Our study evaluated the preprocedural CHA2DS2-VASc score and the brachial arteries FMD as predictors for the no reflow phenomenon in patients with STEMI undergoing primary PCI. The rate of no-reflow following primary PCI in our study was 26%, which was in agreement with previously described no-reflow rates between 11 and 41% with variation between different studies according to the patient characteristics, angiographic factors, and management methods [9].
The current study evaluated the risk factors with a statistically significant effect on the incidence of no-reflow using univariate regression analysis. Those factors included age > 59 years, BMI > 30 m2/kg, diabetes mellitus, glycated haemoglobin (HbA1c) among diabetic patients (> 8.3%), hypertension, history of heart failure, dyslipidemia, Killip class on admission, number of affected vessels, thrombus grade, PTCA, stents number, stent length > 33 mm. Yang et al. [8] revealed that low systolic blood pressure on admission < 100 mmHg, and pre PCI high thrombus score were risk factors for no-reflow as confirmed by our study findings. In another study, advanced age, prolonged pain to door time, and Killip class IV on admission were demonstrated to be independent predictors for no-reflow [9]. Moreover, Durante et al. [10] found that hypertension, dyslipidemia, and larger ischemic regions were independent risk factors for no-reflow. Dean et al. [11] also discovered an association between diabetes mellitus and micro-vascular dysfunction, one of the underlying processes of no-reflow. Also, 443 patients with acute STEMI and underwent primary PCI were studied in another study that found a significant statistical relation between the HbA1c level and one year 1ry adverse cardiovascular complications, including mortality, recurrent ischemia, and stroke [12]. Our studied patients with longer pain-to-door time had a significantly greater thrombus burden and an increase in no-reflow rates than patients with short reperfusion times (p-value = 0.000) and this was confirmed by Sabin et al. and his colleagues [13], who showed that patients with a long time before reperfusion (> 6 h) had a considerably higher thrombus burden and a 1.3 fold greater no-reflow rate than those with a short reperfusion interval. The incidence of angiographic no-reflow among our studied population was 15% among the direct stenting group and the conventional stenting group was 33%. This ratio between both groups is similar to the ratio of Antoniucci et al. [14] showing that the incidence of angiographic no-reflow was 12% in the conventional stenting group and 5.5% in the direct stenting group (p-value = 0.040).
The current study's findings confirmed the clinical significance of the CHA2DS2 VASc score in predicting no-reflow after primary PCI where the CHA2DS VASc score was significantly higher in patients with < TIMI III flow (p-value = 0.000) and patients with MBG < II (p-value = 0.002) compared to those with TIMI III and MBG ≥ II. These findings were consistent with those of Mirbolouk et al. [15], who discovered that the CHA2DS2VASc score was an important predictor of no-reflow in 398 patients with acute STEMI (p-value = 0.001). Significantly, the CHA2DS2 VASc score was associated with suboptimal revascularization and short-term adverse cardiovascular outcomes after primary PCI in patients with acute STEMI, which may indicate that the score effectively predicts the outcomes in patients by predicting no-reflow [16]. So, high-risk patients for no reflow could be identified with simpler risk scores, more effective medications and follow up of patients may be given.
The median of FMD% in the studied population was higher in patients with TIMI III Flow (p-value = 0.000) and in patients with MBG ≥ II (p-value = 0.027) than in those with TIMI < III flow and MBG < II adding a value in addition to the CHA2DS2 VASc score to identify high-risk patients for no-reflow and follow up them. In addition, the multivariate regression analysis of different independent factors increasing no-reflow risk showed significant value only for FMD% ≤ 11% (p-value = 0.000) (odds ratio = 68.250). A limited number of studies have tried to identify the relation between endothelial dysfunction, and suboptimal reperfusion, and short-term adverse cardiac events after primary PCI. In a recent study, the endothelial function was assessed for patients with acute STEMI using brachial artery FMD during a hospital stay after being revascularized by primary PCI and a strong correlation was found between the FMD and the MBG among the studied population (p = 0.029) [17]. However, drugs with a well-established effect on improving endothelial dysfunction such as nitrates and statins could have influenced the results of that study, which was avoided in our study by doing the FMD test during patient preparation in the cath lab before the procedure. Neunteufl et al. [18] also showed that endothelial dysfunction using FMD is related to cardiovascular complications in patients without known IHD but have chest pain and have undergone coronary angiography. In addition, Karatzis et al. [19] found that FMD is an independent indicator of subsequent cardiovascular events in patients who survive non-STEMI admission [19]. Furthermore, intravascular ultrasonography has recently confirmed the link between a lower FMD value and a larger necrotic core in coronary plaque in both culprit and non-culprit arteries [20]. In 26 individuals without any coronary plaques and with only sluggish coronary flow, Ari et al. [21] found a statistically significant negative correlation between FMD and TIMI frame count (p-value = 0.004). This study differs from ours in terms of the group population and the patient preparation. However, the independent relationship between nitric oxide synthase inhibitor and brachial artery FMD, as well as the association between impaired brachial artery FMD and higher TIMI frame count, validated the significance of nitric oxide and its production inhibitors in endothelial dysfunction in coronary vessels. The results of Ari et al. [21] enforced our work theory that there is an obvious correlation between endothelial dysfunction and slow coronary flow even in angiographically normal coronary arteries. Thus, before and after the primary PCI, a clinical assessment of the brachial artery FMD gives valuable prognostic information in the long-term care of patients at high risk for no-reflow.
There was a significant negative correlation between the CHA2DS VAS score and preprocedural FMD% in our study, with the higher the score indicating lower FMD among cases (p-value = 0.000). Endothelial dysfunction is an important risk factor in most cardiovascular diseases, and it is associated with advanced age, hypertension, diabetes mellitus, and vascular disease and these factors are part of the CHA2DS2-VASc score [22]. So, FMD is expected to be impaired in a patient with a higher CHA2DS VAS score as suggested from the current study.
The current study didn't find a significant relationship between the CHA2DS VASc score or FMD% and the incidence of inpatient MACE (p-value = 0.164, 0.723 respectively). These findings differed from those of Guazzi et al. [23], who discovered a significant correlation (p-value = 0.01) between the values of brachial artery FMD in 197 patients who presented with myocardial infarction and the incidence of MACE over a period of 13.7 (± 9.5) months [23]. The discrepancy between the two trials could be attributable to the Guazzi et al. study having a longer follow-up period and a larger number of participants. However, Frick et al. [24] discovered a non-significant correlation (p-value = 0.79) between brachial artery FMD and MACE in 398 male patients who underwent coronary angiography due to chest pain over a 4-year follow up period. Patients admitted with acute coronary syndrome were omitted from Frick's study, which could explain the disparity in results between Frick et al. [24] and Guazzi et al. [23].
Limitations
The study is based on single-center data with a small sample size. Also, micro-vascular perfusion was not accurately assessed by nuclear imaging or better by cardiac magnetic resonance imaging. In addition, the short follow-up period made the MACE assessment suboptimal.
