Factor ANALYSIS of Cardiogenic Shock Complicating Acute Myocardial Infarction: Shiraz Experience
Bahram Aminian MD*, Farrokh Habibzadeh MD?**, Ali Reza Moarref MD*
*Division of Cardiology, Department of Internal Medicine, Shiraz University of Medical Sciences, **National Iranian Oil Company Outpatient Polyclinics, Shiraz, Iran
Background-During the past decades,
improvement in health standards has resulted in lower
mortality due to malnutrition and infectious diseases in
Iran. This has led to greater prominence of
cardiovascular disease as a cause of mortality. In some
developing countries, the treatment of acute myocardial
infarction (AMI) does not follow the latest
recommendations. Thrombolytic therapy and early
revascularization are not available to all centers in
Iran. The mortality of cardiogenic shock (CS)
complicating AMI is around 77%. However, limited
information is available on independent predictors for
development of post-AMI CS.
Objective-To identify the important
factors determining development of post-AMI CS.
Methods- Of 652 patients with the
diagnosis of AMI, admitted to our Coronary Care Units
between March 1997 and March 1998, 70 (11.2%) developed
post-AMI CS (group A) while in hospital. One-hundred and
forty subjects were selected at random from those who did
not develop post-AMI CS (group B). The medical records of
these patients were reviewed for
several variables
including gender, age, peak total plasma creatine kinase
activity, AMI location, history of previous MI, smoking,
diabetes mellitus, hypertension and hyperlipidemia.
Results-A univariate analysis revealed
that group A was older (65.04 vs.
58.8 years; p < 0.001), had a higher prevalence of
previous myocardial infarctions (44.8% vs.
18.1%; p < 0.001), had a higher prevalence rate of
global or anterior wall AMI (90% vs.
38.8%; p < 0.001), and a higher median peak total
plasma creatine kinase activity (1359 vs.
627 U/L; p < 0.001) than group B. A logistic
regression analysis identified the first 3 variables,
i.e., age, history of previous MI, and AMI location, as
independent predictors for the development of post-AMI
CS.
Conclusion-Age, history of previous MI, and
the site of MI can predict the development of post-AMI CS
with an acceptable level of accuracy (78%). A
discriminant equation is proposed by which the patients
at risk of developing post–AMI CS can be identified,
so that appropriate treatment can be started immediately.
Keywords • Myocardial infarction • myocardial reperfusion • myocardial revascularization • cardiogenic shock
Introduction
During the past decades, improvement in health standards in Iran, has led to lower mortality and morbidity rates due to undernutrion and infectious diseases. On the other hand, the mortality and disability due to cardiovascular diseases have become more frequent. The state of the art treatment for acute myocardial infarction (AMI), namely early coronary artery reperfusion therapy, is not readily available to all centers in Iran. Cardiogenic shock is a state of inadequate tissue perfusion caused by cardiac dysfunction and is associated with poor prognosis and a high mortality rate.1
Despite improved management of acute myocardial infarction, the incidence of CS remains relatively constant over time, averaging 7.1% of cases2 and carries a high risk of mortality. There are several reports on different aspects of post-AMI CS.3,4 Recently, it was shown that early aggressive coronary reperfusion strategies may increase the survival rate in these patients.5,6 Early diagnosis helps in better planning and selection of the most appropriate therapy. However, limited information is available about the risk factors involved in the development of CS after AMI. In this study, we attempted to determine the independent predictors for the development of in-hospital post-AMI CS.
Materials and Methods
Patients
The medical records of all patients admitted to our Coronary Care Units from March 1997 to March 1998 who were diagnosed as AMI were reviewed to identify those who had developed post-AMI CS. The medical charts of all patients with post-AMI CS, and a randomly proportion of patients selected who had not developed post-AMI shock were reviewed for several variables including gender, age, peak total plasma creatine kinase (PCK) activity, AMI location, history of previous myocardial infarction, smoking, diabetes mellitus, hypertension, and hyperlipidemia.
Definitions
The diagnosis of AMI was made when at least 2 of the following 3 standard criteria were met: 1) sustained ischemic chest pain; 2) electrocardiogram on admission indicating ST elevation in 2 contiguous leads (³ 0.1 mV in limb leads or ³ 0.2 mV in pericordial leads) or evolution of Q waves in serial electrocardiogram tracings; 3) changes in serum enzyme levels consistent with the diagnosis.7 Localization of AMI was based on the electrocardiogram on admission depending on the leads with ST elevation or presumed Q waves. Cardiogenic shock was defined as a systolic blood pressure persistently (>1 hour) under 90 mm Hg, associated with signs of tissue hypoperfusion (cold extremities, cyanosis, oliguria, or altered mental status).
Exclusion criteria
Patients with AMI who had been admitted to the CCU in a state of shock, or who developed other types of shock, and those who died on admission were excluded from the study.
Study groups
The population under study was divided into 2 groups according to the state of shock. The first group included patients who developed post-AMI CS (group A). The second group consisted of a number of patients randomly selected from those who had not developed post-AMI CS (group B).
Statistical analysis
The Kolmogrov-Smirnov (Lilliefors) goodness of fit test was used to determine whether continuous variables follow a normal distribution. Continuous variables which were not distributed normally were expressed as median, 25th and 75th percentiles ((Tukey’s hinges). For comparison of these variables the Mann-Whitney U-test was used. Normally distributed variables are expressed as mean± SD. The student t-test for independent samples was used to compare the means of such variables and the chi-square test was used to compare categorical variables between groups. In any case, if expected values were under 5, the Fisher exact test was employed. Additionally, a logistic regression analysis was performed to identify the independent factors for development of in-hospital post-AMI CS, with the shock status as the dependent variable. All results were analyzed with a two-tailed significance level of 0.05. Data analyses were performed by the software SPSS® ver. 6.0 for Windows™.
Results
Study population and groups
Among 652 patients with AMI admitted to our CCUs from March 1997 to March 1998 who fulfilled the inclusion criteria described above, 70 (11.2%) developed in-hospital post-AMI CS unrelated to mechanical complications, 64.3% of whom developed shock within the first 48 hours of CCU admission (group A). Fifty-four of the 70 patients (77.1%) with CS (group A) did not survive. One-hundred and forty patients were selected at random from the remaining 582 patients who had not developed CS (group B). None of our patients underwent any invasive coronary reperfusion therapy.
Baseline characteristics
Table 1 shows the baseline characteristics of the study groups. Group A was significantly older than group B (p<0.001). Statistically significant differences were not observed for the prevalences of the important cardiovascular risk factors (gender, diabetes mellitus, hyperlipidemia, hypertension, and smoking) between the groups. Group A had a significantly higher prevalence of previous MI (p<0.001), especially global and anterior wall AMI (p<0.001), than group B. Group A patients, also had a significantly higher PCK activity (p<0.001) than those of group B. Patients with global or anterior wall AMI, had a significantly higher PCK activity (median [25th and 75th percentiles]: 1306 [445, 2276] U/L), than those with AMI at other locations (median [25th and 75th percentiles]: 510 [345, 1010] U/L) (p < 0.0001).
Twenty-eight of the 210 patients (70 in group A, and 140 in group B), had at least one missing discriminant variable, and thus, were excluded from the multivariate analysis. Logistic regression analysis disclosed that of the variables studied, only age, previous MI, and AMI location are independent predictors of in-hospital post-AMI CS (Table 2). Using the equation derived by multivariate analysis, a discriminant score (Discore) can be calculated for any case as follows:
Discore = 0.041 × age + 1.433 × previous MI + 2.052 × AMI location – 5.384.
The more positive the calculated Discore, the higher was the probability of developing in-hospital post-AMI CS. As part of its multivariate analysis, the software SPSS®, optionally, can calculate the probability corresponding to a given Discore. Based on these data, a curve was developed by which the probability for developing in-hospital post-AMI CS corresponding to a given Discore could be determined (Figure 1). The above discriminant equation classified 78% of our patients correctly (the overall accuracy).
Discussion
A better understanding of the pathophysiology of shock and MI has led to improved management of post-AMI CS. During the past decades however, there has been no significant change in the incidence of post-AMI CS. Cardiogenic shock is a state of forward cardiac failure associated with a systolic blood pressure of <90 mm Hg and inadequate tissue perfusion despite sufficient volume load. The pathophysiologic steps involved in post-AMI CS fuel a self-destructive machinery consisting of a downward spiral; ischemia impairs myocardial function and results in a low cardiac output state. The latter condition, in turn, decreases coronary artery blood flow and worsens ischemia. If left untreated, this process very soon leads to CS that has a grave prognosis with a mortality rate of 80% to 100%. The incidence of 11.2% of in-hospital post-AMI CS observed among our patients, is significantly higher than the expected value of 7% to 8% reported by other researchers (p<0.05).2,8-11 This figure, however, is significantly lower than the incidence of 18%, reported from Slovakia (p<0.01).12 This high incidence is perhaps, in part, due to the prolonged door-to-needle time that some of our patients experience due to inadequate emergency facilities. This delay might increase the infarct focus size resulting in a higher risk for the development of CS. On the other hand, in spite of dramatic advances in the management of AMI, no significant changes in the incidence of CS complicating AMI has been found during the past 2 decades, even in well-equipped centers.2 Therefore, ethnic and socio-cultural habits might play a role in the development of in-hospital post- AMI CS.
The mortality rate observed among our patients with post-AMI CS (77.1%) is in keeping with the reported figures by other researchers.2,8,10 None of our patients with CS underwent any invasive coronary reperfusion strategies. Thus it seems that invasive reperfusion modalities may have limited effect on the survival of patients with post-AMI CS (at least on short-term survival) a finding that is in accordance with the results of some previous trials.10,11 On the other hand, numerous well-controlled studies have clearly shown the benefits of such invasive approaches.2,5,13-17 Hochman et al, showed that in patients with cardiogenic shock, emergency revascularization does not significantly reduce overall mortality at 30 days.3 However, after six months there is a significant survival benefit, hence, they strongly recommend early revascularization for patients with AMI complicated by CS.3 This dilemma may become clear when we recall that for the above-mentioned time delay perhaps, many of our patients with poor condition were excluded from our study and thus the value (77.1%), possibly, is an underestimated mortality rate.
Although there is controversy on the efficacy of invasive coronary artery reperfusion therapies on long-term survival of patients with post-AMI CS, it is well accepted that an adequate cardiac output and tissue perfusion should be provided for all patients. The key to achieve a good outcome is rapid diagnosis and prompt initiation of an appropriate therapy. In those centers without direct angioplasty facilities, stabilization of patient’s hemodynamic status with intra-aortic balloon counterpulsation and thrombolysis is crucial. These patients should then be transferred to a center with tertiary care facilities; where more therapeutic options are available.
In the univariate analysis, it was found that age, previous MI, location of AMI, and PCK activity are predictors for development of in-hospital post-AMI CS. Multivariate analysis, however, identified the first 3 variables as independent predictors. In global or anterior wall AMI, a larger mass of myocardium is damaged and a higher creatine kinase level is more likely. These patients who lose much of their left ventricular mass, are more prone to develop CS. Those with previous MI, who have already lost part of their myocardium, are also at higher risk for developing CS. Older patients are also more prone to develop CS due to their lower physiologic cardiac reserves.
On account of the very high mortality rate among patients with post-AMI CS and since almost two thirds of those who develop CS do so within the first 48 hours of admission,18 patients at risk should be identified using the calculated equation, and immediately transferred to a well-equipped center with tertiary care facilities. An appropriate treatment should be initiated at the earliest possible time for these patients.
References