BACKGROUND: Coronary vascular dysfunction comprises VSA and/or MVA and is more common in women than in men with angina without obstructive coronary artery disease (ANOCA). Invasive coronary function testing is considered the reference test for diagnosis, but its burden on patients is large. We aimed to investigate the potential of electrocardiography (ECG) as noninvasive marker for vasospastic angina (VSA) and microvascular angina (MVA) diagnosis.
METHODS: We systematically screened Pubmed and EMBASE databases for studies reporting on ECG characteristics in ANOCA patients with (a suspicion of) coronary vascular dysfunction. We assessed study quality using QUADAS-2. We extracted data on diagnostic values of different ECG characteristics and analyzed whether the studies were sex-stratified.
RESULTS: Thirty publications met our criteria, 13 reported on VSA and 17 on MVA. The majority addressed repolarization-related ECG parameters. Only 1 of the 13 VSA papers and 4 of the 17 MVA papers showed diagnostic accuracy measures of the ECG characteristics. The presence of early repolarization, T-wave alternans, and inverted U waves showed of predictive value for VSA diagnosis. The QTc interval was predictive for MVA diagnosis in all six studies reporting on QTc interval. Sex-stratified results were reported in only 5 of the 30 studies and 3 of those observed sex-based differences.
CONCLUSIONS: ECG features are not widely evaluated in diagnostic studies for VSA and MVA. Those features predictive for VSA and MVA diagnosis mostly point to repolarization abnormalities and may contribute to noninvasive risk stratification.

BACKGROUND: In the current systematic review and meta-analysis, we aim to analyze the existing literature to evaluate the role of inflammatory biomarkers, including neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), C-reactive protein (CRP), tumor necrosis factor-a (TNF-a), and interleukin-6 (IL-6) among individuals with cardiac syndrome X (CSX) compared to healthy controls.
METHODS: We used PubMed, Web of Science, Scopus, Science Direct, and Embase to systematically search relevant publications published before April 2, 2023. We performed the meta-analysis using Stata 11.2 software (Stata Corp, College Station, TX). So, we used standardized mean difference (SMD) with a 95% confidence interval (CI) to compare the biomarker level between patients and healthy controls. The I2 and Cochran\'s Q tests were adopted to determine the heterogeneity of the included studies.
RESULTS: Overall, 29 articles with 3480 participants (1855 with CSX and 1625 healthy controls) were included in the analysis. There was a significantly higher level of NLR (SMD = 0.85, 95%CI = 0.55-1.15, I2 = 89.0 %), CRP (SMD = 0.69, 95%CI = 0.38 to 1.02, p < 0.0001), IL-6 (SMD = 5.70, 95%CI = 1.91 to 9.50, p = 0.003), TNF-a (SMD = 3.78, 95%CI = 0.63 to 6.92, p = 0.019), and PLR (SMD = 1.38, 95%CI = 0.50 to 2.28, p = 0.02) in the CSX group in comparison with healthy controls.
CONCLUSIONS: The results of this study showed that CSX leads to a significant increase in inflammatory biomarkers, including NLR, CRP, IL-6, TNF-a, and PLR.

Coronary microvascular dysfunction (CMD) is becoming increasingly recognized as an important contributor to the development of ischemic heart diseases. Without obstructive coronary artery disease, the physiological function of the coronary microcirculation can be altered by structural, functional, and molecular factors, leading to myocardial ischemia. CMD can significantly impact the quality of life and prognosis and imposes a huge financial burden on healthcare systems and people. This meta-analysis aims to investigate the efficacy of angiotensin-converting enzyme inhibitors (ACEIs) for treating CMD. A systematic literature review identified randomized controlled trials (RCTs) comparing ACEIs with placebo in CMD patients. Review Manager, 5.3 for Windows, was utilized. Using the Mantel-Haenszel (M-H) method, improvement in coronary flow reserve (CFR) and systolic blood pressure events was pooled as mean difference (MD) in a meta-analysis model with a fixed effect model, whereas the number of chest pain episodes was pooled as MD with a random effect model. Five randomized controlled trials involving 209 patients were included in the analysis. The analysis demonstrated a statistically significant improvement in CFR in the ACEIs group compared to the placebo group (MD -0.3, 95% CI -0.61 to 0.01, P = 0.05). However, there was no significant difference in the number of chest pain episodes between the ACEIs and placebo groups (MD 1.79, 95% CI -3.99 to 7.58, P = 0.54). Similarly, no significant difference in blood pressure change was observed between the two groups (MD 4.02, 95% CI -3.25 to 11.28, P = 0.28). In conclusion, the appropriate treatment for CMD is a source of contention because adequate data is lacking. Our findings suggest that ACEIs may have a positive effect on improving CFR in patients with microvascular angina. However, ACEIs did not demonstrate a significant impact on the number of chest pain episodes or systolic blood pressure in this patient population. Further research, including RCTs with larger sample sizes and longer follow-up durations, is warranted to provide more conclusive evidence on the role of ACEIs in CMD management.

The coronary microcirculation plays a cardinal role in regulating coronary blood flow to meet the changing metabolic demands of the myocardium. Coronary microvascular dysfunction (CMD) refers to structural and functional remodeling of the coronary microcirculation. CMD plays a role in the pathogenesis of obstructive and non-obstructive coronary syndromes as well as myocardial diseases, including heart failure with preserved ejection fraction (HFpEF). Despite recent diagnostic advancements, CMD is often under-appreciated in clinical practice, and may allow for the development of novel therapeutic targets. This review explores the diagnosis and pathogenic role of CMD across a range of cardiovascular diseases, its prognostic significance, and the current therapeutic landscape.

Despite optimal medical treatment, many individuals suffering from severe coronary artery disease are not suitable candidates for further revascularization. Therapeutic angiogenesis has attracted continuous interest to increase myocardial perfusion. Cell therapy using autologous stem cells expressing Cluster of Differentiation 34 plus (CD34+) offers a special therapeutic choice for individuals with refractory angina, seeing as CD34+ stem cells can restore microcirculation. We searched PubMed, PubMed Central (PMC), and Google Scholar to find the relevant articles to write this systematic review about the role of CD34+ stem cell therapy in the management of refractory angina. Additionally, we provided a brief explanation of CD34+ cells and their mechanism of action. Along with the positive finding of other trials, a recent open-label, single-center intracoronary CD34+ cell therapy for the treatment of coronary endothelial dysfunction in patients with angina and nonobstructive coronary arteries (IMPROvE-CED) clinical trial published in 2022 concluded improvement in coronary blood flow, a significant reduction in daily as-needed sublingual nitroglycerin use and improvement in Canadian Cardiovascular Society (CCS) angina class were observed after autologous CD34+ cell treatment. In conclusion, refractory angina management and overall prognosis may be revolutionized once this treatment is approved.

Coronary artery vasospasm is an abnormal spasm of coronary arteries that cause transient or complete occlusion without exertion. It causes stable angina to ACS. However, this can be prevented by calcium channel blockers (CCBs) which suppress Ca2+ influx into the vascular muscle cells. Nevertheless, several CCBs adverse effects are harmful for these patients. Selecting the right CCBs would give the best clinical practice.
The studies were obtained from four major medical databases by various keywords. Inclusion and exclusion criteria were implemented as adult >18 years, observational study, English language and drug of interest. Duplicates were eliminated, and the remaining studies were reviewed. Final full-texts assessment was conducted independently by Newcastle-Ottawa Scale and Revised Cochrane.
The search found 1378 articles. However, six studies were selected after implementing the study criteria. Diltiazem was found to decrease angina and increase quality of life until 12th week of treatment; however, some adverse effects include atrioventricular block and recurrent angina up till 4th week were found. Meanwhile, nifedipine was found to decrease vasospastic angina (VSA) by the fourth and eighth weeks of treatment. Nevertheless, it caused excessive drop in BP and increase heart rate by eighth week. In addition, slow-release preparation of both CCBs were found to increase efficacy and compliance. Lastly amlodipine was also found to decrease VSA by 17%±140% and 33% after 6 weeks, but further studies needed.
Diltiazem, nifedipine and amlodipine are potent in decreasing VSA, however, tailoring specific CCBs adverse reactions to patient condition and the drug preparation would be substantially beneficial for the outcome.

OBJECTIVE: Coronary vasomotor dysfunction embraces two specific clinical entities: coronary (micro)vascular spasm and microvascular dysfunction. The clinical manifestations of these entities are respectively called vasospastic angina (VSA) and microvascular angina (MVA). Over the years, these diseases have become more and more prominent and several studies aimed to investigate the best diagnostic and therapeutic strategies. Patients with coronary vasomotor disorders are often undertreated due to the absence of evidence-based guidelines. The purpose of this overview is to illustrate the various therapeutic options available for the optimized management of these patients.
METHODS: A Medline search of full-text articles published in English from 1980 to April 2022 was performed. The main analyzed aspects of vasomotor disorders were treatment options. We also performed research on \"Clinicaltrial.gov\" for ongoing trials.
CONCLUSIONS: Coronary (micro)vascular spasm and microvascular dysfunction are clinical entities characterized by high prevalence and clinical representation. Several therapeutic strategies, both innovative and established, are available to optimize treatment and improve the quality of life of these patients.

Up to 60-70% of patients, undergoing invasive coronary angiography due to angina and demonstrable myocardial ischemia with provocative tests, do not have any obstructive coronary disease. Coronary microvascular angina due to a dysfunction of the coronary microcirculation is the underlying cause in almost 50% of these patients, associated with a bad prognosis and poor quality of life. In recent years, progress has been made in the diagnosis and management of this condition. The aim of this review is to provide an insight into current knowledge of this condition, from current diagnostic methods to the latest treatments.

Background A relevant proportion of patients with suspected coronary artery disease undergo invasive coronary angiography showing normal or nonobstructive coronary arteries. However, the prevalence of coronary microvascular disease (CMD) and coronary spasm in patients with nonobstructive coronary artery disease remains to be determined. The objective of this study was to determine the prevalence of coronary CMD and coronary vasospastic angina in patients with no obstructive coronary artery disease. Methods and Results A systematic review and meta-analysis of studies assessing the prevalence of CMD and vasospastic angina in patients with no obstructive coronary artery disease was performed. Random-effects models were used to determine the prevalence of these 2 disease entities. Fifty-six studies comprising 14 427 patients were included. The pooled prevalence of CMD was 0.41 (95% CI, 0.36-0.47), epicardial vasospasm 0.40 (95% CI, 0.34-0.46) and microvascular spasm 24% (95% CI, 0.21-0.28). The prevalence of combined CMD and vasospastic angina was 0.23 (95% CI, 0.17-0.31). Female patients had a higher risk of presenting with CMD compared with male patients (risk ratio, 1.45 [95% CI, 1.11-1.90]). CMD prevalence was similar when assessed using noninvasive or invasive diagnostic methods. Conclusions In patients with no obstructive coronary artery disease, approximately half of the cases were reported to have CMD and/or coronary spasm. CMD was more prevalent among female patients. Greater awareness among physicians of ischemia with no obstructive coronary arteries is urgently needed for accurate diagnosis and patient-tailored management.

Coronary microvascular dysfunction (CMD) encompasses several pathogenetic mechanisms involving coronary microcirculation and plays a major role in determining myocardial ischemia in patients with angina without obstructive coronary artery disease, as well as in several other conditions, including obstructive coronary artery disease, nonischemic cardiomyopathies, takotsubo syndrome, and heart failure, especially the phenotype associated with preserved ejection fraction. Unfortunately, despite the identified pathophysiological and prognostic role of CMD in several conditions, to date, there is no specific treatment for CMD. Due to the emerging role of CMD as common denominator in different clinical phenotypes, additional research in this area is warranted to provide personalized treatments in this \"garden variety\" of patients. The purpose of this review is to describe the pathophysiological mechanisms of CMD and its mechanistic and prognostic role across different cardiovascular diseases. We will also discuss diagnostic modalities and the potential therapeutic strategies resulting from recent clinical studies.