ABC | Volume 114, Nº3, March 2020

Original Article Candemir et al. Slow Flow and Magnetic Resonance Imaging Arq Bras Cardiol. 2020; 114(3):540-551 tissue. The etiology of CSFP has not been clearly understood since it was first described. Although CSFP may be the result of microvascular alterations, increased microvascular resistance and early stage widespread atherosclerosis have also been shown to play a role in the etiology. 22,23 In addition, histological and pathological changes in the coronary arteries have been tried to be used for elucidating the etiology. In a study conducted in patients with CSFP, Mangieri et al. 17 found changes such as cellular edema, fibromuscular hyperplasia, medial hypertrophy, myointimal proliferation, irregular fibrosis, capillary damage and decreased capillary lumen, as a result of myocardial biopsy, and claimed that these pathological changes slowed blood flow by increasing vascular resistance. 22,23 Moreover, in CSFP, intravascular ultrasonography (IVUS) has shown diffuse intimal thickening and widespread calcification, and coronary angiography has shown atheromatous plaques that do not cause luminal irregularity. 24 Although coronary slow flow has been reported to be associated withmany pathologic conditions, it appears to be the onset of a widespread atherosclerotic disease that is coincidental with a microvascular disease in which endothelial dysfunction is in the forefront. It can be considered that microvascular ischemia and fibrosis may develop in the myocardial tissue in patients with CSFP as a result of changes that take place at the microvascular level and our study supports this view. The deteriorated coronary microvascular function in CSFP has been shown to be associated with increased risk of cardiovascular events. 25-27 It has also been reported that, in patients with microvascular dysfunction, the prognosis is similar to that observed in obstructive coronary artery disease, and that this dysfunction is not as benign as it is thought to be. 28-30 Clinical manifestations of this pathology are also associated with significant findings. Atypical chest pain, 16-31 typical chest pain 32 and resting chest pain that require urgent intervention 4,33 frequently occur in patients with coronary slow flow. Similarly, patients with CSFP were found to be more symptomatic and their hospital admissions were found to be more frequent. 34 Based on this, CMR may be considered a good choice for investigating whether the myocardial tissue is affected or not, as well as providing a favorable option to evaluate the extent of the injury in patients with CSFP. Delayed contrast-enhanced CMR has high spatial resolution. With this method, the boundary between the infarcted tissue on the LV wall and the viable myocardium can be identified by examining the area of coronary slow flow. In addition, the transmural spread of the infarction area can be determined with this method. It is also possible to distinguish between vascular and non-vascular ischemia owing to the diffusion of gadolinium. 8 In non-ischemic cardiomyopathy, gadolinium involvement is independent of vascular perfusion and occurs in the subendocardial region. Gadolinium involvement is directly associated with vascular feeding in ischemic cardiomyopathy. In addition, this involvement is in the subendocardial or transmural region. 35 Panting et al. 31 demonstrated subendocardial hypoperfusion with CMR in patients with syndrome X, which is believed to be associated with microvascular dysfunction. 36 In the same way, Lanza et al. 32 detected perfusion defects in the LAD region of the myocardium in syndrome X patients. 37 It is also shown that there is an important relationship between a myocardial perfusion reserve, which is examined with CMR and coronary microvascular dysfunction, and is a precursor of early atherosclerosis. 38 NT-proBNP may be considered after an effort test in patients with coronary slow flow. It can give information about cardiac fibrosis, although it may be affected by several conditions. However, it is not possible to perform a CMR in all patients with low TIMI frame count due to cost effectiveness. CMR may be considered in patients with severe coronary slow flow degree, severe chest pain and high biomarker values after exercise. Because of the small number of patients in our study, we cannot make any recommendations about treatment, CMR or biomarker control. However, this study will shed light on studies on both treatment (anti-fibrotic drugs) and examination (CMR, NT-ProBNP, among others). Study Limitations Our study had a few limitations. First, the number of patients was low. Second, coronary angiographies were performed by different clinicians and, although angiographic images were standardized, there were negligible differences between the projections. Finally, the intravascular ultrasound (IVUS) technique, which can show the structure and functions of coronary arteries in detail, fractional flow reserve (FFR) and intracoronary pressure (pressure-wire) measurements, and acetylcholine testing were not performed in our study. However, performing these invasive tests, with their potential complications, in patients with no epicardial stenosis is not appropriate due to ethical reasons. Conclusion In this study, which was conducted to demonstrate scar tissue related to CSFP, CMR with delayed gadolinium enhancement technique has been found to yield valuable results. CMR showed scar tissue in patients with slow flow. These results suggest that the slow flow phenomenon may result in irreversible changes in myocardial tissue. The probable consequences of these changes should be investigated in further studies. Author Contributions Conception and design of the research: Candemir M, Şahinarslan A, Yazol M, Boyacı B; Acquisition of data and analysis and interpretation of the data: Candemir M, Şahinarslan A, Yazol M, Öner YA, Boyacı B; Statistical analysis and obtaining financing: Candemir M, Boyacı B; Writing of the manuscript: Candemir M; Critical revision of the manuscript for intellectual content: Şahinarslan A, Öner YA. Potential Conflict of Interest No potential conflict of interest relevant to this article was reported. Sources of Funding This study was funded by Gazi University Scentific Research Projects. Study Association This article is part of the thesis of Doctoral submitted by Mustafa Candemir, from Gazi University. Ethics Approval and Consent to Participate This study was approved by the Ethics Committee of the Gazi University under the protocol number 83. All the procedures in this study were in accordance with the 1975 Helsinki Declaration, updated in 2013. Informed consent was obtained from all participants included in the study. 549