REGENERATE-COBRA: A phase II randomized sham-controlled trial assessing the safety and efficacy of intracoronary administration of autologous bone marrow-derived cells in patients with refractory angina.

AIMS: The REGENERATE-COBRA trial (NCT05711849) will assess the safety and efficacy of an intracoronary infusion of autologous bone marrow-derived mononuclear cells in refractory angina patients with no revascularization options who are symptomatic despite optimal medical and device therapy. METHODS: REGENERATE-COBRA is a single site, blinded, randomized, sham-controlled, Phase II clinical trial enrolling 110 refractory angina patients with no revascularization options who are symptomatic despite optimal medical and device therapy. Patients will be randomized to either autologous bone marrow derived-mononuclear cells or a sham procedure. Patients in the cell-treated arm will undergo a bone marrow aspiration and an intracoronary infusion of autologous bone marrow derived-mononuclear cells. Patients in the control arm will undergo a sham bone marrow aspiration and a sham intracoronary infusion. The trial's primary endpoint is an improvement in Canadian Cardiovascular Society (CCS) angina class by 2 classes between baseline and 6 months. Secondary endpoints include change in: CCS class at 12 months, myocardial ischemic burden (as measured by perfusion imaging) at 6 months, quality of life at 6 and 12 months (as measured by EQ-5D-5L, EQ-5D-VAS and Seattle Angina Questionnaire), angina frequency at 6 and 12 months, total exercise time (as measured by a modified Bruce protocol) and major adverse cardiovascular events at 6 and 12 months. CONCLUSIONS: This is the first trial to assess the safety and efficacy of an intracoronary infusion of autologous bone marrow-derived unfractionated mononuclear cells in symptomatic refractory angina patients who have exhausted conventional therapeutic options.

Hyperventilation testing in the diagnosis of vasospastic angina: A clinical review and meta-analysis.

BACKGROUND: Given the limited access to invasive vasospastic reactivity testing in Western Countries, there is a need to further develop alternative non-invasive diagnostic methods for vasospastic angina (VSA). Hyperventilation testing (HVT) is defined as a class IIa recommendation to diagnose VSA by the Japanese Society of Cardiology. METHODS: In this systematic review and meta-analysis reported according to the PRISMA statement, we review the mechanisms, methods, modalities and diagnostic accuracy of non-invasive HVT for the diagnostic of VSA. RESULTS: A total of 106 articles published between 1980 and 2022 about VSA and HVT were included in the systematic review, among which 16 were included in the meta-analysis for diagnostic accuracy. Twelve electrocardiogram-HVT studies including 804 patients showed a pooled sensitivity of 54% (95% confidence intervals [CI]; 30%-76%) and a pooled specificity of 99% (95% CI; 88%-100%). Four transthoracic echocardiography-HVT studies including 197 patients revealed a pooled sensitivity of 90% (95% CI; 82%-94%) and a pooled specificity of 98% (95% CI; 86%-100%). Six myocardial perfusion imaging-HVT studies including 112 patients yielded a pooled sensitivity of 95% (95% CI; 63%-100%) and a pooled specificity of 78% (95% CI; 19%-98%). Non-invasive HVT resulted in a low rate of adverse events, ventricular arrhythmias being the most frequently reported, and were resolved with the administration of nitroglycerin. CONCLUSIONS: Non-invasive HVT offers a safe alternative with high diagnostic accuracy to diagnose VSA in patients with otherwise undiagnosed causes of chest pain.

The Efficacy of Traditional Chinese Herbal Medicine Across Multiple Cardiovascular Diseases: An Umbrella Review of Systematic Reviews of Randomized Controlled Trials.

ABSTRACT: Traditional Chinese herbal medicine (CHM) has been extensively used in cardiovascular disease (CVD) in modern clinical practice, alone or in combination with conventional treatment. However, its efficacy has not been assessed extensively. From inception until August 2023, we systematically searched 5 public literature databases to conduct the umbrella review. The inclusion criterion is systematic reviews of randomized controlled trials investigating the effect of CHM in the contemporary management of CVDs. The quality of the included systematic reviews, the certainty of the evidence, and the potential risk of bias were assessed. Five hundred and thirty-nine systematic reviews, including 346 studies in Chinese and 193 in English, were selected before the quantitative synthesis. The methodological quality was generally moderate, with a median value of 11. The favorable efficacy of CHM was primarily presented on 5 main conditions: coronary artery disease, hypertension, heart failure, restenosis, and angina pectoris. CHM, with or without conventional treatment, showed a consistent beneficial effect in various CVDs. Nevertheless, the magnitude of the effect requires further investigation as the lack of relevant research and the complexity of the clinical practice of CHM.

Is typical angina still prognostically important? The influence of "treatment bias" upon prognostic assessments.

BACKGROUND: Since typical angina has become less frequent, it is unclear if this symptom still has prognostic significance. METHODS: We evaluated 38,383 patients undergoing stress/rest SPECT myocardial perfusion imaging followed for a median of 10.9 years. After dividing patients by clinical symptoms, we evaluated the magnitude of myocardial ischemia and subsequent mortality among medically treated versus revascularized subgroups following testing. RESULTS: Patients with typical angina had more frequent and greater ischemia than other symptom groups, but not higher mortality. Among typical angina patients, those who underwent early revascularization had substantially greater ischemia than the medically treated subgroup, including a far higher proportion with severe ischemia (44.9% vs 4.3%, P < 0.001) and transient ischemic dilation of the LV (31.3% vs 4.7%, P < 0.001). Nevertheless, the revascularized typical angina subgroup had a lower adjusted mortality risk than the medically treated subgroup (HR = 0.72, 95% CI: 0.57-0.92, P = 0.009) CONCLUSIONS: Typical angina is associated with substantially more ischemia than other clinical symptoms. However, the high referral of patients with typical angina patients with ischemia to early revascularization resulted in this group having a lower rather than higher mortality risk versus other symptom groups. These findings illustrate the need to account for "treatment bias" among prognostic studies.

Health-related quality of life and healthcare costs of symptoms and cardiovascular disease events in patients with atrial fibrillation: a longitudinal analysis of 27 countries from the EURObservational Research Programme on Atrial Fibrillation general long-term registry.

AIMS: We examine the effects of symptoms and cardiovascular disease (CVD) events on health-related quality of life (HRQOL) and healthcare costs in a European population with atrial fibrillation (AF). METHODS AND RESULTS: In the EURObservational Research Programme on AF long-term general registry, AF patients from 250 centres in 27 European countries were enrolled and followed for 2 years. We used fixed effects models to estimate the association of symptoms and CVD events on HRQOL and annual healthcare costs. We found significant decrements in HRQOL in AF patients in whom ST-segment elevation myocardial infarction (STEMI) [-0.075 (95% confidence interval -0.144, -0.006)], angina or non-ST-elevation myocardial infarction (NSTEMI) [-0.037 (-0.071, -0.003)], new-onset/worsening heart failure [-0.064 (-0.088, -0.039)], bleeding events [-0.031 (-0.059, -0.003)], thromboembolic events [-0.071 (-0.115, -0.027)], mild symptoms [0.037 (-0.048, -0.026)], or severe/disabling symptoms [-0.090 (-0.108, -0.072)] occurred during the follow-up. During follow-up, annual healthcare costs were associated with an increase of €11 718 (€8497, €14 939) in patients with STEMI, €5823 (€4757, €6889) in patients with angina/NSTEMI, €3689 (€3219, €4158) in patients with new-onset or worsening heart failure, €3792 (€3315, €4270) in patients with bleeding events, and €3182 (€2483, €3881) in patients with thromboembolic events, compared with AF patients without these events. Healthcare costs were primarily driven by inpatient costs. There were no significant differences in HRQOL or healthcare resource use between EU regions or by sex. CONCLUSION: Symptoms and CVD events are associated with a high burden on AF patients and healthcare systems throughout Europe.

Benign Prostatic Hyperplasia and Incident Cardiovascular Disease.

BACKGROUND: Data regarding the relationship between benign prostatic hyperplasia (BPH) and incident cardiovascular disease (CVD) are scarce. We aimed to clarify the association of BPH with the risk of developing CVD using a nationwide epidemiological database.Methods and Results: This retrospective observational cohort study analyzed data from the JMDC Claims Database between 2005 and 2022, including 2,370,986 men (median age 44 years). The primary endpoints were myocardial infarction (MI), angina pectoris (AP), stroke, heart failure (HF), and atrial fibrillation (AF), which were assessed separately. BPH was observed in 48,651 (2.1%) men. During a mean (±SD) follow-up of 1,359±1,020 days, 7,638 MI, 52,167 AP, 25,355 stroke, 58,183 HF, and 16,693 AF events were detected. Hazard ratios of BPH for MI, AP, stroke, HF, and AF were 1.04 (95% confidence interval [CI] 0.92-1.18), 1.31 (95% CI 1.25-1.37), 1.26 (95% CI 1.18-1.33), 1.21 (95% CI 1.16-1.27), and 1.15 (95% CI 1.07-1.24), respectively. We confirmed the robustness of our primary findings through a multitude of sensitivity analyses. In particular, a history of BPH was associated with a higher risk of developing CVD, even in participants without obesity, hypertension, diabetes, or dyslipidemia. CONCLUSIONS: Our analysis of a nationwide epidemiological dataset demonstrated that BPH was associated with a greater risk of developing CVD in middle-aged men.

Long-term PM2.5 exposure associated with severity of angina pectoris and related health status in patients admitted with acute coronary syndrome: Modification effect of genetic susceptibility and disease history.

Long-term particulate matter with aerodynamic diameters ≤2.5 µm (PM2.5) exposure has been associated with the occurrence of acute coronary syndrome (ACS). However, the impact of PM2.5 exposure and its components on the severity of angina pectoris and disease-related health status in patients hospitalized for ACS is understudied. To assess the association between long-term exposure to PM2.5 components and the angina pectoris severity in ACS patients, as well as the modification effects of genetic factors and disease history in north China. During 2017-2019, 6729 ACS patients were collected in Shandong Province and Beijing, with their angina pectoris severity evaluated using Seattle Angina Questionnaire (SAQ). The 0-3 years' average concentrations of PM2.5 and its five major components were assigned to each patient's residential address. Linear mixed-effects model, weighted quantile regression, and quantile g-computation were used to estimate the effects of both single and joint associations between PM2.5 components and SAQ scores. The interactive effect was estimated by polygenic risk scores and disease history. For each interquartile range increase in PM2.5, the overall SAQ score changed by -3.71% (95%CI: -4.54% to -2.88%), with score of angina stability more affected than angina frequency and other dimensions of angina pectoris severity. Sulfate and ammonium were major contributors to the effect of PM2.5 exposure. Significant modification effect was only observed for disease history, especially for the dimension of physical limitation. Among a series of pre-existing diseases, patients with a family history of coronary artery disease, previous percutaneous coronary intervention or coronary artery bypass grafting, and stroke were more susceptible to PM2.5 exposure than others. Greater exposure to PM2.5 is associated with more serious angina pectoris and worse disease-related health status in ACS patients. Public health and clinical priority should be given to cutting down key effective components and protecting highly vulnerable individuals.

Response shift in coronary artery disease.

PURPOSE: Patients with coronary artery disease (CAD) experience significant angina symptoms and lifestyle changes. Revascularization procedures can result in better patient-reported outcomes (PROs) than optimal medical therapy (OMT) alone. This study evaluates the impact of response shift (RS) on changes in PROs of patients with CAD across treatment strategies. METHODS: Data were from patients with CAD in the Alberta Provincial Project on Outcome Assessment in Coronary Heart Disease (APPROACH) registry who completed the 16-item Canadian version of the Seattle Angina Questionnaire at 2 weeks and 1 year following a coronary angiogram. Multi-group confirmatory factor analysis (MG-CFA) was used to assess measurement invariance across treatment groups at week 2. Longitudinal MG-CFA was used to test for RS according to receipt of coronary artery bypass grafting (CABG), percutaneous coronary intervention (PCI), or optimal medical therapy (OMT) alone. RESULTS: Of the 3116 patients included in the analysis, 443 (14.2%) received CABG, 2049(65.8%) PCI, and the remainder OMT alone. The MG-CFA revealed a partial-strong invariance across the treatment groups at 2 weeks (CFI = 0.98, RMSEA [90% CI] = 0.05 [0.03, 0.06]). Recalibration RS was detected on the Angina Symptoms and Burden subscale and its magnitude in the OMT, PCI, and CABG groups were 0.32, 0.28, and 0.53, respectively. After adjusting for RS effects, the estimated target changes were largest in the CABG group and negligible in the OMT group. CONCLUSION: Adjusting for RS is recommended in studies that use SAQ-CAN to assess changes in patients with CAD who have received revascularization versus OMT alone.

Mapping Kansas City cardiomyopathy, Seattle Angina, and minnesota living with heart failure to the MacNew-7D in patients with heart disease.

INTRODUCTION: The Kansas City Cardiomyopathy Questionnaire (KCCQ), Seattle Angina Questionnaire (SAQ), and Minnesota Living with Heart Failure Questionnaire (MLHFQ) are widely used non-preference-based instruments that measure health-related quality of life (QOL) in people with heart disease. However, currently it is not possible to estimate quality-adjusted life-years (QALYs) for economic evaluation using these instruments as the summary scores produced are not preference-based. The MacNew-7D is a heart disease-specific preference-based instrument. This study provides different mapping algorithms for allocating utility scores to KCCQ, MLHFQ, and SAQ from MacNew-7D to calculate QALYs for economic evaluations. METHODS: The study included 493 participants with heart failure or angina who completed the KCCQ, MLHFQ, SAQ, and MacNew-7D questionnaires. Regression techniques, namely, Gamma Generalized Linear Model (GLM), Bayesian GLM, Linear regression with stepwise selection and Random Forest were used to develop direct mapping algorithms. Cross-validation was employed due to the absence of an external validation dataset. The study followed the Mapping onto Preference-based measures reporting Standards checklist. RESULTS: The best models to predict MacNew-7D utility scores were determined using KCCQ, MLHFQ, and SAQ item and domain scores. Random Forest performed well for item scores for all questionnaires and domain score for KCCQ, while Bayesian GLM and Linear Regression were best for MLHFQ and SAQ domain scores. However, models tended to over-predict severe health states. CONCLUSION: The three cardiac-specific non-preference-based QOL instruments can be mapped onto MacNew-7D utilities with good predictive accuracy using both direct response mapping techniques. The reported mapping algorithms may facilitate estimation of health utility for economic evaluations that have used these QOL instruments.

Cheese consumption on atherosclerosis, atherosclerotic cardiovascular diseases and its complications: A two-sample Mendelian randomization study.

BACKGROUND AND AIM: Evidence from prospective cohort studies has revealed an inverse association between cheese consumption and the development of atherosclerosis (AS), atherosclerotic cardiovascular diseases (ASCVD), and their complications. However, it remains unclear whether this observed association is influenced by potential confounding factors that may arise during the long-term development process of AS, ASCVD, and its complications. Therefore, to further clarify the causal relationship between cheese consumption and AS, ASCVD, and its complications, we conducted a two-sample Mendelian randomization (MR) analysis to explore the causal association between cheese intake and the aforementioned health outcomes. METHODS AND RESULTS: We employed a two-sample MR analysis based on publicly available genome-wide association studies (GWAS) to infer the causal relationship, with no overlap between their participating populations. The effect estimates were calculated using the random-effects inverse-variance-weighted method. Sensitivity analyses were conducted using Cochran's Q statistic, funnel plot, leave-one-out analysis, and MR-Egger intercept tests. The genetically predicted cheese intake was found to be associated with lower risks of coronary AS (odds ratio [OR] = 0.72, 95 % confidence interval [CI] 0.59-0.88, P = 0.001), peripheral vascular AS (OR = 0.56, 95 % CI 0.37-0.84, P = 0.006), other vascular AS (OR = 0.66, 95 % CI 0.44-0.99, P = 0.043), coronary artery disease (OR = 0.64, 95 % CI 0.56-0.74, P = 1.57e-09), angina pectoris (OR = 0.70, 95 % CI 0.58-0.84, P = 4.92e-05), myocardial infarction (OR = 0.63, 95 % CI 0.52-0.77, P = 3.56e-06), heart failure (OR = 0.62, 0.49-0.79, P = 1.20e-04), total ischemic stroke (OR = 0.76, 95 % CI 0.63-0.91, P = 0.003), peripheral artery disease (OR = 0.64, 95 % CI 0.43-0.95, P = 0.028), and cognitive impairment (OR = 0.65, 95 % CI 0.56-0.74, P = 3.40e-10). However, no associations were observed for cerebrovascular AS, arrhythmia, cardiac death, ischemic stroke (large artery AS), ischemic stroke (small vessel), ischemic stroke (cardioembolic), and transient ischemic attack. CONCLUSION: This two-sample MR analysis reveals a causally inverse association between cheese intake and multi-vascular AS (including coronary AS, peripheral vascular AS, and other vascular AS), as well as multiple types of ASCVD and its complications (such as coronary artery disease, angina pectoris, myocardial infarction, heart failure, total ischemic stroke, and peripheral artery disease). The findings from this study may lay a stronger theoretical foundation and present new opportunities for the dietary management of future atherosclerotic cardiovascular diseases.

Long-term prognostic factors for cardiovascular events in patients with chest pain without diabetes mellitus nor significant coronary stenosis.

Chest pain is the most common symptom of coronary artery disease (CAD) and diabetes mellitus (DM) is a well-known single strongest risk factor for cardiovascular diseases. Thus, the impact of CAD nor DM on long-term clinical effects is reported widely, but the prognostic factors of non-DM patients presenting with chest pain without significant CAD are limited. A total of 1,046 patients with chest pain without DM and significant CAD who underwent coronary angiography (CAG) and acetylcholine (ACH) provocation tests were finally enrolled. Propensity score matching and multivariate Cox-proportional hazard ratio analysis were performed to adjust for baseline potential confounders. Major adverse cardiac and cerebrovascular events (MACCE) were defined as the composite of total death, myocardial infarction (MI), revascularization, stroke, and recurrent angina. This study aimed to evaluate the long-term prognostic factors for MACCE in patients with chest pain without DM and CAD up to 5 years. Coronary artery spasm (CAS) was the most common cause of chest pain. However, long-term MACCE of CAS was not worse than those of patients with chest pain without CAS when patients with CAS had subsequent optimal antianginal medication therapy. However, a recurrent chest pain remains a problem even with continuous antianginal medication therapy. Up to 5 years, the incidence of MACCE was in 7.3%, including recurrent angina 6.9%. Dyslipidemia (HR: 2.010, 95% CI 1.166-3.466, P = 0.012), mild-moderate (30-70%) coronary stenosis (HR: 2.369, 95% CI 1.118-5.018, P = 0.024), the use of aspirin (HR: 2.885, 95% CI 1.588-5.238, P < 0.001), and the use of nitrates (HR: 1.938, 95% CI 1.094-3.433, P = 0.023) were independent risk factors for MACCE. Among the patients with chest pain without DM and significant CAD, the incidence of MACE were rare, but recurrent angina was still a challenging problem who had treated with antianginal medications.

Effect of rifampicin administration on CYP induction in a dermatomyositis patient with vasospastic angina attributable to nilmatrelvir/ritonavir-induced blood tacrolimus elevation: A case report.

Ritonavir (RTV), which is used in combination with nilmatrelvir (NMV) to treat coronavirus disease 2019 (COVID-19), inhibits cytochrome P450 (CYP) 3A, thereby increasing blood tacrolimus (TAC) levels through a drug-drug interaction (DDI). We experienced a case in which a DDI between the two drugs led to markedly increased blood TAC levels, resulting in vasospastic angina (VSA) and acute kidney injury (AKI). Rifampicin (RFP) was administered to induce CYP3A and promote TAC metabolism. A 60-year-old man with dermatomyositis who was taking 3 mg/day TAC contracted COVID-19. The patient started oral NMV/RTV therapy, and he was admitted to the hospital after 4 days because of chest pain and AKI. On day 5, his blood TAC level increased markedly to 119.8 ng/mL. RFP 600 mg was administered once daily for 3 days, and his blood TAC level decreased to the therapeutic range of 9.6 ng/mL on day 9, leading to AKI improvement. Transient complete atrioventricular block and nonsustained ventricular tachycardia were present during chest pain. In the coronary spasm provocation test, complete occlusion was observed in the right coronary artery, leading to a diagnosis of VSA. VSA and AKI are possible side effects of high blood TAC levels caused by DDI, and attention should be paid to cardiovascular side effects such as VSA and AKI associated with increased blood levels of TAC when it is used together with NMV/RTV. When blood levels of TAC increase, oral RFP can rapidly decrease TAC blood levels and potentially reduce its toxicity.

Effects of major air pollutants on angina hospitalizations: a correlation study.

BACKGROUND: Angina is a crucial risk signal for cardiovascular disease. However, few studies have evaluated the effects of ambient air pollution exposure on angina. OBJECTIVE: We aimed to explore the short-term effects of air pollution on hospitalization for angina and its lag effects. METHODS: We collected data on air pollutant concentrations and angina hospitalizations from 2013 to 2020. Distributed lag nonlinear model (DLNM) was used to evaluate the short-term effects of air pollutants on angina hospitalization under different lag structures. Stratified analysis by sex, age and season was obtained. RESULTS: A total of 39,110 cases of angina hospitalization were included in the study. The results showed a significant positive correlation between PM2.5, SO2, NO2, and CO and angina hospitalization. Their maximum harmful effects were observed at lag0-7 (RR = 1.042; 95% CI: 1.017, 1.068), lag0-3 (RR = 1.067; 95% CI: 1.005, 1.133), lag0-6 (RR = 1.078; 95% CI: 1.041, 1.117), and lag0-6 (RR = 1.244; 95% CI: 1.109, 1.397), respectively. PM10 did not have an overall risk effect on angina hospitalization, but it did have a risk effect on women and the elderly. O3 was significantly negatively correlated with angina hospitalization, with the most pronounced effect observed at lag0-6 (RR = 0.960; 95% CI: 0.940, 0.982). Stratified analysis results showed that women and the elderly were more susceptible to pollutants, and the adverse effects of pollutants were stronger in the cold season. CONCLUSION: Short-term exposure to PM2.5, SO2, NO2, and CO increases the risk of hospitalization for angina.

Association of relative hand grip strength with myocardial infarction and angina pectoris in the Korean population: a large-scale cross-sectional study.

BACKGROUND: Low hand grip strength (HGS) is associated with the risk of cardiovascular diseases, but the association between HGS and myocardial infarction/angina pectoris (MIAP) is unclear. Furthermore, there have been no studies examining the associations of MIAP with anthropometric indices, absolute HGS indices, and relative HGS indices calculated by dividing absolute HGS values by body mass index (BMI), waist circumference (WC), waist-to-height ratio (WHtR), or weight values. Therefore, the objective of this study was to examine the associations of MIAP with absolute and relative HGS combined with several anthropometric indices. METHODS: In this large-scale cross-sectional study, a total of 12,963 subjects from the National Health and Nutrition Examination Survey were included. Odds ratios and 95% confidence intervals for the associations of MIAP with anthropometric indices, absolute HGS indices, and relative HGS indices were computed from binary logistic regression models. We built 3 models: a crude model, a model that was adjusted for age (Model 1), and a model that was adjusted for other relevant covariates (Model 2). RESULTS: For men, the average age was 61.55 ± 0.16 years in the MIAP group and 66.49 ± 0.61 years in the non-MIAP group. For women, the average age was 61.99 ± 0.14 years in the MIAP group and 70.48 ± 0.61 years in the non-MIAP group. For both sexes, the MIAP group had lower diastolic blood pressure, shorter stature, greater WC, and a greater WHtR than did the non-MIAP group, and women tended to have greater systolic blood pressure, weight, and BMI than in men. HGS was strongly associated with the risk of MIAP in the Korean population. In men, relative HGS indices combined with WC and the WHtR had greater associations with MIAP than did the anthropometric indices and absolute HGS indices. However, in women, anthropometric indices, including weight, BMI, WC, and WHtR, were more strongly associated with MIAP than were absolute and relative HGS indices, unlike in men. When comparing absolute and relative HGS indices in women, relative HGS indices combined with BMI and weight was more strongly related to MIAP than was absolute HGS indices. CONCLUSIONS: MIAP might be better identified by relative HGS than absolute HGS in both sexes. The overall magnitudes of the associations of MIAP with absolute and relative HGS are greater in men than in women.

Psychological burden in patients with angina and unobstructed coronary arteries-underestimated, underexplored, undertreated.

Patients with angina and unobstructed coronary arteries (ANOCA) are frequently encountered in clinical practice. These cases represent a diagnostic and therapeutic challenge and are often characterized by a long patient journey until a diagnosis of coronary vasomotor disorders is established. Moreover, the unsatisfactory management of such patients leads to insecurity, ongoing symptoms, and psychological sequelae such as anxiety or depression. Currently, the psychological burden in patients with ANOCA is underestimated, underexplored, and undertreated. This review gives a new perspective on the pathophysiology of coronary vasomotor disorders including psychological risk factors and calls for comprehensive care by interdisciplinary ANOCA clinics.

Neuromodulation of Cardiac Ischemic Pain: Role of the Autonomic Nervous System and Vasopressin.

Cardiac pain is an index of cardiac ischemia that helps the detection of cardiac hypoxia and adjustment of activity in the sufferer. Drivers and thresholds of cardiac pain markedly differ in different subjects and can oscillate in the same individual, showing a distinct circadian rhythmicity and clinical picture. In patients with syndrome X or silent ischemia, cardiac pain intensity may cause neurogenic stress that potentiates the cardiac work and intensifies the cardiac hypoxia and discomfort of the patient. The reasons for individual differences in cardiac pain sensation are not fully understood. Thus far, most attention has been focused on inappropriate regulation of the heart by the autonomic nervous system, autacoids, and cardiovascular hormones. Herein, we summarize evidence showing that the autonomic nervous system regulates cardiac pain sensation in cooperation with vasopressin (AVP). AVP is an essential analgesic compound and it exerts its antinociceptive function through actions in the brain (the periaqueductal gray, caudate nucleus, nucleus raphe magnus), spinal cord, and heart and coronary vessels. Vasopressin acts directly by means of V1 and V2 receptors as well as through multiple interactions with the autonomic nervous system and cardiovascular hormones, in particular, angiotensin II and endothelin. The pain regulatory effects of the autonomic nervous system and vasopressin are significantly impaired in cardiovascular diseases.

Potential Effects of Ischemic Postconditioning and Changes in Heat Shock Protein 72 in Patients with Acute Myocardial Infarction without Prodromal Angina.

The effectiveness of ischemic postconditioning (iPoC) in patients with ST-elevation myocardial infarction (STEMI) without ischemic preconditioning has not been determined. Therefore, we investigated the impact of iPoC and its potential mechanism related to heat shock protein 72 (HSP72) induction on myocardial salvage in patients with STEMI without prodromal angina (PA).We retrospectively analyzed data from 102 patients with STEMI with successful reperfusion among 323 consecutive patients with acute coronary syndrome. Among these, 55 patients with iPoC (iPoC (+) ) underwent 4 cycles of 60-second inflation and 30-second deflation of the angioplasty balloon. Both the iPoC (+) and iPoC (-) groups were divided into 2 further subgroups: patients with PA (PA (+) ) and those without (PA (-) ). We analyzed HSP72 levels in neutrophils, which were measured until 48 hours after reperfusion. I-123 ß-methyl-p-iodophenyl-pentadecanoic acid (BMIPP) scintigraphy was performed within a week of reperfusion therapy. In 64% of patients, thallium-201 (TL) scintigraphy was performed 6-8 months after STEMI onset.Using BMIPP and TL, in the PA (-) subgroups, the iPoC (+) group had a significantly greater myocardial salvage ratio than the iPoC (-) group. iPoC was identified as an independent predictor of the myocardial salvage ratio. The HSP72 increase ratio was significantly elevated in the iPoC (+) PA (-) group. Importantly, the myocardial salvage effect in patients without PA was significantly correlated with the HSP72 increase ratio, which was greater in patients with iPoC.These results suggest the potential impact of iPoC via HSP72 induction on myocardial salvage; however, the effects may be limited to patients with STEMI without PA.

Angina Pectoris Is Associated with Cervical Disc Disease: A Cross-Sectional, Population-Based Study Using the Medicare Expenditure Panel Survey (MEPS).

Atherosclerotic disease in the vessels that supply the cervical spine may lead to degenerative disease. In angina pectoris (AP), atherosclerotic disease leads to coronary vessel occlusion and resulting symptoms. This study aims to determine the relationship between AP and neck pain. Analysis was focused on respondents who had a history of cervical pain disorders, adjusting for demographic, education, and mental health confounders. A total of 30,461 participated in the survey. Of 1,049 respondents, 21% reported neck pain. Mean age of the respondents was 62.6 ± 16.1 years. Nonwhite race, current everyday smokers, lower family income, hypertension, and diabetes had higher prevalence of neck pain (p < 0.05). On multivariate analysis, AP was associated with increased odds of neck pain (odds ratio [OR] = 1.42 [95% confidence interval (CI) 1.04 to 1.92], p = 0.026). AP was independently associated with 42% increased odds of having neck pain. Further study into the association of cardiovascular disease with degenerative disc disease pain should be performed. (Journal of Surgical Orthopaedic Advances 33(2):093-096, 2024).

[Clinical comprehensive evaluation of Shexiang Tongxin Dropping Pills].

Based on literature and questionnaire research, related evidence and related data on Shexiang Tongxin Dropping Pills were collected in terms of safety, effectiveness, economy, innovation, suitability, and accessibility. In addition, multi-criteria decision analysis(MCDA) model was used to comprehensively evaluate the clinical value of Shexiang Tongxin Dropping Pills. Quality control was carried out strictly based on evidence-based medicine evaluation. Shexiang Tongxin Dropping Pills were recommended for stable fatigue angina of coronary heart disease with Qi deficiency and blood stasis by guidelines and experts. The conventional treatment of western medicine adds Shexiang Tongxin Dropping Pills to reduce the frequency of angina attacks, shorten the duration, improve exercise tolerance, and improve the quality of life and Chinese symptoms, and the effectiveness is rated as grade A. Adverse reactions are mostly general adverse reactions, and no serious adverse reactions have been reported, consistent with the known risks listed in the instruction for adverse events, contraindications, and precautions. The safety is rated as grade A, and the daily cost is 7.74 yuan. The cost-effectiveness shows that it is a treatment regimen with pharmacoeconomic advantages, and the economic performance is rated as grade A. According to specialist research, Shexiang Tongxin Dropping Pills have good clinical innovation and service innovation, and innovation is rated as grade A. There are no special storage conditions, medicinal material ingredients, or other restrictions, and the clinical use meets the specifications of the medication guidelines. The suitability is rated as grade A. The price level, availability, and affordability of drugs are generally good, and the accessibility is rated as grade A. The clinical value of Shexiang Tongxin Dropping Pills is great.

[Meta-analysis and trial sequential analysis of Shenshao Capsules in treatment of angina pectoris in coronary heart disease].

The efficacy and safety of Shenshao Capsules in combination with conventional western medicine for the treatment of angina pectoris in coronary heart disease were systematically evaluated. Computer search of seven databases, including CNKI, Wanfang, VIP, SinoMed, PubMed, EMbase, and Cochrane Library, was conducted to identify randomized controlled trial(RCT) on Shenshao Capsules for the treatment of angina pectoris in coronary heart disease up to December 2023. According to inclusion and exclusion criteria, articles were screened, and data was extracted. Cochrane bias risk assessment tool 2.0(RoB 2.0) was used to evaluate the quality of the included articles. Meta-analysis was performed by RevMan 5.4 and Stata/SE 15.1 software, and evidence quality was rated by the GRADE system. TSA 0.9.5.10 beta software was used for the trial sequential analysis(TSA). Twelve RCTs, with a total of 1 128 participants(567 in the experimental group and 561 in the control group), were included. Meta-analysis showed that Shenshao Capsules + conventional western medicine significantly improved clinical efficacy(RR=1.20, 95%CI[1.15, 1.26], P<0.000 01) and electrocardiogram efficacy(RR=1.16, 95%CI[1.04, 1.30], P=0.01), reduced the frequency of weekly angina pectoris attacks(MD=-2.85, 95%CI[-5.27,-0.43], P=0.02), daily angina pectoris attacks(MD=-0.30, 95%CI[-0.57,-0.03], P=0.03) and the duration of angina pectoris attacks(RR=-2.28, 95%CI[-3.44,-1.12], P=0.000 1). There was no statistically significant difference in adverse reactions between the two groups(RR=1.33, 95%CI[0.71, 2.51], P=0.37). TSA indicated that the cumulative evidence for clinical efficacy exceeded the traditional boundary but did not exceed the TSA boundary, suggesting a potential false positive result. According to GRADE assessment, except for clinical efficacy, which was rated as low-quality evidence, the remaining outcomes were rated as very low-quality evidence. The results indicate that Shenshao Capsules + conventional western medicine may have certain advantages in improving clinical efficacy and electrocardiographic efficacy, reducing the frequency and duration of angina pectoris attacks. However, due to the limitations of this study, more rigorous and high-quality RCT is needed to validate its efficacy and safety.