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ORIGINAL ARTICLE
Year : 2021  |  Volume : 34  |  Issue : 1  |  Page : 154-161

Recent myocardial ischemia in patients presented with upper gastrointestinal bleeding with and without portal hypertension


1 Department of Tropical Medicine, Faculty of Medicine, Menoufia University, Menoufia, Egypt
2 Department of Cardiology, Faculty of Medicine, Menoufia University, Menoufia, Egypt
3 Department of Clinical Pathology, Faculty of Medicine, Menoufia University, Menoufia, Egypt
4 Department of Tropical Medicine, Shebin El-Kom Teaching Hospital, Menoufia, Egypt

Date of Submission27-Aug-2019
Date of Decision16-Sep-2019
Date of Acceptance29-Sep-2019
Date of Web Publication27-Mar-2021

Correspondence Address:
Dina Y Abd Alshafy
Berkit El-Sabae, Menoufia
Egypt
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/mmj.mmj_262_19

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  Abstract 


Objective
To assess the relationship between upper gastrointestinal bleeding (UGIB) in both cirrhotic and noncirrhotic groups and the development of acute myocardial infarction (AMI).
Background
UGIB can cause myocardial ischemia and necrosis. Both UGIB and liver cirrhosis have a higher mortality with the development of AMI, than either of them alone.
Patients and methods
A cross-sectional comparative study was done on 263 patients who presented with UGIB, and they were divided into four groups: GI (n = 118), cirrhotic patients; GII (n = 85), noncirrhotic patients; GIII (n = 30), cirrhotic patients with no history of UGIB; and GIV (n = 30), the control group. They were all subjected to history taking, examination, and investigations.
Results
Age was higher in GI than GII (P = 0.0001). Cardiac troponin I (cTn-I) was positive for MI in 18/118 (15.3%) in GI, 20/85 (23.5%) in GII, and 0% in GIII and GIV (P = 0.001). Mortality rate was 11/118 (9.3%) in GI and 4/85 (4.7%) in GII and 0% in GIII and GIV (P = 0.0001). Length of hospital stay (LOS) was higher in GI than GII. There was a positive correlation between Glasgow-Blatchford score and cTn-I elevation (R=+0.19, P = 0.003) (P = 0.0001). Odds ratio of smoking, viral hepatitis, and LOS in cTn-I-positive patients was 12.61, 14.49, and 2.76 times higher than troponin-negative patients, respectively (P = 0.0001).
Conclusion
Patients with cirrhosis when developing UGIB may be predisposed to AMI especially older ages, men, comorbid diseases, patients with increased LOS;in addition to more complications and higher mortality rate than non-cirrhotic patients.

Keywords: myocardial ischemia, portal hypertension, upper gastrointestinal bleeding


How to cite this article:
Ali AA, Shalaby AG, El-Zaiat RS, Abd Alshafy DY, Sakr AA. Recent myocardial ischemia in patients presented with upper gastrointestinal bleeding with and without portal hypertension. Menoufia Med J 2021;34:154-61

How to cite this URL:
Ali AA, Shalaby AG, El-Zaiat RS, Abd Alshafy DY, Sakr AA. Recent myocardial ischemia in patients presented with upper gastrointestinal bleeding with and without portal hypertension. Menoufia Med J [serial online] 2021 [cited 2021 Dec 4];34:154-61. Available from: http://www.mmj.eg.net/text.asp?2021/34/1/154/312040




  Introduction Top


Acute upper gastrointestinal bleeding (UGIB) is the most common emergency managed by gastroenterologists. UGIB has been divided into nonvariceal and variceal, owing to the significantly different prognosis associated with each category. There has been an increasing trend of interventional endoscopic therapy used for brisk UGIB; therefore, not surprisingly, the mortality from UGIB has halved over the past two decades [1].

The most common cause of death in acute UGIB apart from hemorrhage was from a cardiovascular cause with a reported rate up to 40%. UGIB can cause hypotension and hypovolemia, resulting in a diminished blood supply to the heart causing myocardial injury [2].

Liver cirrhosis is characterized by high cardiac output and severe hemodynamic instability that can potentiate myocardial injury especially when exposed to variceal bleeding. Moreover, pharmacological drugs used to stop variceal bleeding such as terlipressin and vasopressin can cause coronary artery vasoconstriction resulting in myocardial injury [3].

Myocardial infarction (MI) requires cardiac myocyte necrosis with an increase in plasma level of cardiac troponin I (cTn-I), at least one cTn-I measurement should be greater than the 99th percentile normal reference limit during symptoms of myocardial ischemia, new (or presumably new) significant ECG ST-segment/T-wave changes or left bundle branch block, the development of pathological ECG Q waves, new loss of viable myocardium or regional wall motion abnormality identified by an imaging procedure or identification of intracoronary thrombus by angiography or autopsy [4].

Different predictors have been reported to predict increased mortality in patients with UGIB including hypotension on admission, impaired kidney function, and albumin. Serum cTn-I has also been studied as a mortality marker particularly in UGIB [5].

UGIB and MI may occur simultaneously due to myocardial hypoperfusion and reflex tachycardia resulting increased myocardial oxygen demand. Both conditions if occurred together may be underestimated with one predominating over the other [3].

Many studies previously reported the effect of UGIB on the development of MI, regardless whether the patients were cirrhotic or noncirrhotic. To the best of our knowledge, the study described herein may be one of the fewer studies that focus on the effect of UGIB in two different groups (cirrhotic and noncirrhotic patients).

The aim of this study was to assess the relationship between UGIB in both portal hypertensive cirrhotic and noncirrhotic groups and the development of acute myocardial infarction (AMI).


  Patients and methods Top


This was a cross-sectional comparative study on 263 patients admitted to Gastroenterology Department of our tertiary Menoufia University hospitals with UGIB either hematemesis and/or melena for whom esophagogastroduodenoscopy (EGD) was indicated and UGI cause was discovered.

Patients with chronic kidney diseases, cardiac decompensation, history of cardiac ischemia or infarction, sepsis, pulmonary embolism or severe pulmonary hypertension (HTN), and critically ill patients due to any cause and all causes that may affect cTn-I serum level were excluded from the study.

All patients were subjected to the following: (a) history taking, with special attention to age, sex, smoking, given drugs, comorbid diseases, history of previous MI or ICU admission, history of viral hepatitis, or previous endoscopy, cardiac symptoms as chest pain or tightness, syncopal attacks, hepatic symptoms, and GI symptoms. (b) Examination was performed, especially vital signs, signs of hemodynamic instability (postural hypotension, dizziness, or syncopal attacks), and calculation of BMI. Then, severity of UGIB was assessed using Glasgow-Blatchford score (GBS) and correlated with level of cTn-I. Portal HTN and liver cirrhosis were diagnosed by stigmata of chronic liver disease either clinically, laboratory, abdominal ultrasound and by the presence of esophageal varices (OVs) and/or portal hypertensive gastropathy by EGD. Cardiac examination for signs of MI. (c) Investigation encompassed laboratory investigations, including complete blood count, liver function tests, viral markers (HbsAg and HCV-Ab), bleeding and coagulation profile, renal function tests, lipid profile, and measurement of high-sensitive cTn-I by ELISA (Abbott Laboratories, Abbott Park, Illinois, USA) within 24 h of presentation. cTn-I level of more than 0.1 ng/ml was considered elevated and indicated myocardial injury. Radiological investigations included ECG, echocardiography (for selected patients who need further assessment of cardiac functions), and abdominal ultrasonography. Endoscopic procedure was as follows: all enrolled patients who were fit for EGD were examined endoscopically till the second part of duodenum. Endoscopic findings were reported and probable causes of UGIB were recorded. An integration between symptoms, signs, elevated cTn-I level, and/or recent ECG changes was used to define MI.

According to the clinical, laboratory, and EGD findings, all patients were divided into four groups: GI (n = 118), cirrhotic patients with UGIB; GII (n = 85), noncirrhotic patients with UGIB; GIII (n = 30), cirrhotic patients with no prior history of UGIB whose examination and investigations were done at outpatient clinic; and GIV (n = 30), the healthy control group.

Statistical analysis

Frequency data were summarized as percentages. Continuous variables were summarized as median and range of distribution. P value less than 0.05 was considered significant. To identify univariate regression analysis of risk factors associated with myocardial injury in patients with UGIB, the χ2/Fisher's exact test and t tests were used. The SPSS, 23.0 (SPSS Inc., IBM Corporation, Armonk, New York, USA) software was used for statistical analysis.

Written informed consents were taken from every patient before participation in the study, and the project was approved by our university ethical board.


  Results Top


Age is higher in GI than GII, with a high statistically significant difference (P = 0.0001). Male sex was more prominent in both groups (63.6% in GI versus 72.9% in GII; P = 0.003). BMI was comparable in all groups, with no significant difference (P = 0.6). Smoking history was highly statistically significant between the groups (12% in GI vs. 54.1% in GII; P = 0.0001). Additionally, diabetes mellitus (DM) and HTN were a major risk factor in both groups (44.1 and 54.1% were diabetic in GI and GII, respectively, and 8.5 and 35.3% had HTN in GI and GII, respectively) [Table 1].
Table 1: Medical history of the studied groups

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UGIB presented with melena only in 54 (22%) patients in GI and 28 (32%) patients in GII. However, both hematemesis and melena presented in 127 (72%) patients in GI and 42 (49.5%) patients in GII, and microcytic hypochromic anemia was seen in seven (5.9%) patients in GI and 12 (14.1%) patients in GII, with a high statistically significant difference between the groups (P = 0.0001). Typical chest pain was detected in six patients (four in GI and two in GII); however, atypical chest pain was detected in 37 patients [22 (18.6%) in GI and 15 (17.6%) in GII], with a statistically significant difference (P = 0.03) [Table 2].
Table 2: Symptoms and signs of the studied population

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Regarding laboratory values, hemoglobin level and platelet count were the lowest in GI (8.6 ± 2.03 and 94.42 ± 30, respectively), with a highly statistically significant difference (P = 0.0001), but white blood cells count was not significant (P = 0.2). Among all endoscopic causes of UGIB, OVs were the commonest in GI [75 (63.6%)], but peptic ulcers (PU) were the commonest in GII [77 (90.6%)] (P = 0.0001). cTn-I was higher in GII (2.22 ± 8.5) than in GI (1.7 ± 5.02) but was not statistically significant (P = 0.16). Pathologically significant elevated cTn-I value were found in 18 (15.3%) of 118 patients in GI and 20 (23.5%) out of 85 patients in GII, with a highly statistically significant difference between both groups (P = 0.001) [Table 3].
Table 3: Laboratory investigations, ECG, and esophagogastroduodenoscopy findings of the studied groups

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In univariate regression analysis model, odds of high troponin in smokers were 1.5 times than in nonsmokers. Odds of troponin elevation increase with age, female sex, high BMI, presence of DM, HTN, chronic liver disease, and severity of bleeding (GBS) [Table 4].
Table 4: Univariate regression analysis for cardiac troponin I level

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Hospital stay was longer (>5 days) in GI than GII (83.1 vs. 31.8%) (P = 0.0001). In-hospital mortality rate was 9.3% in GI and 4.7% in GII (P = 0.0001). The most common complication in GI was hepatic encephalopathy [13 (11%) patients] followed by shock nine (7.6%). However, in GII, shock represented 9.4% (P = 0.0001). GBS more than 15 occurred in 41.7% in GII and 29.7% in GI (P = 0.0001) [Table 5], [Table 6], [Table 7], [Table 8], [Table 9].
Table 5: Length of hospital stay and outcome during the hospital stay in the studied groups

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Table 6: Medical history of group I versus group III

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Table 7: Medical history of group I versus group II

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Table 8: Medical history of group I and group III versus group IV

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Table 9: Medical history of group I and group II versus group IV

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There was a positive correlation between the severity of bleeding estimated by GBS and troponin levels (P = 0.003) [Figure 1].
Figure 1: The correlation between severity of UGIB by GBS and cTn-I level. cTn-I, cardiac troponin I; GBS, Glasgow-Blatchford score; UGIB, upper gastrointestinal bleeding.

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  Discussion Top


Myocardial injury after UGIB is frequently ignored because the signs and symptoms may be overshadowed by the severity of UGIB [6]. Several studies showed that this process is common, especially in critically ill patients [7].

UGIB may predispose to myocardial ischemia/infarction as massive bleeding compromises myocardial perfusion and the resulting reflex tachycardia increases myocardial oxygen consumption [6].

Troponin is the biomarker of choice for detection of MI [8]. Its release in the blood stream can also be an indicator of hypovolemic shock, acute heart failure, and transient loss of membrane integrity and reperfusion injury, all of which can be a complication of UGIB [9].

In this project, approximately 58% of patients admitted to the hospital by UGIB were cirrhotic whose ages were higher than noncirrhotic patients with UGIB (42%). These data compared with Lecleire et al. [10] who did their study on 2133 patients with UGIB and revealed almost one-fifth (21.9%) of UGIB occurred in cirrhotic patients, who had a younger age than noncirrhotic patients. The discrepancy in percentage of cirrhotic group with our study could be explained by the high frequency of the liver diseases due to endemic chronic hepatitis C in Egypt.

In this study, smoking, DM, HTN, and high BMI were cofounders on increase in the development of AMI (P = 0.001, 0.09, 0.9, and 0.0001, respectively). Our results were consistent with Iqbal et al. [2] who revealed that diabetes and HTN were also more prevalent in patients with troponin elevation (P = 0.001 and 0.015, respectively).

In our study, the frequency of AMI was approximately 14% (38 of 263 patients included in the study). In comparison, Iqbal et al. [2] reported 10% (29 of 290 patients) and Emenike et al. [11] reported a rate of 13% of 83 American patients with MI complicating gastrointestinal hemorrhage. Similarly, Wu et al. [3] documented a prevalence of simultaneous UGIB and MI of 7.74%. Other similar studies showed a lower prevalence (0.94–14%). The variability in prevalence may be owing to different parameters used to detect MI or some of these studies may be retrospective ones.

There was a statistically significant difference between the groups regarding cTn-I level. The prevalence of cTn-I elevation was found in 18 (15.3%) of 118 cirrhotic patients presenting with UGIB and 20 (23.5%) of 85 noncirrhotic patients presenting with UGIB (P = 0.001), with no troponin elevation noticed in GIII or GIV, which suggests UGIB as a major risk factor for AMI. This was in agreement with Nagata et al. [12] who identified that acute GIB was a significant risk factor for late thromboembolism and death, compared with patients without GIB.

In this study, cirrhosis appears protective against myocardial ischemia, with no cases recorded in GIII. This was comparable with Berzigotti et al. [13] who yielded only two of 118 cirrhotic patients with MI compared with controls (15/236), confirming the previous sporadic studies of low prevalence of ischemic events in cirrhotic patients, which may be owing to impaired liver functions with decreased production of coagulation factors and thrombocytopenia.

In this study, there was a highly statistically significant difference between the groups regarding cause of bleeding according to the endoscopic findings (P = 0.0001). OVs and gastric varices were the most common causes (78%) of UGIB in cirrhotic patients (GI), whereas PU was responsible for 90.6% of causes of UGIB in noncirrhotic patients (GII) and the second most frequent bleeding lesion in cirrhotic patients (7.6%). This was comparable with Lecleire et al. [10] who revealed that the most frequent bleeding lesion observed in cirrhotic patients was esophageal or gastric varices (59.1%), whereas the most frequent bleeding lesion in noncirrhotic patients was PU (41.8%), which also was detected in 15.7% of cirrhotic patients (P = 0.001).

Our study showed that there was a significant difference between patients with UGIB with MI and those without regarding the length of hospital stay (LOS) (odds of LOS in troponin I-positive patients was 2.76 times than troponin-negative patients) (P = 0.0001). These results were in concordance with Iqbal et al. [2] which showed that the LOS was higher in patients with troponin elevation than those with normal values (6 vs. 5 days, P = 0.02).

In this study, there was a statistically significant difference between groups regarding LOS, as cirrhotic patients (GI) stayed longer in hospital (about 83.1% stayed ≥5 days) than noncirrhotic (31.8% stayed ≥5 days) (P = 0.0001). This was comparable with Lecleire et al. [10] who revealed that the mean LOS was similar in hospitalized cirrhotic and noncirrhotic patients [13.4 (range, 0–153 days) versus 13.7 days (range, 0–193 days), respectively], which was not significant. This may be due to endoscopic hemostasis techniques that were more frequently performed in cirrhotic patients who often required more than one procedure during hospitalization in contrast with noncirrhotic patients who were primarily successfully treated by only a single procedure.

In this study, there was a highly statistically significant difference between the groups regarding the outcome during hospital stay, showing increase in hospital mortality among cirrhotic versus noncirrhotic patients presented by UGIB (9.3 versus 4.7%; P = 0.0001). Additionally, complications like shock, sepsis, and hepatic encephalopathy predominated in cirrhotic groups (GI). This was in agreement with the study by Lecleire et al. [10] which revealed the mortality during hospitalization was 23.5% in cirrhotic patients and 11.2% in noncirrhotic patients. The significant decline in mortality observed during the past 20 years and confirmed by our study could be explained by the major improvement in medical and endoscopic management modalities of UGIB in cirrhotic patients. Moreover, the study by Lyles et al. [14], which included 521 patients with variceal bleeding and 363 patients with nonvariceal bleeding, revealed that mortality was 8.6 and 8.3% in patients with variceal bleeding and nonvariceal bleeding, respectively.

In this study, there was a positive correlation between severity of bleeding estimated by GBS and cTn-I levels (P = 0.003). This was in agreement with Wu et al. [3] who reported that the development of concurrent myocardial injury was associated with the amount and acuteness of blood loss, which could be estimated by the presence of hypotension, tachycardia, orthostatic hypotension, and azotemia (blood urea nitrogen >40 mg/dl or blood urea nitrogen/creatinine >20). Because it takes hours to achieve full compensation, the initial hematocrit or hemoglobin measurement is not considered to be a good indicator of severity during acute blood loss.


  Conclusion Top


UGIB in cirrhotic patients may predispose to AMI, especially in older ages, men, and with comorbid diseases, than noncirrhotic. Patients with cirrhosis when developing UGIB have increased LOS, more complications, and higher mortality than noncirrhotic. Moreover, bleeding severity is positively correlated with developing AMI in all groups. cTn-I level is not different statistically between the groups.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
  References Top

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2.
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Bellotto F, Fagiuoli S, Pavei A, Gregory SA, Cati A, Silverj E, et al. Anemia and ischemia: myocardial injury in patients with gastrointestinal bleeding. Am J Med 2005; 118:548–551.  Back to cited text no. 7
    
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Emenike E, Srivastava S, Amoateng-Adjepong Y, Al-Kharrat T, Zarich S, Manthous CA. Myocardial infarction complicating gastrointestinal hemorrhage. Mayo Clin Proc 1999; 74:235–241.  Back to cited text no. 11
    
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Nagata N, Sakurai T, Shimbo T, Moriyasu S, Okubo H, Watanabe K, et al. Acute severe gastrointestinal tract bleeding is associated with an increased risk of thromboembolism and death. Clin Gastroenterol Hepatol 2017; 15:1882–1889.  Back to cited text no. 12
    
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Berzigotti A, Bonfiglioli A, Muscari A, Bianchi G, LiBassi S, Bernardi M, et al. Reduced prevalence of ischemic events and abnormal supraortic flow patterns in patients with liver cirrhosis. Liver Int 2005; 25:331–336.  Back to cited text no. 13
    
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