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ABSTRACT

Background Limited information is available on trends in the incidence of and mortality due to cardiogenic shock complicating acute myocardial infarction. We studied the incidence of cardiogenic shock complicating acute myocardial infarction and in-hospital death rates among patients with this condition in a single community from 1975 through 1997.

Methods We conducted an observational study of 9076 residents of metropolitan Worcester, Massachusetts, who were hospitalized with confirmed acute myocardial infarction in all local hospitals during 11 one-year periods between 1975 and 1997. Our study included periods before and after the advent of reperfusion therapy.

Results The incidence of cardiogenic shock remained relatively stable over time, averaging 7.1 percent among patients with acute myocardial infarction. The results of a multivariable regression analysis indicated that the patients hospitalized during recent study years were not at a substantially lower risk for shock than patients hospitalized in the mid-to-late 1970s. Patients in whom cardiogenic shock developed had a significantly greater risk of dying during hospitalization (71.7 percent) than those who did not have cardiogenic shock (12.0 percent, P<0.001). A significant trend toward an increase in in-hospital survival among patients with cardiogenic shock in the mid-to-late 1990s was found in crude and adjusted analyses.

Conclusions Our findings indicate no significant change in the incidence of cardiogenic shock complicating acute myocardial infarction over a 23-year period. However, the short-term survival rate has increased in recent years at the same time as the use of coronary reperfusion strategies has increased.

A growing trend has been to use more aggressive therapeutic interventions early in patients who have cardiogenic shock as a result of acute myocardial infarction.¹⁶ In the current era of research on cost effectiveness and outcomes and of aggressive efforts to limit infarct size and maintain left ventricular function, it remains important to study trends in the incidence of cardiogenic shock complicating acute myocardial infarction and in case fatality rates and to study the possible effect of new treatment strategies.

We undertook a communitywide study in order to extend the findings of a report on temporal trends (for the period from 1975 through 1988) in the incidence of cardiogenic shock and in-hospital death rates among patients with confirmed acute myocardial infarction who had been admitted to all hospitals in metropolitan Worcester, Massachusetts.¹¹ The earlier study predated the use of thrombolytic agents and the increasing use of myocardial-revascularization approaches in patients with acute coronary disease. The current findings are based on data on 9076 residents of the Worcester metropolitan area who had acute myocardial infarction and were admitted to hospitals in greater Worcester from 1975 through 1997.

Methods

Study Population

The study population consisted of residents of metropolitan Worcester who were assigned a diagnosis of acute myocardial infarction at discharge from 1 of the 16 teaching and community hospitals (the number of hospitals became smaller during the course of the study as a result of hospital mergers and consolidations) in the standard metropolitan statistical area (1990 population, 437,000) during 1975, 1978, 1981, 1984, 1986, 1988, 1990, 1991, 1993, 1995, and 1997.^17,18,19 The medical records of all potentially eligible patients were reviewed and the diagnosis was confirmed according to preestablished criteria.^17,18,19

Cardiogenic shock was defined as a systolic blood pressure of less than 80 mm Hg in the absence of hypovolemia and associated with cyanosis, cold extremities, changes in mental status, persistent oliguria, or congestive heart failure.¹¹ The definition of cardiogenic shock remained the same in all periods studied; the disorder was defined in the study so that patients with classic signs and symptoms of this clinical syndrome would be included.

Data Collection

From the hospital records of patients with validated acute myocardial infarction, we abstracted demographic, medical-history, and clinical data as well as information about the use of therapeutic interventions and specialized procedures.^{17,18,19,20,21} Data regarding the use of thrombolytic agents, coronary-artery bypass grafting, and percutaneous transluminal coronary angioplasty were included as these therapies became available in clinical practice.

Statistical Analysis

Differences in the distribution of characteristics between patients with cardiogenic shock and those without, and between patients with shock who survived to be discharged from the hospital and those who did not, were studied with the use of chi-square tests for categorical variables and t-tests for continuous variables, as appropriate. All tests of statistical significance were two-tailed. Multivariable logistic-regression models were used to assess the significance of temporal trends in the incidence of cardiogenic shock while controlling for potentially confounding demographic, medical-history, and clinical factors. Control variables included indicators for the following: age, male sex, history of various coexisting disorders (angina, diabetes, hypertension, or stroke), and type of acute myocardial infarction (initial vs. recurrent, Q-wave vs. non–Q-wave, and anterior vs. inferior or posterior).

Because of the observational, nonrandomized nature of this study, and because of our methods of data collection, which did not allow us to determine whether a medical therapy or surgical intervention preceded or came after the occurrence of cardiogenic shock, we did not control for the use of various interventional procedures (cardiac catheterization, coronary-artery bypass grafting, or percutaneous transluminal coronary angioplasty) or medical therapies (such as thrombolytic agents). Another reason that we did not control for these practices is the difficulty of interpreting any observed adjusted estimates of association. Our approach to model building focused on the hypothesis that variations in the incidence of cardiogenic shock over time were the result of changes in the demographic or clinical characteristics (or both) of the study sample. We recognize that these trends might also reflect improvements in the use of various approaches to care — and increasing use of these approaches — over time.

We studied the effect of cardiogenic shock on in-hospital death rates by calculating in-hospital case fatality rates. Multivariable logistic-regression analyses were carried out to assess the effect of cardiogenic shock on mortality during hospitalization and to study changes over time in the in-hospital case fatality rates associated with cardiogenic shock while controlling for potentially confounding factors. This approach to model development was similar to that described for the end point of cardiogenic shock.

Results

Base-Line Characteristics

During all the study years combined, the patients with cardiogenic shock were significantly older than those who did not have this complication (Table 1). A significantly greater proportion of the patients who had cardiogenic shock were women, had a history of diabetes or stroke, and had acute myocardial infarction that was recurrent, Q-wave in type, and anterior in location. Patients with cardiogenic shock were significantly more likely to undergo coronary-artery bypass grafting, intraaortic balloon counterpulsation, and percutaneous transluminal coronary angioplasty than those without shock. From the mid-1980s until the late 1990s, thrombolytic therapy was used in slightly less than one quarter of patients, irrespective of the presence or absence of cardiogenic shock.

View this table: [in this window] [in a new window]   Table 1. Characteristics of Patients with Acute Myocardial Infarction According to the Presence or Absence of Cardiogenic Shock.

 
Table 2 summarizes changes in the characteristics of patients in whom cardiogenic shock developed or did not develop over the 23-year period under study. The characteristics are categorized in five periods combining two years each and one single-year period to make analyses of the data easier to interpret and to coincide with changes in the care of patients with acute myocardial infarction. Over time, patients with acute myocardial infarction were increasingly older, more likely to have selected coexisting conditions, and more likely to have a non–Q-wave myocardial infarction. The use of thrombolytic therapy, cardiac catheterization, percutaneous transluminal coronary angioplasty, and coronary-artery bypass grafting increased over time among all patients; the use of myocardial-revascularization techniques increased markedly during the mid-to-late 1990s. An increasing proportion of the patients with cardiogenic shock presented with an initial acute myocardial infarction over time. Over the 23-year study period, the use of intraaortic balloon counterpulsation increased dramatically among patients with cardiogenic shock.

View this table: [in this window] [in a new window]   Table 2. Temporal Trends in the Characteristics of Patients with Acute Myocardial Infarction According to the Presence or Absence of Cardiogenic Shock.

 
Incidence of Cardiogenic Shock

The incidence of cardiogenic shock remained relatively stable over the initial decade of this study; incidence peaked in 1988, after which there was an inconsistent decline in the proportion of patients with shock. The overall incidence of cardiogenic shock averaged 7.1 percent over the 23-year study period (Figure 1).

View larger version (5K): [in this window] [in a new window]   Figure 1. Temporal Trends in the Incidence of Cardiogenic Shock in Patients with Acute Myocardial Infarction.

 
We carried out two regression analyses to study changes over time in the incidence of cardiogenic shock while adjusting for various potentially confounding factors (Table 3). After controlling for age, sex, and history of cardiovascular disease, we found nonsignificant trends in the multivariable-adjusted risk of shock over the period under study — results similar to the unadjusted findings (Table 3). After controlling for age, sex, medical history, and characteristics of acute myocardial infarction, we found that the risk of cardiogenic shock also did not change significantly over time.

View this table: [in this window] [in a new window]   Table 3. Temporal Trends in the Crude and Multivariable-Adjusted Odds of Cardiogenic Shock in Patients with Acute Myocardial Infarction.

 
In-Hospital Case Fatality Rates

Patients with acute myocardial infarction in whom cardiogenic shock developed had significantly higher in-hospital case fatality rates overall (71.7 percent, vs. 12.0 percent among those without shock; P<0.001) and during each of the periods under study (Figure 2). The in-hospital death rates among the patients with cardiogenic shock remained relatively constant until the mid-to-late 1990s, averaging approximately 77 percent; 61 percent of patients with cardiogenic shock died in 1993 and 1995 and 59 percent in 1997.

View larger version (6K): [in this window] [in a new window]   Figure 2. Temporal Trends in In-Hospital Death Rates among Patients with Acute Myocardial Infarction According to the Presence or Absence of Cardiogenic Shock.

 
A logistic-regression analysis was carried out to control simultaneously for age, sex, medical history, and characteristics of acute myocardial infarction in determining the association between the occurrence of cardiogenic shock and in-hospital mortality. This analysis confirmed the markedly higher risk of in-hospital death among patients who had cardiogenic shock, as compared with those who did not (adjusted odds of dying, 21.0; 95 percent confidence interval, 17.2 to 25.6) for the combined study periods. A similar adverse effect of cardiogenic shock on in-hospital death rates was found when this analysis was restricted to patients in whom shock developed over the period of increasing use of myocardial-reperfusion strategies (1986 through 1997).

As in the analysis of trends over time in the incidence of cardiogenic shock, we performed two separate multivariable regression analyses to evaluate changes over time in in-hospital mortality of patients with cardiogenic shock while controlling for previously described prognostic characteristics. The results suggested considerable improvements in the in-hospital survival of patients with shock, particularly during the 1990s (Table 4). Depending on the covariates adjusted for, the risk of dying from cardiogenic shock was markedly lower in the mid-to-late 1990s than in the two previous decades.

View this table: [in this window] [in a new window]   Table 4. Temporal Trends in the Crude and Multivariable-Adjusted Odds of In-Hospital Death among Patients with Cardiogenic Shock Complicating Acute Myocardial Infarction.

 
The patients with cardiogenic shock who survived to discharge were significantly younger than those who did not survive (Table 5). The patients who survived were significantly more likely to have received angiotensin-converting–enzyme inhibitors, antiplatelet agents, beta-blockers, digoxin, and thrombolytic agents. Patients who died from this complication were less likely to have undergone coronary-artery bypass grafting, percutaneous transluminal coronary angioplasty, or intraaortic balloon counterpulsation.

View this table: [in this window] [in a new window]   Table 5. Characteristics of Patients with Cardiogenic Shock Complicating Acute Myocardial Infarction According to Whether They Survived to Discharge or Died in the Hospital.

 
Discussion

The results of this population-based study suggest a relatively constant incidence of cardiogenic shock over the 23-year period under study; a significantly higher in-hospital death rate among patients in whom shock developed; and improvement over time in the in-hospital survival rate of patients with cardiogenic shock, particularly during the mid-to-late 1990s.

The incidence of cardiogenic shock after acute myocardial infarction ranges from 5 to 15 percent in published studies.^{1,4,5,6,7,8,9,10,11} This relatively wide range reflects, in part, the varying definitions of acute myocardial infarction and cardiogenic shock, the use of representative as opposed to more highly selected patient samples, and the rates of use of therapeutic options that may reduce the risk of cardiogenic shock. The overall incidence of cardiogenic shock in the current study falls within this range. In the worldwide Global Utilization of Streptokinase and Tissue Plasminogen Activator for Occluded Coronary Arteries (GUSTO-1) randomized trial, cardiogenic shock developed in 7.2 percent of approximately 41,000 patients with acute myocardial infarction.²² In GUSTO-1, patients treated with accelerated recombinant tissue plasminogen activator were significantly less likely to have shock; this finding suggests the possible benefit of early reperfusion that is associated with the use of this thrombolytic regimen.²²

We have previously documented progressive declines since the mid-1970s in the in-hospital death rates of patients with acute myocardial infarction.^17,18,19,23 We have also found declines in the rates of out-of-hospital death attributed to coronary heart disease.²⁴ Therefore, it is possible that the patients who make it to the hospital and in whom cardiogenic shock subsequently develops are sicker, and thus at greater risk, than those who do not; this explains in part some of the nonsignificant changes in the incidence of cardiogenic shock that were found. Because of the nonrandomized nature of the current study, we could not address directly the association between the increased use of thrombolytic agents and surgical interventions and the risk of shock.

Patients should be encouraged to seek medical care as soon as possible after having symptoms of acute myocardial infarction, because immediate care may reduce the incidence of cardiogenic shock and the associated mortality. Efforts to decrease the incidence of cardiogenic shock should focus on identifying patients who are at high risk for this complication and instructing them to seek care immediately after the onset of acute coronary symptoms so that appropriate monitoring, risk stratification, and intervention can be undertaken.²⁵ Aggressive intervention may result in improved survival rates among patients in whom cardiogenic shock has developed, because the early detection of precursors of shock or signs of circulatory failure are likely to result in increased and timely intervention.

Patients in whom cardiogenic shock has developed continue to have a markedly higher risk of dying in the hospital than do patients without cardiogenic shock. However, the prognosis for patients with cardiogenic shock who are in the hospital has improved considerably in recent years. This improvement may be due to the increasingly aggressive strategies of intervention used or to changes in the natural history of shock, with fewer cases that subsequently result in death identified early in the course of the illness. In our unadjusted analyses, patients who survived cardiogenic shock were significantly more likely than those who died from it to have received beneficial therapies for cardiac disease, and they were more likely to have received aggressive treatment for acute coronary disease through interventional approaches. The findings suggest that these therapies have a beneficial effect on the survival of patients with acute myocardial infarction in whom cardiogenic shock has developed.

The use of intraaortic balloon counterpulsation in patients with cardiogenic shock has been shown to result in initially favorable clinical and hemodynamic responses; however, in the majority of studies in which this intervention was used, death was merely delayed.^26,27 A number of nonrandomized studies suggest that percutaneous transluminal coronary angioplasty improves short-term survival among patients with cardiogenic shock, with survival contingent on the successful establishment of coronary reperfusion.^14,15,28,29 Uncontrolled studies of bypass grafting show that this therapy improves short-term survival among patients with cardiogenic shock when they are treated soon after shock has developed.^30,31

Although thrombolytic therapy has consistently been shown to decrease mortality after acute myocardial infarction,^32,33 no large, randomized, controlled trial has found that the use of clot-lysing therapy reduces the incidence of cardiogenic shock or improves survival after cardiogenic shock has developed. In GUSTO-1, 56 percent of all patients with cardiogenic shock died in the hospital, regardless of the thrombolytic regimen used.²² Nonetheless, it has been hypothesized that the early resumption of coronary blood flow in the infarct-affected artery by means of thrombolytic agents, percutaneous transluminal coronary angioplasty or coronary-artery bypass grafting supported by intraaortic balloon counterpulsation, or both, reduces the size of the infarct, decreases the risk of ongoing myocardial ischemia and left ventricular dysfunction, and improves survival among patients with cardiogenic shock.^12,28 Recent analyses from the GUSTO-1 trial suggest that the use of a more aggressive revascularization strategy in patients with cardiogenic shock, after initial treatment with a thrombolytic regimen, is associated with a reduction in short-term mortality even after control for differences that affected the selection of treatment.^34,35

The current study was carried out in a well-defined metropolitan area whose sociodemographic and economic characteristics reflect those of the U.S. population with the exception of race (the vast majority of the residents of metropolitan Worcester are white). The strengths of this study are its large sample; its population-based design, which enhances the generalizability of the findings; and the inclusion of all hospitals in the area. The study has several limitations, however. Specific therapies for patients with cardiogenic shock were not determined by a standardized study protocol but, rather, by the many individual physicians practicing at the hospitals. In addition, because of the methods of data collection and the recording of data from hospitals, it was difficult to determine whether a particular drug or procedure was used before or after cardiogenic shock developed; therefore, we did not control for the use of these therapies in additional multivariable-adjusted regression analyses. Finally, in analyzing the declining mortality associated with cardiogenic shock over time, one must be careful in interpreting the multivariable-adjusted odds of dying, because they may overestimate the actual risk ratio calculated in cohort studies.³⁶

The rate of use of thrombolytic agents and interventional procedures was lower in our communitywide observational study than in other studies that have focused specifically on the use of targeted interventions in patients with cardiogenic shock.^12,28,31 Most patients failed to receive clot-lysing therapy because of prolonged delays in seeking medical care. An extended prehospital delay may be associated with more extensive myocardial necrosis and a greater risk of shock. Patients with cardiogenic shock may also be more likely to be excluded from clinical trials of new approaches to treating acute myocardial infarction that are ultimately found to be beneficial.³⁷

As evidenced by the results of this study, cardiogenic shock continues to develop at a relatively high rate after acute myocardial infarction, even though thrombolytic agents and interventional procedures are being used more. The in-hospital death rate among patients with this complication remains high. Until the results of a multicenter, randomized trial that has been designed to study the effect of aggressive interventional approaches on the incidence and prognosis of cardiogenic shock in association with acute myocardial infarction are published,^12,38 it remains important to study trends in incidence and prognosis. This is particularly crucial if the use of surgical interventions and myocardial-reperfusion strategies continues to increase.

Supported by a grant (R01 HL35434) from the National Heart, Lung, and Blood Institute.

We are indebted to the departments of cardiology, administration, and medical records of the participating metropolitan Worcester hospitals for their cooperation.

Source Information

From the Department of Medicine, University of Massachusetts Medical School, Worcester (R.J.G., J.Y., J.G., J.M.G.); and the Department of Biostatistics and Epidemiology, School of Public Health and Health Sciences, University of Massachusetts, Amherst (N.A.S., C.B.).

Address reprint requests to Dr. Goldberg at the Department of Medicine, Division of Cardiovascular Medicine, University of Massachusetts Medical School, 55 Lake Ave. N., Worcester, MA 01655, or at robert.goldberg{at}ummc.ummed.edu.

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