Barsness, Gregory W.

Background: Prior studies suggest an association between naturally high circulating levels of CD34+ cells (CD34) and better outcomes following ischemic events. Pts in the treatment arm of the PreSERVE-AMI study were infused with all CD34 yielded from their bone marrow harvest, resulting in pts with naturally higher CD34 cell counts being infused with a higher cell dose. To determine whether selection bias may have influenced results, we performed an analysis of the relationship between BM CD34 content and outcomes in PreSERVE-AMI. Methods: PreSERVE-AMI is a Phase 2, randomized, double-blind, placebo-controlled trial of autologous, BM derived CD34 (CLBS10) in pts with LV dysfunction (LVEF ≤48% by MRI) ≥4 days post-STEMI. All pts underwent mini BM harvest and were randomized 1:1 to intracoronary infusion of CD34 (minimum dose 10M±20% cells) or placebo (cell diluent). Primary safety endpoints included AEs, SAEs and MACE (CV mortality, HF hospitalization, reinfarction, revascularization). Secondary endpoints included LVEF change from baseline. Regression analyses were performed to assess the influence of BM CD34 content on outcomes. Results: 161 patients were randomized and received intracoronary infusion (Jan 2013-Dec 2014). Mean age was 57±10 and 82% were men. Mean follow-up time was 18 mo, and safety data are accruing. BM CD34 content was not associated with differences in baseline characteristics with the exception of diabetes prevalence being higher in those with higher BM CD34 count (p=0.03). In controls, regression analyses showed no association of BM CD34 content with rates of MACE (p=0.2), SAEs (p=0.4), or change in LVEF (p=0.9). However, in CD34 treated pts, there was a dose-dependent improvement in LV function (p=0.045) and dose-dependent trends in MACE and SAE reduction compared to controls. As previously reported SPECT perfusion improved to a similar degree in control and treated pts. Conclusions: These data suggest that intracoronary infusion of CD34 cells, rather than BM CD34 cell content, is responsible for the benefit observed in the CD34 treatment group. The finding of a dose-response relationship is an important advance for defining the CD34 as an active agent for tissue repair. Future studies will further define CD34 dosimetry.

Advances in molecular and cellular biology have supported the development of new therapeutic approaches to limiting ischemia. Most often these approaches target patients with ischemia post coronary artery bypass grafting (CABG). Currently, there are few data available on the incidence and outcomes of such patients. To understand this important patient cohort and to estimate the potential need for new therapies, we performed a population-based study of post CABG patients who underwent coronary and graft angiography for angina from 2001 – 2005. Patients who underwent coronary artery and bypass graft angiography at Mayo Clinic from 2001 – 2005 were identified. Medical records were reviewed to determine indication for angiography, and angiographic analysis was performed in all patients. The study cohort was then followed prospectively until March 1 2008. Among 133,000 residents of Olmsted County, Minnesota, 347 post bypass patients with angina underwent coronary angiography from 2001 – 2005. Of those, 51% (177 patients) received further revascularization (endovascular and surgical) and the remaining 170 patients were managed medically. There was no statistical difference in terms of all cause mortality and cardiac mortality between the group that received further revascularization and the group that did not. Adjusting for age and sex for differences between the Olmsted County population and the US white 2000 population yields a yearly incidence rate of 17.9 (95% CI 14.2–21.6) to 33.2 (95% CI 28.2 – 38.3) patients with non-revascularizable angina following CABG per 100,000 population. There was no difference in all cause or cardiac mortality in post-CABG patients presenting with angina whether they received further endovascular/surgical revascularization or not. We estimate that non-revascularizable coronary artery disease post CABG arises in approximately 50,000 (95% CI 40,000 – 61,000) to 93,000 (95% CI 79,000 – 110,000) patients per year extrapolating to the entire US population as a whole.

Introduction: Renal dysfunction, as defined by elevated serum creatinine, is associated with decreased survival among patients resuscitated after out-of-hospital cardiac arrest (OHCA). Less is known about other measures of renal function and outcomes after OHCA. Hypothesis: BUN and urine output will predict mortality after OHCA. Methods: Retrospective single-center cohort study of 276 adult OHCA patients treated with targeted temperature management after OHCA between December 2005 and September 2016. Fluid balance and urine output were recorded for the first 6, 12 and 24 hours. Initial laboratory values were determined from electronic records. Hospital survivors and non-survivors were compared using the Wilcoxon test, and multivariate analysis was performed to determine predictors of hospital death. Results: Mean age was 63±12 years, and 204 (73%) were male; shockable rhythm occurred in 241 (87%). Inpatient death occurred in 111 (40%). Hospital survivors had lower initial BUN (13 vs. 20 mg/dL) and creatinine (1.1 vs. 1.5 mg/dL); all p <.001. Hospital survivors had higher (p <.001) urine output during the first 6 hours (1,091 vs. 559 ml), 12 hours (1,583 vs. 843 ml), and 24 hours (2,215 vs. 1,294 ml). Higher initial BUN (OR 1.12, 95% CI 1.07-1.18) and creatinine (OR 3.036, 95% CI 1.65-5.59) predicted hospital mortality; all p <.001. Urine output during the first 24 hours was associated with hospital mortality (OR 0.57 per each 1 L, 95% CI 0.45-0.72, p <.001; AUROC 0.73, optimal cut-off 1 L). Patients with 24-hour urine output <1 L were at increased risk of hospital death (66.3% vs. 26.0%, unadjusted OR 5.61, 95% CI 3.27-9.63, p <.001). Initial BUN (adjusted OR 1.09, 95% CI 1.01-1.16, p=.02) and urine output during the first 24 hours (adjusted OR 0.71 per each 1 L; 95% CI 0.52-0.97, p=.03) remained predictive of hospital mortality after adjustment for patient characteristics and illness severity. Conclusions: Lower 24-hour urine output and higher initial BUN were associated with higher hospital mortality among patients resuscitated from OHCA, even after adjustment for illness severity. Serum creatinine was not a significant predictor of mortality. This emphasizes the importance of low urine output as a prognostic marker and therapeutic target after OHCA.

Introduction: Lactate is a known prognostic marker in critically ill patients, including patients with shock and cardiac arrest (CA). We sought to describe the association between admission lactate and hospital mortality in cardiac intensive care unit (CICU) patients, particularly those with CA. Methods: We retrospectively evaluated adult patients admitted to a tertiary care CICU from January 1, 2007, to April 30, 2018, with measured lactate on admission. We examined hospital mortality as a function of admission lactate level in patients with and without CA. Multivariable logistic regression was used to determine predictors of hospital mortality in the overall cohort, after adjustment for clinical characteristics, therapies, and illness severity. Results: We included 3,042 patients with a median age of 70 years (IQR 60-80), including 40.5% (n=1,233) females. There were 789 patients (26.1%) with a diagnosis of CA. The median APACHE-4 predicted mortality was 24.2% (IQR 10.9-50.7), and 50.8% (n=1546) were treated with vasoactive infusions. The median lactate on admission was 1.8 mmol/L (IQR 1.1-3.0). CICU mortality occurred in 478 (15.7%) patients) and hospital mortality occurred in 706 (23.2%) patients. Hospital mortality rose progressively as a function of admission lactate ( Figure ). On univariable analysis, lactate was associated with increased hospital mortality among the overall cohort (OR 1.36, CI 1.31-1.42, P < .001; AUROC 0.71), patients with CA (OR 1.33 (95% CI 1.25-1.41, P < .01; AUROC 0.73), and patients without CA (OR 1.27, CI 1.21-1.34, P < .01; AUROC 0.64). On multivariable analysis, lactate was one of the most significant predictors of hospital mortality (adjusted OR 1.13 per mmol/L, 95% CI 1.08-1.18, P < .001). Conclusions: Admission lactate levels are strongly associated with increased hospital mortality among CICU patients, especially those with CA. The prognostic value of lactate levels may help inform clinicians caring for CICU patients.

AbstractBackgroundRandomized studies of intra‐aortic balloon pump (IABP) in cardiogenic shock (CS) have only included on patients with acute coronary syndromes (ACS) without stratification according to shock severity. We examined the association between IABP and mortality in CS patients across the Society for Cardiovascular Angiography and Intervention (SCAI) shock stages.MethodsWe included cardiac intensive care unit patients admitted from 2007 to 2015 with CS from any etiology. In‐hospital mortality associated with IABP was examined in each SCAI shock stage. Multivariable logistic regression was performed using inverse probability of treatment weighting (IPTW) to determine the association between IABP and in‐hospital mortality.ResultsWe included 934 patients, with a mean age of 68 ± 14 years; 60% had ACS. The distribution of SCAI shock stages was: B, 41%; C, 13%; D, 38%; E, 8%. In‐hospital mortality was lower in the 39% of patients who received IABP (27% vs. 43%, adjusted OR with IABP after IPTW 0.53, 95% CI 0.40–0.72, p < .0001). IABP use was associated with lower crude in‐hospital mortality in each SCAI shock stage (all p < .05, except p = .08 in SCAI shock stage E). We did not observe any significant heterogeneity in the association between IABP use and in‐hospital mortality as a function of SCAI shock stage.ConclusionsPatients with CS who were selected to receive an IABP had lower in‐hospital mortality, without differences in this effect across the SCAI shock stages. Future studies should account for the severity and etiology of shock when evaluating the efficacy of IABP for CS.

Background The role of race and ethnicity in the outcomes of cardiac arrest (CA) complicating acute myocardial infarction (AMI) is incompletely understood. Methods and Results This was a retrospective cohort study of adult admissions with AMI‐CA from the National Inpatient Sample (2012–2017). Self‐reported race/ethnicity was classified as White, Black, and others (Hispanic, Asian or Pacific Islander, Native American, Other). Outcomes of interest included in‐hospital mortality, coronary angiography, percutaneous coronary intervention, palliative care consultation, do‐not‐resuscitate status use, hospitalization costs, hospital length of stay, and discharge disposition. Of the 3.5 million admissions with AMI, CA was noted in 182 750 (5.2%), with White, Black, and other races/ethnicities constituting 74.8%, 10.7%, and 14.5%, respectively. Black patients admitted with AMI‐CA were more likely to be female, with more comorbidities, higher rates of non–ST‐segment–elevation myocardial infarction, and higher neurological and renal failure. Admissions of patients of Black and other races/ethnicities underwent coronary angiography (61.9% versus 70.2% versus 73.1%) and percutaneous coronary intervention (44.6% versus 53.0% versus 58.1%) less frequently compared to patients of white race ( p <0.001). Admissions of patients with AMI‐CA had significantly higher unadjusted mortality (47.4% and 47.4%) as compared with White patients admitted (40.9%). In adjusted analyses, Black race was associated with lower in‐hospital mortality (odds ratio [OR], 0.95; 95% CI, 0.91–0.99; P =0.007) whereas other races had higher in‐hospital mortality (OR, 1.11; 95% CI, 1.08–1.15; P <0.001) compared with White race. Admissions of Black patients with AMI‐CA had longer length of hospital stay, higher rates of palliative care consultation, less frequent do‐not‐resuscitate status use, and fewer discharges to home (all P <0.001). Conclusions Racial and ethnic minorities received less frequent guideline‐directed procedures and had higher in‐hospital mortality and worse outcomes in AMI‐CA.

Introduction: The Mayo Clinic Cardiac Intensive Care Unit Admission Risk Score (M-CARS) has been shown to predict hospital mortality in the CICU population better than conventional critical care scoring models. We tested the hypothesis that M-CARS could similarly be used to predict one-year mortality. Methods: We retrospectively reviewed adult CICU patients admitted from 2007 to 2018. M-CARS was calculated using admission data. Groups were compared using Wilcoxon test for continuous variables and chi-squared test for categorical variables. Results: This study included 12428 unique patients with a mean age of 67 ± 15 years (37% females), of whom 11279 (90.8%) survived hospitalization and 2839 patients (22.8%) died within 1 year of admission. The 1-year survival decreased incrementally as a function of increasing M-CARS ( Figure 1A , p<0.0001), and all components of M-CARS were significant predictors of 1-year mortality (p<0.001). 1690 hospital survivors (15.0%) died within 1 year. The 1-year survival decreased incrementally as a function of increasing M-CARS for scores <3 (all p<0.001); however, there was no further adverse 1-year survival for patients with M-CARS ≥3 ( Figure 1B, p=0.99). M-CARS components associated with 1-year mortality among hospital survivors included blood urea nitrogen, red blood cell distribution width, Braden score, and respiratory failure (all p<0.001), while cardiac arrest, cardiogenic shock, and anion gap were not. Conclusions: M-CARS accurately predicts 1-year mortality among CICU admissions, with a plateau effects at high M-CARS scores ≥3. Significant predictors of 1-year mortality among CICU survivors include frailty markers rather than admission severity.

Introduction: Acute kidney injury (AKI) is a highly prevalent risk factor for mortality among patients with cardiogenic shock (CS). We sought to assess the incidence and prognostic relevance of AKI as a function of shock severity in unselected Cardiac Intensive Care Unit (CICU) patients, as measured by the Society for the Cardiovascular Angiography and Interventions (SCAI) shock stage. Methods: We retrospectively reviewed admissions to the Mayo Clinic from 2007 to 2015 and stratified patients by the SCAI shock stage. AKI was defined and staged based on changes in serum creatinine during hospitalization as per KDIGO guidelines. Predictors of in-hospital mortality were analyzed using Kaplan-Meier survival analysis, and one-year mortality was analyzed using Cox proportional-hazards analysis. Results: The final study population included 10,004 unique patients with a mean age of 67 years and 37% females. The percentage of patients with SCAI shock stages A, B, C, D, and E were 47%, 30%, 15%, 7%, and 1%, respectively. AKI of any severity occurred in 51% of patients during hospitalization, including severe (stage 2/3) AKI in 16%. The incidence of AKI and severe AKI increased with the SCAI shock stage. Hospital mortality occurred in 8% of patients and increased as a function of the AKI stage and SCAI shock stage. AKI was associated with increased hospital mortality after multivariable adjustment (adjusted OR per AKI stage 1.17, 95% CI 1.05-1.30, p=0.005). Twenty-one percent of patients died within one year of CICU admission, and worse AKI was associated with increased one-year mortality (adjusted HR per AKI stage 1.11, 95% CI 1.05-1.18, p=<0.001). Hospital survivors with AKI of any severity had higher mortality compared with patients who did not have AKI (p<0.001). Conclusions: AKI was increasingly common in CICU patients with higher shock severity. In-hospital and one-year mortality risk increased as a function of the severity of AKI and the SCAI shock stage. This analysis emphasizes the importance of AKI as a complication of shock and as a predictor of adverse outcomes in CICU patients.

Introduction: A low cardiac power output (CPO), measured invasively, identifies critically ill patients at increased risk of mortality. CPO can also be measured non-invasively with transthoracic echocardiography (TTE), although prognostic data in critically ill patients is not available. Hypothesis: Reduced CPO measured by TTE is associated with increased hospital mortality in cardiac intensive care unit (CICU) patients. Methods: Using a database of CICU patients admitted between 2007 and 2018, we identified patients with TTE within one day (before or after) of CICU admission who had data necessary for calculation of CPO. Multivariable logistic regression determined the relationship between CPO and adjusted hospital mortality. Results: We included 5,585 patients with a mean age of 68.3±14.8 years, including 36.7% females. Admission diagnoses included acute coronary syndrome (ACS) in 57%, heart failure (HF) in 50%, cardiac arrest (CA) in 12%, and cardiogenic shock (CS) in 13%. The mean left ventricular ejection fraction (LVEF) was 47±16%, and the mean CPO was 1.0±0.4 W. CPO was inversely associated with the risk of hospital mortality (Figure A), including among patients with ACS, HF, and CS (Figure B). On multivariable analysis, lower CPO was associated with higher hospital mortality (OR 0.96 per 0.1 W, 95% CI 0.0.93-0.99, p=0.03). Hospital mortality was highest in patients with low CPO coupled with reduced LVEF, increased vasopressor requirements, or higher admission lactate. Hospital mortality was higher among patients with a CPO <0.6 W (adjusted OR 1.57, 95% CI 1.13-2.19, p = 0.007), particularly in the presence of admission lactate level >4 mmol/L (50.9%). Conclusions: Echocardiographic CPO was inversely associated with hospital mortality in CICU patients, particularly among patients with increased lactate and vasopressor requirements. Routine measurement of CPO provides important information beyond LVEF and should be considered in CICU patients.

AbstractBackgroundAcute kidney injury (AKI) is common among patients with cardiogenic shock (CS) and it is independently associated with mortality. We sought to assess the prevalence, severity, and prognosis of AKI as a function of cardiogenic shock severity in unselected Cardiac Intensive Care Unit (CICU) patients.MethodsWe retrospectively reviewed admissions to the Mayo Clinic between 2007 to 2015 and stratified patients by the AKI stage (based on modified Kidney Disease: Improving Global Outcomes criteria) and Society for cardiovascular angiography and interventions (SCAI) shock stage. The association with in‐hospital mortality was analyzed using multivariable logistic regression.ResultsWe included 9,311 unique patients with a mean age of 67 years and 37% females. SCAI shock stages A, B, C, D, and E were present in 47%, 30%, 15%, 7%, and 1% of patients. The incidence of AKI of any severity was 39% in the CICU and 51% during the hospitalization. Hospital mortality occurred in 8% of all patients, and the risk increased as a function of the rising AKI and SCAI shock stage. Worsening AKI stage was associated with increased adjusted hospital mortality (adjusted OR per AKI stage 1.22, 95% CI 1.10–1.36, p < .001). Higher AKI stages were associated with increased adjusted hospital mortality in SCAI stage A/B (p < .001), but not in SCAI stage C, D, or E (all p > .05).ConclusionsHigher AKI stages were independently associated with mortality in CICU patients after accounting for shock severity and may add incremental prognostic utility in patients with lower SCAI stages.