Ischemic Symptoms Research Articles

Combining metabolomics and network pharmacology to investigate the protective effect of Jiawei Xinglou Chengqi Granules in ischemic stroke.

Jiawei Xinglou Chengqi Granule (JXCG) is an effective herbal medicine for the treatment of ischemic stroke (IS). JXCG has been shown to effectively ameliorate cerebral ischemic symptoms in clinical practice, but the underlying mechanisms are unclear. In this study, we investigated the mechanisms of action of JXCG in the treatment of IS by combining metabolomics with network pharmacology. The chemical composition of JXCG was analyzed using ultra-high performance liquid chromatography-high resolution mass spectrometry (UHPLC-HRMS). Ultra-high performance liquid chromatography-tandem time-of-flight mass spectrometry (UHPLC-Q-TOF MS) untargeted metabolomics were used to identify differential metabolites within metabolic pathways. Network pharmacology was applied to mine potential targets of JXCG in the treatment of IS. The identified key targets were validated by constructing an integrated network of metabolomics and network pharmacology and by molecular docking using Cytoscape. The effect of JXCG on IS was evaluated in vivo, and the predicted targets and pathways of JXCG in IS therapy were assessed using immunoblotting. Combining metabolomics and network pharmacology, we identified the therapeutic targets of JXCG for IS. Notably, JXCG lessened neuronal damage and reduced cerebral infarct size in rats with IS. Western blot analysis showed that JXCG upregulated PRKCH and downregulated PRKCE and PRKCQ proteins. Our combined network pharmacology and metabolomics findings showed that JXCG may have therapeutic potential in the treatment of IS by targeting multiple factors and pathways.

Outcomes of Aortoiliac Occlusive Disease Treated by Aorto-femoro-popliteal and Distal Bypass Surgeries: A Prospective Cohort Study

Introduction: Aortoiliac occlusive disease can contribute to lower extremity ischaemic symptoms requiring intervention. Though proximal aorto-femoral bypass surgery has been the mainstay of intervention, the delayed healing in many patients necessitates exploration of other techniques, including sequential revascularisation. Aim: To estimate the outcomes of aortoiliac occlusive disease treated by aorto-femoro-popliteal and distal bypass surgeries. Materials and Methods: A prospective cohort study was conducted to determine the treatment outcomes of 25 patients with aortoiliac occlusive disease visiting a tertiary care centre of Government Stanley Medical College and Hospital, Chennai, Tamil Nadu, India from October 2012 to December 2014. Data regarding the aetiology of the disease, co-morbidities including substance use, degree of disease involvement, and treatment modalities were collected. Data was analysed by Statistical Package for Social Sciences (SPSS) software version 22.0. The Chi-square test was used to compare outcomes with different treatment modalities, and a p-value <0.05 was considered statistically significant. Results: The mean age of the study participants was 58.3±2 years (range 40 to 70 years). The study noted that the most common aetiology for aortoiliac occlusive disease was atherosclerosis in 18 (72%) cases. The most common associated co-morbidity was smoking in 18 (72%) cases. Abnormal profunda patency was noted in 15 (60%) cases and synthetic Polytetrafluoroethylene (PTFE) was used in 80% of sequential bypass cases. A significantly higher proportion (86.7% vs 30%) of people treated by the sequential procedure achieved relief from claudication pain (p-value<0.05). The complication noted after the proximal bypass was pseudoaneurysm (20%), and the only complication noted after the sequential bypass was graft thrombosis (13.33%). The mean Ankle-brachial Index (ABI) score and ulcer healing time were also significantly higher in the sequential bypass procedure (p-value<0.05). Conclusion: Sequential bypass offers better advantages than proximal bypass for treating aortoiliac occlusive disease. It was found to be a safe and effective method for successful limb salvage, ensuring successful limb revascularisation and sufficient outflow to maintain graft patency.

사포그릴레이트 염산염을 함유하는 신규 OROS 정의 제제 설계 및 용출 거동

Sarpogrelate hydrochloride (SGH) is a drug that improves ischemic symptoms such as ulcers, pain, and feeling of cold caused by chronic arterial occlusion, and has a short half-life of 0.6 to 0.8 hours. Also, reference drug (SarpodipilⓇ SR tablet) is affected by drug release depending on pH. To overcome this, the osmotic controlled release oral delivery system (OROS) utilizes push-pull osmotic pump (PPOP) technology that can achieve zero-order drug release over 24 hours by osmotic pressure. OROS tablet is double-layer tablet consisting of a drug layer (L200-PEO) and a push layer (H5,000- PEO). OROS tablet coated with a semi-permeable film has a orifice of a certain size made by a laser drill, so that the drug is released at a constant rate. The dissolution of the OROS tablet was not affected by the amount of sodium chloride in the drug layer and the number of orifice, but was affected by amount of coating, cellulose acetate (CA) : polyethylene glycol 3350 (PEG 3350) ratio and the size of orifice. Accordingly, as the amount of coating increased and PEG 3350 decreased, the dissolution rate decreased. The developed OROS tablet (formulation C), unlike the reference drug, is not affected by pH, showing high similarity factors of 76.0, 86.1, and 91.2 at pH 1.2, pH 4.0, and pH 6.8 when compared to distilled water. In conclusion, we developed OROS tablet containing SGH, showing zero-order release that continuously releases the drug for 24 hours regardless of pH, and confirmed the factors affecting dissolution.

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.

Circulus Willis Anomalies Diagnosed with CT Angiography and Evaluation of Their Relations with Ischemic Stroke

Our aim in this study is examining the frequency of posterior communicating artery (PCoM), Anterior Cerebral Artery A1 segment (ACA AI) and Fetal type posterior cerebral artery (FPCA) anomalies and their effects on ischemic stroke by retrospectively analyzing examinations of Computerized Tomography Angiography (CTA) taken in our hospital within 2017. 22 cases (26.5%) diagnosed with bilateral hypoplastic / aplastic PCoA anomaly, were diagnosed with anterior circulation infarct, 24 cases (28.9%) were diagnosed with posterior circulation infarct, but 37 cases (44.6%) were not diagnosed with ischemic stroke. 17 (37.8%) of the cases who have unilateral hypoplastic / aplastic PCoA anomaly, were diagnosed with anterior circulation infarct, 14 cases (31.1%) were diagnosed with posterior circulation infarct. 13 (26%) of 50 cases diagnosed with unilateral hypoplastic / aplastic ACA A1 segment, were diagnosed with anterior circulation infarct, 10 cases (20%) were diagnosed with posterior circulation infarct. 27 cases (54%) were not diagnosed with ischemic stroke. Both of 2 cases diagnosed with bilateral hypoplastic / aplastic ACA A1 segment, had anterior circulation infarct. 4 (30.8%) of 13 cases diagnosed with unilateral FPCA anomaly, were diagnosed with anterior circulation infarct, 3 cases (23.1%) were diagnosed with posterior circulation infarct, 6 cases (46.2%) did not have ischemic stroke symptoms. In conclusion, even though these variations’ role in optimum stroke prophylaxis in individuals having one or more stroke risk factors, has not determined yet, there is no doubt that clinical researcher will eliminate these uncertainties in future studies.

Contemporary outcomes of distal radial artery ligation for access related hand ischemia.

Access related hand ischemia (ARHI) is a rare albeit morbid complication of hemodialysis access creation. Distal radial artery ligation (DRAL) has been described as a strategy to improve perfusion to the hand while maintaining the access. The objective of this study was to report longitudinal outcomes of DRAL for ARHI. Retrospective cohort study (2015-2021) of all patients who underwent DRAL for ARHI at a tertiary care vascular center. Subjects were identified using the Mass General Brigham clinical data warehouse and data collection was supplemented with chart adjudication. Outcomes captured included 30-day complications and improvement in ARHI-related symptoms at 1 year. Thirty-one patients were included. Mean (SD) age was 59.9 (14.5) and 67.7% were male. Wrist radial-cephalic (74.2%) and proximal radial-cephalic (9.7%) configurations were most common. ARHI severity was: 9.7% stage 1 (retrograde flow without symptoms); 38.7% stage 2 (pain during exercise or dialysis); 41.9% stage 3 (pain at rest); and 9.7% stage 4 (tissue loss). High flow was present in 35.5% of patients at baseline with median (IQR) flow of 1670 ml/min (1478-1954). After DRAL, median (IQR) flow reduction in the high flow group was 953 ml/min (645-993); concurrent precision banding was performed in 29% to reduce flow. The 30-day risk of complication was 3.2% (n = 1 access thrombosis). During follow-up, 82.1% showed improvement in symptoms and 3.6% of patients needed an additional procedure for ARHI. Carpal tunnel surgery was required for improvement in 7.1% of patients and was suspected as the culprit of symptoms in 7.1%. Distal radial artery ligation for ARHI is safe and can improve ischemic symptoms in most patients while salvaging access function. Precision banding can serve as a useful adjunct in high flow accesses. Carpal tunnel syndrome should be considered as part of the differential diagnosis of hand pain in this population.

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.

Thrombotic thrombocytopenic purpura presenting as stroke mimics with normal diffusion-weighted MRI

BackgroundThrombotic thrombocytopenic purpura (TTP) is a rare and fatal thrombotic microangiopathy-based hematologic disease. Stroke has been reported as atypical neurological manifestations of TTP in some cases.Case presentationA 65-year-old male presented with typical acute ischemic stroke symptoms including sudden-onset dysarthria, right-sided facial paralysis and hemiplegia. However, his CT and MRI scans were negative without showing any new ischemic lesions. He was diagnosed with TTP with severe thrombocytopenia, mild anemia, increased LDH, and low ADAMTS-13 activity. The symptoms and positive signs were rapidly resolved after administrating the plasma exchange therapy.ConclusionClinicians should consider the possibility of TTP when a patient presents with acute stroke-like symptoms and thrombocytopenia, especially in an emergency room, either with or without new stroke lesions on the brain CT and MRI.

Clinical Features and Risk Factors of Postoperative Stroke in Adult Moyamoya Disease.

The clinical features of and risk factors for postoperative stroke after surgical revascularization in adult moyamoya disease (MMD) have not been fully elucidated. To this end, the baseline clinical features were hereby described, and the risk factors for postoperative stroke were determined. Data of 4078 MMD inpatients were collected retrospectively across all secondary- and higher-level hospitals of Hubei Province from January 2019 to December 2020. In accordance with inclusion and exclusion criteria, 559 adult MMD inpatients were finally enrolled. The associated characteristics and potential risk factors were analyzed, and the Kaplan-Meier risk of stroke was also calculated. The patients consisted of 286 females and 273 males, with a mean age of 49.1 ± 10.0 years, all of whom had at least 1 year of follow-up (median 25.1 months). There were 356 cases of preoperative ischemic symptoms and 203 cases of preoperative hemorrhage symptoms. Indirect, direct, and combined revascularization were conducted on 97, 105 and 357 patients, respectively. Among these patients, 17 had postoperative hemorrhagic stroke (PHS), and 43 had postoperative ischemic stroke (PIS). A comparison between PHS/PIS group and control group (patients without postoperative stroke events) showed that preoperative hemorrhage was significantly associated with PHS (p = 0.003), while hypertension (p = 0.003), diabetes mellitus (p = 0.003) and modified Rankin scale (mRS) (p = 0.034) at admission were associated with a higher rate of PIS. Furthermore, preoperative hemorrhagic stroke was identified as a risk factor for PHS (odds ratio [OR], 4.229 [95% CI, 1.244-14.376]; p = 0.021), while hypertension (odds ratio [OR], 0.424 [95% CI, 0.210-0.855]; p = 0.017), diabetes mellitus (odds ratio [OR], 0.368 [95% CI, 0.163-0.827]; p = 0.016) and admission mRS (odds ratio [OR], 2.301 [95% CI, 1.157-4.575]; p = 0.017) were found to be risk factors for PIS. The age distribution of adult MMD patients with revascularization was predominantly concentrated within the range from 46 to 55 years. Preoperative hemorrhage events were considered the risk factor for PHS. Hypertension, diabetes and admission mRS were correlated with PIS, and were also the risk factors for PIS. These results indicated the possible contribution of enhancing systematic disease management to the prevention of postoperative cerebrovascular accidents.

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.

Trapdoor endarterectomy for coral reef plaque of the paravisceral aorta in the modern era

Coral reef atherosclerosis of the paravisceral aorta is a rare disease whose description is confined to before contemporary vascular surgical techniques. This study aims to describe the characteristics and outcomes of patients with coral reef aorta treated with trapdoor endarterectomy at a single high-volume quaternary referral center since 2010. From 2010 to 2022, 14 patients with coral reef aorta were treated with trapdoor endarterectomy. The patient data were obtained via a retrospective medical record review. The patients were predominantly women (79%) with a median age of 65 years (interquartile range [IQR], 60-70 years). The patients universally had a tobacco smoking history and hypertension. More than 85% had previously diagnosed carotid stenosis. Two patients (14%) had undergone prior aortofemoral reconstruction, and one patient (7%) had undergone prior axillobifemoral bypass. The most common presenting symptoms were claudication (71%), chronic mesenteric ischemia (50%), and renovascular hypertension (43%). Of the 14 patients, 8 (57%) underwent isolated endarterectomy and 6 (43%) underwent concomitant aortobifemoral bypass. In addition, 13 patients (93%) required a supraceliac aortic clamp position with a median clamp time of 23 minutes (IQR, 20-30 minutes). The median estimated blood loss was 1650 mL (IQR, 1025-3000 mL). A cell saver was used in 13 procedures (93%), with a median transfusion of 563 mL (IQR, 231-900 mL). The median operative time was 341 minutes (IQR, 315-416 minutes). Eight patients (57%) experienced acute kidney injury in the postoperative period with a peak creatinine of 1.96 mg/dL (IQR, 1.50-2.84 mg/dL). The median length of stay was 11 days (IQR, 6-16 days), with an intensive care unit stay of 4 days (IQR, 2-7 days). One patient (7%) required reoperation in the immediate perioperative period for a retroperitoneal hematoma. The postoperative ankle brachial index increased from a median of 0.58 (right) and 0.57 (left) bilaterally in the preoperative period to 1.09 (right) and 1.10 (left) postoperatively. Eight patients (57%) had follow-up data available for >2 years postoperatively, with five patients (36%) having follow-up data available for >3 years. Two major adverse cardiac events were reported at the last follow-up. One patient reported mild recurrent symptoms of chronic mesenteric ischemia during 3 years of postoperatively, with no concurrent imaging findings or loss of patency found on computed tomography angiography. Symptomatic coral reef atherosclerosis of the paravisceral aorta is a complex disease rarely encountered even at high-volume referral centers. These patients can be expected to experience short-term postoperative morbidity and require intensive care. Despite these challenges, trapdoor endarterectomy is a safe and effective procedure for coral reef aorta, and most patients achieve dramatic symptomatic improvement with durable results.

Subclinical Atherosclerosis: Part 1: What Is it? Can it Be Defined at the Histological Level?

While coronary artery disease remains a major cause of death, it is preventable. Therefore, the focus needs to shift to the early detection and prevention of atherosclerosis. Asymptomatic atherosclerosis is widely termed subclinical atherosclerosis, which is an early indicator of atherosclerotic burden, and understanding this disease is important because timely intervention could prevent future cardiovascular morbidity and mortality. We histologically recognize the earliest lesion of atherosclerosis as pathological intimal thickening, which is characterized by the presence of lipid pools. The difference between clinical atherosclerosis and subclinical atherosclerosis is whether the presence of atherosclerosis results in the clinical symptoms of ischemia, such as stroke, myocardial infarction, or chronic limb-threatening ischemia. In the absence of thrombosis, there are various types of histological plaque that encompass subclinical atherosclerosis: pathological intimal thickening, fibroatheroma, thin-cap fibroatheroma, plaque rupture, healed plaque ruptures, and fibrocalcific plaque. Plaque morphology that is most frequently responsible for acute coronary thrombosis is plaque rupture. Calcification of coronary arteries is the hallmark of atherosclerosis and is a predictor of future coronary events. Atherosclerosis occurs in other vascular beds and is most frequent in arteries of the lower extremity, followed by carotid, aorta, and coronary arteries, and the mechanisms leading to clinical symptoms are unique for each location.

When Microvasculature Rules: microvascular assessment in invasive coronary angiogram

Patients with symptoms of ischaemia without obstructive coronary artery disease present a diagnostic and therapeutic challenge. Microvascular angina (MVA) was called before syndrome X. Invasive coronary angiography used commonly to assess those patients. This article provides a common pathway to diagnose MVA using different invasive and non-invasive tests. In addition, it provides insights for treatment and management of patients in this common clinical scenario.

MAGNETIC RESONANCE ANGIOGRAPHY AND BRAIN ISCHEMIA IN PATIENTS WITH ACUTE STROKE

This research investigates if Magnetic Resonance Angiography (MRA) can detect arterial disorders in patients with acute ischemic stroke with diffusion-positive infarction. The study was conducted at KRL Hospital in Islamabad from May 1, 2022, to September 30, 2022, after receiving ethical approval from the institutional review board. The study included participants between the ages of 45 and 60 of any gender who had symptoms of localized cerebral ischemia lasting less than 24 hours and were referred for MRI evaluation. Non-probability consecutive sampling was used to select participants. The Chi-square test compared MRA findings of vascular illness with MRI findings of brain parenchymal abnormalities. Out of 95 individuals, 89 (93.6%) showed a statistically significant correlation (p=0.001) between the arterial lesion and acute infarctions in the same region of the brain parenchyma on MRI. Only 6 (6.3%) of the 95 individuals showed a discrepancy between the location of the infarction on MRI and the results of the MRA. This study's findings suggest a significant positive association (95.34%) between MRA and MR diffusion restriction in acute ischemic strokes. This association supports the theory that an arterial vasculopathy is the underlying cause of the MR signal. However, in some cases, the discrepancy between MRA and infarction location might be due to an occlusive illness of an arterial branch that MRA did not detect.

Difficulties in diagnosing moyamoya disease

Moyamoya disease is a progressive cerebrovascular disease characterized by bilateral stenosis of the supraclinoid (proximal) part of the internal carotid arteries and the initial segments of the anterior and middle cerebral arteries, with subsequent involvement of the vertebrobasilar basin and accompanied by the development of a basal network of anastomoses. The disease most often manifests itself at the age of 5 to 30–40 years, which makes this pathology an actual and significant cause of functional disorders in children and young people. Diagnosis of moyamoya disease can be difficult because of the polymorphism of its clinical manifestations. This disease must be taken into account in the differential diagnosis of symptoms of cerebral ischemia, since early detection and therapeutic intervention can improve the prognosis by preventing irreversible brain damage. The article presents its own clinical observation of a 6-year-old child with moyamoya disease with a predominant lesion of the right internal carotid artery basin.

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).

High sensitivity cardiac troponin I in response to handgrip in women with signs and symptoms of ischemia with no obstructive coronary arteries

Abstract Background Women with signs and symptoms of ischemia and no obstructive coronary arteries (INOCA) are suspected to have myocardial ischemia, ∼10% have prior myocardial scar often in the absence of acute myocardial infarction (AMI) diagnosis and the development of heart failure with preserved ejection fraction (HFpEF) is relatively frequent. The mechanisms contributing to AMI and HFpEF progression are poorly understood in INOCA. Purpose To compare clinical, invasive, and high sensitivity cardiac troponin I (hsTnI) parameters in women with INOCA at rest and in response to isometric handgrip exercise. Methods Women with suspected INOCA underwent cannulation of the coronary sinus (CS), handgrip exercise testing and serial CS plasma sampling before, after 3 minutes of isometric handgrip stress at 30% of maximal voluntary contraction, and after 5 minutes of recovery. hsTnI was measured using a commercial immunoassay (R-PLEX, Meso Scale Discovery, Rockville, MD) and compared using t-tests. Results A total of 54 women with complete invasive data were included with a mean age of 53 ± 10 years, mean body mass index 28 ± 7 kg/m2. 20 women (37% of the cohort) had detectable CS hsTnI from baseline. Among these women, median values were elevated in response to handgrip (Figure) (baseline median 33.75 (IQR 18.12-67.75) pg/mL vs peak handgrip median 56.23 (IQR 32.84-97.83) pg/mL, signed rank p=0.0007, baseline vs recovery median 52.35 (IQR 32.59-106.27) pg/mL, signed rank p=0.0002). Conclusion Among women with INOCA, handgrip stress leads to an increase in hsTnI in more than a third, demonstrating objective evidence of myocardial injury. More work is needed to better understand contribution of coronary microvascular dysfunction to HFpEF progression.

Men with non-obstructive coronary disease have higher risk of exercise-induced myocardial ischemia detected by cardiopulmonary exercise test

Abstract Background Non-obstructive coronary artery disease (NOCAD) had similar morbidity and mortality as patients with obstructive coronary artery disease but less understood. Limited studies analyzed the gender differences in inducible myocardial ischemia assessed by cardiopulmonary exercise test (CPET) in NOCAD. Methods A total of 289 NOCAD patients (mean age 60, 56% women) who had ischemic symptoms and ⫹ 50% coronaries stenoses confirmed by coronary angiography performed the symptom-limited CPET. We used the predicted % peak VO2, O2 pulse trajectory, and exercise ECG test to assess inducible myocardial ischemia. Results Compared with women, men with NOCAD had significantly lower predicted % peak VO2 (62% vs. 73%), higher proportions of flattening pattern (16% vs. 2%) and downward pattern of O2 pulse trajectory (2% vs. 0%) (P &amp;lt; 0.0001). Instead, women with NOCAD had higher prevalence of shallow pattern of O2 pulse trajectory (21% vs. 6%, P &amp;lt; 0.0001). Men with NOCAD had higher proportions of increased risk of exercise-induced myocardial ischemia (medium risk: 63% vs. 54%, high risk: 18% vs. 4%, P &amp;lt; 0.0001). After adjustment, men with NOCAD demonstrated significantly lower predicted % peak VO2 (β -27.4, 95% CI -30.74 – -24.07), higher risk for abnormal O2 pulse trajectories (OR 4.21, 95% CI 1.93 – 9.19) and myocardial ischemia risk detected by CPET (OR 3.14, 95% CI 1.78 – 5.54) (P &amp;lt; 0.0001). Conclusion Men with NOCAD had higher risk of exercise-induced myocardial ischemia detected by CPET that should be given rigorous management and follow-up to prevent cardiovascular events.

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.

Effect of symptoms recognition in patients with recurrent acute myocardial infarction: from KRAMI-RCC

Abstract Background Clinical significance of self-recognition for myocardial infarction symptom in the general population has been well-known. However, evidence of self-recognition for ischemic symptoms in patients with recurrent myocardial infarction is limited. The study is aimed to verify the association between self-recognition and clinical characteristics, and clinical outcomes in patients with recurrent myocardial infarction. Method From 2016 to 2019, the Korean Registry of Acute Myocardial Infarction for Regional Cardiocerebrovascular Centers (KRAMI-RCC), a web-based registry for myocardial infarction in South Korea, was used. We divided into two groups based on self-recognition in questionnaire. Patient characteristics and clinical outcomes were analyzed. Result Among 11,894 MI patients, the rate of recurrent MI was 9.7%. The rate of self-recognition in subjects with first MI and recurrent MI was 14.4% and 52.0%, respectively (p&amp;lt;0.001). Patients without responses to the self-recognition questionnaire were excluded (n=86). Finally, enrolled subjects were 1,050. Males had a higher rate of self-recognition (79.3% vs. 69.0%). Younger patients, higher graduation levels, and living with a spouse were associated with the well-recognized symptoms. Chest pain, cold sweating, and radiating pain were related to being noticed as a symptom of MI. However, no difference of respiratory difficulties and stomachache in both groups was observed. The unrecognized group had more frequently occurred with cardiogenic shock and heart failure. A history of stroke and malignancy was associated with a low incidence of recognition. Patients with dyslipidemia had a high recognition rate. There was no difference of symptom recognition between ST elevation MI and non-ST elevation MI. Interestingly, previously registered patients in KRAMI-RCC were significantly associated with higher recognition. The symptom recognition was related to prompt visit in regional cardiovascular centers (57% vs. 47%, p=0.002). The in-hospital mortality rate in the unrecognized group was higher at 6.7% compared to the recognized group (1.5%, p&amp;lt;0.000). Unrecognized MI symptoms and a presentation with cardiogenic shock were independent predictors in multivariate analysis to predict a model for in-hospital mortality. Conclusion The MI symptom recognition rate was still low in patients with recurrent MI. Self-recognition of MI symptoms was an independent predictor for in-hospital mortality. In this study, it is thought that rapid symptom recognition might help patients with myocardial infarction visit the hospital as soon as possible, thereby reducing cardiogenic shock and death.Multivariable analysisSelf-recognition and Outcomes