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Institute for Clinical Research and Health Policy Studies

Center for Cardiovascular Health Services Research

For over 25 years, the ICRHPS Center for Cardiovascular Health Services Research (CCHSR) has focused on the development of treatment strategies, decision aids, methods, and systems aimed at improving medical care, especially emergency and cardiac care.  It has particularly been known for a series of studies of the factors influencing emergency cardiac care and for development of clinical predictive instruments as decision aids that provide emergency physicians and paramedics with predictions for their patients’ likely cardiac diagnoses and outcomes for real-time use in clinical care, and also for retrospective review of care.

This and related work has included conduct of multiple large national clinical effectiveness trials, including demonstrating better treatment and clinical outcomes for patients with acute coronary syndromes and acute myocardial infarction.

Research Focus Areas

For over 25 years, the ICRHPS Center for Cardiovascular Health Services Research (CCHSR) has focused on the development of treatment strategies, decision aids, methods, and systems aimed at improving medical care, especially emergency and cardiac care.  It has particularly been known for a series of studies of the factors influencing emergency cardiac care and for development of clinical predictive instruments as decision aids that provide emergency physicians and paramedics with predictions for their patients’ likely cardiac diagnoses and outcomes for real-time use in clinical care, and also for retrospective review of care.  This and related work has included conduct of multiple large national clinical effectiveness trials, including demonstrating better treatment and clinical outcomes for patients with acute coronary syndromes and acute myocardial infarction.  

The cardiac predictive instruments, for which the CCHSR is perhaps best known, help clinicians make better diagnoses of cardiac conditions, better emergency triage and hospitalization decisions, and more rapid and appropriate emergency cardiac treatments.  The CCHSR team was involved in developing and testing the original predictive instrument for acute cardiac ischemia (ACI), also known as acute coronary syndromes (ACS), which include both unstable angina pectoris and acute myocardial infarction (AMI).1  In 1991, as part of a study of how to improve coronary care unit (CCU) admitting practices in teaching and non-teaching hospitals, CCHSR researchers further developed the original predictive instrument to make it applicable for retrospective assessment of appropriateness and quality of care.  Such “time-insensitive predictive instruments” (TIPIs) can be used in real-time to predict whether a patient in an emergency setting is likely to have ACS, and the probability of death, and also can be used later to assess if the care was appropriate.2-5  To improve their usefulness for clinical practice, these new predictive instruments were incorporated into computerized electrocardiographs where their predictions are printed on the top of electrocardiograms (ECGs) and tested in clinical trials.  In a 10,689-patient multicenter clinical effectiveness trial of the ACI-TIPI, the new version of the original instrument improved hospital triage of patients with ACS and AMI.6 It is now is available in conventional electrocardiographs for emergency departments (EDs) and ambulances.

CCHSR investigators developed the Thrombolytic Predictive Instrument (TPI) to improve identification of patients with ST-elevation AMI for immediate reperfusion therapy.  The TPI provides the clinician with real-time predictions printed on the ECG of 30-day mortality, 1-year mortality, cardiac arrest, all both for if a patient is not treated with thrombolytic (or other reperfusion) therapy, and if they are so-treated.  It also provides predictions of the possible complications of thrombolytic therapy, including bleeding and stroke.7  To see if the use of the predictive instrument improved care, CCHSR ran a 28-hospital, 1,197-patient trial of its impact on the speed and use of acute reperfusion.8 The result was that indeed the TPI improved the use and speed of use of reperfusion in those patients less likely to get treated, such as women and those with harder to diagnose AMIs (inferior location). It also improved reperfusion use and speed of use in settings where there was less expertise on-site, such as when a phone call to a cardiologist was needed to make the treatment decision and when there was no on-site emergency physician.  

Building on this experience, more recently, CCHSR ran a national randomized placebo-controlled clinical trial to determine if a long-neglected treatment for AMI, an intravenous solution of glucose, insulin, and potassium, called “GIK,” if given very early in the course of ACS and AMI, could reduce cardiac arrests and death.  This was particularly of interest because prior clinical trials of GIK, used in-hospital after a patient had a document AMI, had not shown a clear benefit.  However, based on experimental animal data that showed that GIK prevents cardiac damage if started right at the onset of ACS, CCHSR researchers reasoned that a benefit might be found if paramedics in the community could give GIK to patients with early ACS, perhaps even before AMI had developed,.  The CCHSR researchers showed that, using the ACI-TIPI and TPI, paramedics could identify ACS well enough to treat with intravenous GIK in the community in follow-up of a 9-1-1 call for possible ACS/AMI.9  Thus, funded by the National Heart Lung and Blood Institute of the National Institutes of Health, the IMMEDIATE (Immediate Myocardial Metabolic Enhancement During Initial Assessment and Treatment in Emergency care) Trial tested if GIK, administered by paramedics in the field, aided by the predictive instruments, could prevent a threatening AMI from occurring, and could decrease cardiac damage and death from an AMI already underway.10 The results of this 871-participant study done across the US showed that, although progression to AMI was not significantly reduced, the odds for having cardiac arrest or dying were reduced by half, and the size of AMI was reduced by 80%.11    An additional trial is planned to confirm this result, which if true, would represent a readily available, inexpensive treatment that could have a dramatic impact,  used in ambulances and EDs, where it potentially  could save the lives of tens of thousands of patients in the United States each year.

Other recent and ongoing projects include the implementation and use of a TIPI information system (TIPI-IS) to reduce medical errors in ED triage and treatment for patients with ACS,12 the development and incorporation into electrocardiographs of mathematical models that allow the delineation of the time interval of “mathematical equipoise” during which referral to a cardiac center for potential percutaneous coronary intervention (PCI, “angioplasty”) is justified,13  and the development of risk-adjusted models that predict both in-hospital morbidity and mortality for stroke patients based on admission characteristics.  The TIPI-IS is also used to measure and monitor the quality of prehospital stroke care and support group learning through an EMS quality improvement collaborative.

Other studies14-16 by the CCHSR include the study of what kinds of factors increase the likelihood of a patient’s ACS/AMI being missed in the ED and mistakenly being sent home, and other issues of diagnosis and treatment of emergency cardiac condition.17  These studies have also included clinical trials, such as a prospective controlled clinical effectiveness trial to test whether incorporating myocardial perfusion imaging into an ED evaluation protocol for patients with symptoms suggestive of ACS would improve clinical decision making.18


References

1. Pozen MW, D'Agostino RB, Selker HP, Sytkowski PA, Hood WB Jr.  A predictive instrument to improve coronary care unit admission practices in acute ischemic heart disease:  A prospective multicenter clinical trial. N Engl J Med. 310:1273 78, 1984. PMID: 6371525.
2. Selker HP, Griffith JL, D'Agostino RB.  A tool for judging coronary care unit admission appropriateness valid for both real-time and retrospective use:  A time-insensitive predictive instrument (TIPI) for acute cardiac ischemia: A multicenter study.  Med Care. 29:610-627, 1991. PMID: 2072767.
3. Selker HP, Griffith JL, D'Agostino RB.  A time-insensitive predictive instrument for acute myocardial infarction mortality:  A multicenter study.  Med Care. 29:1196-1211, 1991. PMID: 1745078.
4. Selker HP.  Systems for comparing actual and predicted mortality rates:  Characteristics to promote cooperation in improving hospital care.  Ann Intern Med. 118:820-822, 1993. PMID: 8470856.
5. Selker HP, Griffith JL, D'Agostino RB.  A time-insensitive predictive instrument for acute mortality due to congestive heart failure:  Development, testing, and use for comparing hospitals: A multicenter study.  Med Care. 32:1040-1052, 1994. PMID: 7934270.
6. Selker HP, Beshansky JR, Griffith JL, Aufderheide TP, Ballin DS, Bernard SA, Crespo SG, Feldman J, Fish SS, Gibler WB, Kiez DA, McNutt RA, Moulton AW, Ornato JP, Podrid PJ, Salem DN, Sayre MR, Woolard RH.  The use of the Acute Cardiac Ischemia Time-Insensitive Predictive Instrument (ACI-TIPI) to assist emergency department triage of patients with chest pain or other symptoms suggestive of acute cardiac ischemia: a multicenter controlled clinical trial. Ann Intern Med. 1998. 129:845-855. PMID: 9867725.
7. Selker HP, Griffith JL, Beshansky JR, Schmid CH, Califf RM, D'Agostino RB, Laks MM, Lee KL, Manyard C, Selvester RH, Wagner GS, Weaver WD.  Patient-specific predictions of outcomes in myocardial infarction for real-time emergency use:  A thrombolytic predictive instrument.  Ann Intern Med 1997. 127:538-556.  PMID: 9313022
8. Selker HP, Beshansky JR, Griffith JL, for the TPI Trial Investigators. Use of the electrocardiograph-based thrombolytic predictive instrument to assist thrombolytic and reperfusion therapy for acute myocardial infarction: a multicenter randomized clinical effectiveness trial. Ann Intern Med. 2002. 137:87-95. PMID: 12118963.
9. Selker HP, Beshansky JR, Ruthazer R, Sheehan PR, Sayah AJ, Atkins JM, Aufderheide  TP, Pirrallo RG, D’Agostino RB, Massaro JM, Griffith JL.  Emergency medical service predictive instrument aided diagnosis and treatment of acute coronary syndromes and ST elevation myocardial infarction in the IMMEDIATE Trial.  Prehosp Emerg Care.  2011:15(2)139-148. PMID: 21366431.
10.     Selker HP, Beshansky JR, Griffith JL, D’Agostino RB, Massaro JM, Udelson JE, Rashba EJ, Ruthazer R, Sheehan PR, Desvigne-Nickens P, Rosenberg YD, Atkins JM, Sayah AJ,Aufderheide TP, Rackley CE, Opie LH, Lambrew CT, Cobb LA, MacLeod BA, Ingwall JS, Zalenski RJ, Apstein CS.  Study design for the IMMEDIATE (Immediate Myocardial Metabolic Enhancement During Initial Assessment and Treatment in Emergency care) Trial: a double-blind randomized controlled trial of intravenous glucose, insulin, and potassium (GIK) for acute coronary syndromes in emergency medical services. Am Heart J. 2012 Mar:163(3):315-22. PMID: 22424000.
11. Selker HP, Beshansky JR, Sheehan PR, Massaro JM, Griffith JL, D’Agostino RB,  Ruthazer R, Atkins JA, Sayah AJ, Levy MK, Richards ME, Aufderheide TP, Braude DA, Pirrallo RG, Doyle DD, Frascone RJ, Kosiak DJ, Leaming JM, Van Gelder CM, Walter G-P, Wayne MA, Woolard RH, Opie LH, Rackley CE, Apstein CS, Udelson JE.  Effect of Out-of-Hospital Administration of Intravenous Glucose, Insulin, and Potassium (GIK) in Patients with Suspected Acute Coronary Syndromes: The IMMEDIATE Randomized Controlled Trial.  JAMA. 2012:307:18:1925-1933. PMID: 22452807.
12. Daudelin D, Selker HP.  Medical Error Prevention in ED Triage for ACS: Use of Cardiac Care Decision Support and Quality Improvement Feedback.  Cardiology Clinics, 23:4, 601-614, 2005.
13. Selker HP, Ruthazer R, Terrin N, Griffith JL, Concannon T, Kent DM.  Random treatment assignment using mathematical equipoise for comparative effectiveness trials.  Clin Transl Sci. 2011:4(1)10-16. PMID: 2134895.
14. Kent DM, Ruthazer R, Selker HP.  Are Some Patients Likely to Benefit From Recombinant Tissue-Type Plasminogen Activator for Acute Ischemic Stroke Even Beyond 3 Hours From Symptom Onset? Stroke. 34:464–467, 2003. PMID: 12574561.
15. Kent DM, Price LL, Ringleb P, Hill MD, Selker HP. Sex-based differences in response to recombinant tissue plasminogen activator in acute ischemic stroke: a pooled analysis of randomized clinical trials. Stroke. 2005;36:62-5. PMID: 15569865.
16. Kent DM, Selker HP, Ruthazer R, Bluhmki E, Hacke W. Can multivariable risk-benefit profiling be used to select treatment-favorable patients for thrombolysis in stroke in the 3- to 6-hour time window? Stroke. 2006 Dec;37(12):2963-69. PMID: 17068306.
17. Pope JH, Aufderheide TP, Ruthazer R, Woolard RH, Feldman JA, Beshansky JR, Griffith JL, Selker HP.  A multicenter prospective study of missed diagnoses of acute myocardial infarction and unstable angina pectoris in the emergency department.  N Engl J Med. 342:1163-70, 2000. PMID: 10770981.
18. Udelson JE, Beshansky JR, Ballin DS, Feldman JA, Griffith JL, Heller GV, Hendel RC, Pope JH, Ruthazer R, Spiegler EJ, Woolard RH, Handler J, Selker HP.  Emergency department assessment of Tc-99m sestamibi imaging for evaluation and triage of patients with suspected acute cardiac ischemia: a randomized, multicenter, controlled clinical trial.  JAMA. 288:2693-2700, 2002. PMID: 12460092.

Sample ACI TIPI-ECG

The original ACI predictive instrument and its newer version, the electrocardiograph-based Acute Cardiac Ischemia Time-Insensitive Predictive Instrument (ACI-TIPI) have been shown effective in large prospective clinical trials. These models provide a predicted probability, based on presenting characteristics, that a patient has acute cardiac ischemia (ACI). These predictions can be printed on the electrocardiogram (ECG) by currently available conventional electrocardiographs that have ACI-TIPI software installed.

A related AMI mortality TIPI, predicting cardiac mortality among presenting ED patients has been published, but has been primarily used for retrospective comparisons between hospitals of clinically accurately risk-adjusted mortality rates rather than for real-time clinical use.

View a sample ACI-TIPI and TPI ECG.

However, a newer version of the mortality TIPI that includes in its predictions the impact of the use of thrombolytic therapy, the Thrombolytic Predictive Instrument (TPI) is now available in conventional electrocardiographs. When implemented in an electrocardiograph, the TPI software detects the ST segment elevation of AMI, and then immediately prints on the ECG header its predictions of the likely beneficial and adverse effects on clinical outcomes from the use of thrombolytic therapy for AMI for a given patient.

These predictions assist ED clinicians' real-time clinical decision-making. Given the great importance of very rapid appropriate triage and treatment for patients with suspected ACI/AMI, these decision aids seem to hold considerable promise.

Visit the Immediate Trial website

Researchers and Staff

Harry P. Selker, MD, MSPH
Director, CCHSR and Professor of Medicine

Joni Beshansky, RN, MPH
Associate Professor of Medicine

Denise Daudelin, RN, MPH
Assistant Professor of Medicine

David Kent, MD, MS
Professor of Medicine

Rebecca Lorenzana, BA
Research Assistant

Manlik Kwong, BSEE, BSCS
Instructor of Medicine

Robin Ruthazer, MPH
Assistant Professor of Medicine