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Abstract
Background: Gastrointestinal bleeding (GIB) complicating acute myocardial infarction (AMI) is a severe clinical condition with treatment contradiction and poor prognosis. This study aimed to evaluate the rate of in-hospital mortality in patients with GIB who subsequently suffered from AMI and to explore the potential risk factors for this condition.
Methods: In this retrospective study, a total of 77 patients diagnosed with GIB, who subsequently suffered from AMI, were enrolled from January 2013 to March 2022. Demographic, laboratory, and clinical data were collected. The in-hospital mortality was the outcome of interest. Logistic regression analysis was used to investigate the potential risk factors of in-hospital mortality.
Results: Among the 77 patients included in this study, 62 (80.52%) were males. The mean age of patients was 65.88 ± 12.15 years, and 48 patients (62.34%) were non-ST-segment elevation myocardial infarction (NSTEMI). There were 16 (20.78%) cases of in-hospital deaths. The subjects who died showed higher levels of white blood cell count (13.05 ± 5.76 vs. 9.31 ± 4.07 × 109/L, P = 0.003) and troponin I (TnI) (9.23 ± 9.17 vs. 4.12 ± 5.03 μg/L, P = 0.003). Besides, there were higher proportions of cardiogenic shock (81.25% vs. 26.23%, P < 0.001) and mechanical ventilator usage (75.0% vs. 11.48%, P < 0.001) among the patients who died. The multivariate logistic regression analysis showed that white blood cell count (odds ratio [OR] 1.19, 95% confidence interval [CI] 1.02–1.39, P = 0.030), cardiogenic shock (OR 12.18, 95% CI 3.06–48.39, P = 0.017), and mechanical ventilator usage (OR 7.21, 95% CI 1.28–40.51, P = 0.025) were independently associated with in-hospital mortality.
Conclusions: The in-hospital mortality of patients with GIB who subsequently develop AMI is high. White blood cell count, cardiogenic shock, and mechanical ventilator usage are independent predictors of in-hospital mortality.
Keywords: Acute myocardial infarction, cardiogenic shock, gastrointestinal bleeding, in-hospital mortality, mechanical ventilator
How to cite this article: Introduction 
Gastrointestinal bleeding (GIB) is one of the common emergencies with substantial morbidity and mortality.[1],[2],[3] Acute myocardial infarction (AMI) is a category of disease associated with the greatest mortality and morbidity.[4],[5] The situation worsens when an individual diagnosed with GIB subsequently suffers from AMI.
GIB causes decrease of effective circulating volume and affects the blood supply of the myocardium, thus leading to AMI.[6] Meanwhile, massive blood loss in the digestive tract leads to decrease of oxygen-carrying hemoglobin, reduction of cardiac oxygen supply capacity, activation of the coagulation system, formation of thrombosis, and then aggravation of AMI. Importantly, there is a contradiction in treatment of the above situation. GIB needs hemostatic treatment, while patients with AMI need antithrombotic therapy. AMI limits the use of endoscopy, although endoscopic hemostasis is a fast and effective method to control GIB. Meanwhile, percutaneous coronary intervention (PCI) and antithrombotic therapy which are crucial treatments for AMI are of limited use because of GIB. Multiple factors lead to a worse prognosis in patients with GIB complicating AMI.
Presently, there is limited data on AMI post-GIB. In this present study, we aimed to identify the current status, evaluate the rate of in-hospital mortality in patients with GIB who subsequently suffer from AMI, and explore the potential risk factors for this condition.
Patients and Methods Study population
This study was a retrospective analysis of hospitalized patients with AMI post-GIB at the First Affiliated Hospital of Zhengzhou University. Patients admitted for GIB with subsequent AMI were retrospectively enrolled, from January 2013 to March 2022. The inclusion criterion was confirmed admission diagnosis of GIB with subsequent AMI. Patients with a positive fecal occult blood test but no visible melena or without any other clinical evidence of GIB were excluded. In addition, subjects with AMI who subsequently suffered GIB were also excluded. This research was approved by the ethics committee of the institution.
Data collection
We retrospectively collected data concerning patients' demographic information (age, sex), timing and main manifestations of GIB, types of AMI (ST-elevation myocardial infarction [STEMI] and non-ST-segment elevation myocardial infarction [NSTEMI]), comorbidities (hypertension, diabetes mellitus, coronary artery disease, stroke, and gastrointestinal disease), medication history (aspirin, P2Y12 receptor inhibitor, and nonsteroidal anti-inflammatory drugs [NSAIDs]), admission features (admission heart rate, systolic blood pressure, and diastolic blood pressure), echocardiographic features (left ventricular ejection fraction [LVEF]), laboratory data (hemoglobin, red blood cells, platelet, white blood cells, aspartate aminotransferase [AST], albumin, creatinine, blood urea nitrogen [BUN], estimated glomerular filtration rate [eGFR], N-terminal pro-B-type natriuretic peptide [NT-proBNP], troponin I [TnI], prothrombin time [PT], activated partial thromboplastin time [APTT], total cholesterol [TC], triglycerides [TG], low-density lipoprotein cholesterol [LDL-C], and C-reactive protein [CRP]), and clinical characteristics (blood transfusion, cardiogenic shock, and mechanical ventilator usage). Laboratory data were recorded at admission and re-checked during hospitalization.
Definitions
GIB was defined as clinically evident GIB (hematemesis, coffee-ground emesis and melena, and bloody stool) accompanied by decreased hemoglobin levels. AMI was diagnosed according to the fourth universal definition,[7] containing STEMI and NSTEMI. Each variable was defined following cardiovascular data standards.[8] The primary outcome was in-hospital mortality from all causes, including cardiac death, multiple organ failure, massive hemorrhage/intracranial hemorrhage, and sudden death.
Statistical analysis
Categorical variables are shown as frequencies and percentages, whereas continuous variables are presented as mean ± standard deviation. Continuous variables were compared using the Mann–Whitney U test, whereas categorical variables were compared using the Chi-square test or Fisher's exact test. Logistical regression was performed to evaluate the odds ratio (OR) and 95% confidence interval (CI) for the association between risk factors and in-hospital mortality. Variables related to in-hospital mortality in univariate analysis (P < 0.10) were included in the multiple logistic regression model. The factors entered into the multivariate logistical regression analysis were as follows: white blood cells, NT-proBNP, TnI, D-dimer, cardiogenic shock, and mechanical ventilator usage. Statistical analyses were performed using Statistical Package for the Social Sciences (SPSS) 23.0 software. A two-sided P value < 0.05 was considered statistically significant.
Results A total of 77 patients diagnosed with GIB complicating AMI were included in the present analysis. Among the 77 subjects, 62 (80.52%) were males; the mean age of the subjects was 65.88 ± 12.15 years and 48 (62.34%) were NSTEMI. In addition, 36 (46.75%) patients had coronary artery disease, 18 (23.38%) patients had gastrointestinal disease, 28 (36.36%) were on aspirin, and 12 (15.58%) were on P2Y12 receptor inhibitors. Besides, 49 (63.64%) received blood transfusion, 29 (37.66%) had cardiogenic shock, and 19 (24.68%) were on mechanical ventilator [Table 1].
There were 16 (20.78%) cases of in-hospital deaths. Causes of death included refractory heart failure (11, 68.75%), hemorrhage event (2, 12.50%), and multiple system organ failure (3, 18.75%). The subjects who died showed higher levels of white blood cell count (13.05 ± 5.76 vs. 9.31 ± 4.07 × 109/L, P = 0.003) and TnI (9.23 ± 9.17 vs. 4.12 ± 5.03 μg/L, P = 0.003). Besides, there were higher proportions of cardiogenic shock (81.25% vs. 26.23%, P < 0.001) and use of mechanical ventilator (75.00% vs. 11.48%, P < 0.001) among the patients who died. The other characteristics had no difference between the two groups. Among the 61 survivors, 14 underwent PCI after GIB control and three underwent coronary artery bypass grafting (CABG).
We further conducted multivariable logistic regression analysis of factors associated with in-hospital mortality. The factors that showed statistical differences between the survival group and death group were selected for analysis. The factors entered into the multivariate logistical regression analysis were as follows: white blood cells, NT-proBNP, TnI, D-dimer, cardiogenic shock, and mechanical ventilator. The multivariate logistic regression analysis showed that white blood cell count (OR 1.19, 95% CI 1.02–1.39, P = 0.030), cardiogenic shock (OR 12.18, 95% CI 3.06–48.39, P = 0.017), and mechanical ventilator usage (OR 7.21, 95% CI 1.28–40.51, P = 0.025) were independently associated with in-hospital mortality [Table 2].
Discussion In this retrospective study, we found that the in-hospital mortality of patients with GIB who subsequently suffered from AMI was extremely high. High levels of white blood cell count, cardiogenic shock, and mechanical ventilator usage were found to be independent predictors of poor prognosis.
To our knowledge, our study is the largest in terms of number of patients with AMI post-GIB. Previous studies have mainly focused on GIB post-AMI, and these findings demonstrated that GIB, including lower and upper gastrointestinal origins, was independently associated with increased mortality.[9],[10],[11],[12],[13],[14] However, few studies have focused on AMI post-GIB. Although there are similar situations, the pathogenesis of the two conditions is different. GIB post-AMI is mainly related to antithrombotic therapy, while AMI post-GIB is a cardiovascular event induced by reduced blood volume. One population-based, nested case–control study illustrated that AMI risk in patients with coronary artery disease doubled after GIB.[6]
In our study, the in-hospital mortality of GIB patients who subsequently suffered from AMI was 20.78%. The mechanism of poor prognosis in patients with GIB complicating AMI may be multifactorial. Firstly, GIB reduces effective circulation volume, resulting in bleeding-related hemodynamic instability and affecting the blood supply to the myocardium. Secondly, massive blood loss in the digestive tract leads to decrease of oxygen-carrying hemoglobin, activation of the coagulation system, formation of thrombosis, and then aggravation of AMI. Thirdly, GIB usually requires massive rehydration and blood transfusion, undoubtedly increasing the fluid load and easily inducing acute heart failure. Meanwhile, blood transfusion after GIB may have indirect effects, leading to systemic inflammation in the prethrombotic state, increasing oxidative stress, and paradoxically reducing oxygen delivery, all of which could lead to worse results.[15] Moreover, given the risk of major bleeding, AMI post-GIB patients are usually unable to receive antithrombotic therapy and PCI in time, which are crucial treatments for AMI. In addition, patients with AMI post-GIB had poor baseline clinical characteristics, such as older age and more comorbidities, which might be associated with poor outcomes. Based on the combined effect of the above reasons, the mortality of GIB complicating AMI is higher than that of each condition.
In the present study, patients with GIB complicating AMI were older, had more comorbidities, and most of them were NSTEMI. Previous studies have shown that NSTEMI patients often have a high likelihood of multi-vessel coronary artery disease,[16] which may be one of the factors of poor prognosis in patients with AMI post-GIB. Besides, in our study, 36 (46.75%) patients had coronary artery disease, 18 (23.38%) patients had gastrointestinal disease, 28 (36.36%) patients were on aspirin, and 12 (15.58%) patients were on P2Y12 receptor inhibitor. These indirectly suggest that the risk of GIB is high for patients with gastrointestinal and previous coronary heart disease treated with antiplatelet therapy. For those patients at high risk of GIB, proton pump inhibitors (PPIs) or other gastroprotective drugs can be used to prevent GIB.[17],[18] In addition, individualized antiplatelet therapy, such as shorter dual antiplatelet therapy or aspirin-free strategy, may reduce the risk of GIB.[19],[20],[21]
Our study aims to describe and explore potential predictors of in-hospital mortality in patients with GIB complicating AMI. In our study, white blood cell count, cardiogenic shock, and mechanical ventilator usage were independent risk predictors of in-hospital mortality in GIB patients with AMI. Previous studies demonstrated that white blood cell count was associated with mortality in patients with AMI.[22],[23] Our study found that white blood cell count was an independent risk predictor of inhospital mortality in GIB patients with AMI. Patients with cardiogenic shock often present with poor cardiac function and serious conditions, and these patients tend to have poor outcomes.[24] At the same time, patients using mechanical ventilation generally suffer from refractory heart failure and respiratory failure and then have a poor prognosis.[25],[26]
This study is helpful in identifying AMI post-GIB patients with a high risk of in-hospital mortality, so as to pay more attention to these individuals. Patients with AMI post-GIB are in severe condition and need to be treated in the intensive care unit. Close monitoring should be done during the treatment to prevent the complications of AMI and GIB. Given the poor prognosis of AMI post-GIB, it is critical to prevent GIB in high-risk individuals. In addition, patients with GIB need to be closely monitored for cardiovascular events. Once AMI occurs, symptomatic treatment should be given as soon as possible.
The present study has several limitations. Firstly, as a retrospective study, there is a common disadvantage, that is, the analysis of pre-recorded data. Secondly, in our study, few patients underwent endoscopy. Although some studies have shown that endoscopic treatment of GIB in AMI patients is relatively safe,[27],[28],[29] clinicians usually choose relatively conservative therapy to avoid medical disputes. In addition, these patients usually received conservative treatment, so there were little coronary angiography data in the record. Besides, it was a retrospective single-center study with a small number of cases, and therefore, the power is limited. Finally, there is no definitive guideline for this particular situation, and clinicians usually deal with this complex condition based on experience.
In conclusion, the in-hospital mortality of patients with GIB who subsequently suffered from AMI is high. High levels of white blood cell count, cardiogenic shock, and mechanical ventilator usage were found to be independent predictors of in-hospital mortality.
Financial support and sponsorship
Nil.
Conflicts of interest
There are no conflicts of interest.
References 
Correspondence Address:
Dr. Yuzhen Wei
No. 1 Jianshe Dong Road, ErQi District, Zhengzhou, Henan
China
Source of Support: None, Conflict of Interest: None
CheckDOI: 10.4103/sjg.sjg_301_22
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