Early Serial Assessment of Aggregate Vasoactive Support and Mortality in Cardiogenic Shock: Insights From the Critical Care Cardiology Trials Network Registry.

BACKGROUND: Associations of early changes in vasoactive support with cardiogenic shock (CS) mortality remain incompletely defined. METHODS: The Critical Care Cardiology Trials Network is a multicenter registry of cardiac intensive care units. Patients admitted with CS (2018-2023) had vasoactive dosing assessed at 4 and 24 hours from cardiac intensive care unit admission and quantified by the vasoactive-inotropic score (VIS). Prognostic associations of VIS at both time points, as well as change in VIS from 4 to 24 hours, were examined. Interaction testing was performed based on mechanical circulatory support status. RESULTS: Among 3665 patients, 82% had a change in VIS <10, with 7% and 11% having a ≥10-point increase and decrease from 4 to 24 hours, respectively. The 4 and 24-hour VIS were each associated with cardiac intensive care unit mortality (13%-45% and 11%-73% for VIS <10 to ≥40, respectively; Ptrend <0.0001 for each). Stratifying by the 4-hour VIS, changes in VIS from 4 to 24 hours had a graded association with mortality, ranging from a 2- to >4-fold difference in mortality comparing those with a ≥10-point increase to ≥10-point decrease in VIS (Ptrend <0.0001). The change in VIS alone provided good discrimination of cardiac intensive care unit mortality (C-statistic, 0.72 [95% CI, 0.70-0.75]) and improved discrimination of the 24-hour Sequential Organ Failure Assessment score (0.72 [95% CI, 0.69-0.74] to 0.76 [95% CI, 0.74-0.78]) and the clinician-assessed Society for Cardiovascular Angiography and Interventions shock stage (0.72 [95% CI, 0.70-0.74] to 0.77 [95% CI, 0.75-0.79]). Although present in both groups, the mortality risk associated with VIS was attenuated in patients managed with versus without mechanical circulatory support (odds ratio per 10-point higher 24-hour VIS, 1.36 [95% CI, 1.23-1.49] versus 1.84 [95% CI, 1.69-2.01]; Pinteraction <0.0001). CONCLUSIONS: Early changes in the magnitude of vasoactive support in CS are associated with a gradient of risk for mortality. These data suggest that early VIS trajectory may improve CS prognostication, with the potential to be leveraged for clinical decision-making and research applications in CS.

Claims-based cardiovascular outcome identification for clinical research: Results from 7 large randomized cardiovascular clinical trials.

BACKGROUND: Medicare insurance claims may provide an efficient means to ascertain follow-up of older participants in clinical research. We sought to determine the accuracy and completeness of claims- versus site-based follow-up with clinical event committee (+CEC) adjudication of cardiovascular outcomes. METHODS: We performed a retrospective study using linked Medicare and Duke Database of Clinical Trials data. Medicare claims were linked to clinical data from 7 randomized cardiovascular clinical trials. Of 52,476 trial participants, linking resulted in 5,839 (of 10,497 linkage-eligible) Medicare-linked trial participants with fee-for-service A and B coverage. Death, myocardial infarction (MI), stroke, and revascularization incidences were compared using Medicare inpatient claims only, site-reported events (+CEC) only, or a combination of the 2. Randomized treatment effects were compared as a function of whether claims-based, site-based (+CEC), or a combined system was used for event detection. RESULTS: Among the 5,839 study participants, the annual event rates were similar between claims- and site-based (+CEC) follow-up: death (overall rate 5.2% vs 5.2%; adjusted κ 0.99), MI (2.2% vs 2.3%; adjusted κ 0.96), stroke (0.7% vs 0.7%; adjusted κ 0.99), and any revascularization (7.4% vs 7.9%; adjusted κ 0.95). Of events detected by claims yet not reported by CEC, a minority were reported by sites but negatively adjudicated by CEC (39% of MIs and 18% of strokes). Differences in individual case concordance led to higher event rates when claims- and site-based (+CEC) systems were combined. Randomized treatment effects were similar among the 3 approaches for each outcome of interest. CONCLUSIONS: Claims- versus site-based (+CEC) follow-up identified similar overall cardiovascular event rates despite meaningful differences in the events detected. Randomized treatment effects were similar using the 2 methods, suggesting claims data could be used to support clinical research leveraging routinely collected data. This approach may lead to more effective evidence generation, synthesis, and appraisal of medical products and inform the strategic approaches toward the National Evaluation System for Health Technology.

Assessment and Treatment of Patients With Type 2 Myocardial Infarction and Acute Nonischemic Myocardial Injury.

Although coronary thrombus overlying a disrupted atherosclerotic plaque has long been considered the hallmark and the primary therapeutic target for acute myocardial infarction (MI), multiple other mechanisms are now known to cause or contribute to MI. It is further recognized that an MI is just one of many types of acute myocardial injury. The Fourth Universal Definition of Myocardial Infarction provides a taxonomy for acute myocardial injury, including 5 subtypes of MI and nonischemic myocardial injury. The diagnosis of MI is reserved for patients with myocardial ischemia as the cause of myocardial injury, whether attributable to acute atherothrombosis (type 1 MI) or supply/demand mismatch without acute atherothrombosis (type 2 MI). Myocardial injury in the absence of ischemia is categorized as acute or chronic nonischemic myocardial injury. However, optimal evaluation and treatment strategies for these etiologically distinct diagnoses have yet to be defined. Herein, we review the epidemiology, risk factor associations, and diagnostic tools that may assist in differentiating between nonischemic myocardial injury, type 1 MI, and type 2 MI. We identify limitations, review new research, and propose a framework for the diagnostic and therapeutic approach for patients who have suspected MI or other causes of myocardial injury.

The high cost of critical care unit over-utilization for patients with NSTE ACS.

BACKGROUND: There is substantial variability among hospitals in critical care unit (CCU) utilization for patients admitted with non-ST-Segment Elevation Acute Coronary Syndromes (NSTE ACS). We estimated the potential cost saving if all hospitals adopted low CCU utilization practices for patients with NSTE ACS. METHODS: National hospital claims data were used to identify all patients with a primary diagnosis of NSTE ACS initially admitted to an acute care hospital between 2007 and 2013. Hospital CCU utilization was classified as low (<30%), medium (30-70%), or high (>70%). RESULTS: Among the 270,564 NSTE ACS hospitalizations (71.6% non-ST-segment elevation myocardial infarction; 28.4% unstable angina) admitted to 261 hospitals, 41.9% (inter-hospital range 0.3%-95.1%) were admitted to a CCU. The proportion of patients admitted to a CCU in low, medium and high utilization hospitals was 16.3%, 49.5%, and high 81.1%, respectively. No differences in adjusted inpatient mortality were observed by hospital CCU utilization. The overall inpatient costs of caring for NSTE ACS were $1.1 billion. CCU care accounted for 45.2% of all hospitalization costs including 22.6%, 49.9%, and 69.0% (P < .001) of costs in low, medium and high utilization centers. The national potential direct cost savings of medium and high CCU utilization centers adopting low NSTE ACS CCU utilization practices was $113.4 million over the study period. CONCLUSIONS: In a population-based contemporary cohort, CCU utilization for patients with NSTE ACS varied widely and in-hospital mortality was similar between low, medium and high utilization centers. CCU care accounted for 45% of hospitalization costs; thus, implementing policies and admission practices to align hospital resources with patient care needs have the potential to reduce overall health care costs.

Risk Score to Predict Need for Intensive Care in Initially Hemodynamically Stable Adults With Non-ST-Segment-Elevation Myocardial Infarction.

BACKGROUND: Intensive care unit (ICU) use for initially stable patients presenting with non-ST-segment-elevation myocardial infarction (NSTEMI) varies widely across hospitals and minimally correlates with severity of illness. We aimed to develop a bedside risk score to assist in identifying high-risk patients with NSTEMI for ICU admission. METHODS AND RESULTS: Using the Acute Coronary Treatment and Intervention Outcomes Network (ACTION) Registry linked to Medicare data, we identified patients with NSTEMI aged ≥65 years without cardiogenic shock or cardiac arrest on presentation. Complications requiring ICU care were defined as subsequent development of cardiac arrest, shock, high-grade atrioventricular block, respiratory failure, stroke, or death during the index hospitalization. We developed and validated a model and integer risk score (Acute Coronary Treatment and Intervention Outcomes Network (ACTION) ICU risk score) that uses variables present at hospital admission to predict requirement for ICU care. Of 29 973 patients with NSTEMI, 4282 (14%) developed a complication requiring ICU-level care, yet 12 879 (43%) received care in an ICU. Signs or symptoms of heart failure, initial heart rate, initial systolic blood pressure, initial troponin, initial serum creatinine, prior revascularization, chronic lung disease, ST-segment depression, and age had statistically significant associations with requirement for ICU care after adjusting for other risk factors. The ACTION ICU risk score had a C-statistic of 0.72. It identified 11% of patients as having very high risk (>30%) of developing complications requiring ICU care and 49% as having low likelihood (<10%) of requiring an ICU. CONCLUSIONS: The ACTION ICU risk score quantifies the risk of initially stable patients with NSTEMI developing a complication requiring ICU care, and could be used to more effectively allocate limited ICU resources.

Intensive Care Unit Utilization and Mortality Among Medicare Patients Hospitalized With Non-ST-Segment Elevation Myocardial Infarction.

Importance: Intensive care unit (ICU) utilization may have important implications for the care and outcomes of patients with non-ST-segment elevation myocardial infarction (NSTEMI). Objectives: To examine interhospital variation in ICU utilization in the United States for older adults with hemodynamically stable NSTEMI and outcomes associated with ICU utilization among patients with low, moderate, or high mortality risk. Design, Setting, and Participants: This study was a retrospective analysis of 28 018 Medicare patients 65 years or older admitted with NSTEMI to 346 hospitals participating in the Acute Coronary Treatment and Intervention Outcomes Network (ACTION)-Get With the Guidelines from April 1, 2011, through December 31, 2012. Patients with cardiogenic shock or cardiac arrest on presentation were excluded. Data analysis was performed from May 7 through October 8, 2015. Exposures: Hospitals with high (>70% of patients with NSTEMI treated in an ICU during the index hospitalization), intermediate (30%-70%), or low (<30%) ICU utilization. Main Outcomes and Measures: Thirty-day mortality. Results: Of 28 018 patients with NSTEMI 65 years or older (median age, 77 years [interquartile range, 71-84 years]; female, 13 055 [46.6%]; nonwhite race, 3931 [14.0%]), 11 934 (42.6%) had an ICU stay. The proportion of patients with NSTEMI treated in the ICU varied across hospitals (median, 38%; interquartile range, 26%-54%), but no significant differences were found in hospital or patient characteristics among high, intermediate, or low ICU utilization hospitals. Compared with high ICU utilization hospitals, low or intermediate ICU utilization hospitals were only marginally more selective of higher-risk patients, as determined by ACTION in-hospital mortality risk score or initial troponin level. The median ACTION risk score for patients treated in the ICU at low and intermediate ICU utilization hospitals was 34 compared with 33 for patients not treated in the ICU; at high ICU utilization hospitals, the median ACTION mortality risk score was 33 for patients treated in the ICU and 34 for patients not treated in the ICU. Thirty-day mortality rates did not significantly differ based on hospital ICU utilization (high vs low: 8.7% vs 8.7%; adjusted odds ratio, 0.91; 95% CI, 0.76-1.08; intermediate vs low: 9.6% vs 8.7%; adjusted odds ratio, 1.06; 95% CI, 0.94-1.20). The association between hospital ICU utilization and mortality did not change when considered among patients with ACTION risk scores greater than 40, 30 to 40, and less than 30 (adjusted interaction P = .86). Conclusions and Relevance: Utilization of the ICU for older patients with NSTEMI varied significantly among hospitals. This variability was not explained by hospital characteristics or driven by patient risk. Mortality after myocardial infarction did not significantly differ among high, intermediate, or low ICU utilization hospitals.

Do stable non-ST-segment elevation acute coronary syndromes require admission to coronary care units?

BACKGROUND: Clinical practice guidelines recommend admitting patients with stable non-ST-segment elevation acute coronary syndrome (NSTE ACS) to telemetry units, yet up to two-thirds of patients are admitted to higher-acuity critical care units (CCUs). The outcomes of patients with stable NSTE ACS initially admitted to a CCU vs a cardiology ward with telemetry have not been described. METHODS: We used population-based data of 7,869 patients hospitalized with NSTE ACS admitted to hospitals in Alberta, Canada, between April 1, 2007, and March 31, 2013. We compared outcomes among patients initially admitted to a CCU (n=5,141) with those admitted to cardiology telemetry wards (n=2,728). RESULTS: Patients admitted to cardiology telemetry wards were older (median 69 vs 65years, P<.001) and more likely to be female (37.2% vs 32.1%, P<.001) and have a prior myocardial infarction (14.3% vs 11.5%, P<.001) compared with patients admitted to a CCU. Patients admitted directly to cardiology telemetry wards had similar hospital stays (6.2 vs 5.7days, P=.29) and fewer cardiac procedures (40.3% vs 48.5%, P<.001) compared with patients initially admitted to CCUs. There were no differences in the frequency of in-hospital mortality (1.3% vs 1.2%, adjusted odds ratio [aOR] 1.57, 95% CI 0.98-2.52), cardiac arrest (0.7% vs 0.9%, aOR 1.37, 95% CI 0.94-2.00), 30-day all-cause mortality (1.6% vs 1.5%, aOR 1.50, 95% CI 0.82-2.75), or 30-day all-cause postdischarge readmission (10.6% vs 10.8%, aOR 1.07, 95% CI 0.90-1.28) between cardiology telemetry ward and CCU patients. Results were similar across low-, intermediate-, and high-risk Duke Jeopardy Scores, and in patients with non-ST-segment myocardial infarction or unstable angina. CONCLUSIONS: There were no differences in clinical outcomes observed between patients with NSTE ACS initially admitted to a ward or a CCU. These findings suggest that stable NSTE ACS may be managed appropriately on telemetry wards and presents an opportunity to reduce hospital costs and critical care capacity strain.

A Guide for a Cardiovascular Genomics Biorepository: the CATHGEN Experience.

The CATHeterization GENetics (CATHGEN) biorepository was assembled in four phases. First, project start-up began in 2000. Second, between 2001 and 2010, we collected clinical data and biological samples from 9334 individuals undergoing cardiac catheterization. Samples were matched at the individual level to clinical data collected at the time of catheterization and stored in the Duke Databank for Cardiovascular Diseases (DDCD). Clinical data included the following: subject demographics (birth date, race, gender, etc.); cardiometabolic history including symptoms; coronary anatomy and cardiac function at catheterization; and fasting chemistry data. Third, as part of the DDCD regular follow-up protocol, yearly evaluations included interim information: vital status (verified via National Death Index search and supplemented by Social Security Death Index search), myocardial infarction (MI), stroke, rehospitalization, coronary revascularization procedures, medication use, and lifestyle habits including smoking. Fourth, samples were used to generate molecular data. CATHGEN offers the opportunity to discover biomarkers and explore mechanisms of cardiovascular disease.

Future translational applications from the contemporary genomics era: a scientific statement from the American Heart Association.

The field of genetics and genomics has advanced considerably with the achievement of recent milestones encompassing the identification of many loci for cardiovascular disease and variable drug responses. Despite this achievement, a gap exists in the understanding and advancement to meaningful translation that directly affects disease prevention and clinical care. The purpose of this scientific statement is to address the gap between genetic discoveries and their practical application to cardiovascular clinical care. In brief, this scientific statement assesses the current timeline for effective translation of basic discoveries to clinical advances, highlighting past successes. Current discoveries in the area of genetics and genomics are covered next, followed by future expectations, tools, and competencies for achieving the goal of improving clinical care.

Practice patterns and clinical outcomes among non-ST-segment elevation acute coronary syndrome (NSTE-ACS) patients presenting to primary and tertiary hospitals: insights from the EARLY glycoprotein IIb/IIIa inhibition in NSTE-ACS (EARLY-ACS) trial.

OBJECTIVES: We evaluated patients at tertiary [both percutaneous coronary intervention (PCI) and coronary artery bypass grafting (CABG) capable] and primary hospitals in the EARLY-ACS trial. BACKGROUND: Early invasive management is recommended for high-risk non-ST-segment elevation acute coronary syndromes. METHODS: We evaluated outcomes in 9,204 patients presenting to: tertiary sites, primary sites with transfer to tertiary sites ("transferred") and those who remained at primary sites ("non-transfer"). RESULTS: There were 348 tertiary (n = 7,455 patients) and 89 primary hospitals [n = 1,749 patients (729 transferred; 1,020 non-transfer)]. Significant delays occurred in time from symptom onset to angiography (49 hr), PCI (53h), and CABG (178 hr) for transferred patients (P < 0.001). Non-transfer patients had less 30-day death/myocardial infarction [9.4% vs. 11.7% (tertiary); adjusted odds ratio (OR): 0.78 (0.62-0.97), P = 0.026]; transferred (14.0%) and tertiary patients were similar [adjusted OR: 1.23 (0.98-1.53), P = 0.074]. Non-transfer patients had lower 1-year mortality [4.3% vs. 6.3% (tertiary); adjusted hazard ratio (HR): 0.64 (0.47-0.87), P = 0.005]: there was no difference between transferred and tertiary patients [5.2% vs. 6.3%; adjusted HR: 0.80 (0.58-1.12), P = 0.202]. Despite similar rates of catheterization, GUSTO severe/moderate bleeding within 120 hr was less in non-transfer [3.1% vs. 6.7% (tertiary); adjusted OR: 0.47 (0.32-0.68), P < 0.001], whereas transferred (6.1%) and tertiary patients were similar [adjusted OR: 0.94 (0.68-1.30), P = 0.693]. There was no difference in non-CABG bleeding. CONCLUSIONS: Timely angiography and revascularization were often not achieved in transferred patients. Non-transferred patients presenting to primary sites had the lowest event rates and the best long-term survival.

Implementation of standardized assessment and reporting of myocardial infarction in contemporary randomized controlled trials: a systematic review.

Myocardial infarction (MI) is a key endpoint in randomized controlled trials (RCTs), but heterogeneous definitions limit comparisons across RCTs or meta-analyses. The 2000 European Society of Cardiology/American College of Cardiology MI redefinition and the 2007 universal MI definition consensus documents made recommendations to address this issue. In cardiovascular randomized trials, we evaluated the impact of implementation of three key recommendations from these reports-troponin use to define MI; separate reporting of spontaneous and procedure-related MI; and infarct size reporting. We searched ClinicalTrials.gov and MEDLINE databases for cardiovascular RCTs with more than 500 patients in which enrolment began between September 2000 and July 2012 and that listed MI in the primary endpoint. We searched English-language publications with primary results or design papers. Of 3222 studies screened, 96 (3.0%) met our criteria. We extracted enrolment start date, number of patients and MI events, follow-up duration, and coronary revascularization rate. Data extraction quality was assessed by duplicated extractions. Of 96 RCTs, 80 had a primary results publication, comprising 608 091 patients and 43 621 endpoint MIs. Myocardial infarction represented 45.3% (95% confidence interval, 40.2-50.4) of events in the primary composite endpoint. Troponin defined MI in 57% (53/93) of trials with an MI definition available. Of these RCTs, three used troponin only if creatine kinase-MB was unavailable, six used troponin to define peri-procedural MI, seven specified the 99th percentile as the MI decision limit, and three reported spontaneous and procedure-related MI separately. None reported biomarker-based infarct size, but five reported MI as multiples of the assay upper limit of normal. Although MI is a major component of cardiovascular RCT primary endpoints, standardized MI reporting and implementation of consensus document recommendations for MI definition are limited. Developing appropriate strategies for uniform implementation is required.

Reasons for noncompletion of advance directives in a cardiac intensive care unit.

BACKGROUND: The Patient Self-Determination Act of 1990 mandates that hospitals reimbursed by Medicare and Medicaid inform each patient about the patient's right to a natural death. OBJECTIVE: To describe and explore implementation of the Patient Self-Determination Act in a critical care setting. The goal was to assess patients' understanding of advance directives. METHODS: In a semistructured cross-sectional study, all eligible patients 18 years or older admitted to the cardiac intensive care unit at Duke University Medical Center, Durham, North Carolina, were assessed. Each patient was asked the standard question required by the Patient Self-Determination Act-Do you have an advance directive?-and 3 open-ended questions to ascertain the patient's understanding of advance directives. RESULTS: The sample consisted of 505 patients with a mean age of 61.9 years (SD, 14.8), 37.8% (n = 191) were women, and 68.5% (n = 346) were white. Most patients (64.4%; n = 325) did not have an advance directive before admission to the unit. Of the patients who initially declined the opportunity to complete an advance directive (n = 213), 33.8% (n = 72) said they did not understand the question when initially asked and therefore just said no. CONCLUSIONS: Current practice meets the requirement of the Patient Self-Determination Act for documentation of patients' right to a natural death. However, simply asking Do you have an advance directive? does not elicit an accurate reflection of a patient's understanding of advance directives.

Testing of low-risk patients presenting to the emergency department with chest pain: a scientific statement from the American Heart Association.

The management of low-risk patients presenting to emergency departments is a common and challenging clinical problem entailing 8 million emergency department visits annually. Although a majority of these patients do not have a life-threatening condition, the clinician must distinguish between those who require urgent treatment of a serious problem and those with more benign entities who do not require admission. Inadvertent discharge of patients with acute coronary syndrome from the emergency department is associated with increased mortality and liability, whereas inappropriate admission of patients without serious disease is neither indicated nor cost-effective. Clinical judgment and basic clinical tools (history, physical examination, and electrocardiogram) remain primary in meeting this challenge and affording early identification of low-risk patients with chest pain. Additionally, established and newer diagnostic methods have extended clinicians' diagnostic capacity in this setting. Low-risk patients presenting with chest pain are increasingly managed in chest pain units in which accelerated diagnostic protocols are performed, comprising serial electrocardiograms and cardiac injury markers to exclude acute coronary syndrome. Patients with negative findings usually complete the accelerated diagnostic protocol with a confirmatory test to exclude ischemia. This is typically an exercise treadmill test or a cardiac imaging study if the exercise treadmill test is not applicable. Rest myocardial perfusion imaging has assumed an important role in this setting. Computed tomography coronary angiography has also shown promise in this setting. A negative accelerated diagnostic protocol evaluation allows discharge, whereas patients with positive findings are admitted. This approach has been found to be safe, accurate, and cost-effective in low-risk patients presenting with chest pain.