Overview of Microvascular Angina Pectoris and Discussion of Traditional Chinese Medicine Intervention

Previous research and treatment of coronary heart disease mostly focused on the large epicardial vessels, with limited research on the small endocardial coronary arteries or arterioles that could not be detected by coronary angiography, especially microvascular angina caused by microvascular stenosis or microcirculation dysfunction. Conventional Western medicine therapies have no specific efficacy, but traditional Chinese medicine has significant advantages in this regard. In particular, traditional Chinese medicine of supplementing Qi and activating blood circulation protects the vascular endothelium, relaxes coronary microvessels, reduces myocardial no-reflow after ischemia-reperfusion, increases myocardial hypoxia tolerance, constrains the aggregation of platelet, and increases the rate of blood flow. Moreover, these treatments can significantly improve patients’ symptoms through multitarget comprehensive intervention. Here, we analyzed the pathogenesis of microvascular angina pectoris, the treatment status of modern medicine, and the research on the multitarget intervention of traditional Chinese medicine to provide new research ideas for correctly identifying the role of coronary microcirculation in coronary artery disease to solve clinical problems and prevent cardiovascular events.

Clinico-pathophysiological considerations in coronary microvascular disorders

Around half of the patients undergoing an elective coronary angiogram to investigate typical stable angina symptoms are found to have non-obstructive coronary arteries (defined as < 50% stenosis). These patients are younger with a female predilection. While underlying mechanisms responsible for these presentations are heterogeneous, structural and functional abnormalities of the coronary microvasculature are highly prevalent. Thus, coronary microvascular dysfunction (CMD) is increasingly recognised as an important consideration in patients with non-obstructive coronary arteries. This review will focus on primary coronary microvascular disorders and summarise the four common clinical presentation pictures which can be considered as endotypes - Microvascular Ischaemia (formerly “Syndrome X”), Microvascular Angina, Microvascular Spasm, and Coronary Slow Flow. Furthermore, the pathophysiological mechanisms associated with CMD are also heterogenous. CMD may arise from an increased microvascular resistance, impaired microvascular dilation, and/or inducible microvascular spasm, ultimately causing myocardial ischaemia and angina. Alternatively, chest pain may arise from hypersensitivity of myocardial pain receptors rather than myocardial ischaemia. These two major abnormalities should be considered when assessing an individual clinical picture, and ultimately, the question arises whether to target the heart or the pain perception to treat the anginal symptoms.

Coronary Microvascular Vasodilatory Function: Related Clinical Features and Differences According to the Different Coronary Arteries and Types of Coronary Spasm

Background: In the clinical setting; the microvascular vasodilatory function test (MVFT) with a pressure wire has been used in ischaemia patients with non-obstructive coronary arteries (INOCA), including vasospastic angina (VSA) and microvascular angina (MVA). The exact factors that affect the microvascular vasodilatory function (MVF) in such patients are still unknown. We aimed to identify the factors, including clinical parameters and lesion characteristics, affecting the MVF in such patients. Methods: A total of 53 patients who underwent coronary angiography, spasm provocation tests (SPTs) and MVFTs were enrolled. In the MVFT, the coronary flow reserve (CFR) and index of microcirculatory resistance (IMR) were measured. Of the 53 patients, MVFT data in the left anterior descending coronary artery (LAD) were obtained from 49 patients, and the clinical parameters were checked in all of them. Based on the results of the SPT, coronary spasms were divided into focal spasm, diffuse spasm, and microvascular spasm (MVS). To assess the lesion characteristics influencing MVF, MVFT data were compared according to the types of coronary spasm and coronary vessels in 73 vessels of the 53 patients. Results: In 49 patients who underwent the MVFT in the LAD, the IMR was higher in active smokers (n = 7) than in former smokers (n = 15) and never smokers (n = 27, p < 0.01). In the 73 coronary arteries in this study, the type of coronary spasm did not correlate with the CFR or IMR, whereas a higher IMR were more frequently observed in cases of focal spasm than in cases of diffuse spasm (p = 0.03). In addition, the IMR was higher in the right coronary artery (RCA) than in the LAD (p = 0.02). Conclusion: These results indicate that the smoking status affected the MVF in patients with INOCA, suggesting the possibility of improvement in the MVF by smoking cessation in such patients. In addition, in the assessment of MVF, it may be important to take into account which coronary artery or types of coronary spasm are being evaluated.

What an Interventionalist Needs to Know About INOCA

Ischaemia with non-obstructed coronary artery disease (INOCA) remains a diagnostic and therapeutic challenge. An anatomical investigation-based approach to ischaemic heart disease fails to account for disorders of vasomotion. The main INOCA endotypes are microvascular angina, vasospastic angina, mixed (both) or non-cardiac symptoms. The interventional diagnostic procedure (IDP) enables differentiation between clinical endotypes, with linked stratified medical therapy leading to a reduced symptom burden and a better quality of life. Interventionists are therefore well placed to make a positive impact with more personalised care. Despite adjunctive tests of coronary function being supported by contemporary guidelines, IDP use in daily practice remains limited. More widespread adoption should be encouraged. This article reviews a stratified approach to INOCA, describes a streamlined approach to the IDP and highlights some practical and safety considerations.

Microvascular Angina: Diagnosis and Management

Recognition of suspected ischaemia with no obstructive coronary artery disease – termed INOCA – has increased over the past decades, with a key contributor being microvascular angina. Patients with microvascular angina are at higher risk for major adverse cardiac events including MI, stroke, heart failure with preserved ejection fraction and death but to date there are no clear evidence-based guidelines for diagnosis and treatment. Recently, the Coronary Vasomotion Disorders International Study Group proposed standardised criteria for diagnosis of microvascular angina using invasive and non-invasive approaches. The management strategy for remains empirical, largely due to the lack of high-level-evidence-based guidelines and clinical trials. In this review, the authors will illustrate the updated approach to diagnosis of microvascular angina and address evidence-based pharmacological and non-pharmacological treatments for patients with the condition.

236 Variation in cardiac troponin I serum levels after ECG exercise stress test in patients with microvascular angina

Aims Cardiac troponin I (cTnI) is considered a marker of myocardial necrosis. However, several studies have shown that cTnI increases also after short episodes of myocardial ischaemia. Nevertheless, it is unknown whether the changes in cTnI show differences according to the cause of myocardial ischaemia. Thus, our study aimed to evaluate cTnI response to ischaemia in patients with stable coronary artery disease (CAD), patients with microvascular angina (MVA), and transient ischaemia induced during percutaneous coronary intervention (PCI). Methods and results We studied four groups of patients: (1) patients with stable angina and obstructive CAD (coronary stenosis ≥50% and/or fractional flow reserve &lt;0.80) (Group 1, n = 8); (2) patients with stable angina but no obstructive CAD and a final diagnosis of MVA according to positive intracoronary acetylcholine provocation test and/or coronary flow velocity reserve assessment with transthoracic Doppler echocardiography (Group 2, n = 20); (3) patients with stable angina and obstructive CAD undergoing PCI (Group 3, n = 10); (4) a control group of healthy subjects, with no history of cardiovascular disease (CVD) (Group 4, n = 20). Patients in groups 1, 2, and 4 underwent ECG exercise stress test (EST) according to a standard treadmill Bruce protocol. Peripheral venous blood samples were collected immediately before, at the end and 1, 3, and 24 h after test ending. Patients in group 3 underwent PCI with at least one drug-eluting stent implantation. Peripheral venous blood samples were collected immediately before, at the end and 1, 3, and 24 h after PCI ending. High-sensitivity cTnI (hs-cTnI) levels were measured by chemiluminescent microparticle immunoassay (CMIA). The main results of hs-cTnI in the four groups of patients are summarized in the table. Basal hs-cTnI serum levels were significantly higher in group 3, while there were no significant differences among groups 1, 2, and 4. Hs-cTnI serum levels significantly increased in all groups in response to the procedure (EST or PCI). A greater increase of hs-cTnI was found in group 3 (peak level at 24 h) compared to the other groups (peak level at 3 h). Furthermore, among patients undergoing EST, a significantly higher hs-cTnI increase was found in healthy subjects, compared to patients with CAD and MVA. Heart rate (HR) during stress test (both as an absolute value and predicted maximal HR for age) was the only variable statistically predictive of hs-cTnI increase during EST (HRmax: r 0.289, P 0.04; %HRmax: r 0.307; P 0.03). On the other hand, no clinical and laboratory variable was associated to hs-cTnI response after PCI. Conclusions Hs-cTnI serum levels increase after EST, both in patients with obstructive CAD and coronary microvascular dysfunction (CMD), but a similar increase is also observed in healthy subjects. More consistent hs-cTnI level increase with later peak-level is observed in patients with obstructive CAD after transient ischaemia induced during PCI.

Therapeutic effect of Xuezhitong capsule on microvascular angina

Purpose: To determine the therapeutic effect of Xuezhitong capsule in patients with microvascular angina (MVA), and its impact on vascular endothelial function.Methods: In total, 172 MVA patients treated in Beijing City Fengtai District Nanyuan Hospital from September 2017 to September 2019 were selected and randomized into control group which received conventional treatment, and treatment group which received Xuezhitong capsules plus. There were 86 patients in each group. Therapeutic effect, levels of inflammatory factors, i.e., high-sensitivity C- reactive protein (hs-CRP), interleukin-(IL-6), tumor necrosis factor-α (TNF-α), and vascular endothelial factors such as nitric oxide (NO), thromboxane B2 (TXB2) and endothelin (ET), were determined.Results: Markedly higher total treatment effectiveness was observed in the treatment group than in the control group (89.53 % vs. 72.94 %; p < 0.05). In both groups, treatment reduced the levels of hs-CRP, IL-6, TNF-α, TXB2 and ET, but elevated NO, with better results for treatment group than the control group (p < 0.05). Better optimizations of total cholesterol (TC), triglycerides (TGs), low-density lipoprotein cholesterol (LDL-C) and high-density lipoprotein (HDL) were observed in the treatment group, relative to the control group (p < 0.05). Patients in the treatment group experienced fewer (8.14%) adverse reactions than those in control group (21.18 %, p < 0.05).Conclusion: Xuezhitong capsule, when combined with conventional treatment, exerts high therapeutic effectiveness and safety in MVA patients by inhibiting inflammatory reactions, optimizing endothelialfunction, reducing blood lipid levels, and decreasing the incidence of cardiovascular adverse events. Thus, the combination therapy is a potentially superior therapeutic strategy to the conventional approach for the management of MVA patients.

Comorbidities associated with reduced myocardial flow reserve in non-obstructive disease

Introduction Microvascular Dysfunction defined as a Myocardial Flow Reserve (MFR) &lt;2 or &lt;2.5 depending on the center, may present in the absence of significant obstruction (1,2); it is included as a diagnosis criteria of Microvascular Angina (MVA) (3,4) and is an independent risk factor associated with poor prognosis (5–7). Traditional Coronary Artery Disease (CAD)risk factors have also been associated with MVA (8–10), however, there is reduced data in latin populations with high prevalence of comorbidities. The aim of this study was to identify the comorbidities that alter MFR with 13N-ammonia Positron Emission Tomography/Cardiac Tomography (PET/CT) and Cardiac Computed Tomography Angiography (CCTA) in a cardiovascular imaging referral center. Methods Retrospective cross-sectional study of patients with suspected CAD in which both PET/CT and CCTA were performed. Inclusion:CCTA with obstruction &lt;50%. Exclusion: incomplete study, previous infarction or intervention. Clinical data was assessed. Mean (±DE) or median (interquartile range) to present continuous variables according to their distribution; T student or U Man Whitney to compare them. For each variable two groups were conformed depending on its presence or absence in order to compare MFR between them. Statistical analysis was performed with Statistical Package for Social Science (SPSs Inc, Chicago, IL; version 23.0) and GraphPad Prism version 9.0. p&lt;0.05 was considered as significant. Results 335 patients included. MFR difference for each variable: female sex, hypertension (HT), Type 2 diabetes (T2D) and smoking – Appendix 1. Significant MFR difference for HT (p=0.024) and T2D (p=0.046). Severe ischemia had significant MFR reduction (p=0.006); patients with both HT and mild ischemia (p=0.018) – Appendix 2. Discussion Individuals with HT and T2D had a significantly lower MFR, consistent with previous studies (8,9). Absence of correlation with other risk factors, such as smoking (10) and female sex (11); latter may be caused by a significant lower number of women (108 vs 227). Further analysis in this subgroup ought to be done. When comparing MFR between level-of-ischemia groups, microvascular function was not reduced until severe ischemia. Remarkably, if we analyze the coexistence of HT with ischemia, MFR is reduced even in patients with mild ischemia. This finding highlights the importance of HT which alters function in early stages even in the absence of significant obstruction. This is one of the first studies correlating MFR with comorbidities in our population. Limitations the retrospective nature of the study. Conclusions MFR non-invasive assessment by PET/CT allows identifying very early stages of MVD, even in asymptomatic patients and when there's no evidence of ischemia or CAD. Therefore, timely recognition of this problem is mandatory to implement action strategies to stop the triggered events' cascade. FUNDunding Acknowledgement Type of funding sources: None.

The Role of IL-6 and ET-1 in the Diagnosis of Coronary MicroVascular Disease in Women

Background: Microvascular angina is a common clinical entity, with about a three-fold higher frequency in women. The pathogenesis of microvascular angina has not been much studied, but inflammation and endothelial dysfunction have been incriminated as the main mechanisms of this disease. Methoss: Our purpose was to analyze whether certain inflammatory markers, i.e., interleukin 6 (IL-6) and endothelin 1 (ET-1), can play a role in the diagnosis of microvascular angina in women. Results: Ninety women with ischemic heart disease were divided into two groups, based on their affliction with either microvascular or macrovascular disease. In general, the levels of IL6 and ET1 were similar between the two groups. Analyzing these marker levels according to the number of coronary lesions, we obtained an increased IL6 value that was similar for patients with microvascular angina, one-vessel, and two-vessel coronary disease, but significantly lower than in women with three-vessel coronary lesions. Also, in microvascular angina, IL6 level was correlated with the NYHA IV functional class. Unexpectedly, the level of ET1 was correlated with left ventricular systolic dysfunction. Conclusions: In women with an increased suspicion of microvascular angina, in whom microvascular dysfunction cannot be tested invasively, IL-6 level, unlike the ET-1 level, might be considered a diagnostic marker of this disease.