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Coronary Artery Disease: Part I-Medical
Coronary artery disease is due to atherosclerosis and atherosclerotic plaque rupture resulting in arterial occlusion or dislodged materials from plaques blocking smaller branches of coronary artery. The risk factors for atherosclerosis are numerous including dyslipidemia, diabetes, hypertension, cigarette smoking, obesity, hyperhomocysteinemia, C-reactive protein, and advanced glycation end products (AGE) and its cell receptor (RAGE) and soluble receptors sRAGE (soluble receptor for AGE) and esRAGE (endogenous secretory receptor for AGE). Coronary artery stenosis manifests in clinical syndrome called stable angina and acute coronary syndrome (ACS) that includes unstable angina, and ACS [ST-segment elevated myocardial infarction (STEMI), and non-ST-segment elevated myocardial infarction (NSTEMI). Coronary artery disease (CAD) is the main cause of death globally. Fifty percent of all death from cardiovascular disease is due to CAD. This thematic issue contains 10 papers and covers recent development in epidemiology, pathogenesis, diagnosis, prevention, treatment modalities, and future directions. A short summary of each paper is outlined below.
Prasad K in the paper titled “AGE–RAGE Stress and Coronary Artery Disease” has reviewed the role of AGEs and its cell receptor RAGE and soluble receptors sRAGE and esRAGE in the development and progression of CAD. Atherosclerosis and rupture of atherosclerotic plaques lead to CAD. AGE and RAGE are atherogenic, while sRAGE and esRAGE are antiatherogenic. Serum levels of AGE, AGE-RAGE stress (ratio of AGE/sRAGE), expression of RAGE (atherogenic lesion in animal) are elevated, while serum levels of sRAGE and esRAGE are reduced in patients with CAD. Prasad has advised that AGE and sRAGE should be measured simultaneously to assess AGE-RAGE stress that is the best biomarker/risk factor for diseases. Treatment of CAD should also be targeted at reduction in AGE levels, suppression of RAGE expression, blockade of RAGE, elevation of sRAGE and use of antioxidants to prevent, regress, and slow the progression of CAD.
The paper titled “Pathophysiology, Diagnosis, and Management of Coronary No-Reflow Phenomenon” by Kaur G et al provides a succinct review of current understanding of the pathophysiology, clinical predictors, clinical characteristics, and management of coronary no-reflow phenomenon. Incidence of this phenomenon is high following percutaneous coronary intervention (PCI) and is associated with adverse in-hospital and long-term outcomes. Three major distinct mechanisms include ischemia-reperfusion injury, distal artery thromboembolism, and heightened individual susceptibility of coronary circulation injury. They have described pharmacological management of this condition using adenosine, calcium channel blocker, sodium nitroprusside, and glycoprotein IIB/IIIa inhibitors. Intra-aortic balloon pump and mechanical support for this condition have also been mentioned.
In the paper titled “Effect of PCSK9 E670G and R46L Polymorphisms on Major Adverse Cardio-Cerebrovascular Events in Patients with ST-Segment Elevation Myocardial Infarction Undergoing Primary Percutaneous Coronary Intervention” Santoso describes the polymorphism in PCSK9 on major adverse cardiovascular events (MACE) in STEMI patients undergoing PCI). He hypothesized that MACE is possibly associated with polymorphism in proprotein convertase subtilisin/kexin type 9 (PCSK9) in STEMI patients undergoing PCI. The objective of this study was to investigate if there is association between polymorphism of E670G and R46L in PCSK9 gene with MACE in STEMI patients. He observed that GOFE670 G polymorphism of PCSK9 gene was associated with MACE among patients of STEMI undergoing primary PCI within 6 months follow-up. No R46L polymorphism was observed in this study. It was also observed that prior consumption of statin was significantly associated with higher plasma PCSK9 among patients with STEMI.
Ronald R and Veselka J have provided an excellent review on the topic of “Optical Coherence Tomography of the Coronary Arteries” This review summarizes the latest published data on the clinical use of optical coherence tomography (OCT) and practical algorithm for OCT-guided PCI for daily interventional practice. They have described in detail the technical aspects, advantages and disadvantages of OCT technology, and clinical and imaging outcomes of OCT-guided PCI. They have stressed the importance of preinterventional OCT assessment such as plaque morphology, stent sizing, and its length. Mechanisms of stent failure have also been discussed. OCT/IVUS (intravascular ultrasound) catheters and further technological improvement would certainly advance the intracoronary imaging.
Angiography does not accurately assess the functional significance of coronary lesions and often stenosis deemed severe with angiographic assessment but do not restrict coronary blood flow at rest or with maximal dilatation. Patel et al in the review titled “Functional Assessment of Coronary Artery Lesions—Old and New Kids on the Block” have discussed in detail the physiological basis, tools, techniques, and evidence for various invasive ([resting and hyperemic] and noninvasive methods for functional assessment of coronary lesions. Left main stenosis, bifurcation lesions, serial stenosis, and ACS each causes unique disequilibrium that may affect the measurements, and require special consideration for accurate functional assessment. They have described in detail invasive hyperemic (functional flow reserve, contrast flow reserve), invasive nonhyperemic (pressure distal to lesion compared with pressure in aorta, instantaneous free ratio, resting full cycle ratio, diastolic hyperemic free ratio, diastolic pressure ratio), and noninvasive modalities (stress testing, stress echocardiography, myocardial perfusion imaging with single-photon emission computed tomography or positron-emission tomography). Angio-derived fractional flow reserve is a new quick and noninvasive method for the functional assessment of intermediate lesion. Large-scale randomized trials are currently underway to assess this modality.
Mukerjee in the paper titled “Management of Chronic Total Occlusion of Coronary Artery” has provided an extensive review on the optimal management of chronic total occlusion (CTO) of coronary artery including medical therapy, revascularization (PCI, coronary artery bypass graft [CABG]). Coronary artery CTO is defined as completely occluded coronary artery without any antegrade blood flow for more than 3 months. He has examined the contemporary optimal guideline directed medical management of CTO and assessed the clinical outcomes and role of contemporary revascularization. He has mentioned that long-term outcomes of successful CTO-PCI is associated with lower risk of death and stroke, and less recurrent angina as compared with failed procedures. The national guidelines suggest that CTO-PCI is considered only if occluded vessel is responsible for symptoms, and patient has debilitating angina despite optimal guideline directed medical therapy. In patients with CTO, the presence of left main disease, anatomically complex multivessel disease, especially in patients with diabetes, severe left ventricular dysfunction, chronic kidney disease, occluded proximal left anterior descending branch of coronary artery, and presence of multiple CTO favor CABG over PCI as revascularization modalities.
In the paper titled “Management of ST-Elevation Myocardial Infarction in High-Risk Settings” Tak has focused on the management of STEMI patients with high risk such as cardiogenic shock and cardiac arrest or those with certain anatomic features such as multivessel coronary artery disease or left main coronary artery disease. He stresses on therapeutic approaches such as medical treatment, revascularization (PCI, fibrinolysin, CABG), and/or mechanical support (intra-aortic balloon counter pulsation, Impella device, venoarterial extracorporeal membrane oxygenation in STEMI patients with cardiogenic shock). STEMI involving left main coronary artery is infrequent but is associated with high mortality. The treatment option for this problem has been discussed in detail. STEMI with mechanical complications such as papillary muscle rupture, ventricular septal rupture, and free wall rupture have also been mentioned. Risk/benefit profile of multivessel PCI and mechanical support devices may differ between hemodynamically stable STEMI patients and those with shock.
Partow-Navid et al have provided an extensive review on the management of STEMI in the article titled “Management of ST Elevation Myocardial Infarction (STEMI) in Different Settings” They have described the role of pre-hospital fibrinolysis in the management of STEMI and management of STEMI in non-PCI-capable hospital. The management of STEMI with cardiogenic shock, with fibrinolysis when the diagnosis is in doubt, in PCI capable hospital, during coronavirus disease-2019 pandemic, with active or high risk of bleeding and with cardiac arrest have also been described. Different circumstances of each STEMI should be taken into consideration before laboratory activation. An individual treatment plan is required for every patient. With advancement in technology and pharmacologic drugs, the treatment strategies would become more specialized.
Glazier has reviewed in detail the treatment modalities for left main, left main equivalent, and triple vessel disease of coronary artery in the paper titled “Therapeutic Options for Left Main, Left Main Equivalent, and Three-Vessel Disease” The left main, left main equivalent, and triple vessel disease represent an overlapping spectrum of severe coronary artery disease that is associated with adverse prognosis. Guideline-directed medical therapy (statins, angiotensin-converting enzyme inhibitors, angiotensin II receptor blockers, calcium channel blockers, and antiplatelet drugs) is essential but often insufficient treatment option, as such patients, frequently needs CABG or PCI. SYNTAX trial suggests that PCI may be useful alternative in patients with three-vessel disease and low SYNTAX score, and in patients with left main disease and low or intermediate SYNTAX score. EXCEL and NOBLE trials have demonstrated a favorable role of PCI in certain low-to-moderate risk patients with left main stem disease. FREEDOM trial has demonstrated that that CABG is superior in improving outcomes in subsets of patients with diabetes.
In the paper titled “Medical and Revascularization Management of Stable Ischemic Heart Disease: An Overview” Raidaideh et al have discussed the evaluation of risk in stable ischemic heart disease (SIHD) using stress testing, stress imaging and computed tomography angiography, functional flow reserve, instantaneous wave free ratio, and intravascular ultrasound. They have described various treatment modalities of SIHD including control of risk factors and optimal medical therapy to control symptoms and improve mobility, and pharmacological agents (β-blockers, nitrates, Ca2+channel blockers, antiplatelet drugs, anticoagulants, lipid lowering agents, newer sodium-glucose transporter-2 inhibitors, and glucagon-like peptide-1 antagonist) for SIHD. Medical and preventive therapies have become mainstay of treatment for SIHD. Revascularization using PCI and CABG should be tailored to vascular complexity, degree of ischemia, presence of diabetes, other comorbidities, and patient's preference. There is no additional benefit of PCI in improving all-cause death, cardiovascular mortality, or myocardial infarction compared with medical therapy alone. There is no difference in primary outcomes between PCI or CABG, and medical treatment. CABG is superior to medical therapy in reducing adverse outcomes in patents with left main and extensive triple vessel disease particularly with diabetes.
We are grateful to all the authors for their contribution of excellent articles in this thematic issue, and we would like to thank the reviewers for their time, comments, and valuable suggestions. We deeply appreciate the immense support of Denise M. Rossignol, Executive Director, International College of Angiology and Managing Editor, International Journal of Angiology, in completing this task.
Article published online:
17 May 2021
© 2021. International College of Angiology. This article is published by Thieme.
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