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- ↵*Reprint requests and correspondence:
Dr. Thomas J. Ryan, Section of Cardiology, Boston University Medical Center, 88 East Newton Street, Boston, Massachusetts 02118
It is generally agreed that one of the most important contributions made in medicine during the past century was the establishment of the coronary care unit in the early 1960s. Although Herrick (1) had clearly defined the clinical entity of acute myocardial infarction (MI) some 50 years earlier, it required the introduction of techniques of transthoracic defibrillation and cardiac massage to mount a major assault on the inordinate mortality and sudden cardiac death associated with the condition. It is of some importance to note that it took a practical, early bedside assessment of the patient's risk of developing cardiac arrest proposed by Killip and Kimball (2) to convince the medical community that such fatal events could be aborted if patients were segregated in specially designed units with trained personnel immediately available with appropriate equipment. The Killip classification is based on the fraction of the lung fields over which crackles are heard in patients who are monitored for arrhythmias that range from ventricular premature beats to ventricular tachycardia/ventricular fibrillation. Killip classes I to IV translate readily into: class I, no evidence of congestive heart failure (CHF); class II, mild CHF (crackles observed in 50% or less of the lung fields); class III, pulmonary edema (crackles throughout 100% of both lung fields); and class IV, cardiogenic shock. Because the Killip class correlates in a general way with the extent of left ventricular dysfunction, it has proven quite predictive. Easily remembered and simple to apply, it became universally accepted and even today, almost 40 years later, is widely used around the world.
In this issue of the Journal, Wiviott et al. (3)demonstrate the utility of an equally simple risk index, based on age and vital signs that are routinely obtained during the first patient encounter, in predicting mortality among a large, community-based, unselected, heterogeneous population of patients with ST-segment elevation acute myocardial infarction (STEMI). The Thrombolysis In Myocardial Infarction (TIMI) risk index (TRI), calculated using the equation (heart rate × [age/10]2/systolic blood pressure), was derived from observed risk relations among 13,253 patients enrolled in the Intravenous NPA for the Treatment of Infarcting Myocardium Early (In TIME II) randomized trial of lanoteplase versus alteplase as reperfusion therapy for STEMI (4). The prognostic discriminatory capacity of this index was expressed as the c-statistic, equivalent to the area under the receiver operating characteristic curve (5). Among this group, the TRI was a strong and independent predictor of mortality at 24 h (c statistic = 0.81) and at 30 days (p < 0.0001). It was validated in an external data set of STEMI patients from the TIMI-9 trials (n = 3,659) that showed both a high discriminatory capacity (c statistic = 0.79) and concordance between the observed 30-day mortality and the predictions based on the In TIME II data (goodness of fit, p = 0.7) (6).
The customary criticism of risk-assessment tools derived and validated from randomized controlled trial cohorts is that they overestimate the performance of the risk score because the randomized patients have been “sanitized” by the inclusion and exclusion criteria used in the trials of patients with similar disease in the population at large. The elderly are underrepresented and, being older with a greater comorbidity burden, they qualify less often for particular therapies such as fibrinolytic therapy. An examination of Table 1 of Wiviott et al. (3), which presents the baseline characteristics of the cohorts used, certainly shows striking differences in mean age for those in the derivation set compared with the National Registry of Myocardial Infarction population at large and also divided into those who received reperfusion therapy and those who did not. Paralleling these changes in age among the four cohorts are the major morbidities of diabetes, hypertension, renal failure, and the history of previous MI, cerebrovascular incident, or CHF. Rathore et al. (7) focused on this very point after evaluating the discrimination and calibration performance of the TRI in a community-based cohort of elderly patients taken from the Cooperative Cardiovascular Project and found the index performed poorly with a c statistic = 0.62. The TIMI investigators would appear to have responded successfully to this criticism. They showed that this apparent lack of discriminatory power of the TRI, when applied to the less homogeneous general population and a select population of the elderly as well, is resolved when the TRI is used as a continuous variable. This serves to minimize the wider range of values observed in a diverse population. The data supporting this claim appear in Table 2 and Figure 2 of their publication (3), in which the risk index is modeled as a continuous variable. For STEMI patients treated with reperfusion therapy (n = 81,679; Table 2), there was a strong graded relationship with in-hospital mortality, ranging from 0.6% to 60% across the risk index categories providing a c statistic = 0.81. For patients treated without reperfusion therapy (n = 71,807; Table 2) and among the elderly as well (n = 89,385; Table 2) there was still a strong graded relationship with in-hospital mortality ranging from 1.9% to 53% across risk index groups that yields an acceptable c statistic = 0.71.
As with most TIMI publications, it is critical to discriminate one study from the other to understand exactly where it fits in the large TIMI mosaic. It is important here to recognize that the present TRI is a derivative of a previously published TIMI risk score, the variables of which were weighted according to adjusted odds ratios from logistic regression analyses to arrive at a prognostic discriminatory score that was comparable with a full multivariable model (8). The risk score had its origins in one of the first articles in the thrombolytic era to show that certain readily available clinical variables taken from the patient's history, physical exam, chest X-ray, and electrocardiogram, assessed before treatment, were independent predictors of mortality in patients with evolving infarction (9). The TIMI Risk Index thus arose as a logical extension of this work and uses the three strongest clinical predictors of outcome (age, heart rate, and systolic blood pressure) to provide a very simple instrument for establishing a more than 20-fold gradient of risk for early events with high discriminatory capacity
Because the TRI has been convincingly validated against more than 150,000 heterogeneous, real-world patients with STEMI in the National Registry of Myocardial Infarction databases and continues to show a very good discriminatory capacity, it would seem now is the time to make use of its full potential. The fact that the TRI can be calculated using basic arithmetic by anyone capable of measuring vital signs and that it does not require a hospital setting or the use of a nomogram makes it extremely transportable. Considering such ideal suitability for use in the field, it has the exciting potential for effecting the next “major happening” that will be required to reduce further our seemingly low 30-day mortality rate (6.5% to 8.0%) for STEMI patients. The epidemiological truth, however, is that for all patients who will suffer an acute MI during the next 30 days, 30% will die within the next 3 months. Two-thirds of these deaths will occur before the individual enters the medical care system. This speaks to the urgency of the need to bring the acute MI patient into the medical care system at a much earlier time frame. The most practical way is to bring the medical care system to the patient, as suggested in the newly released American College of Cardiology/American Heart Association Guidelines for the Management of STEMI patients (10). They now instruct patients to call 911 within 5 min of the onset of symptoms rather than the previously recommended procedure of taking a nitroglycerine tablet with the onset of symptoms and calling after 15 min if there is no relief.
Another critical need is to improve emergency medical transport within this country with the hope that it can at least equal what has been achieved recently in Europe (11). Before this can happen, however, the nations' Emergency Medical System has to be re-evaluated not only from the operational standpoint but from structural, functional, and fiscal perspectives as well. This will be a daunting and expensive task but is clearly a core need in our country today.
Just as the Killip simple but useful risk assessment tool was instrumental in persuading the establishment to undertake an expensive departure from the time-honored convention of open-ward hospital care, so too should the TRI be used to extend evidence-based care from the hospital coronary care unit to the field. The advances in technology, the miniaturization and computerization of equipment, the progress in pharmacotherapeutics, and the utility of satellite navigational systems all indicate the infrastructure is in place to support this paradigm shift. Reinforced by a reliable predictor of near-term clinical outcome, the health care responders cannot only customize their care at the first point of patient encounter but also can better judge triage routes at a point where time and distance are two of the most critical elements.
Although it is the simplicity of the equation that makes me say this is not just another scorecard but rather a formula with a future, my convictions would be strengthened if it, or some slight modification thereof, could be validated for the non-STEMI patient as well. Nowadays, the non-STEMI outnumbers the STEMI by nearly a 3:1 ratio. The other need is to explore the predictability of heart rates greater and lesser than the 50 to 150 beats/min range set as a boundary in this and earlier evaluations. The cardiovascular response to the adrenergic discharge and neurohumoral releases in the very earliest hours of infarction has not been widely studied in large populations, and some recalibration of these limits may be warranted.
↵* Editorials published in the Journal of the American College of Cardiologyreflect the views of the authors and do not necessarily represent the views of JACCor the American College of Cardiology.
- American College of Cardiology Foundation
- Herrick J.B.
- ↵Wiviott SD, Morrow DA, Frederick PD, et al. Performance of the Thrombolysis In Myocardial Infarction risk index in the National Registry of Myocardial Infarction-3 and -4: a simple index that predicts mortality in ST-segment elevation myocardial infarction. J Am Coll Cardiol 2004;44:783–9.
- InTIME-II Investigators
- Rathore S.S.,
- Weinfurt K.P.,
- Gross G.P.,
- Krumholz H.M.
- Morrow D.A.,
- Antman E.M.,
- Charlesworth A,
- et al.
- Hillis L.D.,
- Forman S.,
- Braunwald E.
- ↵Antman EM, Anbe DT, Armstrong PW, et al. ACC/AHA guideline update for the management of patients with ST-segment elevation myocardial infarction (STEMI)—2004: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Committee on the Management of Acute Myocardial Infarction). Available at: http://www.acc.org/clinical/guidelines/stemi/index.pdfAccessed June 9, 2004.