Symptoms Of Myocardial Ischemia Research Articles

Human coronary blood single-cell sequencing combined with exosome proteomic profiling reveals the molecular mechanism of recurrent in-stent restenosis (R-ISR)

Abstract Background Percutaneous coronary intervention (PCI) is recognized as the core treatment for symptomatic myocardial ischemia and acute coronary syndrome (ACS). However, the complex pathogenesis of recurrent in-stent restenosis (R-ISR) after stent implantation is still insufficiently understood. Purpose This study reports the first single-cell RNA sequencing and proteomic profiling to characterize pathogenesis of R-ISR in humans. Methods To reveal the pathophysiology and molecular mechanism of R-ISR, we performed single-cell RNA sequencing to identify RISR-induced changes in transcriptional landscape in coronary blood mononuclear cell composition. Besides, proteomic profiling of human coronary plasma-derived exosomes was used to further screen different proteins. Transmission electron microscopy (TEM), nanoparticle tracking analysis (NTA) and western blot analysis were performed to identify exosomes. In vitro cell biology experiments were used to validate the discoveries of bioinformatics analysis. Results Compared with normal subjects, the percentage of FCGR3B high monocytes, memory T cells and plasmacytoid dendritic cells (DCs) was increased in R-ISR. Furthermore, we observed a marked increase in the expression of JUN, FOS, CXCL8, S100A8 enriched in the IL-17 signaling pathway that is known to play a crucial role in activating inflammation, mediating immune response, and even maintaining inflammation to chronicity. According to in vitro experiments, the co-cultured system demonstrated that FCGR3B high monocytes isolated from RISR patients activated the expression of inflammatory factors in endothelial cells (ECs), such as IL-1β, IL-6 and TNF-α. Inflammatory activated endothelial cells could release a large amount of exosomes, proteomic profiling of exosomes isolated from ECs observed a significant upregulation of MYLK expression, which could promote proliferation and migration of vascular smooth muscle cells (VSMCs) by activating VEGFR-2 signaling pathway. Conclusions Our study reveals a novel subset of FCGR3B high monocytes in R-ISR patients that could activate ECs inflammation via IL-17 signaling pathway. Activated ECs release exosomes rich in MYLK, which promote proliferation and migration of VSMCs, ultimately leading to repeated restenosis.

Coronary artery compression by dilated pulmonary artery in an early infantile case of tetralogy of Fallot with absent pulmonary valve: ventricular fibrillation as the initial symptom of myocardial ischaemia.

Coronary artery compression by a dilated pulmonary artery is a rare complication in patients with tetralogy of Fallot with absent pulmonary valve. We present a case in which this condition manifested at two months of age, with ventricular fibrillation as the initial symptom of myocardial ischaemia. It is important to recognise that this potentially fatal complication can occur in early infancy.

Plasma metabolic profiling reveals that crude and processed Polygonatum cyrtonema hua extract ameliorates myocardial ischemia-induced damage by regulating branched-chain amino acid and energy metabolism

Polygonatum cyrtonema Hua and its processed products have demonstrated cardio-protective effects, though the underlying mechanisms remain unclear. In this study, plasma metabolic profiling and pattern recognition were employed to explore the cardio-protective mechanisms of both crude and processed P. cyrtonema in a myocardial ischemia model induced by ligation, using gas chromatography-mass spectrometry. Post-modeling, plasma levels of creatine kinase-MB, lactate dehydrogenase, troponin T, and malondialdehyde were significantly elevated but were notably reduced after treatment. Conversely, plasma levels of glutathione peroxidase and superoxide dismutase, which were significantly decreased post-modeling, were restored following treatment. Hematoxylin-eosin (HE) and Masson staining revealed that both crude and processed P. cyrtonema effectively reduced inflammatory infiltration and fibrosis in cardiac tissue. Metabolic profiling identified 34 differential endogenous metabolites in the treatment groups, with 19 confirmed using standard compounds. The linear correlation coefficients (R2) for these standards ranged from 0.9960 to 0.9996, indicating high accuracy. The method exhibited excellent precision and repeatability, with relative standard deviation (RSD) values below 8.57%. Recovery rates were between 95.02% and 105.15%, and the stability of the standard compounds was confirmed after three freeze–thaw cycles, with RSD values under 4.42%. Both crude and processed P. cyrtonema were found to alleviate myocardial ischemia symptoms by regulating branched-chain amino acid metabolism and energy metabolism. These findings provide a solid foundation for the potential clinical use of this herb and its processed products in treating heart disease.

Allergy, infarction, and stress cardiomyopathy: in-depth analysis of a complex clinical case report

Abstract Background Diagnosis of Kounis syndrome, an acute coronary syndrome associated with anaphylactic reactions, is challenging owing to the overlapping symptoms of myocardial ischemia. Takotsubo syndrome (TTS), characterized by stress-induced cardiomyopathy, may share pathophysiological mechanisms with Kounis syndrome and potentially coexist in the same patient. Case Presentation We present a case of a 63-year-old patient who developed an allergic reaction to contrast medium administration, leading to dyspnea and chest pain. Electrocardiography revealed a new-onset left bundle-branch block, and echocardiography indicated wall motion abnormalities with apical ballooning, suggestive of TTS. Coronary angiography displayed a chronic total occlusion of the right coronary artery. Laboratory tests revealed elevated inflammatory markers, supporting the diagnosis of Kounis syndrome and TTS. Conclusion This case highlights the challenges of diagnosing and managing type II Kounis syndrome associated with concurrent TTS. This underscores the need for tailored therapeutic interventions and comprehensive guidelines to address these complex conditions effectively.

Echocardiographic Predictors of Improvement of Left Ventricular Ejection Fraction below 35% in Patients with ST-Segment Elevation Myocardial Infarction.

Introduction: An ST-elevation myocardial infarction (STEMI) is a clinical syndrome defined by symptoms of myocardial ischemia, persistent electrocardiographic ST-segment elevation and subsequent release of biomarkers suggestive of myocardial necrosis. In clinical practice, echocardiography has become essential in evaluating patients after acute myocardial infarction. We aimed to assess clinical and echocardiographic parameters that may affect LV function recovery in patients after STEMI. Methods: This study is a retrospective observational study from a tertiary referral center in Israel. We collected patients that were admitted with STEMI and a left ventricular ejection fraction (LVEF) below 35% on preliminary echocardiography at the index hospitalization and compared the findings to a follow-up study performed within 1-6 months after that event, in order to see if there are predictors of LVEF change > 10% within 90 days following STEMI. Results: This study included 101 patients that were admitted between 2016 and 2021. Within a median follow-up of 9.7 weeks (IQR 5.9-17.1), 27 (25.2%) patients had improved their LVEF, and 74 (69.2%) had no change or further reduced LVEF. Compared to patients without LVEF improvement, those with improved LVEF were more likely to be female (29.6% vs. 9.5%, p = 0.01), less likely to suffer from hypertension (33.3% vs. 56.8%, p = 0.04) and had marginally higher rates of thrombolysis treatment (14.1% vs. 4.1%, p = 0.06). Conclusions: in the population of STEMI patients with residual LVEF < 35%, approximately a quarter will improve at least 10% in their follow-up LVEF, and there were no clear echocardiographic predictors for this improvement.

Potential Targets of Natural Products for Improving Cardiac Ischemic Injury: The Role of Nrf2 Signaling Transduction.

Myocardial ischemia is the leading cause of health loss from cardiovascular disease worldwide. Myocardial ischemia and hypoxia during exercise trigger the risk of sudden exercise death which, in severe cases, will further lead to myocardial infarction. The Nrf2 transcription factor is an important antioxidant regulator that is extensively engaged in biological processes such as oxidative stress, inflammatory response, apoptosis, and mitochondrial malfunction. It has a significant role in the prevention and treatment of several cardiovascular illnesses, since it can control not only the expression of several antioxidant genes, but also the target genes of associated pathological processes. Therefore, targeting Nrf2 will have great potential in the treatment of myocardial ischemic injury. Natural products are widely used to treat myocardial ischemic diseases because of their few side effects. A large number of studies have shown that the Nrf2 transcription factor can be used as an important way for natural products to alleviate myocardial ischemia. However, the specific role and related mechanism of Nrf2 in mediating natural products in the treatment of myocardial ischemia is still unclear. Therefore, this review combs the key role and possible mechanism of Nrf2 in myocardial ischemic injury, and emphatically summarizes the significant role of natural products in treating myocardial ischemic symptoms, thus providing a broad foundation for clinical transformation.

Association between preoperative frailty and myocardial injury after noncardiac surgery in geriatric patients: study protocol for a prospective, multicentre, real-world observational, cohort trial

IntroductionFrailty has become a worldwide health burden that has a large influence on public health and clinical practice. The incidence of frailty is anticipated to increase as the ageing population increases. Myocardial injury after noncardiac surgery (MINS) is associated with short-term and long-term mortality. However, the incidence of MINS in frail geriatric patients is unknown.Methods and analysisThis prospective, multicentre, real-world observational cohort study will be conducted at 18 designated centres in China from January 2023 to December 2024, with an anticipated sample size of 856 patients aged 65 years and older who are scheduled to undergo noncardiac surgery. The primary outcome will be the incidence of MINS. MINS is defined as a fourth-generation plasma cardiac troponin T (cTnT) concentration ≥ 0.03 ng/mL exhibited at least once within 30 days after surgery, with or without symptoms of myocardial ischaemia. All data will be collected via electronic data acquisition.DiscussionThis study will explore the incidence of MINS in frail patients. The characteristics, predictive factors and 30-day outcomes of MINS in frail patients will be further investigated to lay the foundation for identifying clinical interventions.Clinical trial registrationhttps://beta.clinicaltrials.gov/study/NCT05635877, NCT05635877.

Relationship between coronary microvascular dysfunction (CMD) and left ventricular diastolic function in patients with symptoms of myocardial ischemia with non-obstructive coronary artery disease (INOCA) by cardiovascular magnetic resonance feature-tracking

To investigate whether there was an association between coronary microvascular dysfunction (CMD) and left ventricular (LV) diastolic function in patients with myocardial ischemia with non-obstructive coronary artery disease (INOCA). Our study included 115 subjects with suspected myocardial ischemia that underwent stress perfusion cardiac magnetic resonance (CMR). They were divided into non-CMD and CMD two groups. CMR-derived volume-time curves and CMR-FT parameters were used to assess LV diastolic function using CVI42 software. The latter included global/regional LV peak longitudinal, circumferential, radial diastolic strain rate (LDSR, CDSR, RDSR). Logistic regression analysis was performed with CMR-FT strain parameters as independent variables and CMD as dependent variables, and the effect value was expressed as an odds ratio (OR). Of the 115 patients, we excluded data from 23 patients and 92 patients (56.5% male；52±12 years) were finally included in the study. Of these, 19 patients were included in the non-CMD group (49±11 years) and CMD group included 73patient (52±12 years). The regional CDSR (P=0.019), and regional RDSR (P=0.006) were significantly lower in the CMD group than in non-CMD group. But, regional LDSR in CMD group was higher than non-CMD (P=0.003). In logistic regression analysis, regional LDSR (adjusted β= 0.1, 95%CI 0.077, 0.349, p=0.002) and RDSR (adjusted β= 0.1, 95 % CI 0.066, 0.356, p=0.004) were related to CMD. LV myocardial perfusion parameter MPRI was negatively correlated with LV diastolic function (CDSR) which needs to take into account the degree of diastolic dysfunction.

Anomalous Origin of the Left Coronary Artery from the Pulmonary Artery Diagnosed in Adulthood

Introduction: An anomalous left coronary artery from the pulmonary artery (ALCAPA) is a rare heart malformation, with 90% of patients dying during the first year of life. If the right coronary artery compensation and multiple collateral circulation are sufficiently established, the patient's myocardial ischemia symptoms are mild and appear later, which is called the adult type ALCAPA. Case Description: A 42-year-old woman presented to our hospital with one-month history of the aggravation of active shortness of breath which gradually progressed to nocturnal paroxysmal shortness of breath and cough. Admission physical examination suggested mild edema of both lower limbs. Transthoracic echocardiography (TTE) showed that a small vessel shadow was abnormally connected to the pulmonary artery (PA), and moderate pulmonary artery hypertension. Coronary computed tomography angiography (CTA) showed an anomalous origin of the left main coronary artery (LMCA) dividing into the left anterior descending (LAD) and left circumflex (LCX) artery from the PA, with no clear connection to the left coronary sinus. The right coronary artery (RCA) was significantly dilated and originated from the normal Valsalva sinus. It was accompanied by multiple collateral circulations, most of which traveled anterior to the right ventricular free wall and anterior interventricular sulcus, and some emanated from the posterior descending branch of the posterior interventricular sulcus and walked toward the posterolateral wall of the left ventricle. Conclusion: Coronary computed tomography angiography (CTA) can be used to visualize the abnormal origin and distribution of the coronary artery's course and may be the first choice in the diagnosis of ALCAPA.

Men with nonobstructive coronary disease have higher burden of ischemic heart disease detected by cardiopulmonary exercise test.

Nonobstructive coronary artery disease (NOCAD), characterized by the presence of myocardial ischemic symptoms and signs without obstructive coronaries, is a common clinical condition, but it is less well understood. Few studies have analyzed the gender differences in inducible myocardial ischemia assessed by cardiopulmonary exercise test (CPET) in NOCAD. We conducted a study of 289 NOCAD patients (mean age 60, 56% women) with ischemic symptoms and confirmed ⫹50% coronaries stenoses by coronary angiography who underwent symptom-limited CPET. We assessed ischemic response using predicted % peak VO2 , O2 pulse trajectory, and exercise ECG test. Men with NOCAD had significantly lower predicted % peak VO2 (62% vs. 73%), higher proportions of flattening pattern (16% vs. 2%), and downward patterns of O2 pulse trajectory (2% vs. 0%) (p < .0001) compared with women. In contrast, women with NOCAD had a higher prevalence of shallow patterns of O2 pulse trajectory (21% vs. 6%, p < .0001). Men with NOCAD had a higher risk ischemic profile (medium risk: 63% vs. 54%, high risk: 18% vs. 4%, p < .0001). After adjustment, men with NOCAD had significantly lower predicted % peak VO2 (β -27.4, 95% CI -30.74 to -24.07), higher risk for abnormal O2 pulse trajectories (OR 4.21, 95% CI 1.93 to 9.19), and myocardial ischemia risk per CPET parameters (OR 3.14, 95% CI 1.78 to 5.54) (p < .0001). Men with NOCAD had a higher risk profile for ischemic heart disease per CPET. Therefore, they should receive rigorous management and follow-up to prevent cardiovascular events.

In-Stent Restenosis: Achilles’ Heel of Post-PCI Era

Despite advancements in stent design and polymer coatings over the past two decades, 1% to 2% of patients annually still experience instent restenosis (ISR). ISR reduces myocardial perfusion, may develop symptoms of myocardial ischemia, and thus leads to a high risk of myocardial infarction and cardiac death. Given that millions of drug-eluting stents (DES) are implanted globally every year, ISR remains a prevalent clinical issue with significant public health implications. Coronary intravascular imaging, includes intravascular ultrasound (IVUS) and optical coherence tomography (OCT), can help physicians gain deeper insights into the potential mechanisms of ISR. The preferred treatment strategy hinges on an accurate diagnosis and better understanding of etiology. The mechanism of ISR is multifaceted, and its treatment is challenging. Although the risk of ISR continues to decrease with advancements in DES application, further research is still needed to enrich the treatment options for ISR.

Pathogenesis, Assessment, and Treatment of Coronary Microcirculation Dysfunction.

Cardiovascular disease is the predominant cause of mortality on a global scale. Research indicates that women exhibit a greater likelihood of presenting with non-obstructive coronary artery disease (CAD) when experiencing symptoms of myocardial ischemia in comparison to men. Additionally, women tend to experience a higher burden of symptoms relative to men, and despite the presence of ischemic heart disease, they are frequently reassured erroneously due to the absence of obstructive CAD. In cases of ischemic heart disease accompanied by symptoms of myocardial ischemia but lacking obstructive CAD, it is imperative to consider coronary microvascular dysfunction as a potential underlying cause. Coronary microvascular dysfunction, characterized by impaired coronary flow reserve resulting from functional and/or structural abnormalities in the microcirculation, is linked to adverse cardiovascular outcomes. Lifestyle modifications and the use of anti-atherosclerotic and anti-anginal medications may offer potential benefits, although further clinical trials are necessary to inform treatment strategies. This review aims to explore the prevalence, underlying mechanisms, diagnostic approaches, and therapeutic interventions for coronary microvascular dysfunction.

Shock Wave Therapy Alleviates Hypoxia/Reoxygenation-Induced Cardiomyocyte Injury by Inhibiting Both Apoptosis and Ferroptosis.

Shock wave therapy (SWT) is a new alternative therapy for patients with severe coronary artery disease that improves myocardial ischemic symptoms by delivering low-energy shock wave stimulation to ischaemic myocardium with low-energy pulsed waves. However, the specific mechanism of its protective effect is not fully understood, especially for the protective mechanism in cardiomyocytes after hypoxia/reoxygenation (H/R). We selected a rat H9c2 cardiomyocyte cell line to establish a stable H/R cardiomyocyte injury model by hypoxia/reoxygenation, and then used SWT for therapeutic intervention to explore its cardiomyocyte protective mechanisms. The results showed that SWT significantly increased cell viability and GSH levels while decreasing LDH levels, ROS levels, and MDA levels. SWT also improved mitochondrial morphology and function of cells after H/R. Meanwhile, we found that SWT could increase the expression of GPX4, xCT, and Bcl-2, while decreasing the expression of Bax and cleaved caspase-3, and inhibiting cardiomyocyte apoptosis and ferroptosis. Moreover, this protective effect of SWT on cardiomyocytes could be significantly reversed by knockdown of xCT, a key regulator protein of ferroptosis. In conclusion, our study shows that SWT can attenuate hypoxia-reoxygenation-induced myocardial injury and protect cardiomyocyte function by inhibiting H/R-induced apoptosis and ferroptosis, and this therapy may have important applications in the treatment of clinical myocardial ischemic diseases.

Invasive Assessment of Coronary Microcirculation: A State-of-the-Art Review.

A significant proportion of patients presenting with signs and symptoms of myocardial ischemia have no "significant" epicardial disease; thereby, the assessment of coronary microcirculation gained an important role in improving diagnosis and guiding therapy. In fact, coronary microvascular dysfunction (CMD) could be found in a large proportion of these patients, supporting both symptoms and signs of myocardial ischemia. However, CMD represents a diagnostic challenge for two main reasons: (1) the small dimension of the coronary microvasculature prevents direct angiographic visualization, and (2) despite the availability of specific diagnostic tools, they remain invasive and underused in the current clinical practice. For these reasons, CMD remains underdiagnosed, and most of the patients remain with no specific treatment and quality-of-life-limiting symptoms. Of note, recent evidence suggests that a "full physiology" approach for the assessment of the whole coronary vasculature may offer a significant benefit in terms of symptom improvement among patients presenting with ischemia and non-obstructive coronary artery disease. We analyze the pathophysiology of coronary microvascular dysfunction, providing the readers with a guide for the invasive assessment of coronary microcirculation, together with the available evidence supporting its use in clinical practice.

Reduced stress perfusion in myocardial infarction with nonobstructive coronary arteries

Myocardial infarction with nonobstructive coronary arteries (MINOCA) has several possible underlying causes, including coronary microvascular dysfunction (CMD). Early cardiovascular magnetic resonance imaging (CMR) is recommended, however cannot provide a diagnosis in 25% of cases. Quantitative stress CMR perfusion mapping can identify CMD, however it is unknown if CMD is present during long-term follow-up of MINOCA patients. Therefore, this study aimed to evaluate presence of CMD during long-term follow-up in MINOCA patients with an initial normal CMR scan. MINOCA patients from the second Stockholm myocardial infarction with normal coronaries study (SMINC-2), with a normal CMR scan at median 3 days after hospitalization were investigated with comprehensive CMR including stress perfusion mapping a median of 5 years after the index event, together with age- and sex-matched volunteers without symptomatic ischemic heart disease. Cardiovascular risk factors, medication and symptoms of myocardial ischemia measured by the Seattle Angina Questionnaire 7 (SAQ-7), were registered. In total, 15 patients with MINOCA and an initial normal CMR scan (59 ± 7 years old, 60% female), and 15 age- and sex-matched volunteers, underwent CMR. Patients with MINOCA and an initial normal CMR scan had lower global stress perfusion compared to volunteers (2.83 ± 1.8 vs 3.53 ± 0.7 ml/min/g, p = 0.02). There were no differences in other CMR parameters, hemodynamic parameters, or cardiovascular risk factors, except for more frequent use of statins in the MINOCA patient group compared to volunteers. In conclusion, global stress perfusion is lower in MINOCA patients during follow-up, compared to age- and sex-matched volunteers, suggesting that CMD may be a possible pathophysiological mechanism in MINOCA.Clinical Trial Registration: Clinicaltrials.gov identifier NCT02318498. Registered 2014-12-17.

Association of abnormal electrocardiography response on dobutamine stress echocardiogram with longer-term major adverse cardiovascular events in women with symptoms of ischemic heart disease.

Prior work demonstrates patients with positive (+) electrocardiogram (ECG) but negative (-) echocardiogram wall motion abnormalities (WMAs) on dobutamine stress echocardiography (DSE) testing have an elevated of major adverse cardiovascular events (MACEs). In this study, we aimed to evaluate the long-term prognosis of women with suspected ischemia with no obstructive coronary artery (INOCA) disease by utilizing core lab read DSE, specifically focusing on those with + ECG findings. Among women with signs and symptoms of myocardial ischemia undergoing clinically indicated coronary angiography enrolled in the Women's Ischemia Syndrome Evaluation (WISE) [1997-2001], a prospective cohort study, 99 underwent standardized DSE by site design. Women with positive DSE (n=17), defined as an increase in score based on wall motion scoring index were excluded except for akinetic to dyskinetic (n=10), providing 82 patients in this analysis. ECG was assessed by core laboratory and (+) ECG was defined as >1 mm ST change. Non-obstructive coronary artery disease (CAD) was assessed by core laboratory quantitative coronary angiography and defined as <50% epicardial stenosis. All-cause death follow-up was an average of 8 years, while adjudicated MACE [all-cause mortality, nonfatal myocardial infarction (MI), nonfatal stroke, heart failure hospitalization] was an average of 5.5 years. Comparisons among subject groups [i.e., (+) ECG and (-) ECG] were made using chi-square or Fisher's exact tests for categorical variables and t-test or Wilcoxon rank-sum test for continuous variables. Demographic profile included a mean age 59±10 years; 55% had hypertension (HTN), 29% diabetes mellitus (DM), and 72% non-obstructive CAD. Overall, 9/82 women (11%) had (+) ECG in the absence of WMAs. There were significant differences in family history of CAD (P=0.009) and vasodilator (P=0.042) use between the (+) ECG and (-) ECG groups, but otherwise had no significant demographic or clinical differences. At longer-term follow up, patients with (+) ECG had higher risk of MACE [unadjusted hazard ratio (HR): 4.91, 95% confidence interval (CI): 1.83, 13.19, P=0.002]. Abnormal stress ECG findings on dobutamine stress testing with a negative DSE should be viewed as an indicator of longer-term risk in women with signs and symptoms of ischemia.

Protocol: dexmedetomidine on myocardial injury after noncardiac surgery—a multicenter, double-blind, controlled trial

AimsMyocardial injury after noncardiac surgery (MINS) is common in elderly patients and considered as an independent predictor of 30-day mortality after noncardiac surgery. Dexmedetomidine possesses cardiac-protective profile. Previous clinical studies have found that perioperative application of dexmedetomidine is associated with decreased 1-year mortality in patients undergoing cardiac surgery. The current study protocol aims to investigate the effects of dexmedetomidine on the incidence of MINS, complications, and 30-day mortality in elderly patients subjected to noncardiac surgery.MethodsA multicenter, randomized, controlled, double-blind, prospective trial is designed to explore cardiac protection of dexmedetomidine in the elderly patients undergoing noncardiac surgery. A total of 960 patients aged over 65 years will be recruited and randomly assigned to dexmedetomidine group (group Dex) and normal saline placebo group (group NS) in a ratio of 1:1. Patients in group Dex will receive a bolus dose of 0.5 μg/kg dexmedetomidine within 10 min before surgical incision, followed by a consistent infusion at the rate of 0.3–0.5 μg/kg/h throughout the operation. Group NS patients will receive the same volume of normal saline. The primary outcome is the incidence of MINS via detecting the hs-TnT level within 3 days after the operation. The secondary outcome includes myocardial ischemic symptoms, the incidence of major adverse cardiovascular events (MACE) in hospital, length of ICU and postoperative hospital stay, the incidence of inhospital complications, and 30-day all-cause mortality.DiscussionThe results of the current study will illustrate the effect of dexmedetomidine on myocardial injury for elderly patients undergoing major noncardiac surgery.Trial registrationThe trial was registered with Chinese Clinical Trial Registry (CHICTR) on Aug 24, 2021 (ChiCTR2100049946, http://www.chictr.org.cn/showproj.aspx?proj=131804).

Repeat coronary revascularization in high-risk patients treated with ticagrelor monotherapy after PCI: Insights from the randomized TWILIGHT trial

Abstract Background Repeat revascularization after percutaneous coronary intervention (PCI) remains a major concern, even though its impact on mortality is limited. The effect of ticagrelor monotherapy vs. standard dual antiplatelet therapy (DAPT) on this outcome is unclear. Aim To assess the impact of ticagrelor monotherapy vs. DAPT on repeat revascularization after PCI. Methods In the TWILIGHT trial, high-risk patients who were event-free and adherent to a ticagrelor-based DAPT for 3 months after PCI were randomized to ticagrelor plus aspirin or ticagrelor plus placebo for 12 additional months. In this post-hoc analysis, the primary endpoint was repeat revascularization due to recurrent or persistent symptomatic myocardial ischemia. Secondary endpoints included target lesion revascularization (TLR), target vessel revascularization (TVR) and major adverse cardiac and cerebrovascular events (MACCE) and net adverse clinical events (NACE) (Figure). All endpoints were adjudicated and assessed at 12 months after randomization in the per-protocol population. Results Among 6,759 patients, ticagrelor monotherapy and ticagrelor plus aspirin were associated with a similar risk of repeat revascularization (7.1% vs 6.7%, HR 1.07, 95% CI 0.89-1.29), TLR, TVR and MACCE (Figure), while NACE was lower with ticagrelor monotherapy. Conclusion In high-risk patients undergoing PCI, ticagrelor monotherapy after 3 months of ticagrelor plus aspirin was associated with similar rates of recurrent coronary revascularization and MACCE and a lower risk of NACE compared with continued DAPT.

Abstract 13423: Magnetocardiography as a Noninvasive Diagnostic Strategy for Ischemia Evaluating Following Coronary Revascularization of Patients With Non-ST Segment Elevation Myocardial Infarction

Introduction: Magnetocardiography (MCG) constitutes a non-invasive and radiation-free procedure that quantifies the heart's magnetic fields and has exhibited sensitive diagnostic capabilities for ischemia. Typically, MCG presents a distinctive pattern in healthy subjects, characterized by a positive and a negative pole that forms an angle of approximately 45-60 degrees within the T peak segment. Hypothesis: Our study aims to monitor the significant alterations in MCG patterns among patients with Non-ST Segment Elevation Myocardial Infarction (NSTEMI) undergoing revascularization. Methods: Patients were prospectively enrolled and MCG scans were conducted thrice: three days pre-intervention, one week post-intervention, and at a three-month follow-up. Results: Four patients underwent anatomical complete revascularization, while one patient had incomplete revascularization. When comparing the MCG patterns of patients with NSTEMI (Figures B-F) to a normal MCG pattern (Figure A), pre-intervention scans showed angular deflection (80%, except for patient 3) and an anomalous distribution of poles (100%). One week post-intervention, patients who underwent complete revascularization (Figures B-D) had myocardial enzymes normalized, along with slight angle recovery and reshaping of the poles (100%). By the three-month follow-up, these patients experienced symptom resolution, and their MCG patterns showed normalized angles with recovered poles (100%). However, the patient who underwent incomplete revascularization (Figure F) exhibited sustained myocardial ischemia symptoms, with no further angle recovery and continued anomalous distribution of positive poles, both post-intervention and during follow-up. Conclusions: The distribution of poles and angular deflection could potentially serve as indicators of ischemia. MCG may represent a promising strategy for evaluating myocardial recovery in patients with NSTEMI.

Buxu Tongyu Granule Alleviates Myocardial Ischemia by Activating Vascular Smooth Muscle Cell Soluble Guanylate Cyclase to Inhibit Abnormal Vasomotion

Myocardial ischemia is a serious threat to human health, and vascular dysfunction is its main cause. Buxu Tongyu (BXTY) Granule is an effective traditional Chinese medicine (TCM) for treating myocardial ischemia. However, the underlying mechanism of BXTY is still unclear. In this study, we demonstrate that BXTY ameliorates myocardial ischemia by activating the soluble guanylate cyclase (sGC)–3′,5′-cyclic guanosine monophosphate (cGMP)–protein kinase G (PKG) signaling pathway in vascular smooth muscle cells (VSMCs) to dilate the arteries. BXTY was given by gavage for ten consecutive days before establishing an animal model of acute myocardial ischemia in mice via the intraperitoneal injection of pituitrin. The results showed that BXTY alleviated the symptoms of myocardial ischemia induced by pituitrin in mice, including electrocardiogram abnormalities and changes in plasma enzymes. In addition, BXTY dilated pre-constricted blood vessels and inhibited the vasoconstriction of the superior mesenteric artery in a dose-dependent but endothelial-independent manner. These effects were eliminated by pre-incubating vascular rings with the sGC inhibitors NS 2028 or ODQ, or with the PKG inhibitor KT 5823. Moreover, BXTY increased the protein expression of sGC-β1 and the intracellular second messenger cGMP level in mouse aortic vascular smooth muscle cells (MOVAs). NS 2028 or ODQ reversed these effects of BXTY. The expression level of the cGMP downstream effector protein PKG-1 increased after treating MOVAs with BXTY. NS 2028, ODQ, or KT 5823 also reversed this effect of BXTY. In conclusion, BXTY can improve the symptoms of acute myocardial ischemia in mice, and activating the sGC–cGMP–PKG pathway in VSMCs to induce vasodilation is its key pharmacodynamic mechanism.