Study design for the Immediate Myocardial Metabolic Enhancement During Initial Assessment and Treatment in Emergency Care (IMMEDIATE) Trial: A double-blind randomized controlled trial of intravenous glucose, insulin, and potassium for acute coronary syndromes in emergency medical services.

BACKGROUND: Experimental studies suggest that metabolic myocardial support by intravenous (IV) glucose, insulin, and potassium (GIK) reduces ischemia-induced arrhythmias, cardiac arrest, mortality, progression from unstable angina pectoris to acute myocardial infarction (AMI), and myocardial infarction size. However, trials of hospital administration of IV GIK to patients with ST-elevation myocardial infarction (STEMI) have generally not shown favorable effects possibly because of the GIK intervention taking place many hours after ischemic symptom onset. A trial of GIK used in the very first hours of ischemia has been needed, consistent with the timing of benefit seen in experimental studies. OBJECTIVE: The IMMEDIATE Trial tested whether, if given very early, GIK could have the impact seen in experimental studies. Accordingly, distinct from prior trials, IMMEDIATE tested the impact of GIK (1) in patients with acute coronary syndromes (ACS), rather than only AMI or STEMI, and (2) administered in prehospital emergency medical service settings, rather than later, in hospitals, after emergency department evaluation. DESIGN: The IMMEDIATE Trial was an emergency medical service-based randomized placebo-controlled clinical effectiveness trial conducted in 13 cities across the United States that enrolled 911 participants. Eligible were patients 30 years or older for whom a paramedic performed a 12-lead electrocardiogram to evaluate chest pain or other symptoms suggestive of ACS for whom electrocardiograph-based acute cardiac ischemia time-insensitive predictive instrument indicated a ≥75% probability of ACS, and/or the thrombolytic predictive instrument indicated the presence of a STEMI, or if local criteria for STEMI notification of receiving hospitals were met. Prehospital IV GIK or placebo was started immediately. Prespecified were the primary end point of progression of ACS to infarction and, as major secondary end points, the composite of cardiac arrest or in-hospital mortality, 30-day mortality, and the composite of cardiac arrest, 30-day mortality, or hospitalization for heart failure. Analyses were planned on an intent-to-treat basis, on a modified intent-to-treat group who were confirmed in emergency departments to have ACS, and for participants presenting with STEMI. CONCLUSION: The IMMEDIATE Trial tested whether GIK, when administered as early as possible in the course of ACS by paramedics using acute cardiac ischemia time-insensitive predictive instrument and thrombolytic predictive instrument decision support, would reduce progression to AMI, mortality, cardiac arrest, and heart failure. It also tested whether it would provide clinical and pathophysiologic information on GIK's biological mechanisms.

Trends in reperfusion strategies, door-to-needle and door-to-balloon times, and in-hospital mortality among patients with ST-segment elevation myocardial infarction enrolled in the National Registry of Myocardial Infarction from 1990 to 2006.

BACKGROUND: Among patients with ST-segment elevation myocardial infarction (STEMI), rapid reperfusion is associated with improved mortality. As such, door-to-needle (D2N) and door-to-balloon (D2B) times have become metrics of quality of care and targets for intense quality improvement. METHODS: The National Registry of Myocardial Infarction (NRMI) collected data regarding reperfusion therapy, its timing and in-hospital mortality among STEMI patients from 1990 through 2006. RESULTS: Since 1990, NRMI has enrolled 1,374,232 STEMI patients at 2,157 hospitals. Among those, 774,279 (56.3%) were eligible for reperfusion upon arrival. The proportion receiving fibrinolytic therapy fell from 52.5% in 1990 to 27.6% in 2006 (P < .001), while the proportion undergoing primary percutaneous coronary intervention (pPCI) increased from 2.6% to 43.2%. Among reperfusion-eligible patients who received fibrinolytic therapy, there was a nearly linear decline in median D2N time from 59 minutes in 1990 to 29 minutes in 2006 (P < .001 for trend) as well as a decrease in mortality from 7.0% in 1994 to 6.0% in 2006 (P < .001). Among those undergoing pPCI, D2B time among nontransfer patients declined linearly from 111 minutes in 1994 to 79 minutes in 2006 (P < .001) with a decline in mortality from 8.6% to 3.1% (P < .001). The relative improvement in mortality attributable to improvements in D2N time was 16.3% and to D2B time was 7.5%. CONCLUSIONS: Since 1990, there has been a progressive decline in D2N and D2B time among reperfusion-eligible STEMI patients. These improvements have contributed, at least in part, to a progressive decline in mortality.

Evaluation of a noninvasive system for determining left ventricular filling pressure.

BACKGROUND: Measurement of left ventricular filling pressure (LVFP) provides an accurate assessment of left ventricular failure. Clinical and radiographic methods of estimating LVFP are unreliable. The noninvasive method of analyzing the decline in the arterial pressure during the strain phase of the Valsalva maneuver may be used to directly measure LVFP. OBJECTIVE: To examine the relationship and the level of accuracy of a noninvasive system (VeriCor) in directly determining left ventricular end diastolic pressure (LVEDP) using simultaneously recorded VeriCor and LVEDP measurements obtained during left heart catheterization. METHODS: During elective right and left heart catheterization, LVFP was assessed by measuring pulmonary capillary wedge pressure (PCWP) and LVEDP in 57 patients followed immediately by a Valsalva maneuver using the VeriCor assembly to estimate these pressures noninvasively. RESULTS: VeriCor measurements had a significant correlation with the catheter-measured LVEDP (r = 0.86), comparable to the correlation of the catheter-measured PCWP with LVEDP (r = 0.81). The predictive accuracy of VeriCor for LVEDP, however, appeared to be superior to that of catheter-measured PCWP for LVEDP: 84% of VeriCor measurements compared with only 41% of PCWP measurements were within 4 mm Hg of catheter-measured LVEDP, and 93% of VeriCor measurements compared with only 67% of PCWP measurements were within 6 mm Hg of catheter-measured LVEDP. CONCLUSION: VeriCor is a reliable noninvasive tool for measuring LVFP.

Critical pathways for management of patients with acute coronary syndromes: an assessment by the National Heart Attack Alert Program.

BACKGROUND: The use of critical pathways for a variety of clinical conditions has grown rapidly in recent years, particularly pathways for patients with acute coronary syndromes (ACS). However, no systematic review exists regarding the value of critical pathways in this setting. METHODS: The National Heart Attack Alert Program established a Working Group to review the utility of critical pathways on quality of care and outcomes for patients with ACS. A literature search of MEDLINE, cardiology textbooks, and cited references in any article identified was conducted regarding the use of critical pathways for patients with ACS. RESULTS: Several areas for improving the care of patients with ACS through the application of critical pathways were identified: increasing the use of guideline-recommended medications, targeting use of cardiac procedures and other cardiac testing, and reducing the length of stay in hospitals and intensive care units. Initial studies have shown promising results in improving quality of care and reducing costs. No large studies designed to demonstrate an improvement in mortality or morbidity were identified in this literature review. CONCLUSIONS: Critical pathways offer the potential to improve the care of patients with ACS while reducing the cost of care. Their use should improve the process and cost-effectiveness of care, but further research in this field is needed to determine whether these changes in the process of care will translate into improved clinical outcomes.

Assessing the effect of publication of clinical guidelines on the management of unstable angina and non-ST elevation myocardial infarction in the TIMI III (1990-1993) and the GUARANTEE (1995-1996) Registries.

BACKGROUND: The clinical guidelines for unstable angina (UA) and non-ST elevation myocardial infarction (NSTEMI) published in 1994 by the Agency for Health Care Policy Research (AHCPR) were intended to help improve treatment. No large study, however, has evaluated the effect of the guidelines on clinical practice METHODS: We compared the treatment of 3,318 patients admitted with UA/NSTEMI in the preguideline Thrombolysis in Myocardial Infarction (TIMI) III Registry (1990-1993) and 2,948 patients enrolled in the postguideline Global Unstable Angina Registry and Treatment Evaluation (GUARANTEE) Registry (1995-1996). RESULTS: More patients in GUARANTEE received guideline-recommended medication than did those in TIMI III, specifically beta-blockers (50.9% vs. 40.7%, P < 0.001), heparin (63.3% versus 57.5%, P < 0.001), and the combination of aspirin, heparin, and beta-blockers on admission plus aspirin at discharge (26.9% vs. 18.8%, P < 0.001). These changes were similar in all subgroups, but the greatest improvement in medication use was seen in patients admitted to a tertiary care hospital and in those with a final diagnosis of NSTEMI, i.e., with positive cardiac markers. Conversely, fewer patients in GUARANTEE who fulfilled AHCPR criteria for catheterization underwent the procedure (62.3% in GUARANTEE tertiary centers vs. 44.6% in GUARANTEE nontertiary centers vs. 66.0% in TIMI, P < 0.001). CONCLUSION: After publication of clinical guidelines for UA/NSTEMI, more patients received appropriate pharmacologic treatment, but a significant number of patients remained under-treated. Efforts to improve compliance with guideline recommendations via education and critical pathways are warranted, especially in nontertiary care settings.