Background: Cardiovascular diseases (CVD) are one of the leading causes of mortality and morbidity worldwide. Among them the spectrum of ischemic heart disease which encompass stable ischemic heart disease, unstable angina, NSTEMI & STEMI is the commonest cause. Coronary no-reflow is a frequent phenomenon that develops in patients with ST-segment elevation myocardial infarction during reperfusion therapy. In this study, we focused on to assess the prevalence of coronary no reflow in STEMI patients undergoing primary PCI. Methodology: This study was conducted in patients in Cath lab, Coronary Care Unit and different wards of the department of Cardiology in Apollo Multispecialty Hospital Limited during the period of 18 months spanning from November 2021 to April 2023. Consecutive patients of STEMI who had undergone PPCI were enrolled in this study. The patients to be included are those with STEMI above age≥18 years. They were divided into no reflow and normal flow and their characteristics were studied. Results: The prevalence of no reflow was 9.93%. Majority of the patients had age more than 60 years (55%) whereas 45% of the patients were younger than 60 years with males (71%) and females (29%). Common associated condition with patients undergoing percutaneous coronary intervention in present study was hypertension (86%), dyslipidemia (80%) and diabetes mellitus (93%). TIMI thrombus scale and Myocardial blush grade (MBG) was significantly higher in patients with hypertension. There was a significant difference found in TIMI thrombus scale and MBG between diabetic and non-diabetic patients. There were significant differences found in mean LVEF in respect to myocardial blush grade (MBG). Conclusion: The TIMI thrombus scale and myocardial blush grade was found to be higher in patients with no reflow undergoing PCI. The prevalence of no reflow after primary PCI is 9.93%. The co morbidities like DM, hypertension and dyslipidemia were more common among these patients.
Cardiovascular diseases (CVD) are one of the leading causes of mortality and morbidity worldwide. [1] Among them the spectrum of ischemic heart disease which encompass stable ischemic heart disease, unstable angina, NSTEMI & STEMI is the commonest cause. Data from the Framingham Heart Study suggests lifetime risk for ischemic heart diseases among individuals is 37.5% for men and 18.3% in women and the incidence is on the ascendance. [2] The proportion of acute coronary syndrome cases which constitute STEMI varies across observational studies but the ratio has decreased in last decade due to increase in incidence of NSTEMI cases due to more sensitive and diligent detection methods. Reperfusion therapy within the recommended window period by Primary percutaneous coronary intervention (PPCI) is the gold standard of treatment of STEMI. PPCI restores thrombolysis in myocardial infarction (TIMI) 3 flow in over 90% of patients.[3] However there remains a small proportion of patients, who continue to exhibit overt impairment of myocardial perfusion despite successful opening of infarct related epicardial artery (IRA). This phenomenon is called no reflow or no flow, which refers to a state of myocardial hypoperfusion in the presence of patent epicardial coronary artery. Sudden loss of epicardial flow following balloon dilatation or stenting may also occur in incomplete lesion dilation, epicardial vascular spasm, epicardial dissection or in situ thrombosis. These procedural failures are totally different clinical subsets and need careful exclusion from no reflow which is mainly due to microvascular obstruction. Its overall incidence is 2% and in STEMI the incidence is 11-41%. [4] No reflow has a negative effect on the clinical outcome negating the potential benefit of PPCI in STEMI.[5,6,7] Indeed no reflow is regarded as an independent predictor of procedure related mortality and morbidity.[8] No reflow may set in a sudden and dramatic fashion after completion of PCI (within 1–2 h). Recognition of no reflow in the cath lab or coronary care unit is essential for salvaging the patient. [9]
Defined by angiography, the no-reflow phenomenon is manifested by an acute reduction in the coronary flow (thrombolysis in myocardial infarction [TIMI] flow grade=0–1) in the absence of dissection, thrombus, spasm, or high-grade residual stenosis at the original lesion site. Lesser degrees of flow impairment (TIMI score=2) are generally referred to as “slow flow”. Clinically no reflow may present with the recurrence of chest pain, cardiogenic shock with hypotension, malignant arrhythmias or acute dyspnea due to pulmonary edema secondary to heart failure. No reflow is a progressive phenomenon and its presentation may be delayed. Early detection, preventive measures and treatment of no reflow is imperative for a better outcome but often is unsatisfactory. It is crucial to identify which patients are more prone to develop no reflow. As for patient related factors previous studies found that advanced age, diabetes and hypertension are important predictors of no-reflow. Among biochemical parameters elevated White blood cell (WBC) count, thrombus grade/score, mean platelet volume (MPV), platelet-to-lymphocyte ratio (PLR), neutrophil-to-lymphocyte ratio, duration between onset of chest pain and PCI (≥4 h), hyperglycemia and raised serum creatinine were some predictors.[10,11] Coronary angiography is the conventional method to diagnose no reflow in the cath lab. No reflow is quantified by various scales like thrombolysis in myocardial infarction (TIMI) flow, corrected TIMI frame count (CTFC), TIMI myocardial perfusion grade (TMPG) and myocardial blush grade (MBG).[12,13] However, in practice, TIMI flow and MBG are most commonly used. The clinical and biochemical parameters differ in patients with normal flow and those with no reflow which is investigated here. Also from the available literature there has been no study in Eastern India on this subject. Hence, present study was performed to investigate the clinical, laboratory and procedural characteristics associated with the no-reflow phenomenon in patients undergoing PPCI on native coronary arteries for STEMI.
Objectives:
To assess the prevalence of coronary no reflow in STEMI patients undergoing primary PCI and to assess the risk factors for such.
This study was conducted in Coronary Care Unit and different wards of the department of Cardiology in Apollo Multispeciality Hospital Limited from November 2021 to April 2023. Consecutive patients of STEMI in the time frame who had undergone primary percutaneous coronary intervention were selected. Primary PCI was done and they were segregated into normal flow and no reflow groups based on TIMI flow grades.
Surface ECG was done for all patients at the emergency room or within 10 minutes after admission. Coronary angiography was performed and those fulfilling the criteria for intervention were recruited for the study. Contraindications like patients who need CABG or didn’t give consent were excluded. PCI was performed using a standard femoral or radial approach with a 6- or 7-F guiding catheter. All the patients receive 300 mg of oral aspirin and 600 mg of Clopidogrel or 180 mg of Ticagrelor immediately after admission. Patients who had high thrombus burden received GpIIbIIIa inhibitor infusion.
Data collection procedure:
The patients of STE-ACS who fulfill the inclusion criteria were recruited by purposive conventional sampling in the stipulated study period. The patients who develop coronary no reflow were recruited and data were collected from all patients. Those who have any one or more of the exclusion criteria were excluded from the final sample size. For all these patients undergoing primary PCI history were noted and physical examination was done. Patients were taken to the operation theatre and during primary PCI different angiographic features documented during coronary angiography were noted. Biochemical and hematological parameters were noted from investigations done at time of admission.
The Statistical Package for the Social Sciences for Windows version 20 (IBM SPSS Inc., Chicago, IL, USA) were used for the statistical analysis. Normally distributed continuous data is described as mean±standard deviation, while non-normally distributed data is shown as median (range). Categorical variables are shown as number and percentage. For continuous variables, Student’s t test or the Mann Whitney U-test was used. To detect association between categorical variables, the chi-square test was used and Fisher’s exact test in the case of sparse data whenever appropriate.
15x100 |
= 9.93 |
151 |
A total of 151 patients of STEMI were analyzed. Among them 15 patients had no reflow during PCI and 136 patients had normal flow.
So the prevalence of no reflow is
The different clinical, biochemical and angiographic parameters were noted and compared between the groups of patients.
Table 1: Comparison between mean ages of study participants
|
Group |
P value |
||
No reflow |
Normal |
Total |
||
Mean |
66.60 |
60.06 |
60.71 |
0.064 |
SD |
14.242 |
12.762 |
13.014 |
Table 2: Comparison of sex distribution between groups
|
Group |
Total |
P Value |
||
No reflow |
Normal |
||||
Sex |
Female |
5 |
42 |
47 |
0.846 |
Male |
10 |
94 |
104 |
|
|
Total |
15 |
136 |
151 |
|
Table 3: Comparison of co morbidities between the two groups
|
Group |
Total |
P value |
||
No Reflow |
Normal |
||||
Diabetes mellitus |
NO |
1 |
50 |
51 |
0.019 |
YES |
14 |
86 |
100 |
||
Hypertension |
NO |
2 |
85 |
87 |
<0.001 |
YES |
13 |
51 |
64 |
||
Dyslipidemia |
NO |
3 |
45 |
48 |
0.302 |
YES |
12 |
91 |
103 |
||
Hypothyroid
|
NO |
8 |
81 |
89 |
0.642 |
YES |
7 |
55 |
62 |
||
Peripheral vascular disease |
NO |
8 |
110 |
118 |
0.214 |
YES |
7 |
26 |
33 |
||
Ischemic heart disease |
NO |
11 |
101 |
112 |
0.924 |
YES |
4 |
35 |
39 |
||
Family history of coronary artery disease |
NO |
9 |
95 |
104 |
0.676 |
YES |
6 |
41 |
47 |
Table 4: Comparing addiction habits between groups
|
Group |
Total |
P value |
||
No reflow |
Normal |
||||
Smoking |
NO |
9 |
72 |
81 |
0.838 |
YES |
6 |
64 |
70 |
||
Alcohol |
NO |
10 |
80 |
90 |
0.557 |
YES |
5 |
56 |
61 |
Table 5: Association between BMI and TIMI flow
|
TIMI flow |
Total |
P value |
|||
1 |
2 |
3 |
||||
BMI |
Underweight |
0 |
2 |
0 |
2 |
0.022 |
Normal |
4 |
6 |
34 |
44 |
||
Overweight |
4 |
4 |
56 |
64 |
||
Obese |
4 |
4 |
27 |
35 |
||
Severe obese |
0 |
0 |
5 |
5 |
||
Morbid obese |
0 |
1 |
0 |
1 |
||
Total |
12 |
17 |
122 |
151 |
|
Table 6: Correlation between biochemical parameters and flow
Biochemical parameters |
Group |
P value |
|
No reflow |
Normal Flow |
||
H/R |
64.13±14.81 |
69.56±15.77 |
0.206 |
SBP |
105.33±16.41 |
109.89±16.22 |
0.304 |
DBP |
61.33±8.64 |
62.98±10.75 |
0.568 |
Hemoglobin |
11.460±2.32 |
12.05±2.03 |
0.298 |
WBC |
12800.0±3833.87 |
9033.24±2392.44 |
<0.001 |
Neutrophils |
88.67±2.74 |
75.75±7.39 |
<0.001 |
Lymphocyte |
7.73±2.57 |
17.68±6.77 |
<0.001 |
Platelet |
4.16±1.58 |
1.75±0.59 |
<0.001 |
PCV |
34.53±7.57 |
36.95±6.29 |
0.169 |
Urea |
76.13±27.55 |
41.57±24.63 |
<0.001 |
Creatinine |
2.22±0.68 |
1.36±0.47 |
<0.001 |
RBS |
299.60±79.48 |
218.29±72.0 |
<0.001 |
CPK |
200.73±40.03 |
169.59±34.92 |
0.002 |
CPK-MB |
48.40±12.37 |
34.79±13.64 |
<0.001 |
cholesterol |
213.80±43.93 |
192.03±35.54 |
0.030 |
TG |
134.80±23.39 |
126.09±24.16 |
0.186 |
HDL |
39.20±6.27 |
42.94±5.55 |
0.016 |
LDL |
123.53±25.17 |
107.96±25.93 |
0.028 |
Table 7: Correlation between biochemical parameters and TIMI flow
Biochemical parameters |
TIMI flow grade |
P value |
|||||
1 |
2 |
3 |
|||||
Mean |
SD |
Mean |
SD |
Mean |
SD |
||
H/R |
64.33 |
15.808 |
79.82 |
12.953 |
67.98 |
15.549 |
0.007 |
SBP |
107.33 |
17.084 |
111.53 |
14.449 |
109.35 |
16.494 |
0.786 |
DBP |
62.75 |
8.170 |
62.76 |
9.404 |
62.83 |
10.966 |
0.999 |
Haemoglobin |
11.508 |
2.3750 |
12.324 |
2.1727 |
11.988 |
2.0224 |
0.580 |
WBC |
13458.33 |
3888.084 |
8747.06 |
2502.778 |
9100.98 |
2384.314 |
<0.001 |
Neutrophils |
88.25 |
2.864 |
77.47 |
10.578 |
75.87 |
7.152 |
<0.001 |
Lymphocyte |
8.17 |
2.691 |
15.94 |
9.270 |
17.63 |
6.548 |
<0.001 |
Platelet |
4.4908 |
1.39188 |
1.7194 |
1.00338 |
1.7780 |
.58754 |
<0.001 |
PCV |
34.75 |
7.887 |
37.65 |
6.670 |
36.77 |
6.285 |
0.480 |
Urea |
78.50 |
30.183 |
56.29 |
51.700 |
40.13 |
17.571 |
<0.001 |
Creatinine |
2.2333 |
.62426 |
1.5647 |
.95325 |
1.3502 |
.39676 |
<0.001 |
RBS |
279.83 |
67.371 |
249.71 |
100.706 |
217.85 |
71.186 |
0.011 |
CPK |
203.83 |
44.452 |
169.53 |
30.038 |
170.06 |
35.370 |
0.008 |
CPK-MB |
51.25 |
11.841 |
34.76 |
7.387 |
34.84 |
14.211 |
<0.001 |
Cholesterol |
219.50 |
46.349 |
190.24 |
34.572 |
192.25 |
35.582 |
0.045 |
TG |
135.50 |
24.858 |
126.82 |
22.498 |
126.13 |
24.335 |
0.442 |
HDL |
38.75 |
6.580 |
44.65 |
5.733 |
42.66 |
5.495 |
0.021 |
LDL |
124.17 |
28.025 |
108.24 |
22.852 |
108.24 |
26.214 |
0.130 |
Table 8: Comparing localization between groups
|
Group |
Total |
P value |
||
No reflow |
Normal |
||||
Localization |
Anteroseptal |
2 |
19 |
21 |
0.308 |
Anteroapical |
0 |
20 |
20 |
||
Anterolateral |
3 |
17 |
20 |
||
Extensive anterior |
2 |
10 |
12 |
||
Lateral |
0 |
1 |
1 |
||
Posterolateral |
0 |
6 |
6 |
||
Infero lateral |
3 |
7 |
10 |
||
Inferior |
4 |
27 |
31 |
||
Posteroinferior |
1 |
22 |
23 |
||
Anteroinferior |
0 |
7 |
7 |
||
Total |
15 |
136 |
151 |
|
In our study the prevalence of no reflow was 9.93%. This was slightly lower than the previous data. One potential explanation for this difference might be the application of a standardized definition of no-reflow such as angiographically visible flow impairment despite patent epicardial coronary arteries whereas other studies have taken liberal definitions such as failure to achieve TIMI 3 flow at the conclusion of the procedure or usage of more sensitive tests like perfusion imaging. Usage of glycoprotein IIbIIa inhibitors was quite frequent compared to other studies resulting in lower incidence.[39] In our study, majority of the patients had age more than 60 years (55%) whereas the patients with no reflow had a mean age of 66 years compared to 60 years in normal flow. Explanation for this is probably due to pre-existing microvascular dysfunction. There was male preponderance both in patients with STEMI about 69% and in those with no reflow about 66%. This is similar to the study conducted by Refaat et al.[15] who found that the mean age of the no-reflow group was significantly higher than that of the normal flow one (65.21 ± 11.89 vs. 56.61 ± 10.39 years, P < 0.001) with similar proportion of male female proportion. We reported that the majority of the patients of ACS in present study belonged to upper middle class 42%. Among patients of no reflow 26.7% belonged to upper, upper middle and upper lower class category. We reported the most common associated condition with patients of no reflow while undergoing percutaneous coronary intervention in present study was diabetes mellitus (93%), hypertension (86%), dyslipidemia (80%) with lesser prevalence of hypothyroidism (46%), IHD (26%) , family history of CAD (40%), peripheral vascular disease (46%). Among these factors diabetes and hypertension was significantly higher compared to patients with normal flow. Recent studies have suggested that no reflow is more commonly seen in combination with hyperglycemia, hypercholesterolemia, and mild to moderate renal insufficiency. [16]
In our study, out of 151 patients, 46% of patients were smokers whereas 40% indulged in consumption of alcohol. There was no statistical significance among these habits between the two groups. Confounding factor in our study is women are usually teetotalers conforming to Indian society norms so smoking pattern has appeared non-significant. This is further substantiated by the fact; among the 6 smokers who had no reflow 5 were male and a solitary female. In a recent study from Thailand among 22741 subjects no reflow and also long term MACE was more among smokers after adjustment for baseline characteristics. The pathogenesis for smoking related cardiovascular disorders is multifactorial involving inflammation, plaque rupture, augmented thrombotic factors, hepatic enzyme induction, and drug interaction and medication compliance.[17] We reported that the majority of the patients undergoing PCI were overweight (42%). We found a significant association between BMI and TIMI flow (p<0.05) showing that patients with higher BMI had poor flow. This was similar to the results found by Hawkins et al.[18] that the slow flow patients were significantly more obese (BMI 33.9 vs. 29.8 kg/m2, P=0.003) and had significantly lower levels of high-density lipoprotein (HDL) compared with normal flow patients (39.7 vs. 45.7mg/dl, P= 0.04). Kosugeet al. [19] found that there was a trend toward a lower TIMI flow grade with increasing BMI. This may be partly due to alterations in hemostatic variables, associated with hypercoagulable states like plasminogen activator inhibitor. In our study 33% of patients presented in the time frame of 24-48 hours. The time window for reperfusion therapy in STEMI is based on current understanding and evidence of the benefits of reperfusion therapy. As more clinical evidences have showed up, the reperfusion time window for STEMI patients has been expanded from 12 hours to 48 hours.[20] In the recent Polish Registry of Acute Coronary Syndrome (PL-ACS) outcome of reperfusion in late presenters was evaluated at 12 months where there was lower mortality in the invasive arm substantially. Bouisset et al [21] analyzed observational studies enrolled in the monthly FAST-MI program and revascularized patients did well at a median follow up of 58 months. No reflow is a common complication among late presenters but there is no causal association. There was no significant difference found in conventional TIMI flow grade between the two groups with previous use of antiplatelet, dyslipidemic drugs, anti-anginal, ACEIs and diuretics drugs as revealed by insignificant p value of >0.05. The RAS axis activation results in increased production of angiotensin II which subsequently increases vascular resistance, myocardial workload, and myocardial oxygen demand. In our study use of the medicines didn’t have statistically significant effect among the groups because most of the patients were already on these medicines for other indications like hypertension & diabetic nephropathy. But the incidence of no reflow was lower than current data among all the ACS patients. Our study found that inferior wall MI was most common among patients with no reflow but there was no statistical difference. In CREATE registry, 60.6% presented with STEMI, whereas in Kerala ACS registry[22] 37% of total patients with ACS presented with STEMI and in Global Registry of Acute Coronary Events (GRACE) study, STEMI cases ranged between 30 and 40%.[23] There were significant differences in mean LVEF in respect to conventional myocardial blush grade (MBG) as lower LVEF was seen in lower grades. MBG reflects myocardial perfusion and microvascular patency so, it has been termed as an independent predictor of residual ejection fraction >50%, in patients with STEMI. Lower LVEF implies higher chance of heart failure which is one of the effects of no reflow. In addition, the MBG may reflect the patency of the microvasculature and has been found to have an additive predictive value for long term mortality and infarct size after PPCI.[24] TIMI thrombus scale was higher in the no reflow group. There was no significant association with use of GpIIbIIa inhibitors between the two groups.
In conclusion, we found that elderly male patients with higher BMI were more associated with no reflow. The comorbidities like DM, hypertension and dyslipidemia were more common among these patients. We found that TLC, neutrophil, serum urea and creatinine level, CRP and CPK-MB level showed significance regarding the prediction of no reflow. Majority of the patients had the site of ischemia located to the inferior wall followed by antero-apical wall. Delay in time of presentation, higher grade of thrombus are some other predictive factors. The TIMI thrombus scale and myocardial blush grade was found to be higher in patients with no reflow undergoing PCI.
Conflict of interest: None declared
Funding: Nil