Acute Coronary Syndromes (ACS)—Unravelling Biology to Identify New Therapies—The Microcirculation as a Frontier for New Therapies in ACS

Abstract

In acute coronary syndrome (ACS) patients, restoring epicardial culprit vessel patency and flow with percutaneous coronary intervention or coronary artery bypass grafting has been the mainstay of treatment for decades. However, there is an emerging understanding of the crucial role of coronary microcirculation in predicting infarct burden and subsequent left ventricular remodelling, and the prognostic significance of coronary microvascular obstruction (MVO) in mortality and morbidity. This review will elucidate the multifaceted and interconnected pathophysiological processes which underpin MVO in ACS, and the various diagnostic modalities as well as challenges, with a particular focus on the invasive but specific and reproducible index of microcirculatory resistance (IMR). Unfortunately, a multitude of purported therapeutic strategies to address this unmet need in cardiovascular care, outlined in this review, have so far been disappointing with conflicting results and a lack of hard clinical end-point benefit. There are however a number of exciting and novel future prospects in this field that will be evaluated over the coming years in large adequately powered clinical trials, and this review will briefly appraise these.

Optical Coherence Tomography Angiography Changes in Patients Diagnosed With Acute Coronary Syndrome: A Systematic Review and Meta-Analysis

“…Clinical outcomes, prognosis, and cardiac remodeling in ACS can be explained by the underlying pathophysiological mechanisms. Microcirculation resistance and microvascular damage have a cardinal role in the pathogenesis of ACS [ 27 , 28 ]. CMD refers to the structural and functional remodeling of the microcirculation due to both coronary microcirculation and myocardium changes and can be evaluated by both invasive and non-invasive modalities [ 29 ].…”

“…Coronary microvascular obstruction (CMVO) is a term to describe the lack of reperfusion of coronary microcirculation post MI despite the restoration of epicardial vessel patency. Its pathogenesis is based on CMD, ischemic injury, distal embolization, ischemia-reperfusion injury, genetic polymorphisms, ischemic pre-conditioning, and inflammation [ 28 ]. CMVO is associated with poor survival, heart failure (HF), and left ventricular remodeling, and can be assessed by cardiac magnetic resonance (CMR).…”

“…Sideri et al [ 11 ] showed that left ventricular ejection fraction (LVEF) was significantly associated with the perifoveal area of SCP (β coefficient = 0.06; 95% CI: 0.02 - 0.10, p= 0.006), the perifoveal area of the DCP (β coefficient = 0.10; 95% CI: 0.01 - 0.18, p = 0.026), and the CC layer (β coefficient = 0.28; 95% CI: 0.11 - 0.45, p = 0.002). Undoubtedly, LVEF has been described in CMVO [ 28 ]. Wang et al [ 9 ] suggested that changes in retinal and choroidal microvasculature could reveal high-risk CAD patients, despite the early stage of the disease.…”

Impact of Impaired Cholesterol Homeostasis on Neutrophils in Atherosclerosis

“…44 Percutaneous coronary intervention of such lesions causes a rapid increase in the intra-coronary concentration of NETs, 45 which predisposes to microvascular obstruction, subsequent periprocedural events, and worse long-term outcomes. 31,46…”

Acute Coronary Syndrome: Unravelling the Biology to Identify New Therapies

“…In this issue, Khandkar et al [ 2 ] reviewed the most recent evidence regarding the pathophysiology of atherothrombosis and discussed the role of intracoronary imaging to determine the underlying cause of thrombosis and to ultimately guide ACS management. Additionally, Vaidya et al [ 3 ] reviewed the crucial role of coronary microcirculation in ACS and its potential as a therapeutic target. Complications of atherosclerotic disease, including ACS, ischaemic non-cardioembolic stroke and peripheral artery disease, are the leading causes of morbidity and mortality worldwide.…”