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Table of Contents
ORIGINAL ARTICLE
Year : 2019  |  Volume : 8  |  Issue : 2  |  Page : 59-62

Coronary sinus filling time as a marker of microvascular dysfunction in patients with angina and normal coronaries


Cardiovascular Intervention Research Center, Rajaie Cardiovascular, Medical and Research Center, Iran University of Medical Sciences, Tehran, Iran

Date of Submission23-Jul-2019
Date of Decision06-Aug-2019
Date of Acceptance27-Aug-2019
Date of Web Publication03-Oct-2019

Correspondence Address:
Dr. Nasrin Panahifar
Rajaie Cardiovascular, Medical and Research Center, Iran University of Medical Sciences, Tehran
Iran
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/rcm.rcm_17_19

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  Abstract 


Objective: Although chest pain and normal coronary arteries (known as cardiac syndrome X [CSX]) remained a prevalent clinical condition, underlying pathogenesis has not been fully explained. Microvascular dysfunction has been considered as the most likely cause of CSX. In this research, we attempted to evaluate the coronary sinus filling time (CSFT) at angiographic films, and also introducing it as a new indicator for microvascular function. Patients and Methodology: Patients with typical angina or abnormal chest pain with stress-induced ischemia in prior stress tests formed angina group and control group consisted of patients with severe mitral stenosis underwent coronary artery angiography before the balloon mitral valvuloplasty. CSFT was explained as the time necessary for the contrast with pass through myocardial capillaries and reach to the coronary sinus origin at coronary angiography. Furthermore, thrombolysis in myocardial infarction (TIMI), frame count, and myocardial blush score were evaluated for each group. At the end, we compared these parameters and reported the results. Results: The angina group consisted of 128 patients and there were 71 patients in the control group. The mean of the CSFT in angina group was 47.2 ± 9.9 (in frame count), which was greater than the mean of the control group (mean: 32.2 ± 3, P = 0.0001). Corrected TIMI frame count was 21.1 ± 3.4 in angina group and 20.1 ± 3.1 in the control group, and the differences were not statistically significant (P = 0.75). Myocardial blush score in the angina and the control group had not indicate any meaningful difference (P = 0.52). Conclusion: CSFT in contrast with TIMI frame count and myocardial blush score, was significantly prolonged in patients with angina and normal coronary arteries.

Keywords: Cardiac syndrome X, coronary sinus filling time, microvascular dysfunction, myocardial blush score, thrombolysis in myocardial infarction frame count


How to cite this article:
Shakerian F, Panahifar N. Coronary sinus filling time as a marker of microvascular dysfunction in patients with angina and normal coronaries. Res Cardiovasc Med 2019;8:59-62

How to cite this URL:
Shakerian F, Panahifar N. Coronary sinus filling time as a marker of microvascular dysfunction in patients with angina and normal coronaries. Res Cardiovasc Med [serial online] 2019 [cited 2019 Oct 18];8:59-62. Available from: http://www.rcvmonline.com/text.asp?2019/8/2/59/268475




  Introduction Top


Women with cardiac chest pain, which indicated by myocardial ischemia signs and symptoms in the obstructive coronary artery disease (CAD) absence are often labeled as having cardiac syndrome X (CSX).[1] Although CSX (myocardial ischemia symptoms and signs in the CAD absence) occurs in men and women with a certain predisposition, it is acknowledged as a female-predominant disorder classically, and nearly 70% of patients diagnosed as having CSX are women.[2] The etiology of CSX appears nonhomogeneous, and despite of the considerable research effort during the past four decades, there is no generally accepted understanding about the chest pain etiopathophysiology with ischemia and nonobstructive CAD evidence.[3] Coronary microvascular dysfunction (CMD) has been presented as an appropriate explanation for the continued symptoms and higher cardiovascular (CV) morbidity and mortality. CMD is a damaged coronary microcirculatory function. Although epicardial coronary arteries are conduit vessels, the microcirculation consists of resistance vessels, which regulate myocardial blood flow by dilation or contraction, according to cardiac demand.[4] A resistance vessels dysfunction reduces the ability to regulate myocardial perfusion leading to a decreased blood flow, stress-induced ischemia, and altered myocardial metabolism.[5],[6],[7] CMD assessment is very important, therefore, for CMD evaluation, invasive as well as noninvasive methods have been introduced. In this research, we have intended to measure coronary sinus filling time (CSFT) for microvascular dysfunction evaluation in patients with chest pain and normal coronary arteries.


  Patients and Methodology Top


The angina group consisted of patients with typical angina or patients with abnormal chest pain and had stress-induced ischemia in earlier noninvasive stress tests, which had normal coronary arteries in the angiography from March 2015 to February 2017. Typical angina is explained as (1) substernal chest discomfort, (2) initiated by exertion or stress, and (3) relieved with rest or sublingual nitroglycerin. The control group was including patients with severe mitral stenosis undergoing balloon mitral valvuloplasty, who had these inclusion criteria: (1) normal left ventricular size and systolic function at echocardiography, (2) normal pulmonary artery pressure at echocardiography, (3) normal coronary arteries in the angiography, (4) sinus rhythm in the electrocardiography, and (5) no prior cardiac abnormality except mitral stenosis.

The coronary angiography was accomplished at a rate of 15 frames/s. Left coronary arteries by the injector system with 6–8 ml contrast at a rate of 2 ml/s were injected. The vascular access was either femoral or radial artery. We can describe a normal coronary artery as a smooth vessel without any stenosis, irregularity, or ecstasia. Angiographic films were studied in order to assess the thrombolysis in myocardial infarction (TIMI) frame count, myocardial blush score, and CSFT in both of the angina and control group.

The TIMI frame count was explained as the frame numbers, which are required for the contrast with pass through the coronary artery and also reach to the distal landmark. The standardized distal landmark in left coronary system arteries is the last bifurcation. TIMI frame count for left anterior descending artery (LAD) is revised and also corrected by dividing it to 1.7.

CSFT (in frame count) started from the frame, in which LAD has completely opacified, and ended when the contrast reached to the coronary sinus origin. In fact, CSFT is a time mandatory for the contrast in order to transfer throughout myocardial capillaries and reach to the coronary sinus starting site. By dividing the CSFT in frame count into 15, second CSFT can be counted.

Myocardial blush score is a myocardial perfusion semiquantitative measurement, grading from 0 (no myocardial blush) to 3 (normal myocardial blush), according to the myocardial opacification degree. TIMI frame count, CSFT, and myocardial blush score in both groups, and also demographic data just in angina group attained and analyzed with IBM SPSS Statistic (DP Iran Co, Tehran, Iran). For means comparing, the two-tailed t-test was used.


  Results Top


The angina group included 128 patients (83 females and 45 males) with the mean age of 53 ± 9.7 years. Furthermore, there were 71 patients in the control group. Angina group demographic data are shown in [Table 1]. The patients CSFT in angina group (mean: 47.2 ± 9.9 frame count) was evidently longer than that of the control group (mean: 32.2 ± 3 frame count), and the difference was statistically significant (P = 0.0001).
Table 1: Demographic features of angina group

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Corrected TIMI frame count was as 21.1 in the angina group and 20.1 in the control group without any statistical significant difference (P = 0.75). Two mentioned groups were also compared with regard to myocardial blush score (2.95 ± 0.21 in the angina group, and 2.97 ± 0.16 in the control group), and the difference have not any statistical importance (P = 0.52) [Table 2].
Table 2: CS filling time, thrombolysis in myocardial infarction frame count, and myocardial blush score in angina and control groups

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  Discussion Top


A normal coronary angiogram eliminates obstructive epicardial CAD, as the patient's chest pain cause; however, there are a variety of noncardiac and cardiac causes that may be are responsible and warrant for this consideration. The potential cardiac causes for the chest pain are including: both noncoronary and coronary conditions. The noncoronary causes are typically recognizable readily, because of their associated structural valvular or myocardial pathology. Recognizing coronary dysfunction as a reason for the chest pain is more obscure.[8] Provocation test with vasodilator agents has been considered as the major technique for microvascular function evaluation in most of the earlier surveys.

In 1972, Tambe et al.[9] described coronary slow flow pattern (CSFP) as the slow passage of contrast throughout the normal epicardial coronary arteries. Features are similar to CSFP, which may exist in small myocardial arteries. In this research, we attempted to reveal that maybe spontaneous prolonged blood flow transition time, within the myocardial capillaries is responsible for the chest pain in CSX.

Although CSX occurs in men and women with a certain predisposition, it is acknowledged as a female-predominant disorder classically, and nearly 70% of patients diagnosed as having CSX are women.[2] Our study indicated that the female predominance is 64% in angina group.

TIMI frame count and myocardial blush grade (MBG) methods are new angiographic techniques in order to evaluate epicardial coronary blood flow, and myocardial perfusion, respectively.[10],[11] Atmaca et al.[12] have stated that the amount of MBG in patients with syndrome X was decreased significantly, and Mahfouz et al.[13] declared increased TIMI frame count among the patients with CSX; however, other researchers reported no remarkable difference in MBG and TIMI frame count between the patients with syndrome X and the control group.[14],[15] In this study, there were no significant differences in TIMI frame count and myocardial blush score between the two groups.

Sangareddi and Alagesan [14] have defined the CSFT as a time taken for the contrast with the traverse the coronary microvasculature, and coronary sinus, and also, CSFT was a useful parameter in differentiating patients with CSX from the control group. Haridasan et al.[16] introduced CSFT as a novel method for evaluating microvasculur function, and also defined CSFT as the time necessary for the contrast from LAD fully opacification to reach to CS ostium. This research had the same method and findings. We described the CSFT as the time between the LAD maximum opacification frames to the frame in which CS origin was seen. This research established that CSFT in normal coronaries population was prolonged significantly in comparison with the control group, which was similar to earlier researches.[14],[16] Also in this study, the number of cases in the angina and control groups was significantly larger in comparison with the former researches.

CSX prognosis is determined by its components, including chest pain, endothelial dysfunction described as reduced coronary blood flow to acetylcholine, and myocardial ischemia. In a large cohort of women with chest pain and no obstructive CAD by angiography, persistent chest pain happened for the 45% of patients, and was associated with considerably more than twice of the CV events, including MIs, strokes, congestive heart failure, and CV death, compared to those in women without persistent chest pain.[17] This study did not include CSX prognosis.

There were some limitations for this retrospective research. The angiographic films were too short, and it did not show the CS origin; consequently, these cases were excluded. Majority of patients in the angina group were designated by relying just on the background of typical angina (70.3%), and remained cases had positive stress tests. Coronary sinus pressure has important effect on microcirculation time and is correlated with the right atrium pressure. It was not possible for us to have access to the right atrium or pulmonary capillary wedge pressure, and systemic pulmonary artery pressure was considered as the normal CS pressure indicator. Our superiority in this study was large number of cases in both angina and control groups in comparison with the cases of Haridasan et al. research.


  Conclusion Top


CSFT was significantly prolonged in patients with angina and normal coronary arteries. TIMI frame count and myocardial blush score did not show meaningful difference between the angina and control groups in contrast with the CSFT. CSFT may be considered as a useful method for evaluating the microvascular dysfunction.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
  References Top

1.
Kemp HG Jr. Left ventricular function in patients with the anginal syndrome and normal coronary arteriograms. Am J Cardiol 1973;32:375-6.  Back to cited text no. 1
    
2.
Kaski JC, Rosano GM, Collins P, Nihoyannopoulos P, Maseri A, Poole-Wilson PA, et al. Cardiac syndrome X: Clinical characteristics and left ventricular function. Long-term follow-up study. J Am Coll Cardiol 1995;25:807-14.  Back to cited text no. 2
    
3.
Cannon RO 3rd, Watson RM, Rosing DR, Epstein SE. Efficacy of calcium channel blocker therapy for angina pectoris resulting from small-vessel coronary artery disease and abnormal vasodilator reserve. Am J Cardiol 1985;56:242-6.  Back to cited text no. 3
    
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Panza JA. Coronary atherosclerosis: Extending to the microcirculation? Eur Heart J 2010;31:905-7.  Back to cited text no. 4
    
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Crea F, Camici PG, Bairey Merz CN. Coronary microvascular dysfunction: An update. Eur Heart J 2014;35:1101-11.  Back to cited text no. 5
    
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Graf S, Khorsand A, Gwechenberger M, Novotny C, Kletter K, Sochor H, et al. Typical chest pain and normal coronary angiogram: Cardiac risk factor analysis versus PET for detection of microvascular disease. J Nucl Med 2007;48:175-81.  Back to cited text no. 6
    
7.
Reis SE, Holubkov R, Lee JS, Sharaf B, Reichek N, Rogers WJ, et al. Coronary flow velocity response to adenosine characterizes coronary microvascular function in women with chest pain and no obstructive coronary disease. Results from the pilot phase of the women's ischemia syndrome evaluation (WISE) study. J Am Coll Cardiol 1999;33:1469-75.  Back to cited text no. 7
    
8.
Di Fiore DP, Beltrame JF. Chest pain in patients with 'normal angiography': Could it be cardiac? Int J Evid Based Healthc 2013;11:56-68.  Back to cited text no. 8
    
9.
Tambe AA, Demany MA, Zimmerman HA, Mascarenhas E. Angina pectoris and slow flow velocity of dye in coronary arteries – A new angiographic finding. Am Heart J 1972;84:66-71.  Back to cited text no. 9
    
10.
Gibson CM, Cannon CP, Daley WL, Dodge JT Jr., Alexander B Jr., Marble SJ, et al. TIMI frame count: A quantitative method of assessing coronary artery flow. Circulation 1996;93:879-88.  Back to cited text no. 10
    
11.
van 't Hof AW, Liem A, Suryapranata H, Hoorntje JC, de Boer MJ, Zijlstra F, et al. Angiographic assessment of myocardial reperfusion in patients treated with primary angioplasty for acute myocardial infarction: Myocardial blush grade. Zwolle myocardial infarction study group. Circulation 1998;97:2302-6.  Back to cited text no. 11
    
12.
Atmaca Y, Ozdemir AO, Ozdol C, Oguz D, Gulec S, Kumbasar D, et al. Angiographic evaluation of myocardial perfusion in patients with syndrome X. Am J Cardiol 2005;96:803-5.  Back to cited text no. 12
    
13.
Mahfouz Ragab A, Mohamed A, Ashraf E, Kandil Nader T. Cardiac syndrome-X: Is it benign or malignant? An Egyptian follow-up study. Open J Cardiol 2011;2:1.  Back to cited text no. 13
    
14.
Sangareddi V, Alagesan R. Coronary Sinus Filling and Emptying Time: A New Parameter to Assess Coronary Microcirculation by a Simple Angiographic Frame Count. 59th Annual Conference of the Cardiological Society of India; 7-10 December, 2008.  Back to cited text no. 14
    
15.
Chen YC, Hou CJ, Tsai CH. Relationships of the thrombolysis in myocardial infarction frame count withclinical, hemodynamic and medicine variables in syndrome X patients. Int J Gerontol 2008;2:109-14.  Back to cited text no. 15
    
16.
Haridasan V, Nandan D, Raju D, Rajesh GN, Sajeev CG, Vinayakumar D, et al. Coronary sinus filling time: A novel method to assess microcirculatory function in patients with angina and normal coronaries. Indian Heart J 2013;65:142-6.  Back to cited text no. 16
    
17.
Johnson BD, Shaw LJ, Pepine CJ, Reis SE, Kelsey SF, Sopko G, et al. Persistent chest pain predicts cardiovascular events in women without obstructive coronary artery disease: Results from the NIH-NHLBI-sponsored women's ischaemia syndrome evaluation (WISE) study. Eur Heart J 2006;27:1408-15.  Back to cited text no. 17
    



 
 
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