A Clinical Rule To Predict Preserved Left Ventricular Ejection Fraction in Patients after Myocardial Infarction

Left ventricular function is an important prognostic factor after acute myocardial infarction, and for this reason it is often recommended that left ventricular function be assessed in patients after myocardial infarction [1-3]. In addition to providing prognostic information, left ventricular function after myocardial infarction also has specific therapeutic implications. The recent finding [4] that angiotensin-converting-enzyme inhibitor therapy reduces mortality after myocardial infarction in asymptomatic patients with decreased left ventricular ejection fractions (LVEFs) underscores the importance of determining left ventricular function in this patient population. Because more than 600 000 patients in the United States are hospitalized with myocardial infarction each year [5], the aggregate expenditure on assessing LVEF after myocardial infarction is substantial. In attempts to minimize the unnecessary use of expensive technologies for this purpose, investigators [1, 6-10] have identified clinical variables that predict LVEF after myocardial infarction. Several studies have yielded clinical predictors of LVEF that are difficult to use at the bedside. Others have developed prediction rules with substantial misclassification rates [11]. Still other predictive schemes have never been validated [9]. In sum, these studies have been largely unsuccessful in providing validated clinical prediction rules that are easy to use. We hypothesized that simple clinical variables could be used to develop a prediction rule to identify patients after myocardial infarction with a high likelihood of having preserved left ventricular systolic function. The purpose of developing such a prediction rule is to restrict assessment of LVEF to those patients most likely to benefit from the resulting information. Therefore, we first attempted to identify statistically significant, simple clinical correlates of LVEF after myocardial infarction. We then sought to combine these variables into a simple prediction rule that segregated patients after myocardial infarction into two groups: 1) a group likely to have preserved LVEF, in which further testing would be unnecessary; and 2) a group with less predictable LVEF (not necessarily decreased ejection fraction), in which technology-based assessment of LVEF might offer more prognostic information or influence therapy. Methods Patients The study was a retrospective analysis of clinical data obtained as part of a prospective cohort study of 379 consecutive patients diagnosed with acute myocardial infarction at the Massachusetts General Hospital. The 379 patients hospitalized on the medical service between January 1992 and October 1992 who had increases in the creatine kinase MB index to above 3% of total MB and either had a history compatible with myocardial infarction or had new electrocardiographic abnormalities (defined below) were eligible for the study. Patients were identified by daily review of all inpatient charts on patient floors with cardiac monitoring, including coronary and medical intensive care units and intermediate care units. Data were obtained using special data collection forms and were maintained in the Myocardial Infarction Registry. Informed consent was obtained for each patient as a requirement for inclusion in the study. The formation of the Myocardial Infarction Registry was approved by the Human Studies Committee in 1991 and has been reapproved annually. Of 379 consecutive patients entered into the myocardial infarction database, 314 (83%; the study group) had one or more tests for assessing LVEF between days 2 and 21 after their index myocardial infarction. Of the initial 192 consecutive patients, 162 who had assessment of LVEF (methods described below) during the defined period after their myocardial infarction composed the derivation set for the clinical prediction rule. Of the subsequent 187 consecutive patients, 152 who had LVEF assessment during the defined period after myocardial infarction served as the validation set. Data Collection and Definitions Data on clinical history, physical examination, and laboratory tests were recorded by trained research assistants. Information was obtained primarily from patient interviews and chart reviews. Patient interviews largely eliminated the possibility of missing data for the historical information desired for this study. Those patients for whom historical data were missing were still included in the study. The following electrocardiographic criteria were used: 1) Q waves were defined as a negative initial deflection in the QRS complex of at least 1 mV in amplitude and 40 ms in duration; 2) ST-segment elevation and depression were defined as a deflection of at least 1 mm from the baseline PR segment, 80 ms after the J point; 3) T-wave inversion was defined as a complex of at least 1 mm below the baseline PR segment; 4) left bundle-branch block was defined as a QRS duration of at least 110 ms, with a typical QRS morphologic pattern in leads V1 and V6; and 5) left ventricular hypertrophy with QRS widening was defined as a QRS duration of at least 110 ms with associated typical repolarization abnormalities consistent with strain in the presence of standard voltage criteria for left ventricular hypertrophy [12]. Electrocardiographic changes were classified as anterior in location if changes appeared in leads V1 to V4; as inferior if changes occurred in leads II, III, aVF; as apical if changes occurred in leads V5 to V6; and as lateral if changes occurred in leads I and aVL. Electrocardiograms obtained within the first 48 hours of admission were reviewed by one of the investigators (MS), who was blinded to clinical data. Electrocardiograms showing a left bundle-branch block pattern, ventricular pacing, or left ventricular hypertrophy with strain were classified as not interpretable (this occurred in 72 of 379 [19%] patients). Electrocardiograms with Q waves or ST-segment elevation in at least two limb leads or in contiguous precordial leads not known to be old were classified as Q-wave infarctions, and the location of these changes was recorded. If Q waves were present in leads in a location other than the ischemic ST-segment or T-wave changes, the patient was classified as having had a previous Q-wave myocardial infarction. Patients whose electrocardiograms showed ST-segment depression or T-wave inversion in at least two limb leads or two contiguous precordial leads were classified as having non-Q-wave infarctions, and the location of these changes was recorded. Patients whose electrocardiograms did not show clear ischemic changes were also classified as having non-Q-wave infarctions, but no location was recorded. Congestive heart failure was defined as the report in the medical record of a previous episode of congestive heart failure or the presence of alveolar edema on a current chest radiograph. Assessment of Left Ventricular Ejection Fraction The ejection fraction was assessed by one or more of the following three modalities: transthoracic echocardiography, contrast ventriculography, and radionuclide ventriculography. The decision to order these tests was made by the attending physicians of the patients. In this analysis, patients studied by more than one modality were assigned a value for LVEF according to the following hierarchy: 1) echocardiographic LVEF, if not available; then 2) contrast LVEF, if not available; then 3) radionuclide ventriculographic ejection fraction. Echocardiographic and radionuclide LVEFs were obtained from the appropriate reports available to the patients' clinicians. Each contrast LVEF was ascertained by one of the investigators (MS, GR, and CO), blinded to clinical data, using the single-plane modified area-length ellipsoid method of estimating left ventricular chamber volume [13]. The LVEFs were dichotomized as either 40% or more or less than 40%. This cutoff point for left ventricular function was preselected because of its well-recognized clinical significance [4]. For patients who had more than one test to assess LVEF, a statistic and 95% CI was calculated to assess the comparability of the various methods that assigned patients to the two categories (LVEF 40% or LVEF <40%. Identification of Clinically Significant Echocardiographic Findings The following clinically significant echocardiographic findings were sought in the clinical echocardiography report: 1) suspected ventricular thrombus, 2) severe valvular regurgitation, 3) ventricular or aortic aneurysm, 4) ventricular septal defect, and 5) circumferential pericardial effusion. Reports for each patient having echocardiography were reviewed for these findings by one of the investigators (GR), who was blinded to all other data. Derivation of the Prediction Rule The significance of the association between 20 preselected clinical variables and LVEFs of 40% or more was tested in the derivation set using Fisher exact tests, with a two-tailed of 0.05. These variables were then entered into a stepwise logistic regression model (BMDP Statistical Software, Los Angeles, California) to determine multivariate predictors of preserved LVEF. These independent predictors were subsequently used to develop the clinical prediction rule in order to maximize prediction of LVEFs of 40% or more. Predictors adding little discriminatory information, even if statistically significant, were eliminated in order to avoid adding complexity to the rule. In addition, variables found to add substantial discriminatory value to the prediction rule were included even if they were not independent predictors of preserved LVEF. After deriving the clinical prediction rule in the first 162 patients, it was tested in the validation set of 152 patients. Positive and negative predictive values were determined, along with their respective 95% CIs [14]. Results Clinical characteristics of 314 patients included in the derivation and validation sets are listed in Table 1. In these