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Table of Contents
ORIGINAL ARTICLE
Year : 2018  |  Volume : 7  |  Issue : 4  |  Page : 169-175

The value of pre admission Thrombolysis in Myocardial Infarction (TIMI) Risk Index (TRI) in the prediction of no-reflow phenomenon after primary percutaneous coronary intervention in patients presented with ST Segment Elevation Myocardial Infarction (STEMI)


Department of Cardiology, Faculty of Medicine, Benha University, Banha, Egypt

Date of Web Publication31-Dec-2018

Correspondence Address:
Dr. Mohammed S. Abd Elhafeez
Department of Cardiology, Faculty of Medicine, Benha University, Banha
Egypt
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/rcm.rcm_30_18

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  Abstract 


Background: Coronary artery disease and acute coronary syndrome (ACS) are the major causes of death, worldwide. Risk assessment for patients with ACS is necessary to minimize morbidity and mortality. The global registry of acute coronary events risk score (GRS), the in thrombolysis myocardial infarction (TIMI) risk score (TRS), and the TIMI risk index (TRI) have been used for patients with ACS to evaluate their risk. We showed at our study the value of pre-admission TRI, TRS, and GRS in occurrence prediction of no-reflow (NRF) Phenomenon after primary PCI for ST-elevation myocardial infarction (STEMI) patients; and its impact on the in-hospital outcome for those patients. Patients and Methods: Our study included 319 patients presented with STEMI and managed by primary PCI. For all patients, we recorded a detailed history, clinical examination as well as Killip class, electrocardiogram, and echocardiography. TRI as well, TRS, and GRS were calculated for all patients. We observed all patients during their PCI at the catheterization room to monitor the result of the intervention. NRF was defined as TIMI flow grade less than III or TIMI flow Grade III with myocardial blush grade less than or equal to II. Then, we followed the patients during their hospitalization period to record any associated complications and mortality. Results: We found NRF patients older than reflow patients, thus regarding age. They were more males. Killip Class III-IV was found to be more common in NRF patients. TRI as well, TRS and GRS showed higher values among the NRF patients. As well, in-hospital major adverse cardiac events (MACEs) and mortality were more common in NRF patients. Conclusion: We found that the high TRI values were related to the occurrence of NRF, in hospital MACE, and mortality.

Keywords: Acute myocardial infarction, global registry of acute coronary events risk score, no-reflow, percutaneous coronary intervention, thrombolysis in myocardial infarction risk index


How to cite this article:
Elemary MH, Elkeshk ES, Swailem FM, Elhafeez MS. The value of pre admission Thrombolysis in Myocardial Infarction (TIMI) Risk Index (TRI) in the prediction of no-reflow phenomenon after primary percutaneous coronary intervention in patients presented with ST Segment Elevation Myocardial Infarction (STEMI). Res Cardiovasc Med 2018;7:169-75

How to cite this URL:
Elemary MH, Elkeshk ES, Swailem FM, Elhafeez MS. The value of pre admission Thrombolysis in Myocardial Infarction (TIMI) Risk Index (TRI) in the prediction of no-reflow phenomenon after primary percutaneous coronary intervention in patients presented with ST Segment Elevation Myocardial Infarction (STEMI). Res Cardiovasc Med [serial online] 2018 [cited 2019 Jan 17];7:169-75. Available from: http://www.rcvmonline.com/text.asp?2018/7/4/169/249053




  Introduction Top


Worldwide, Coronary artery disease and acute coronary syndrome (ACS), are the major causes of death.[1] Reperfusion of the blood flow rapidly to the injured myocardium is the goal for which primary PCI is present as the most important step in the treatment of acute myocardial infarction (AMI). The usage and invention of stents made the PCI a preferred and effective treatment line for myocardial infarction associated with ST-segment elevation.[2] To have a successful PCI, we should put in consider the fate of the angiographic, procedural, and clinical components. The Angiographic component requires a residual stenosis <10% of the artery lumen after stent implantation; thus with an optimal goal to be near to 0% as possible associated with thrombolysis in myocardial infarction (TIMI) flow Grade III, without complications as; significant side branch occlusion, distal thrombosis embolization, or flow-limiting dissection. The procedural success requires the occurrence of the angiographic success without associated complications during the in-hospital period as; emergency CABG, stroke, MI, or death while the clinical success of PCI requires the occurrence of both angiographic and procedural components as well improvement of myocardial ischemia manifestations.[3]

However, even after the patency achieved within the infarction related artery (IRA) through implantation of a stent, diminished blood flow, and myocardium hypoperfusion have been observed among 2.4%–28% of patients presented with AMI, what is named the no-reflow (NRF) phenomenon.[4] NRF is associated with factors that are related to PCI complications as advanced age, congestive heart failure (HF), chronic kidney disease (CKD), diabetes mellitus (DM), and multivessel CAD. Those who interested with cardiology sciences found multiple risk scores applied to predict the mortality related to PCI. The need for a non-invasive, cost-effective, and easily accessible predictor of p-PCI made those interested with cardiology sciences to search about it. Global registry of acute coronary events (GRACE) risk score (GRS) and TIMI risk score (TRS) have been already reported to Predict early and late mortality among hundreds of thousands of patients.[5] TIMI risk index (TRI) was improved recently to predict mortality among ST-elevation myocardial infarction (STEMI) patients. This risk score consists of fewer parameters that are applied to patients with STEMI. Originally, the TRI was reported in the study of Intravenous lanoteplase for the Treatment of Infarction Myocardium Early-II and has been validated at TIMI 9 trial with a significant discriminatory and prognostic capacity as a method to triage patients presented with STEMI.[6] Thus, we showed at this study the value of TRI in prediction of NRF phenomenon among patients with STEMI and its impact on the outcome of these patients.


  Patients and Methods Top


Study population

This study is a cross-sectional observational study, included 319 patients presented with STEMI to National Heart Institute (NHI) from February 2017 to April 2018. STEMI Patients eligible for p-PCI according to the European Society of Cardiology (ESC) guidelines were included in our study. While the excluded Patients were those were not treated with PPCI, patients who were treated by thrombolytic therapy, patients who presented more than 12 h after symptoms onset and patients with CKD on medical treatment or in dialysis or those with malignancy, bleeding diathesis, hematological disease, or severe liver disorder. We recorded for every patient: informed consent was taken from patients, in the case of incompetent patients; the consent was taken from the guardians. A detailed history taking with a special focus on Risk factors (age, gender, hypertension [HTN], diabetes, dyslipidemia, smoking, and family history). History of ACSs and revascularization was taken. Complete clinical examination, with a focus on admission blood pressure, pulse, and Killip class of the patients were recorded. Creatinine level and CKMB level were measured on admission. A standard 12-lead electrocardiogram (ECG) was performed for all patients as well transthoracic echocardiography was performed for all patients on admission to CCU. We calculated cardiac risk scores for all patients, TIMI risk score (TRS) including age, DM, HTN, or angina, heart rate of more than 100 bpm, systolic blood pressure (SBP) of less than 100 mmHg, Killip class II-IV, weight of less than 67 kg, anterior MI or LBBB presentation, and latency of more than 4 h were recorded.[7] TRS was calculated using a computer program: (https://www.mdcalc.com/timi-risk-score-stemi). In addition, the GRACE risk score (GRS) was calculated for all patients including age, creatinine, heart rate, SBP, Killip class, cardiac arrest on admission, elevated cardiac markers, and ST-segment deviation were recorded.[8] GRS was calculated by a computer program:

(https://www.mdcalc.com.grace-acs-mortality calculator). As well, TRI of all patients was calculated using a manual calculator by the formula:

(Heart rate × [age/10]2)/SBP[9]

Primary PCI has been done for all patients within 12 h of acute MI symptoms. The transfemoral technique had been used in all patients as standard technique using a femoral sheath of 6 Fr and guiding catheters and guide wires. We considered the IRA is the culprit artery. The culprit artery was revascularized by stents implantation. The site of the occlusion and the severity of the occlusion were also assessed as well if there were other lesions. We performed multiple projections to visualize the coronary arteries well, and to avoid superimposition and foreshortening of the coronaries. Coronary blood flow patterns after primary PCI have been studied on the rule of TIMI flow grade, by grades 0, I, II, and III. The grades TIMI blood flow were used to evaluate the quality of coronary flow during coronary angiography and after the vessel recanalization.[10] TIMI perfusion grade “myocardial blush grade (MBG)” has been reported as a measure of the clearance and filling of contrast through the cardiac tissue.[11] We defined the NRF phenomenon as TIMI flow grade less than III or TIMI flow grade III with MBG less than or equal to II.[12],[13] We followed the patients during their hospitalization period to record any associated complications and mortality. The monitored complications were advanced HF, acute pulmonary edema, life-threatening arrhythmia, complete HB, and cardiogenic shock.

Statistical analysis

The collected data were expressed using Statistical program for social sciences (SPSS) for Windows, version 23.0 32 bit (IBM Corporation; Armonk, NY, USA) and MedCalc for Windows, version 15.4 64 bit (MedCalc Software, Ostend, Belgium). The quantitative data were analyzed as the mean ± standard deviation. The qualitative data were analyzed as percentage and frequency. These tests used when comparing between two means, Mann–Whitney U test was used when comparing two means of not normally distributed data, Chi-square test was used in order to compare proportions between two qualitative parameters, and Fisher's Exact test is used in the place of Chi-square test in two by two tables, especially in cases of small samples. Regarding ROC curves, the following were done:

  • Receiver operating characteristic curve analysis has been used to express optimal cut-off values. Area under curve (AUC) was analyzed also, criteria to qualify for AUC were as follow: 0.90–1 = excellent, 0.80–0.90 = good, 0.70–0.80 = fair; 0.60–0.70 = poor; and 0.50–0.6 = fail. The optimal cutoff value was expressed at the point of maximum accuracy
  • Sensitivity: It is the probability that a test result will be positive when the disease is present (true positive rate and expressed as a percentage)
  • Sensitivity = (true +ve)/([false –ve] + [true +ve])
  • Specificity: It is the probability that a test result will be negative when the disease is not present (true negative rate and expressed as a percentage)
  • Specificity = (true –ve)/([false +ve] + [true –ve])
  • Positive predictive value (PPV): It is probability that the disease is present when the test is positive (expressed as a percentage of true positive cases to all positive). PPV = (true +ve)/([false +ve] + [true +ve])
  • Negative predictive value (NPV): It is probability that the disease is not present when the test is negative (expressed as a percentage of true negative subjects to all negative). NPV = (true –ve)/([false –ve] + [true–ve])
  • Accuracy = ([true +ve] + [false +ve])/([true +ve] + [false +ve] + [true –ve] + [false –ve])
  • Probability (P): When the P < 0.05, it is considered significant; while P < 0.001 is considered highly significant and P > 0.05 was considered nonsignificant.



  Results Top


Our study included 319 patients presented with STEMI and have been treated by primary PCI.

We found of all the study population, 70 patients (21.9%) were in the NRF group (group B), thus according to MBG flow. The remaining 249 patients were classified into the reflow group (group A). [Table 1], [Table 2], [Table 3], [Table 4], [Table 5] show our results regarding the baseline demographic data, clinical, laboratory finding, preadmission cardiac risk scores, angiographic data, and in-hospital course. According to age, there was a significant difference between the two groups; patients with no reflow were older. There was a significant difference regarding gender in both groups with a statistically significant P value (0.011), with no significant differences regarding other risk factors for coronary artery disease. We found NRF patients with more Killip class III–IV (P < 0.001). In this study, there is a significant difference between Group A and Group B regarding SBP (110.8 ± 18.7 vs. 95.9 ± 11.4 mmHg respectively), and pulse rate (88.8 ± 17.5 vs. 96.0 ± 17.8 bpm, respectively). As regards the ECG, there was a significant difference between Group A and B in the location of MI (anterior 69.5% vs. 30.5%, nonanterior, 88.6% vs. 11.4%, respectively). In our study, the time from symptoms onset to presentation was relatively longer in Group B than in Group A (mean 4.5 ± 2.5 vs. 5.0 ± 2.4 h) but with no significant P value 0.072.
Table 1: Comparison between the studied groups regarding the demographic data

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Table 2: Comparison between the studied groups regarding the cardiac risk scores

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Table 3: Comparison between the studied groups regarding the clinical, electrocardiogram and laboratory data

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Table 4: Comparison between the studied groups regarding the coronary angiographic data

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Table 5: Comparison between the studied groups regarding the in-hospital course

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In this study, we showed that increased TRI, TRS, and GRS on admission were significantly related to the occurrence of angiographic NRF phenomenon, Moreover, major adverse cardiac events (MACEs), and an increase in hospital duration.

The mean results of TRS, GRACE score, and TRI are higher in group B (6.4 ± 2.5, 131.3 ± 23.2, 40 ± 15.0, respectively) than in group A (4.1 ± 2.6, 113.6 ± 23.9, 26.8 ± 12.7 respectively). There were statistically significant differences between the two groups regarding cardiac risk scores on admission with highly significant P < 0.001. In our study, there was a significant difference between Groups A and B regarding IRA (left anterior descending artery 69.1% vs. 84.3%, left circumflex artery 9.6% vs. 4.2%, and right coronary artery 21.3% vs. 11.4%, respectively). Ther was no significant difference between the two groups regarding the number of vessels occluded. In this study, in-hospital MACE and in-hospital mortality were more common among the NRF group; cardiac mortality occurred in 1.2% in reflow group versus 8.6% in NRF group, in reflow group 4.8% patients developed pulmonary edema versus 18.6% in the NRF group. 0.4% of patients developed cardiogenic shock in Group A (reflow group), versus. 17.1% of patients in group B (no reflow group). 3.2% of patients developed complete AV block in Group A (reflow group), versus 8.6% of patients in group B (no reflow group), In Group, A 3.6% patients had CPR at hospital stay, while in group B, 10% of patients had cardiopulmonary resuscitation. TRI significantly was related to in-hospital MACEs and in-hospital mortality. Hence, we concluded that high TRI values on admission are strongly related to NRF phenomenon. It is an independent predictor for NRF occurrence. This index applies simple, noninvasive and nonexpensive tools for risk stratification of STEMI patients. Hence, it is helpful to determine the best treatment modality for high-risk patients. It also can help in risk prediction in short term as well, long term for STEMI patients.


  Discussion Top


In our study, we concluded that increased TRI, TRS, and GRS on admission were related significantly to the occurrence of angiographic NRF phenomenon in patients presented with acute STEMI who have been treated by primary PCI. Primary PCI is considered the recommended line of management for STEMI patients. The program of stent for life (SFL) was adopted in 2008 by the EuroPCR and the ESC in partnership with the European Association of Percutaneous Cardiovascular Interventions. This work was to put the PCI as a recommended line of treatment for the patients who will have a benefit, especially those who presented by STEMI. Multiple countries participated in this program to decrease morbidity and mortality among hundreds of thousands of their peoples. These countries are already participating in this program: France, Greece, Turkey, Bulgaria, Romania, Portugal, Italy, Spain, Serbia, and Egypt.[14]

The implementation of “SFL” program in Egypt has led to a significant shift in the treatment of acute ST-segment elevation myocardial infarction. With five pilot centers (expanding these days), it has helped to develop an improved system for transport and communication between centers and hospitals, and a quick transfer of the patient to the catheterization laboratory.[15] There is an increase in numbers of PCI-capable centers, especially in Cairo, Alexandria and other large cities across Upper and Lower Egypt. Some peculiarities of coronary artery disease patterns specialize the Egyptian patients. These peculiarities include younger age at presentation, a high incidence of multivessel disease, diffuse involvement, and distal disease of the arteries with a significant left ventricular dysfunction on presentation.[16],[17] Until now, there no identified registry has been developed to demonstrate the accurate figures of cardiac events and procedures; however, the National Heart Institute in collaboration with cardiology departments in Cairo and Ain Shams universities have been undertook a registry for ACS patients in 3-period phases– 2007, 2010 and 2013. It concluded that the presence of atherogenic risk factors such as HTN, smoking, and dyslipidemia was high, in addition, to delay in ACS patients to reach heart centers. The analysis of these data showed an increase in the use of invasive intervention by PCI over the years. In addition, primary PCIs showed a threefold increase over the last 6-year period.[18] The estimated number of angioplasties performed in Egypt in 2015 is just over 55,000. This is more than twice the figure in 2013 when the number of angioplasties was approximately 20,000. There is a projected increase of 20%–25% with the active participation of the Ministry of Health offering an improved medical and interventional service to the population.

Reperfusion of the blood flow rapidly to the injured myocardium and recanalization of the occluded artery form the basis of SSTEMI therapy. Primary PCI already, improve the survival of those patients managed by it.[19] However, even after the patency achieved within the IRA through implantation of stents, we observed insufficient blood flow and myocardium hypoperfusion. This is what is named the NRF phenomenon.[19],[20] Physiologically, the blood flow to the coronaries decreases among menopausal women, elderly patients, and those with multiple risk factors for CAD.[21] Moreover, short-term and long-term follow-up of STEMI patients, NRF patients were found to have more risk of multiple morbidity and mortality.[22] Thus, we concluded, in our study, that the NRF phenomenon was strongly related to the increased rates of in-hospital mortality and MACEs. There are some factors related to increased rates of complication of primary PCI, thus include advanced age, CKD, diabetes, bleeding tendency, multivessel CAD, and congestive HF. Regarding the pathophysiological process of the NRF phenomenon occurrence, we found that it has not been obviously explained and its cause likes to be multifactorial.

The multifactorial nature of NRF has been summarized recently into four interacting processes: ischemic injury, reperfusion injury, distal embolization, and susceptibility of microcirculation to injury.[23] The relation between coagulation, inflammation, and atherosclerosis progression has been used clarify the pathophysiological process of the NRF phenomenon occurrence. Many studies support the important role of the tissue factor (TF) for leading to injury and inflammation in myocardial ischemia-reperfusion. Truly, TF is exposed to platelets, leukocytes, and endothelial cells after local vascular injury leading to thrombosis.[24] Activation of leukocytes with neutrophils accumulation in the re-perfused myocardium and the production of reactive oxygen radicals play the most important role in the pathogenesis of myocardial injury and lead to occurrence NRF phenomenon.[25] In addition, the endothelial dysfunction gives a state of dysregulation between the vasodilators and vasoconstrictors agents, thus leading to inappropriate vasoconstriction process that is considered to be an important mechanism for occurrence NRF phenomenon.[26] In addition, microembolization of the plaque debris (endothelial cells, lipid matrix, and platelet thrombi) is an important factor in the pathogenesis of NRF, especially in the setting of primary PCI.[27] Hence, we should stratify the risk for ACS to manage them properly. There are various risk stratification systems have been already used to monitor and predict morbidity and mortality among STEMI patients and to identify the high-risk groups. TRS, GRS and TRI have been reported to stratify the risk for patients presented with STEMI. We worked at this study to show whether preadmission TRI, GRS, and TRS are related to the occurrence of coronary NRF phenomenon in patients presented with STEMI and have been treated with primary percutaneous coronary intervention (p-PCI). Our study population consisted of 319 consecutive patients admitted at the NHI for primary PCI from February 2017 to April 2018.

The patients are divided into two groups according to the final TIMI flow grade and MBG after the primary PCI as follows: the reflow group (Group A): This group included 249 patients (78.1%), 189 patients were males (75.9%), while the remaining 60 patients were females (24.1%).

The NRF group (Group B): This group included 70 patients (21.9%), 63 patients (90%) were males, while only seven patients were females (10%). Our results demonstrated that TRI is strongly related to the occurrence of NRF phenomenon and an increase in rates of in-hospital MACEs and in-hospital mortality. TRI uses simple and non-expensive tools for assessment of patients with STEMI. In addition, high-TRI values are helpful in determining high-risk patients and to direct for the appropriate treatment strategies. However, our study is limited by the relatively small number of patients and from a single center. In addition, it was of male dominance, thus the results may not be applicable for the female patients. We concluded that the TRI, TRS, and GRS should be routinely used and calculated for risk stratification of patients with ACS.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
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    Tables

  [Table 1], [Table 2], [Table 3], [Table 4], [Table 5]



 

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