharmacological treatment. Most registries have focused on single devices or specific etiologies of shock, limiting data regarding overall practice patterns with temporary MCS in cardiac intensive care units. Methods: The CCCTN (Critical Care Cardiology Trials Network) is a multicenter network of tertiary CICUs in North America. Between September 2017 and September 2018, each center (n=16) contributed a 2-month snapshot of consecutive medical CICU admissions. Results: Of the 270 admissions using temporary MCS, 33% had acute myocardial infarction-related cardiogenic shock (CS), 31% had CS not related to acute myocardial infarction, 11% had mixed shock, and 22% had an indication other than shock. Among all 585 admissions with CS or mixed shock, 34% used temporary MCS during the CICU stay with substantial variation between centers (range: 17%–50%). The most common temporary MCS devices were intraaortic balloon pumps (72%), Impella (17%), and veno-arterial extracorporeal membrane oxygenation (11%), although intraaortic balloon pump use also varied between centers (range: 40%–100%). Patients managed with intraaortic balloon pump versus other forms of MCS (advanced MCS) had lower Sequential Organ Failure Assessment scores and less severe metabolic derangements. Illness severity was similar at high- versus low-MCS utilizing centers and at centers with more advanced MCS use. Conclusions: There is wide variation in the use of temporary MCS among patients with shock in tertiary CICUs. While hospital-level variation in temporary MCS device selection is not explained by differences in illness severity, patient-level variation appears to be related, at least in part, to illness severity.

BackgroundThe optimal anticoagulation strategy for patients with atrial fibrillation (AF) and bioprosthetic valve (BPV) replacement or native valve repair remains uncertain.HypothesisWe evaluated the safety and efficacy of apixaban vs warfarin in patients with AF and a history of BPV replacement or native valve repair.MethodsUsing data from Apixaban for Reduction in Stroke and Other Thromboembolic Events in Atrial Fibrillation (ARISTOTLE) (n = 18 201), a randomized trial comparing apixaban with warfarin in patients with AF, we analyzed the subgroup of patients (n = 251) with prior valve surgery. We contacted sites by telephone to obtain additional data about prior valve surgery. Full data were available for 156 patients. The primary efficacy endpoint was stroke/systemic embolism. The primary safety endpoint was major bleeding. Treatment groups were compared using a Cox regression model.ResultsIn ARISTOTLE, 104 (0.6%) patients had a history of BPV replacement (n = 73 [aortic], n = 26 [mitral], n = 5 [mitral and aortic]) and 52 (0.3%) had a history of valve repair (n = 50 [mitral], n = 2 [aortic]). Among patients with BPVs, 55 were randomized to apixaban and 49 to warfarin. Among those with a history of native valve repair, 32 were randomized to apixaban and 20 to warfarin. Overall clinical event rates were low, with no significant differences between apixaban and warfarin for any outcomes.ConclusionsIn patients with AF and a history of BPV replacement or repair, the safety and efficacy of apixaban compared with warfarin was consistent with results from ARISTOTLE. These data suggest that apixaban may be reasonable for patients with BPVs or prior valve repair, though future larger randomized trials are needed.ClinicalTrials.govNCT00412984.