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INTRODUCTION
Myocardial infarction (MI) is one of the most important health problems in the world, including Iran, and is a critical cause of hospitalization due to its high morbidity and mortality.1)2) MI imposes physical, social, financial, and health-related quality of life limitations on affected individuals.3) Despite the promotion and utilization of new therapeutic approaches, MI-related morbidity and mortality relevant to MI have increased.4) The mortality rate per 100,000 population due to cardiovascular disease is 265 worldwide, 224 in the Eastern Mediterranean region, and 171 in Iran.2)5) Therefore, MI is a serious challenge facing Iran’s healthcare system.6) Premature deaths occur in about 30% of affected individuals in the first 30 days after acute MI.7) Some studies have shown that the location of MI is a risk factor for in-hospital mortality. Furthermore, some types of arrhythmia, such as ventricular fibrillation, also increase the odds of in-hospital mortality.8-11) These findings are further supported by cardiac anatomy.12) In this study, we analyzed a nationally representative MI database to evaluate the impact of the location of acute MI on in-hospital mortality. We also investigated the impacts of arrhythmia, risk factors of cardiovascular disease clinical symptoms, type of treatment, and demographic variables on in-hospital mortality.
METHODS
Participants and methods
Data for this hospital-based prospective cohort study of MI were collected from all hospitals in Iran. Patients who had been hospitalized in the coronary care unit of these hospitals from 2012 to 2014 were eligible for inclusion, resulting in a total of 33,831 patients of both sexes who were studied. For all patients in this study, the follow-up period was the same as the hospitalization time.
Baseline assessment
Online electronic questionnaires were completed by the head nurses of hospitals for each patient who was admitted to the coronary care unit with an acute MI diagnosis. The questionnaires included items on demographic variables, treatment status, cardiovascular risk factors, type of arrhythmia, type of MI, and clinical symptoms at the time of admission.
Definition of exposure categories
The main exposure of this study was the location of MI in the heart. We categorized seven types of MI into three categories: middle location (inferior, anterior, or posterior MI), right location (anteroseptal MI), and left location (lateral, inferolateral, or anterolateral MI). We established nine levels for this exposure. The first level was patients with non-ST-elevation MI (non-STEMI), which was our reference group. The second level was patients with STEMI without any defined location for their MI. The third level was patients with middle-location MI. The subsequent levels were patients with (4) right-location MI, (5) with left-location MI, (6) middle- and right-location MI, (7) middle- and left-location MI, (8) right- and left-location MI, and (9) middle-, right-, and left-location MI.
Statistical analysis
Of the initially available 42,975 patients, 9,144 were excluded from the analysis because they had recurrent MIs. We used multivariable logistic regression to estimate the impact of MI location on in-hospital mortality. Odds ratios (ORs) and corresponding 95% confidence intervals for in-hospital mortality were derived for eight different locations of MI as compared with non-STEMI.
We analyzed four models to estimate the magnitude of risk. The first model involved MI location, age, sex, status of surgical treatment, status of thrombolytic therapy, the presence of arrhythmia (yes or no), number of cardiovascular risk factors, and number of clinical symptoms. The second model was the same as the first model, but arrhythmia was expanded into ten types. The third model was the same as the first model, but the number of clinical symptoms was expanded to six. The final model was the same as the first model, but arrhythmia, the number of clinical symptoms, and the number of cardiovascular risk factors were all expanded.
Sensitivity analysis
As a sensitivity analysis, we calculated the E-value for the variables in the final model with statistically significant ORs. The E-value is “the minimum strength of association on the risk ratio scale that an unmeasured confounder would need to have with both the treatment and the outcome, conditional on the measured covariates, to fully explain away a specific treatment-outcome association.”24)25)
RESULTS
In total, 33,831 participants, including 24,532 males (72.51%) and 9,299 females (27.49%) were studied. The mean age of participants was 61.46 years (standard deviation, 13.3 years). The baseline characteristics of the patients are shown in Table 1. Table 2 shows the distribution of MI locations.
In-hospital mortality most frequently occurred in patients with left-location MI compared to those with right-location MI and middle-location MI. In-hospital mortality was higher in patients with STEMI than in non-STEMI patients. Furthermore, patients with ventricular fibrillation and patients who were treated surgically with a percutaneous coronary intervention or coronary artery bypass graft had the highest and lowest incidence of hospital mortality, respectively (Tables 3, 4).
During hospitalization, 1,056 patients died, resulting in a mortality rate of 3.12%. The rate of in-hospital mortality among patients with left-location MI was higher than that of patients with right- and middle-location MI. The in-hospital mortality in patients with left-location MI was 2.15-fold higher than that of patients with non-STEMI. The rate of in-hospital mortality in STEMI patients without any specific location was also higher than that of patients with non-STEMI. Moreover, patients with both left- and right-location MI had higher odds for in-hospital mortality than patients with both right- and middle-location MI. The OR for in-hospital mortality in patients with MI in three locations was 6.47 compared to non-STEMI patients. Non-STEMI patients had the lowest odds for in-hospital mortality (Table 3).
The rate of in-hospital mortality among patients with history of diabetes was higher than among their counterparts without diabetes. The mortality rate of female patients was also higher than that of male patients. Surgical and thrombolytic treatment was associated with a reduced rate of in-hospital mortality. Some arrhythmias, such as right bundle branch block (RBBB), left bundle branch block (LBBB), ventricular fibrillation, atrial fibrillation, and ventricular tachycardia were associated with an increased risk of hospital mortality (Table 4).
The observed OR of STEMI with no specific location was 2.13 in the final model; therefore, an unmeasured confounder that was associated with both the outcome and the treatment by a risk ratio of 3.68-fold each could explain away the estimate, but weaker confounding could not. An unmeasured confounder that was associated with the outcome and the treatment by a risk ratio of 2.26-fold each could move the confidence interval to include the null, but weaker confounding could not (Table 3).
DISCUSSION
In this study, the rate of in-hospital mortality due to MI was about 3%, which is lower than has been reported in other countries, where reported rates have ranged from 7.7% to 19.2% in different countries.13) The lower rate of mortality in this study can be attributed to this fact that only patients with their first MI were eligible for inclusion, and the patients with their first MI who died before admission to the hospital were not registered in our database. In this study, age increased the OR for mortality in all models by 1.66 for every 10 years of age. This OR was reported as 1.08 in a study by Timoteo et al.11)
The odds of in-hospital mortality in women were twice as high as those for men, and this trend was consistent in all models. Some authors have reported that female sex was a significant risk factor for mortality due to MI.13-15) In contrast, others have found that male sex was associated with mortality due to MI.16)17) In Sweden, a delay has been observed for women with chest pain regarding admission to the coronary care unit, medical treatment, and coronary angiography.18) In a German study examining patients with STEMI, women received less aggressive treatment.19)
We designed a nine-level categorical variable to compare the impact of all MI locations on in-hospital mortality. The logistic regression analysis showed that STEMI without a known site in heart was associated with a 2.13 times higher risk of in-hospital mortality compared with non-STEMI. Middle-location and right-location MI increased these odds by 1.47 and 1.43 times compared with the reference group, respectively. MI in the left location of the heart showed a higher OR for mortality than MI in the right and middle locations, demonstrating that left-location MI plays a significant role in predicting in-hospital mortality. These results are consistent with the anatomical and functional role of left ventricle and auricle.12) In a stroke, the blood supply is cut off partially or completely, and not enough oxygen reaches the tissue of the myocardium; therefore, the function of the heart becomes abnormal. This increases the risk of arrhythmias, especially on the left side of the heart. The ORs of in-hospital mortality in patients with inferolateral and anterior heart attacks were 1.79 and 1.52, respectively, compared with the reference group. These findings are consistent with prior studies that evaluated the impact of the location of acute MI on in-hospital mortality. However, Hreybe et al.9) showed higher rates of in-hospital mortality in patients with anterior or lateral MI than in patients with inferior or posterior MI. Moreover, Medina et al.20) reported that anterior stroke increased the likelihood of in-hospital mortality by 1.85 times and posterior stroke increased this likelihood by 1.57 times.
Our results demonstrate that an anterior location of MI was a risk factor for in-hospital mortality. The ORs for in-hospital mortality were found to be 2.24 and 2.40 in patients with anterolateral MI and patients with MI in more than one location, respectively. Shi et al.10) showed that MI with electrocardiographic changes increased the risk of death after MI within 30 days by 1.78 times. Another study proved that the increase in mortality was more prominent in anterior MI than in inferior MI.21) Furthermore, Timoteo et al.11) stated that ST-elevation stroke increased the risk of in-hospital mortality by 2.24 times compared with non-ST-elevation stroke. This suggests that heart strokes, along with electrocardiographic changes, increase the chances of in-hospital mortality. It is concluded that patients with anterolateral MI have a higher risk of in-hospital mortality, and this factor should be considered during hospitalization.
The highest OR of mortality (7.70) was found for ventricular fibrillation. Hreybe et al.9) found that ventricular fibrillation had an OR of 4.9 for in-hospital mortality. Furthermore, ventricular tachycardia and RBBB arrhythmia were associated with 2.78 and 2.52 times higher risks of mortality, respectively. Collectively, our results are consistent with those of other studies. Atrial fibrillation was found to increase the likelihood of in-hospital mortality by 1.69 times, and LBBB arrhythmia increased this likelihood by 1.65 times. Thus, the OR for in-hospital mortality for patients with RBBB arrhythmia was higher than that of patients with LBBB arrhythmia. This can be attributed to the delay in the onset of left ventricular depolarization in RBBB arrhythmia, which explains the higher risk of in-hospital mortality.8)
In this study, dyspnea and diabetes increased the likelihood of in-hospital mortality by 1.59 and 1.64 times, respectively. Kirchberger et al.22) reported that the OR for in-hospital mortality in MI patients with dyspnea was 1.5 times higher than that of other patients. The high mortality risk in these patients is associated with their poorer health status and the presence of other underlying conditions such as high blood pressure, diabetes, heart failure, and chronic pulmonary disease.23) An increased risk of death in patients with dyspnea may also be related to left ventricular failure.8) In another study, diabetes increased the likelihood of in-hospital mortality (within 1 month) by 2.23 times.10) Therefore, diabetes can be considered as a risk factor for death in these patients.
In the sensitivity analysis, according to the E-value (evidence for causality), an unmeasured confounder that was associated with both the outcome and the treatment by a risk ratio of 3.72-fold each could explain away the estimate of association between left-location MI and hospital mortality. The E-values for RBBB, ventricular tachycardia, and ventricular fibrillation were 4.48, 5, and 14.88, respectively, but an unmeasured confounder with a risk ratio of 1.92 could explain away the estimate of the association between thrombolytic treatment and in-hospital mortality.
Strengths and limitations
This study was performed on MI registry data from most hospitals in Iran with national coverage and a large sample size; hence, its results can be generalized to the whole country. Our study also had some limitations. In this study, it was not possible to record patients’ pre-heart attack blood pressure or cholesterol levels. Moreover, the fact that this study did not include MI patients who died before admission to the hospital may have caused an underestimation of short-term MI survival.
This study showed that age, sex, RBBB arrhythmia, atrial fibrillation, ventricular tachycardia, LBBB arrhythmia, ventricular fibrillation, dyspnea, diabetes, and STEMI were associated with an increased risk of in-hospital mortality. Thus, patients with these risk factors require particular attention during their hospitalization in order to reduce in-hospital mortality.
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