INTRODUCTION — All patients with ST-elevation myocardial infarction (STEMI) should undergo early and late risk stratification soon after presentation. Since most patients with STEMI undergo reperfusion therapy, early risk stratification provides the patient and family with some sense of what the future holds. Late risk stratification attempts to identify patients who are at increased risk for late arrhythmic or nonarrhythmic death.

The general approach to risk stratification for patients with STEMI will be reviewed here. Risk stratification is accomplished with the use of validated risk prediction models that include the most important predictors of outcome. These individual predictors are discussed separately. (See "Risk factors for adverse outcomes after ST-elevation myocardial infarction".) Risk stratification for patients with acute non-ST elevation acute coronary syndromes and for those at risk for life-threatening arrhythmias is discussed separately. (See "Risk stratification after non-ST elevation acute coronary syndrome" and "Incidence of and risk stratification for sudden cardiac death after myocardial infarction".)

EARLY RISK STRATIFICATION — All STEMI patients should undergo risk assessment with one of the tools presented below within the first four to six hours of hospitalization. We prefer the TIMI risk score or the GRACE risk model. These tools include predictors of poor outcomes identified in large databases of patients with STEMI (table 1). (See "Risk factors for adverse outcomes after ST-elevation myocardial infarction".)

A report published in 1998 from the National Registry of Myocardial Infarction (NRMI) evaluated data on 170,143 patients admitted with an acute myocardial infarction (MI) (with or without ST-segment elevation) in an attempt to identify patients at high risk [1]. Significant risk factors included age over 70 years, prior MI, Killip class at admission (table 2), anterior MI, and the combination of hypotension and tachycardia.

Similar data were reported by the GUSTO trial of 41,021 patients, which found that predictors of one-year mortality among those who survived to 30 days after their MI included [2]:

●Demographics, including older age (>55), lower weight (≤80 kg), previous MI, and previous bypass surgery. In another population-based study of 2541 patients, severe obesity (BMI >30 kg/m²) also increased the risk of a cardiac event [3]. (See "Overweight and obesity in adults: Health consequences", section on 'Heart disease'.)

●Larger MIs, as determined by higher Killip class, anterior wall MI, lower blood pressure, faster heart rate (>115 bpm), longer QRS duration (>125 ms), lower left ventricular ejection fraction (LVEF), heart failure (HF) and pulmonary edema, and cardiogenic shock.

●Presence of cardiac risk factors, including smoking, hypertension, and prior cerebrovascular disease.

●Other findings such as in-hospital stroke, ventricular or supraventricular arrhythmias, absence of revascularization, and being a Black person.

Based upon these findings and analyses from other large clinical trials and registries, a number of different risk scores have been developed to assess short- and long-term outcomes after STEMI [4-10]. Only two specifically addressed patients treated with primary percutaneous coronary intervention, which is the current modality of choice [5,7].

TIMI risk score — The TIMI risk score, based upon data from 15,000 patients with an STEMI eligible for fibrinolytic therapy, is an arithmetic sum of eight independent predictors of mortality [4]:

●Age ≥75 years – 3 points

●Age 65 to 74 years – 2 points

●History of diabetes, hypertension, or angina – 1 point

●Systolic blood pressure <100 mmHg – 3 points

●Heart rate >100/min – 2 points

●Killip class II to IV (table 2) and – 2 points

●Weight <67 kg – 1 point

●Anterior ST elevation or left bundle branch block – 1 point

●Time to reperfusion therapy >4 hours – 1 point

There is a continuous relationship between mortality and score; a score of 0 to >8 was associated with a 30-day mortality of 0.8 to 36 percent, while the one-year mortality among those surviving the first 30 days ranges from 1 to 17 percent (calculator 1).

The usefulness of the TIMI risk score to predict in-hospital mortality was validated in a community-based population of 84,029 patients; the predictive accuracy of the TIMI risk score was the same in those treated with fibrinolysis or percutaneous coronary intervention, but underestimated mortality in those not undergoing reperfusion therapy (calculator 1) [11].

TIMI risk index — The TIMI risk index (TRI) is a simpler model derived from the InTIME-II trial of fibrinolytic therapy [8] and then validated in other populations to predict in-hospital mortality [12,13]. It can be used simultaneously with the TIMI risk score

The TRI is calculated from the following equation, using data obtained at presentation (table 3) [8]:

The TRI was applied to over 153,000 patients with STEMI in the National Registry of Myocardial Infarction (NRMI) in the United States [12]. There was a graded relationship to in-hospital mortality, ranging from 0.6 to 60 percent from the lowest (0 to <10) to the highest scores (≥80) in patients who received reperfusion therapy and from 1.9 to 52.2 percent in patients who did not receive reperfusion therapy [12]. Patients with a TRI <30 were at low risk. The percent of patients at high risk (TRI >60) was 14.1 percent in those who were not reperfused compared to 2.1 percent in those who were reperfused [14].

GRACE risk model — The TIMI risk score was derived from clinical trial databases, although it has been validated in a community-based populations [11,12]. The GRACE registry, a global registry of acute coronary syndrome (ACS) patients from 94 hospitals in 14 countries, developed two models to estimate the risk of both in-hospital and six-month mortality among all patients with an ACS.

The in-hospital model was based upon data from 11,389 patients with either an STEMI or a non-ST elevation ACS [5]. This model was then validated based upon data from an additional 3972 patients from GRACE and 12,142 patients from the GUSTO IIb trial. Eight independent risk factors were found to account for almost 90 percent of the prognostic information:

●Age

●Killip class (table 2)

●Systolic blood pressure

●Presence of ST-segment deviation

●Cardiac arrest during presentation

●Serum creatinine concentration

●Presence of elevated serum cardiac biomarkers

●Heart rate

Point scores were assigned for each predictive factor and are added together to arrive at an estimate of the risk of in-hospital mortality. A nomogram was published with the GRACE risk model to allow calculation of the risk score [5,15].

The six-month model was based upon data from 15,007 patients and validated in a cohort of 7638 patients, all in the GRACE registry [15]. The variables incorporated into this model include age, prior history of heart failure, prior history of myocardial infarction, resting heart rate, systolic blood pressure, ST-segment depression, initial serum creatinine concentration, elevated serum cardiac biomarkers, and performance of in-hospital percutaneous coronary intervention (PCI). The six-month mortality risk based upon this model can be calculated using a website.

CHADS2 score — While the GRACE prediction model is well validated and its use is recommended by multiple guideline organizations, its complexity makes it somewhat difficult to use in some clinical settings. The value of the CHADS2-VASc score, which is a well validated tool for predicting the risk of stroke in patients with atrial fibrillation, was evaluated in a study of more than 2300 patients with ACS (37 percent with STEMI; 19 percent with atrial fibrillation [AF]) cared for between 1995 and 2001 [16]. All-cause mortality at 10 years was strongly associated with the CHADS2 score in patients with and without AF. As expected, the more complex GRACE score provided a better prediction for short- and long-term mortality. (See "Atrial fibrillation in adults: Selection of candidates for anticoagulation", section on 'Use'.)

ACTION registry score — The Acute Coronary Treatment and Intervention Outcomes Network (ACTION) Registry was used to develop a risk score to predict in-hospital mortality following STEMI and NSTEMI [17]. Multivariable analyses of data from 243,440 patients showed that greater heart rate, lower systolic blood pressure, life-threatening presentations (cardiac arrest, cardiogenic shock, or heart failure), STEMI at presentation, lower creatinine clearance, and higher troponin values were associated with death during the hospitalization. The C statistic was very good at 0.88.

The ACTION score is likely to be most helpful for persons with moderate to severe disease and reflects more contemporary experience than TIMI or GRACE.

Two additional multivariable models have been devised and validated for patients exclusively undergoing primary PCI: the Zwolle primary PCI risk index and the CADILLAC risk score.

Zwolle primary PCI index — A risk index based upon a primary PCI population was developed in Zwolle, the Netherlands from data on 1791 patients undergoing primary PCI between 1994 and 2001 [6]. Significant independent risk factors for 30-day mortality were incorporated into the Zwolle index, including Killip class (table 2) and post-PCI TIMI flow grade (table 4), age, number of diseased vessels, location of infarction, and time to reperfusion. The risk index was validated in an additional group of 747 patients with similar characteristics treated with primary PCI between 2001 and 2003.

Based upon the Zwolle risk index, more than two-thirds of patients undergoing primary PCI were classified as low risk (risk score ≤3) [6]. For these patients, the mortality rate was 0.1 percent at two days and 0.2 percent between 2 and 10 days post-MI. It was suggested that such low-risk patients could safely be discharged early (48 hours after PCI).

CADILLAC risk score — A second primary PCI risk model was derived from the 2082 patients in the CADILLAC trial of abciximab or placebo and stenting or angioplasty in primary PCI and then validated using data from the 900 patients in the Stent-PAMI trial [7]. Seven variables, which are readily available at the time of intervention, were weighted according to their odds ratio for one-year mortality (table 5):

●LVEF <40 percent – 4 points

●Killip class 2/3 – 3 points

●Renal insufficiency (estimated creatinine clearance <60 mL/min) – 3 points

●TIMI flow grade after PCI 0 to 2 – 2 points

●Age >65 years – 2 points

●Anemia (hematocrit <39 percent in men and <36 percent in women) – 2 points

●Triple-vessel disease – 2 points

In both the derivation and validation models, patients could be stratified into three risk groups that predicted 30-day and one-year mortality:

●Low risk (score 0 to 2) – 0.1 to 0.2 percent at 30 days and 0.8 to 0.9 percent at one year

●Intermediate risk (score 3 to 5) – 1.3 to 1.9 percent at 30 days and 4.0 to 4.5 percent at one year

●High risk (score ≥6) – 6.6 to 8.1 percent at 30 days and 12.4 to 13.2 percent at one year

The percentage of patients in these three groups was 56, 24, and 20 percent, respectively. The results compared favorably with the TIMI risk score, which was based upon patients undergoing fibrinolysis, and Zwolle primary PCI index.

Comparison of risk scores — The prognostic value of the TIMI, PAMI, CADILLAC, and GRACE risk scores was directly compared in 855 registry patients with STEMI, but without cardiogenic shock, who underwent primary PCI [18]. The TIMI, PAMI, and CADILLAC scores had relatively high and similar predictive accuracies for 30-day and one-year mortality; the GRACE model performed less well. The CADILLAC score was judged to be unhelpful prior to angiography because LVEF is a key component.

LATE RISK STRATIFICATION — Late risk stratification is performed before or sometimes after discharge (generally three to seven days after the myocardial infarction [MI]) and can be used to consider early discharge in patients with a low risk of complications and to help patients understand their long-term prognosis. The main components are measurement of the left ventricular ejection fraction and occasionally following stress testing. The latter is used to detect possible residual ischemia in those patients who did not undergo coronary angiography or to assess the functional significance of residual coronary artery stenoses.

Methods used for risk stratification for arrhythmic death are discussed separately. These include ventricular arrhythmias and late potentials on signal-averaged electrocardiogram (ECG). (See "Incidence of and risk stratification for sudden cardiac death after myocardial infarction".)

Left ventricular ejection fraction — Assessment of resting left ventricular function is an important part of risk stratification in patients with acute MI and was recommended by the American College of Cardiology Foundation/American Heart Association (ACCF/AHA) and 2012 European Society of Cardiology ST-elevation myocardial infarction (STEMI) guidelines [19-21]. Echocardiography is preferred to magnetic resonance imaging in the European guideline, while the United States guideline makes no preference for the type of imaging modality. Patients with left ventricular systolic dysfunction have increased mortality at six months and one year (figure 1 and figure 2) [22-24]. The increase in mortality is most pronounced in the minority of patients with a left ventricular ejection fraction (LVEF) ≤30 percent. In addition, patients with LVEF ≤35 percent are at increased risk for sudden cardiac death after MI and should be considered candidates for an implantable cardioverter-defibrillator. Moreover, the degree of LVEF between two and seven days following an acute MI and second determination 2 to 12 weeks following an MI predicted a high risk of sudden death and mortality. Patients with no recovery of LVEF between these two time intervals were at risk for these complications [25]. (See "Primary prevention of sudden cardiac death in patients with cardiomyopathy and heart failure with reduced LVEF".)

LVEF is usually measured before discharge in the absence of a specific indication (eg, heart failure or suspected mechanical complication) for which echocardiography may be indicated early in the hospitalization. However, measurements during hospitalization may be misleading, since improvement in LVEF, beginning within three days and largely complete by 14 days, is common in patients who are re-perfused. Two separate studies have shown that approximately 58 percent of patients significantly improve their LVEF after reperfusion in acute STEMI [26,27]. This may reflect, at least in part, recovery from myocardial stunning [26,28] since it is associated with a reduction in the size of the myocardial perfusion defect [27]. Patients with improved LVEF may have significantly lower mortality than those who show no improvement (1.2 versus 5.6 percent at three years in one study) [27]. (See "Clinical syndromes of stunned or hibernating myocardium", section on 'Acute myocardial infarction'.)

Among patients with an STEMI who have an interpretable ECG (ie, no left bundle branch block, paced rhythm, or left ventricular hypertrophy with strain pattern), the absence of an anterior infarction, a previous Q wave MI, or a history of heart failure (HF) predicts an LVEF of at least 40 percent (positive predictive value of 91 to 98 percent) [29,30]. The LVEF is variable among patients who do not fit the prediction rule.

Right ventricular ejection fraction — Long-term impairment of right ventricular systolic function after MI is associated with a worse prognosis. (See "Right ventricular myocardial infarction", section on 'Long-term prognosis'.)

Stress testing — A noninvasive stress test, usually with exercise, is occasionally performed after STEMI to detect residual ischemia in those patients who did not undergo coronary angiography or to assess the functional significant of residual coronary artery stenoses. Stress testing also permits assessment of the exercise capacity needed for the cardiac rehabilitation exercise prescription and can, in some patients, identify arrhythmias. It may be required by some cardiac rehabilitation programs, but most programs screen patients with clinical variables without requiring an exercise test.

Stress testing should not be performed in patients with unstable post-infarction angina, decompensated heart failure, or life-threatening cardiac arrhythmias.

Other post-myocardial infarction associations — A variety of other variables have been shown to correlate with late prognosis following acute myocardial infarction. For example, the extent of angiographic coronary artery disease is a predictor for the development of heart failure [31]. Environmental factors such as living in a low-income country (United States) increased the risk for post-MI hospitalization and mortality [32]. Two biomarkers, NT-proBNP (N-terminal pro-B-type natriuretic peptide) and GDF-15 (growth differentiation factor-15) were strongly associated with all-cause death in patients with an acute coronary syndrome (ACS), with the majority of ACS patients having suffered an acute MI [33]. Worsening post-discharge renal function in patients with type 2 diabetes mellitus and a recent ACS were strong predictors of adverse cardiovascular events, including all-cause mortality [34]. Additionally, patients who had influenza and other viral respiratory infections concomitant with acute MI had worse outcomes than patients without viral syndromes [35].

SOCIETY GUIDELINE LINKS — Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: ST-elevation myocardial infarction (STEMI)".)

SUMMARY

●All patients with ST-elevation myocardial infarction (STEMI) should undergo risk stratification soon after presentation. Since most patients with STEMI undergo reperfusion therapy, early risk stratification provides the patient and family with some sense of what the future holds. Late risk stratification attempts to identify patients who are at increased risk for late arrhythmic or nonarrhythmic death.

●Risk stratification in a patient with STEMI occurs in two phases: early in-hospital identification of patients at increased risk for recurrent ischemic events and identification of patients after an MI who are at increased risk for arrhythmic or nonarrhythmic death. (See 'Early risk stratification' above and 'Late risk stratification' above.)

●Risk scores that contain multiple individual risk factors have been developed. For early risk stratification, we prefer the TIMI risk score or the GRACE risk model. This preference is based on the large experience with these models and generally demonstrated external validations. (See 'Early risk stratification' above.)

●Late risk stratification is performed before or sometimes after discharge. The main components are measurement of the left ventricular ejection fraction and, in many patients, stress testing to detect possible residual ischemia. (See 'Late risk stratification' above.)

Predischarge stress testing to detect residual ischemia is generally not performed in patients who have undergone percutaneous coronary intervention (PCI) or coronary artery bypass graft surgery (CABG) and have been fully revascularized (eg, single vessel disease and successful PCI). Such patients often undergo exercise testing a few weeks or more after discharge as part of a cardiac rehabilitation program or for activity counseling.

●Methods used for risk stratification for arrhythmic death are discussed separately. These include ventricular arrhythmias and late potentials on signal-averaged ECG. (See "Incidence of and risk stratification for sudden cardiac death after myocardial infarction".)