|Year : 2022 | Volume
| Issue : 1 | Page : 19-24
Assessment of risk factors, clinical presentation and angiographic profile of coronary slow flow phenomenon
Sara Ashraf Abd-Elghaffar1, Raghda Ghonimy El Sheikh2, Ayman Ahmed Gaafar2, Yasser Hussein Elbarbary2
1 Department of Cardiology, Faculty of Medicine, Tanta University, Tanta, Egypt
2 Department of Cardiology, Tanta University, Tanta, Egypt
|Date of Submission||22-Jan-2021|
|Date of Decision||01-Feb-2021|
|Date of Acceptance||09-Feb-2021|
|Date of Web Publication||08-Feb-2022|
Dr. Sara Ashraf Abd-Elghaffar
Agricultural Road, EL-Bahr Street, Tanta
Source of Support: None, Conflict of Interest: None
Background: Primary coronary slow flow phenomenon (PCSFP) is a clinical entity that causes attacks of mild to severe chest pain. It is characterized by delayed coronary vessel opacification in the absence of epicardial stenosis. This work aimed for the assessment of predictors, clinical presentation, and angiographic profile of PCSFP. Subjects and Methods: This cross-sectional case–control study was done between February 2019 and January 2020, including 150 patients who presented by ST-segment myocardial infarction, non-ST segment myocardial infarction, unstable angina, chronic coronary syndrome, or atypical chest pain. The patients were divided into two groups: group 1: consisted of 100 patients who had PCSFP and Group 2: consisted of 50 patients who had normal coronary flow (NCF). Results: PCSFP was significantly more prevalent in young male patients. Among the traditional risk factors, there was significantly more prevalence of hypertension (63.0% vs. 28.0%, P = 0.001), obesity (body mass index ≥30 kg/m2 (47.0% vs. 4.0%, P = 0.001), and history of smoking (66.0% vs. 40.0%, P < 0.002) in PCSFP patients as compared to NCF patients. Triglyceride (TG), cholesterol, low-density lipoprotein, high-sensitivity C-reactive protein (hs-CRP), and hemoglobin all were higher in patients with PCSFP. Low high-density lipoprotein levels were associated with PCSFP. In multivariable analysis, PCSFP was significantly independently associated with male sex, high TG, cholesterol, and hs-CRP. TG (odds ratio [OR]: 14.427, 95% confidence interval [CI]: 3.514–59.226) and cholesterol (OR: 11.739, 95% CI, 2.439–56.513) are the strongest independent predictors for PCSFP. Conclusion: PCSFP is more common in young smoker males, is associated with hypertension, obesity, high hs-CRP, TG, and cholesterol levels. High cholesterol and TG and male sex are the strongest risk factors for PCSFP. Furthermore, inflammation plays an important factor in the pathogenesis of PCSFP due to the association of high hs-CRP level in those patients.
Keywords: Angiographic profile, clinical presentation, coronary slow flow, risk factors
|How to cite this article:|
Abd-Elghaffar SA, El Sheikh RG, Gaafar AA, Elbarbary YH. Assessment of risk factors, clinical presentation and angiographic profile of coronary slow flow phenomenon. J Indian coll cardiol 2022;12:19-24
|How to cite this URL:|
Abd-Elghaffar SA, El Sheikh RG, Gaafar AA, Elbarbary YH. Assessment of risk factors, clinical presentation and angiographic profile of coronary slow flow phenomenon. J Indian coll cardiol [serial online] 2022 [cited 2022 May 27];12:19-24. Available from: https://www.joicc.org/text.asp?2022/12/1/19/337352
| Introduction|| |
Primary coronary slow flow phenomenon (PCSFP) is characterized by delayed coronary vessel opacification in the absence of epicardial stenosis as well as angiographically by a delayed progression of the contrast medium injected into the coronary tree.
Slow opacification of distal parts of normal epicardial coronary arteries in the absence of ventricular dysfunction, connective tissue disorder, valvular heart diseases, and coronary spasm characterizes this phenomenon.
Although there has been a great interest in identifying the underlying mechanisms of PCSFP, the etiology and pathogenesis remain uncertain. Endothelial dysfunction, microvascular abnormalities, occult atherosclerosis, and inflammatory processes are among the proposed factors that contribute to the pathogenesis of PCSFP.
PCSFP is an important angiographic finding typically observed in patients presenting with acute coronary syndrome (ACS), in particularly unstable angina. This phenomenon should be considered a separate clinical entity with peculiar characteristics, pathogenic mechanisms, and defined diagnostic criteria. Clinicians should be aware of this condition and its clinical significance. Further experimental investigations are needed to reveal the pathogenesis involved in PCSFP. In addition, large-scale clinical studies are warranted to better characterize this phenomenon and most importantly investigate potential therapeutic approaches.
This work aimed for the assessment of predictors, clinical presentation, and angiographic profile of PCSFP.
| Subjects and Methods|| |
This cross-sectional observational study was done between February 2019 and January 2020 in the Cardiology Department in Tanta University, including 150 patients which included study group comprising 100 consecutive patients who had undergone coronary angiography (CAG) and showed features of PCSFP and control group comprised 50 consecutive patients who had undergone CAG and showed normal coronary flow (NCF).
- Inclusion criteria: Patients of age >18 years, who presented with ACS, chronic stable angina, atypical chest pain whose coronary angiogram showed normal coronaries with PCSFP (n = 50) and NCF (n = 100) were included in the study
- Exclusion criteria were conditions associated with “secondary” PCSFP (e.g., coronary artery plaque, spasm, or obstructive lesion, myocardial bridge, cardiomyopathy, valvular heart disease, and connective tissue disease).
All recruited patients were subjected to:
- Request to sign a consent form
- Through history taking and physical examination
- Height and weight were measured using a standardized protocol. Body mass index (BMI) was calculated by dividing weight in kilograms by height in meters squared
- Standard 12-lead electrocardiogram (ECG) at rest was routinely recorded for abnormalities
- Laboratory investigation included complete blood count, lipid profile including (total cholesterol, high-density lipoprotein [HDL], low-density lipoprotein [LDL], triglycerides [TGs]), serum creatinine and urea, virology (HCV antibodies, HBVs antigen, and HIV antibodies), and high sensitivity C-reactive protein (hs-CRP) (≥2 mg/dl represent a marker for inflammation)
All patients underwent CAG using cine angiographic equipment: Philips Integris FD (flat detector 10/10): cine frame: (15 fps) A conversion factor of 2 was used to convert the frame rate values filmed at 15 frames/s, to adjust for the 30 frames/s acquisition speed used in the original cine angiographic studies.
Selective CAG with standard multiangulated angiographic views right and left as well as cranial and caudal angulations was performed through the femoral or radial artery under local anesthesia (2% lidocaine) using the 6 Fr Judkins catheters and iopromide (Ultravist) as the contrast agent. Significant CAD was defined as lumen diameter stenosis of ≥50% in any of the major coronary arteries. The vascular sheaths were removed, and homeostasis was achieved by applying direct pressure over the puncture site (generally 1.0–1.5 cm cephalic to the skin incision) for sufficient time to ensure the cessation of bleeding at least 10 min.
The diagnosis of PCSFP was made at the time of CAG using the corrected thrombolysis in myocardial infarction (TIMI) frame count. Corrected TIMI frame count (CTFC) represents the number of cine frames required for contrast to reach the standardized distal coronary artery landmarks. We measured the number of cine frames required for contrast to reach standard distal coronary landmarks in the left anterior descending (LAD) artery, left circumflex (LCX) artery, and right coronary artery (RCA) using the cine viewer frame counter. The first frame is defined as the frame in which dye fully enters the artery, it extends across the entire width and touches both borders of origin of the artery with the antegrade flow. The last frame was defined as the one in which dye enters but not necessarily completely opacifies the distal landmark branch.
The distal landmark branch of LAD artery was whale's tail at the apex of heart. The distal landmark for LCX artery was distal bifurcation of the major obtuse marginal and that of the RCA, It was the first branch arising from the posterior lateral extension of the RCA after the origin of the posterior descending artery regardless of the size of this branch [Figure 1].
|Figure 1: Thrombolysis in myocardial infarction frame count method. Adapted from Gibson et al.|
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The TIMI frame count of the LAD artery was corrected by dividing the final count by 1.7. The cutoff values were defined according to the TIMI frame count method of Gibson et al. (36 ± 2.6 for LAD, 22.2 ± 4.1 for Cx, 20.4 ± 3.0 for RCA). In the present study CSFP was defined as CTFC greater than 2 standard deviations (SD) from normal published range for that particular vessel(CTFC greater than 24 frames for LAD, 26 for RCA and 30 for LCX).
All statistical data were processed using IBM SPSS Statistics for Windows, Version 19.0. Armonk, NY: IBM Corp. Qualitative data were described using number and percent. Quantitative data were described using range (minimum and maximum), mean, and SD. Student's t-test and Chi-square test were used to compare the variables. A stepwise multivariate analysis was done for independent variables. Odds ratios and 95% confidence intervals were also calculated. P < 0.05 was considered statistically significant.
| Results|| |
The mean age of participants was 51.36 ± 10.24 years; the mean age did not differ between the PCSFP and NCF group, however PCSFP was significantly more prevalent in males (76.0%) than females (24.0%) (P = 0.001).
Among the traditional risk factors, there was significantly more prevalence of hypertension (63.0% vs. 21.0%, P = 0.001), obesity (BMI ≥30 kg/m2 (47.0% vs. 4.0%, P = 0.001), and history of smoking (66.0% vs. 40.0%, P = 0.002) in PPCSFP patients as compared to NCF patients. Diabetes mellitus (48.0% vs. 36.0%, P = 0.163) and renal disease (14.0% vs. 6.0% P = 0.145) were more prevalent in PCSFP group than in NCF group; however, this difference was not statistically significant.
Chronic coronary syndrome (CCS) was the most common mode of presentation in the PCSFP group (53.0%) and was also statistically more significant than the NCF group (53.0% versus 14.0%). In the PCSFP group, the remaining 47% represented whose presenting with the ACS and atypical chest pain. Among ACS patients, unstable angina presentation was “15.0%” versus 10.0% “in PCSFP and NCF groups, respectively. NSTEMI presentation was 14.0% in the PCSFP group versus 6.0% in the NCF group. STEMI was 3.0% in the PCSFP group versus 4.0%” in NCF group.[Figure 2] Atypical chest pain was more common mode of clinical presentation in the NCF group compared to the PCSFP group (66.0% versus 15.0%, respectively) [Table 1].
|Figure 2: Percentage of clinical presentation in primary coronary slow flow phenomenon patients|
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|Table 1: Comparison between both groups according to demographic data, clinical presentation, and risk factors|
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Normal ECG was the most common ECG finding in the PCSFP group representing 68% of patients. Resting ECG abnormalities in the PCSFP group were present in 32%. LBBB was the most common abnormality among these ECG changes (16%). Other abnormalities included RBBB in (8%) and resting ST/T wave changes is present in 8% [Table 2].
Out of the 100 cases, 69% of cases had slow flow in one vessel, 11% had slow flow in 2 vessels being LAD, and LCX was the most common combination and 20% had slow flow in triple vessels. The PCSFP was found in the LAD artery in 68% of patients, in the LCX artery in 46.0%, and in RCA in 37.0% [Figure 3].
|Figure 3: Percentage of the affected coronary vessel in primary coronary slow flow phenomenon patients|
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The mean CTFC was 45.2 ± 16.2 for LAD, 46.7 ± 11.5 for LCX, and 44.4 ± 10.0 for RCA [Table 3].
|Table 3: Mean thrombolysis in myocardial infarction frame count of each coronary vessel in both groups|
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Hemoglobin (Hb) level was higher in the PCSFP group than in the NCF group with a statistically significant difference between the two groups (P = 0.044). Serum creatinine level, urea level, and INR were similar in the two groups. White blood cell (WBC) and platelet count were also similar in the patients of both groups [Table 4].
Patients with PPCSFP had higher TG, cholesterol, and LDL levels compared to those in the NCF group, with a high statistical significant difference (P = 0.001). HDL levels were lower in the PPCSFP group compared to the NCF group with a statistically significant difference between the two groups (P = 0.001). Hs-CRP levels were higher in the PPCSFP group than in the NCF group with a statistically significant difference between the two groups (P = 0.001) [Table 3].
Using univariable analysis, we found that PPCSFP is significantly associated with (HTN, smoking, male sex, and obesity (BMI >29 kg/m2), high TG, cholesterol, LDL, hs-CRP, Hb, and low HDL. However, multivariable analysis using the significant variables showed that PCSFP was significantly independently associated with male sex, high TG, cholesterol, and hs-CRP. TG with odds ratio (OR):14.427, 95% confidence interval (CI):3.514 – 59.226, P value= 0.001, Cholesterol with OR: 11.739, 95% CI, 2.439 – 56.513, P value= 0.002 were the strongest independent predictors for PCSFP. [Table 5]
|Table 5: Univariable and multivariable logistic regression analysis for determinants associated with primary coronary slow flow phenomenon|
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| Discussion|| |
We have aimed in our study to explore the clinical and angiographic characteristics of the PPCSFP condition among Egyptian people. To assess coronary flow, the TIMI frame counting method (CTFC) is quantitative and relatively objective.
Risk factors and pathophysiology of the PCSFP phenomenon are still unclear and studies done in different populations have found various risk factors to be related to the PCSFP phenomenon.
In our study, the mean age of our patients was 54.80 ± 9.11 years, which is comparable well with previous studies that reported these people to be generally younger than those with obstructive coronary artery disease. We found that PCSFP is more often encountered in males as 76% of our patients were male. Male gender was statistically significant in PCSFP than in NCF, also on multivariable regression analysis, an independent association of male sex with PCSFP was found, being one of the strongest predictors for PCSFP. This is consistent with other studies as Hawkins et al. and Sanghvi et al. where they found that male sex was significant in PCSFP than in NCF.
Regarding smoking, our study revealed that the PCSFP phenomenon was more common in smokers with a high statistical significant difference between both groups, and we considered smoking as an independent predictor of PCSFP using multiple variable regression analysis. This was in agreement with Kalayci et al. and disagree with Güneş t al.
Our study revealed that BMI may be considered as an independent predictor of the PCSFP following a multivariable analysis. The average BMI of our cohort was 29.07 ± 2.67 kg/m2, with 47% had BMI ≥30 kg/m2 (obese). This might be due to an increase in the incidence of obesity in the Egyptians. This came in agreement by Hawkins et al., where they found patients with PCSFP had higher BMI.
Our study had observed that hypertension is considered as a significant risk factor for PCSFP. The prevalence of HTN in PCSFP was 63.0% in comparison with NCF (28.0%) with high statistical significant difference. This is agreed with a study was done by (Mohammad Muthiullah and Sanati et al. in which the majority of PCSFP patients had hypertension in comparison with NCF with high statistical significant difference between the two groups.
In our study, diabetes mellitus was not significantly associated with PCSFP. This is consistent with Sanghvi et al. where diabetics and fasting blood glucose values were not significantly different between the slow flow and normal flow groups.
Regarding renal and hepatic diseases, there was no significant difference between the two groups.
According to clinical presentation, the PCSFP presentation is extremely varied from atypical chest pain, stable angina, or ACS. In our study, CCS was the most common mode of presentation. This is agreed with Kumar S et al. study where the common clinical presentation was CCS (56%) and 44% with ACS.
According to ECG, in our study, most patients presented by typical angina pain with normal ECG. This is disagreed with a prospective cross-sectional study performed by Mohammad Muthiullah where 76% of patients with PCSFP had an abnormal resting ECG.
According to the vessel affected by PCSFP, slow flow in one vessel was the most common angiographic finding (69%) and LAD was the most common artery involved. LAD, LCX, and RCA were involved in 68%, 46%, and 37% of cases, respectively.
This agreed with the study of Sanghvi et al., 2018 in which the LAD artery (82.5%) was the most commonly involved vessel followed by the LCX artery (67.5%) and RCA (60%).
Regarding laboratory findings, in an attempt to identify readily available laboratory markers of PCSFP, the changes of circulating platelets, WBCs, and Hb level of patients were investigated. In the present study, we found no association between PCSFP and white blood cell count or platelet count and there was no significant difference between PCSFP and NCF groups. This agreed with the study conducted by Ghaffari et al. where there was no association of PCSFP with WBCs, unlike platelet count that was high in PCSFP in comparison with NCF in this study.
The hemoglobin levels of patients in the PCSFP group were higher than in the NCF with a statistically significant difference between both groups, but no strong association between Hb level and PCSFP was found following multivariable analysis. This is agreed with Ghaffari et al. and with Nough et al. where the hemoglobin of patients in the PCSFP group was higher than in the NCF group. Along with other explanations for PCSFP, increased hemoglobin in patients with PCSFP, as described in our study, may contribute to decreased blood flow in coronary arteries.
According to hs-CRP, we found that PCSFP patients had higher levels of Hs-CRP, 60% of the study population had hs-CRP levels of ≥2 mg/L at baseline versus 14.0% in NCF patients with a statistically significant difference between both groups. Using the multivariable analysis, hs-CRP was found to be an independent predictor of PCSFP. This was in agreement with Mahfouz et al. and Nough et al. which showed high levels of Hs-CRP in patients with PCSFP pointing to the involvement of Hs-CRP as an inflammatory marker to the PCSFP process.
There was a statistically significant difference regarding the lipid panel (cholesterol level, LDL, TG, and HDL) between both groups. The levels of cholesterol, TG, and LDL were higher in the PCSFP group relative to the NCF group, and the HDL-c level was significantly lower in the PCSFP group. However, only high cholesterol and TG levels were found to be independent predictors of PCSFP using multivariable analysis. This comes in agreement with Kalayci et al. where there was a significant association between the PCSFP phenomenon and higher TG, cholesterol, and LDL. In accordance with our findings, Yokoyama et al. showed that vascular dilatation was reduced in hypertriglyceridemic patients without significant coronary stenosis, and they reported that hypertriglyceridemia was an independent risk factor for microvessel dysfunction. Sezgin et al. also reported that high TG levels and low HDL might cause endothelial dysfunction in PCSFP patients.
According to serum creatinine, urea, and INR level, there was no statistically significant difference between PCSFP and NCF groups; this is consistent with many studies as Kalayci et al. and Hamid et al.
We would like to emphasize some of the limitations of our study; this is a single-center experience with a small number of cases due to the rarity of the disease, so these observed results may have encountered selection bias, the or using was not assessed. Future studies should also be done assessing these indices.
| Conclusion|| |
PCSFP is an important clinical entity that is more common in young smoker males, is associated with hypertension, obesity, high hs-CRP, TG, and cholesterol levels. High cholesterol and TG and male sex are the strongest risk factors for PPCSFP. Furthermore, inflammation plays an important factor in the pathogenesis of PPCSFP due to the association of high hs-CRP level in those patients.
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Conflicts of interest
There are no conflicts of interest.
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[Figure 1], [Figure 2], [Figure 3]
[Table 1], [Table 2], [Table 3], [Table 4], [Table 5]