Assessment of risk factors and MACE rate among occluded and non-occluded NSTEMI patients undergoing coronary artery angiography: A retrospective cross-sectional study in Multan, Pakistan

Methods: A retrospective, cross-sectional study was conducted in Multan Institute of Cardiology, Pakistan between 1st February, 2017, and 31st September, 2017. The data were collected from medical records of the outpatients and inpatients who were index hospitalized. Data were analyzed by using Statistical Packages for Social Sciences (IBM SPSS Statistics for Windows, Version 21.0. Armonk, NY: IBM Corp.) And Microsoft Excel (MS Offi ce 2010).


Introduction
Non-ST elevated myocardial infarction (NSTEMI) is the primary cause of index hospitalization because its symptoms are common among patients suffering from acute coronary syndrome [1,2]. During index hospitalization, coronary angiography is mainly performed to assess the conditions of coronary arteries especially to identify the area of coronary artery which is being blocked or narrowed [3]. Although it is a routine medical practice to perform angiography on both NSTEMI and ST elevated myocardial infarction (STEMI) patients but the timing of this invasive strategy is much delayed for NSTEMI patients as compared to STEMI patients [4]. According to the guidelines of European Society of Cardiology (ESC), angiography must be performed within < 2 hours of index hospitalization on patients suffering from STEMI and unstable NSTEMI. While those suffering from stable NSTEMI must undergo angiography within 24 or 48 hours of hospitalization [5]. In STEMI patients, emergency angiography is performed prior to angioplasty because one of the major coronary artery (CA) is occluded with thrombus which hinders the low of blood and enhances the chances of developing necrosis in the tissue [6]. But if the blood low is restored then many complications associated with STEMI (e.g., size of the infarct) can be lessened [7,8]. It is assumed that either the blood low is lessened or the transient occlusion has developed in one or more vessels. Also, no favorable evidences are available for emergency angioplasty in patients suffering from NSTEMI [9,10]. These are the reasons due to which the guidelines of American Heart Association (AHA) also don't recommend emergency angioplasty and angiography (within 120 minutes of hospitalization) among stable NSTEMI patients [11].
Although electrocardiography (ECG) is not ef icient enough in detecting acute MI (AMI) but in many clinical situations ECG is the foremost diagnostic criteria to differentiate NSTEMI and STEMI [12]. The reports of angiography in previously published literature revealed complete occlusion of CA even in the absence of ST in standard 12-lead ECG [13]. Also, in many cases if there is a delay in angiography and re-vascularization then it negatively effects myocardial function with irreversible loss [14]. There is a limited availability of data on the type of most occluded coronary artery (OCA) in NSTEMI and difference in outcome of patients undergoing angiography [15].
The prime focus of present study was to evaluate the most OCA among NSTEMI patients, risk factors associated with occluded and non-occluded NSTEMI as well as major adverse cardiovascular event (MACE).

Study design and setting
A retrospective, cross-sectional study was conducted in Multan Institute of Cardiology, Pakistan. Data were collected between 1st February, 2017, and 31st September, 2017. The selected healthcare setting was a tertiary care public hospital providing comprehensive care to the cardiac patients of all age groups. In this setting there were two angiography labs, where facilities of performing different procedures e.g., diagnostic coronary angiography, pacemaker implantation, right and left cardiac catheterization, and coronary angiography with stent implantation were available.

Study population and sample size
The records of 1,598 patients were scrutinized for the study. Both inpatients and outpatients were included in the study if they were of ≥18 years of age, suffering from NSTEMI, had no history of cardiac revascularization, and underwent angiography for the irst time. NSTEMI patients were excluded if they were not going for angiography due to any reason. The records of 624 patients were ful illed our inclusion criteria and consequently selected for the study.

Data collection
A data collection tool was developed to collect the data. The questionnaire was structured and consisted of ive parts: (1) Demographic details and co-morbidities of the patient, (2) Lab test results of cardiac markers (Troponin I and II), (3) Angiographic indings (occluded or non-occluded NSTEMI, single vessel or multi-vessel NSTEMI), (4) type of coronary artery which shows occlusion, and (5) incidence of MACE.
The investigational team included general medical practitioner and a trained nurse. The investigators received the same training prior to the survey for the collection and validation of data. During the survey, one investigator illed out the investigational form and the other reviewed the data. The expert opinion of an experienced radiologist and histopathologist was taken into account when needed.
If the patient was experiencing NSTEMI signs and symptoms and referred for CA angiography, then such patient was called consecutive patients with recent NSTEMI. Also, those patients who were diagnosed with NSTEMI, during last four weeks, merely on the basis of ECG indings, new left bundle branch blockade (LBBB) and true posterior MI. The record of each patient was assessed only once. If the same patient underwent angiography again, then his record was excluded to avoid duplication. If the stenosis in left main (LM) coronary vessel was 50% and 70% in all other coronary vessels, then this condition was termed as coronary artery disease (CAD). Coronary artery was said to be non-occluded if the stenosis is <30%. But if there was 100% stenosis with thrombolysis in any major coronary vessel, then the condition was termed as OCA.
Due to limitation of data availability, MACE was recorded only among hospitalized patients. If the patient suffered from re-MI, congestive heart failure (CHF), stroke or died during hospitalization then it was termed as MACE.

Data analysis
Continuous variables were presented as mean and standard deviation (SD) while descriptive statistics including frequency and percentages were employed on categorical data. The statistical signi icant association between continuous variables was found using student's independent t-test and chi-square test. Multivariate logistic regression analysis was used to make comparison between NSTEMI patients undergoing angiography having OCA and non-OCA. The comparison among OCA and non-OCA patients was also made on the basis of MACE by using chi-square test The permission to conduct this study was also obtained from the administrators of the healthcare settings.
Initially, multivariate logistic regression analysis was applied on age, gender, comorbidities, and patient's history. Among them age (p=0.001) and left ventricular ejection fraction (LVEF) (p=0.001) showed a statistically signi icant association. Also revascularization was performed on 50.2% (n=313) of the total inpatients who were index hospitalized. 37.1% (n=116) of patients who underwent revascularization were having OCA while 62.9% (n=197) were suffering from non-OCA. But their difference was not statistically signi icant. The mode of revascularization between OCA and non-OCA groups was different. 24% (n=54) patients in OCA group underwent CABG while in non-OCA CABG was performed on 10.8% (n=43) of the patients. Also, 38.6% (n=154) of non-OCA patients undertook PCI while only 27.6% (n=62) of the OCA patients were underwent PCI (Table 4). 4.6% (n=18) of the NSTEMI patients experienced MACE during index hospitalization. While only 2.6% (n=10) died. The incidence of MACE was high among non-OCA patients as compared to OCA patients but no statistically signi icant association was found (p=0.44) ( Table 5).

Discussion
The diagnosis of coronary artery occlusion via angiography among patients suffering from NSTEMI is not occasional. In the present study angiographic indings   con irmed that 36.1% NSTEMI patients had occluded coronary artery. The frequency of all the occlusions in coronary arteries were fairly uniform. The clinical outcomes of hospitalized NSTEMI patients were not signi icantly differ from those who had coronary artery occlusion. Also, advancement in age and low LVEF were among the predictors of coronary artery occlusion among NSTEMI patients. The indings of present study are in line with the previously published literature. A study conducted in USA on patients undergoing percutaneous coronary intervention (PCI) revealed that 24% of the NSTEMI patients had occluded coronary artery [15]. Furthermore, a single occluded culprit artery was found per NSTEMI patient. There are variations in indings among different studies because of the difference in criteria of patient selection. This is the reason that in a study the frequency of coronary artery occlusion was found to be 29% [16] while in another study it was found to be 63% [17]. The incidence of coronary artery occlusion was high in this study. This might be because of the fact that many patients hesitate to visit medical facilities due to inancial constraints and poor diagnostic facilities. These reasons contribute towards the late detection of ischemic heart diseases. In STEMI patients LAD is the most commonly occluded vessel. But no such predominance of artery with respect to occlusion has reported in NSTEMI. Also, studies concluded LCX occlusion in many cases of NSTEMI [18,19]. Another study revealed occlusion of posterolateral vessels in NSTEMI because of late diagnosis of posterior infarct [13]. While in a study there was uniform distribution of occluded coronary vessels found [15]. In this study LCX occlusion was not commonly found because ECG of those patients was performed regularly who showed precordial ST-T changes.  The risk factors associated with coronary artery occlusion among NSTEMI patients were found to be advancement in age, co-morbidities (e.g., diabetes), gender and low LVEF. These indings are in line with a previously published study [13]. Most of them, excluding age and LVEF, were found to have non-signi icant association in the multivariate regression analysis. Hence, further investigation is needed for exploring these contradictory results.
Furthermore, a study revealed that mortality rate of NSTEMI patients were high among those who had OCA as compared to non-OCA patients [20]. Although no follow up was performed in this study, but in both groups there was no statistical difference found with respect to MACE rates. The rate of mortality was found to be similar among both OCA and non-OCA groups. In contrast to our inding, the previously published studies revealed that the death rate was found to be higher among OCA patients as compared to non-OCA [20,21].
The clinical signs and symptoms of NSTEMI patients varies with the angiographic judgements. But our indings can be bene icial for those NSTEMI patients who undergo angiographic examination during the earlier stage of CAD. These can also be applied to those who are at risk of developing OCA, have CHF, low LVEF, and left ventricular (LV) pump dysfunctioning. For providing better facilities to the patients, it is recommended that non-invasive diagnostic facilities must be provided to those who are suspected to CAD. These facilities may include 80-lead body surface potential mapping (BSPM) [22] and transthoracic echo for LV function, Coronary computed tomography (CT) angiogram or strain rate echocardiography [23].
Like other studies, the present study also have some limitations. First, it is single center study conducted on a very small number of patients for a short duration of time. Second, the study is con ined to those patients who underwent angiography but didn't evaluate the reasons which hinder NSTEMI patients from angiography. It might be possible that therapeutic management is more preferred than angiography for patients having low risk of NSTEMI. Furthermore, elderly patients and renal impaired patients are not allowed to go through this procedure. Thus, this biasness in the selection of patients can negatively effects the interpretation of indings. Third, most of the records were of patients who came to OPDs and it might be possible that among them acute events had passed earlier. Thus, the angiographic indings couldn't be well interpreted because in these patients therapeutic regimen recanalized the coronary lesions. Fourth, the study included those patients who had history of MI, so silent MI could be the cause of OCA on angiogram. Thus, longitudinal prospective studies are requisite to overcome these issues.

Conclusion
It is concluded that most of the NSTEMI patients undergoing angiography were diagnosed with OCA. No vessel was found to be most occluded among majority of the cases. The MACE rate was not signi icantly differ among OCA and non-OCA patients. The risk factors associated with OCA were low LVEF and age. Longitudinal prospective studies in the future are requisite for elaborating this relationship.