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Evolution of the Coronary Microcirculation After Restoration of Epicardial Blood Flow in STEMI

Commented by ESC Working Group on Coronary Pathophysiology & Microcirculation

Pathophysiology and Mechanisms


Successful primary PCI leads to immediate improvements in the index of microcirculatory resistance (IMR) [1], however, there is little knowledge about the natural evolution in the state of the microcirculation.

Methods and Results

Wong CCY et al performed a prospective multicenter study which enrolled 22 patients (8 female) who underwent successful primary PCI for the treatment of ST segment elevation myocardial infarction (STEMI). Mean age of the study population was 65 ± 12 years. The mean time from symptom onset to presentation was 176  ±105 minutes. All patients had serial evaluation of index of microcirculatory resistance (IMR), coronary flow reserve (CFR), and resistive reserve ratio (RRR) performed at 0, 10, 15, and 30 minutes after PCI. A total of 88 physiology measurements were obtained. Authors found that there was a significant decrease in IMR over time (from 0 to 30 minutes post-PCI). Also, both CFR and RRR improved over time (p<0.05). Compared with baseline, CFR was significantly increased already at 15 minutes, and RRR was significantly increased at 30 minutes. Improvements in the microcirculatory indices were predominantly driven by a significant decrease in hyperemic transit time, with no significant changes in resting transit time, resting distal pressure, or hyperemic distal pressure.


The study highlights the dynamism and plasticity of the coronary microcirculation in the early stages after successful epicardial artery reperfusion in STEMI.


Restoration of epicardial coronary artery patency does not always translate into restoration of regular myocardial perfusion. The phenomenon referred to as ‘no reflow’ is associated with severe coronary microvascular injury [2]. The pathophysiological mechanisms behind this phenomenon remain incompletely understood. In reperfusion-related no-reflow, coronary microvascular endothelial damage resulting from either ischemia-reperfusion and/or the associated comorbidities is thought to play a critical role. However, other mechanisms have also been proposed, including time from symptom onset to reperfusion, which penalizes especially women [3-6].  The ‘no reflow’ is a relatively common complication (1-5%) in the setting of STEMI. And, since the extent in the loss of microvascular integrity is associate with a worse prognosis [3], various strategies have been proposed to minimize or prevent it after stenting. Results are conflicting. As mentioned, the study in comment has highlighted the dynamism and plasticity of the coronary microcirculation in the early stages of STEMI reperfusion with stent. Therefore, it provides one more reason to support research devoted to microcirulation as a therapeutic target during myocardial revascularization.

Clear understanding of the pathophysiology of the coronary microvasculature during STEMI is a critical step to improve primary PCI outcomes.

During the two last decades several diagnostic tests have been proposed for the evaluation of microvascular function in the cath lab [3]. In the present study, patients underwent the evaluation of CFR, IMR, RRR. CFR is the ratio between maximum and rest myocardial blood flow. The technique interrogates the overall coronary circulation, evaluating coronary macro- and micro-compartments without distinction. IMR measures the resistance to myocardial flow, specifically related to the coronary microcirculation compartment. IMR is defined as the ratio of distal coronary pressure and the thermodilution-derived mean transit time during maximal hyperaemia, measured with a pressure/temperature wire. RRR represents the vasodilatory capacity of interrogated vessels including both epicardial coronary artery and microvascular circulation. All the above techniques are invasive and give a functional/hemodynamic evaluation. Direct assessment of the coronary microcirculation has long been hampered by the limited spatial and temporal resolutions of cardiac imaging modalities. Currently, there is no available tool to image directly the entire coronary microcirculation in clinical or preclinical settings, which in turn has limited considerably the knowledge on the coronary microcirculation pathophysiology and the development of effective therapeutic strategies. However, a new technique is under developed to image and quantify the microvascular coronary flow of beating perfused hearts [8].  The coronary ultrasound localization microscopy (CorULM) has just provided unprecedented insights (<20 micron resolution) into the anatomy and function of coronary arteries at the microvasculature level in beating rat hearts [7]. This new technology is highly translational and has the potential to become an important tool for the clinical investigation of the coronary microcirculation.

In conclusion, the study demonstrates the plasticity of the coronary microcirculation immediately after primary PCI. The observation is relevant to the development of targeting treatment interventions, which will also benefit from information deriving from a promising tool (CorULM) that enables visualization and quantification of the coronary microvascular flow.  



  1. De Maria GL, Cuculi F, Patel N, et al. How does coronary stent implantation impact on the status of the microcirculation during primary percutaneous coronary intervention in patients with ST-elevation myocardial infarction? Eur Heart J. 2015;36:3165–3177.
  2. Scarpone M, Cenko E, Manfrini O. Coronary no-reflow phenomenon in clinical practice. Curr Pharm Des. 2018;24(25):2927-2933. doi: 10.2174/1381612824666180702112536.
  3. Padro T, Manfrini O, Bugiardini R, Canty J, Cenko E, De Luca G, Duncker DJ, Eringa EC, Koller A, Tousoulis D, Trifunovic D, Vavlukis M, de Wit C, Badimon L. ESC Working Group on Coronary Pathophysiology and Microcirculation position paper on 'coronary microvascular dysfunction in cardiovascular disease'. Cardiovasc Res. 2020 Mar 1;116(4):741-755. doi: 10.1093/cvr/cvaa003
  4. Cenko E, Ricci B, Kedev S, Kalpak O, Câlmâc L, Vasiljevic Z, Knežević B, Dilic M, Miličić D, Manfrini O, Koller A, Dorobantu M, Badimon L, Bugiardini R. The no-reflow phenomenon in the young and in the elderly. Int J Cardiol. 2016 Nov 1;222:1122-1128. doi: 10.1016/j.ijcard.2016.07.209.
  5. Cenko E, Yoon J, Kedev S, et al (2019) Sex-Specific Treatment Effects After Primary Percutaneous Intervention: A Study on Coronary Blood Flow and Delay to Hospital Presentation. In: Assoc. JAH, ed. p e011190
  6. Bugiardini R, Ricci B, Cenko E, et al (2017) Delayed Care and Mortality Among Women and Men With Myocardial Infarction. J Am Heart Assoc 6:.
  7. Demeulenaere O, Sandoval Z, Mateo P, Dizeux A, Villemain O, Gallet R, Ghaleh B, Deffieux T, Deméné C, Tanter M, Papadacci C, Pernot M. Coronary Flow Assessment Using 3-Dimensional Ultrafast Ultrasound Localization Microscopy. JACC Cardiovasc Imaging. 2022 Jul;15(7):1193-1208. doi: 10.1016/j.jcmg.2022.02.008.




Notes to editor

Olivia Manfrini, MD, FESC,
Laboratory of Epidemiological and Clinical Cardiology, Department of Experimental, Diagnostic and Speciality Medicine (DIMES), University of Bologna, Italy.

The content of this article reflects the personal opinion of the author/s and is not necessarily the official position of the European Society of Cardiology.

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