Factors affecting adequate myocardial perfusion in patients with acute st-elevation myocardial infarction with successful epicardial flow

Aim: The aim of this study was to evaluate and compare multifarious parameters between complete and incomplete ST-segment resolution (STR) patients groups and to identify associates of STR in patients with acute ST-segment elevation myocardial infarction (STEMI) after successful primary percutaneous coronary intervention (pPCI). Material and Methods: 888 consecutive patients were divided into two groups according to the STR <70% and ≥70% 60-90 min after pPCI. The cardiovascular risk factors and various angiographic parameters were assessed and compared between the groups. Results: There were 346 patients with incomplete STR and 542 patients with complete STR. In multivariable regression analysis, culprit lesion (Left Anterior Descending artery) (Odd’s Ratio (OR)=1.768; p=0.048), door-to-wire crossing time (OR=0.993; p=0.033), total procedure time (OR=0.994; p=<0.001) and glycoprotein 2b/3a inhibitor use (OR=2.135; p=0.013) were found to be independent risk factors for complete STR. The Area Under Curve of door-to-wiring and total procedure time for STR prediction was 0.668, 0.831, the cut-off value was 58, 52 min, and the sensitivity and specificity were 63.9%, 70.8%, and 63.1%, 76.8%. Conclusion: Even if the successful flow is achieved at the end of pPCI, keeping the procedure time as short as possible and using glycoprotein 2b/3a are the factors that can increase perfusion at the myocyte level


Introduction
Over the past years, great endeavors have been made to improve the outcome of patients with acute ST-elevation myocardial infarction (STEMI).In STEMI, primary percutaneous coronary intervention (pPCI) is the cornerstone of therapy that reduces hospital mortality and long-term mortality.1 Rapid recanalization of infarct-related artery (IRA) with pPCI is associated with better cardiac performance and lower mortality.2 The success of pPCI can be established electrocardiographically (ECG) by measuring ST-segment resolution (STR) after the procedure and angiographically by evaluating Thrombolysis in Myocardial Infarction (TIMI) flow.3 Although revascularization therapy provides complete epicardial blood flow recovery in most STEMI patients sometimes its beneficial effects are not sufficient.Because epicardial blood flow does not necessarily mean adequate perfusion at the myocyte level, STR is considered a surrogate for reperfusion of cardiac myocytes4 because it reflects the physiology of the cardiac cells.5 Complete STR is defined by a drop ≥70% of the ST-segment elevation recorded after PCI. 6 In studies on STR, some patients in the incomplete STR group consisted of patients with post-PCI TIMI flow 0-2.The prognosis is affected due to this situation and worse in this group, as expected, due to more procedural complications and comorbidities.5,7-9 There was a need for re-evaluation on this subject due to reasons such as expanded medical treatment options, shortening of the time to reach pPCI, new procedural techniques, and the quality of the materials used.Additionally, considering that these studies were performed in the first-generation drug-eluting stent (DES) and bare-metal stent (BMS) era, STR predictors in patients with the successful epicardial flow at the end of the procedure arouse curiosity.Our study aimed to evaluate and compare clinical parameters between complete STR and incomplete STR patients' groups in post-PCI normal epicardial flow and to identify clinical associates and their impact on STR.

Electrocardiographic evaluation
The electrocardiographic analysis followed the prevalent normative guidelines, considering complete an ST-segment resolution ≥ 70%.11 Technically adequate 12-lead ECGs before and 60-90 min after pPCI was finished were registered using a speed of 25 mm/s and amplitude of 10 mm/mV.STsegment resolution in ECG was assessed based on ST-segment regression percentage on 60-90th minute ECG, and 70% and above ST resolution was concluded as successful reperfusion.
The elevation of the ST segment was measured at the J point in mm.The arithmetic mean of ST-segment elevation was calculated for anterior STEMI from V1-V6 leads and inferior STEMI from II, III, and aVF leads.

Angiographic evaluation
Coronary angiography was routinely performed through the femoral and radial approach using Judkins catheters (Philips DCI-SX Integris Monoplane system).pPCI was applied to the culprit's vessel in all patients.Patients who underwent pPCI were treated with direct stenting if possible; otherwise, stent implantation was done after balloon angioplasty.Angiograms were recorded at 15 frames/s.The calculated value was doubled to reach the standardized 30 frames/second.The TIMI flow grade was assessed previously at the TIMI Angiographic Core Laboratory.12 Frame counts were determined by the method described previously by Gibson et al13 Left anterior descending artery (LAD) measurements were divided by 1.7 and used as corrected TIMI frame count (TFC).TFC of those with an before the procedure TFG >0 was calculated.The GpIIb-IIIa inhibitor [tirofiban (Aggrastat) 12.5 mg/50 mL; DSM Pharmaceuticals, Greenville, North Carolina] was applied as recommended by ad-hoc guidelines according to the operator's decision based on the coronary angiography result.The total processing time was obtained by calculating the time between the first cine recording and the last recording, which is the time after the removal of the guidewire and no no-reflow detected after that.Door-wiring time was calculated as the time between the patient's admission to the emergency department and the time the wire passed through the lesion angiographically.
The American College of Cardiology (ACC) and the American Heart Association (AHA) classification was used to evaluate the morphology of coronary stenotic lesions.14 The study was conducted in accordance with the protocol, the Declaration of Helsinki revised in 2013, and applicable local requirements.İnformed consent was not obnained from the patients because of retrospective nature.

Statistical analysis
Statistical analyses were performed using SPSS software for Windows 20 (IBM SPSS Inc., Chicago, IL).The distributional properties of the variables were assessed using the Shapiro-Wilk test.Student t-test was used to analyze the normally distributed variables expressed as mean ± standard deviation.
Mann-Whitney U test was used for non-normally distributed variables expressed as median (interquartile range).The parameters that may be clinically related to STR were first evaluated by univariable regression analysis.Then, a multivariable regression analysis including the variables with a p-value ≤0.05 at univariate analysis was performed.A receiver operating characteristic (ROC) curve was generated, and the area under the curve (AUC) was calculated to assess diagnostic value.ROC curve plots the true-positive rate (sensitivity) against the false-positive rate (1-specificity) for all possible cut-off values (Youden's index).AUC and %CI for variables in the ROC analysis are indicated as 1-for easier understanding.P values 2-sided <0.05 were considered statistically significant.
Angiographic parameters are shown in Table 2   We used ROC analysis to examine the ability of door-to-wiring and total procedure time to discriminate STR.The AUC of doorto-wiring time for STR prediction was 0.668 (95% CI = 0.632-0.704;p < 0.001), the cut-off value was 58 min, the sensitivity and specificity were 63.9%, and 63.1%.The AUC values were 0.831 (95% CI = 0.804-0.859;p < 0.001), the sensitivity and specificity were 70.8% and 76.8% for total procedure time, and the cutoff value was 52 min.(Figure -1)

Discussion
In this study, we tried to determine the factors affecting the ST-elevation resolution after successful revascularization.As far as we know, this is the first study on this subject.As a result of this study, we determined that short door-wiring time, short procedure time, use of glycoprotein 2b/3a in the procedure, and culprit lesion location (LAD) were predictors for STR.
The fact that the end-of-procedure flow has not been fully provided, as expected, is a more important reason than other factors because it will affect the myocardial blood supply.This There are also possibly operator-related factors affecting STR, but they could not be categorized.

Conclusion
Even if TIMI-3 flow is achieved in patients after PCI, it is important to keep the procedure time as short as possible and increase the use of glycoprotein 2b/3a to ensure adequate perfusion at the myocardial level.
total of 888 consecutive patients with acute STEMI who underwent PPCI from December 1, 2017, to August 31, 2020, were enrolled in the study in a high-volume tertial-level hospital.The necessary patient information was collected from files from the hospital archive.The inclusion criteria have collaborated diagnosis of STEMI 10 (typical chest pain lasting for more than 20 min and ST-segment elevation of ≥2 mm in men or ≥1.5 mm in women in V2-V3 leads and ≥1 mm in at least other two contiguous leads); symptoms of less than 12 h duration and persistent ST-segment elevation; eligibility for pPCI.The exclusion criteria were thrombolytic therapy; symptom onset more than 12 h; absence or doubtable culprit lesion; culprit lesion not crossable with guidewire; history of coronary artery disease; history of previous MI; paced rhythm; left bundle branch block and post-PCI TIMI flow <3.Dual antiplatelet therapy (300 mg acetylsalicylic acid (ASA)+ 600 mg clopidogrel/180 mg ticagrelor) was given to all the patients, and they were anticoagulated with heparin infusion following the indication.This study aimed to compare demographic and procedurerelated characteristics of patients with and without complete ST-segment resolution after performing pPCI and to identify the variables associated with incomplet ST resolution.Cardiovascular disease risk factors (age, arterial hypertension, diabetes mellitus, dyslipidemia, smoking), sex, and door-towiring time were assessed and compared between complete and incomplete STR groups.

Figure 1 .
Figure 1.ROC analysis examines the door-to-wiring ability and total procedure time to discriminate STR.AUC: area under the curve, CI: confidence interval study was planned because the main issue is determining the factors affecting the STR despite the successful flow.Measuring STR after pPCI is one of the most convenient methods of assessing microvascular injury.Microvascular damage can be structural due to myocardium necrosis or functional due to increased restriction of the microvascular region, edema, endothelial dysfunction, or obstruction with platelets or neutrophils.15Also, the PCI itself can cause microvascular obstruction with plaque debris or thrombus particles.16The development of drugs and treatment regimens that can improve blood flow before PCI is crucial to reducing microvascular injury in STEMI patients.5Early restorations of coronary blood flow are gained by the dissolution of clots, which can be promoted by drugs such as aspirin, other adenosine diphosphate receptor inhibitors (ADP), and heparin.Especially, new generation anti-aggregates play an active role due to more potent platelet inhibition.However, ticagrelor do not affect STR at the end of the pPCI, as in the subgroup analysis of the PLATO study.17Probably because the onset effect of the ticagrelor is between 30 minutes and 2 hours, the procedure often ends until the effect begins.However, ticagrelor's long-term effects are likely superior to clopidogrel, especially in patients with TFG <3.Previous studies have provided evidence of the beneficial effect of GP IIb/IIIa inhibition in acute coronary syndromes.18,19In the Platelet Receptor Inhibition for Ischemic Syndrome Management in Patients Limited by Unstable Signs and Symptoms (PRISM-PLUS) trial, tirofiban was shown to reduce intracoronary thrombus.20These studies demonstrate that GP IIb/IIIa inhibition is valuable in maintaining microvascular perfusion and associated with ST-segment resolution.One of the results in the study in patients with anterior MI had lower STR compared with non.The likely mechanism is that the affected area is more extensive in patients with anterior MI.This finding is concordant with other studies.6,15Theprevalence of hypertension was a prominent finding in STR <70% of patients.Parallel to this finding, the thickness of the IVS was more remarkable.Additionally, IVS was also an independent prognostic factor for an incomplete STR.These results support the possibility that microvascular dysfunction is common in patients with hypertension and that ST-segment recovery is less measured in hypertensive patients with left ventricular hypertrophy.5Optical coherence tomography detected a smaller thrombus volume in the culprit lesion in patients with the acute coronary syndrome who took aspirin before their first presentation compared to those who did not use aspirin before.21In addition to the effects of secondary prevention, antiplatelet therapy may improve coronary reperfusion and clinical outcomes.22In our study, the rate of aspirin users before the procedure was higher in the complete STR group, but it did not reach statistical significance.Lesion complexity is one of the most critical determinants of procedural success and survival in patients undergoing pPCI.23In particular, the type of vessel (according to the criteria of lesion length, calcification, tortuosity, angled segments, and major side branches to be protected) expressed as a type C lesion according to the ACC lesion classification system causes the intensive use of pre dilatation and post-dilation, the need for extra support material and the possibility of bifurcation of the procedure and prolongation of the procedure time.It is one of the most important parameters affecting adequate flow at epicardial and myocardial levels since the risk of developing no-reflow during the procedure is high in patients with vessels with this feature.In our study group, the most remarkable proportional difference between the groups was observed in patients with type C lesions.Over the years, stent technology has come a long way.Significant advantages have been achieved with newgeneration DESs.Late and very late stent micro and macro thrombosis (ST) is more common in BMS compared to firstgeneration DES.Also, this stent group is associated with incomplete strut reendothelialization, polymer-induced chronic inflammation, hypersensitivity reaction, stent malapposition, and accelerated neoatherosclerosis.24,25The probability of successful myocardial blood supply at the end of the procedure increases due to more potent antiaggregant therapies, shorter transportation times to PCI centers, and increased operator experience in the new generation stents era.Stent length and multiple stent treatments may not be as related to damage to the microvascular area as before due to the factors mentioned.Early intervention and the use of potent agents are closely associated with STR.The most critical point of the study is that the shorter duration of the PCI time provides more effective angiographic and electrocardiographic results.This data should be supplemented with symptom-balloon time.Durmaz et al. found that even if no reflow developed, a short ischemic time was significantly associated with its reversibility.26The prolongation of the procedure may be associated with complications, complex intervention during the process, or the desire to achieve the best angiographic image.Sometimes the effort to search for the best can result in problems because of deceleration of the heparin effect due to prolonged processing time, endothelial damage and microthrombuses due to further material transport, and excessive post-dilatation.According to an interesting study on this subject, an increase in peak cardiac troponin levels was detected when balloon occlusion in the coronary arteries lasted for 30 seconds or more, and thus cardiac ischemia was detected.27.Moreover, Reidar Winter et al. showed that catheter and balloon induced ischemia using automated frame-to-frame tracking of gray-scale speckle pattern and subsequent 2D quantification of myocardial motions.28Our findings support keeping the procedure time short in patients with acute MI unless strictly necessary.According to SINCERE database results, procedure time is one of the important parameters in terms of long-term prognosis.29Our study has some limitations.Firstly this study was designed as a retrospective.It is a study investigating the short-term effects of the factors affecting STR and does not show longterm results.Myocardial blush grade calculation was not made.

Table 1 .
. Baseline characteristics of the patients.

Table 2 .
Angiographic characteristics of patients The data without normal distribution is presented as median (interquartile range-IQR).TIMI = Thrombolysis in Myocardial Infarction

Table 3 .
Univariate and multivariate analysis for prediction of STR