Myocardial Ischemic Events Research Articles

Protective effects of tetramethylpyrazine on myocardial ischemia/reperfusion injury involve NLRP3 inflammasome suppression by autophagy activation

Tetramethylpyrazine (TMP) belongs to the active ingredients of the traditional Chinese medicine Chuanxiong, which has a certain protective effect in myocardial ischemia–reperfusion (I/R) injury. It can improve postoperative cardiac function and alleviate ventricular remodeling in acute myocardial infarction patients. However, its specific protective mechanism is still unclear. In this study, a certain concentration of TMP was introduced into I/R mice or H9C2 cells after oxygen-glucose deprivation/reoxygenation (OGD/R) treatment to observe the effects of TMP on cardiomyocyte activity, cytotoxicity, apoptosis, autophagy, pyroptosis, and NLRP3 inflammasome activation. The results displayed that TMP intervention could reduce OGD/R and I/R-induced cardiomyocyte apoptosis, accelerate cellular activity and autophagy levels, and ameliorate myocardial tissue necrosis in I/R mice in a dose-dependent manner. Further, TMP prevented the formation of NLRP3 inflammasomes to suppress pyroptosis by increasing the level of cardiomyocyte autophagy after I/R and OGD/R modelling, the introduction of chloroquine to suppress autophagic activity in vivo and in vitro was further analyzed to confirm whether TMP inhibits NLRP3 inflammasome activation and pyroptosis by increasing autophagy, and we found the inhibitory effect of TMP on NLRP3 inflammasomes and its protective effect against myocardial injury were blocked when autophagy was inhibited with chloroquine. In conclusion, this experiment demonstrated that TMP unusually attenuated I/R injury in mice, and this protective effect was achieved by inhibiting the activation of NLRP3 inflammasomes through enhancing autophagic activity.

Research progress of exosomes from different sources in myocardial ischemia.

Ischemic heart disease refers to the imbalance between the supply and demand of myocardial blood; it has various causes and results in a class of clinical diseases characterized by myocardial ischemia (MI). In recent years, the incidence of cardiovascular disease has become higher and higher, and the number of patients with ischemic heart disease has also increased year by year. Traditional treatment methods include drug therapy and surgical treatment, both of which have limitations. The former maybe develop risks of drug resistance and has more significant side effects, while the latter may damage blood vessels and risk infection. At this stage, a new cell-free treatment method needs to be explored. Many research results have shown that exosomes from different cell sources can protect the ischemic myocardium via intercellular action methods, such as promoting angiogenesis, inhibiting myocardial fibrosis, apoptosis and pyroptosis, and providing a new basis for the treatment of MI. In this review, we briefly introduce the formation and consequences of myocardial ischemia and the biology of exosomes, and then focus on the role and mechanism of exosomes from different sources in MI. We also discuss the role and mechanism of exosomes pretreated with Chinese and Western medicines on myocardial ischemia. We also discuss the potential of exosomes as diagnostic markers and therapeutic drug for MI.

Occurrence of Transient Myocardial Ischemic Events Among Non-ST Segment Elevation Acute Coronary Syndrome Patients Before or After Invasive Coronary Angiography.

The occurrence of transient myocardial ischemia (TMI) is an important pathology in patients with non-ST elevation acute coronary syndrome (NSTE-ACS), yet studies are scarce regarding when TMI occurs during hospitalization, particularly in relation to invasive coronary angiography (ICA). This study examined: (1) TMI before or after ICA; (2) patient characteristics and ischemic burden by TMI group (before or after ICA); and (3) major in-hospital complications (transfer to critical care, death) and length of stay by TMI group (before or after ICA). Secondary data analysis in hospitalized NSTE-ACS patients with TMI event(s) identified from 12-lead electrocardiographic Holter. Patient records were reviewed to assess ischemic burden [TMI time (min) ÷ hours recording duration], outcomes, and TMI timing, before or after ICA. In 38 patients, 3 (8%) had TMI before and after ICA. Of the remaining 35 patients (92%), TMI occurred before ICA (16; 46%), and after ICA (9; 26%), and 10 (28%) did not have ICA. Patient characteristics, untoward outcomes, and TMI duration (minutes) did not differ by group. Ischemic burden was higher in patients with TMI after ICA (7.29 ± 8.82 min/h) compared to before ICA (2.54 ± 2.11 min/h), P = 0.039. Hospital length of stay by TMI group was 113 ± 113 (before), 226 ± 244 (after), and 85 ± 65 hours (no ICA); P = 0.172. Almost half of the sample had TMI before ICA; one-third had TMI but did not have ICA. Patients with TMI after an ICA had a higher ischemic burden. Future studies with larger sample sizes are needed to investigate further the short- and long-term clinical significance of TMI among NSTE-ACS patients.

Cardiovascular Safety of Romosozumab vs. PTH Analogs for Osteoporosis Treatment: a Propensity Score Matched Cohort Study.

Romosozumab, a monoclonal sclerostin antibody, is a recently approved highly potent anti-osteoporotic agent with osteoanabolic properties. Clinical use of Romosozumab is hindered by the fear of adverse cardiovascular (CV) events raised following the pivotal ARCH-trial. To assess real-world CV safety of romosozumab vs. alternative osteoanabolic therapies used for treatment of severe osteoporosis. Data was obtained from TriNetX, a global federated health research network including real-time electronic medical records from 113 healthcare organizations with a total of 136,460,930 patients across 16 countries at time of analysis. Inclusion criteria were age ≥ 40 years, a diagnosis of osteoporosis and prescription of romosozumab or a PTH analog (teriparatide/abaloparatide) during 8.2019-8.2022. 1:1 propensity score matched cohorts were created using demographic variables, comorbidities, and medications. Kaplan-Meier analysis was used to estimate the probability of the outcomes. Incident 3-point major adverse CV event or death (3P-MACE) during 1-year of follow-up after the initial prescription. 5,626 and 15,986 patients met the criteria for romosozumab and PTH analog cohorts, respectively, with 5,610 patients per group following propensity score matching. 3P-MACE was significantly less frequent in the romosozumab vs. PTH analog cohort (158 vs 211 patients with an outcome, p=0.003) with reductions in the individual components of the composite outcome: myocardial ischemic events (31 vs 58, p=0.003); cerebrovascular events 56 vs 79, p=0.037; deaths (83 vs 104, p=0.099). In a diverse real-world setting, prescription of romosozumab for osteoporosis is associated with less adverse CV events when compared to PTH analog therapy.

Linarin ameliorates ischemia-reperfusion injury by the inhibition of endoplasmic reticulum stress targeting AKR1B1

Due to various factors, there is still a lack of effective neuroprotective agents for ischemic stroke in clinical practice. Neuroinflammation and neuronal apoptosis mediated by endoplasmic reticulum stress are some of the important pathological mechanisms in ischemic stroke. Linarin has been reported to have anti-inflammation, antioxidant, and anti-apoptotic effects in myocardial ischemia, osteoarthritis, and kidney disease. Whether it exerts neuroprotective functions in ischemic stroke has not been investigated. The results showed that linarin could reduce the infarct volume in cerebral ischemia animal models, improve the neurological function scores and suppress the expression of inflammatory factors mediating the NF-κB. Meanwhile, it could protect the neurons from OGD/R-induced-apoptosis, which was related to the PERK-eIF2α pathway. Our results suggested linarin could inhibit neuronal inflammation and apoptosis induced by endoplasmic reticulum stress. Furthermore, the neuroprotective effect of linarin may be related to the inhibition of AKR1B1. Our study offers new insight into protecting against ischemia-reperfusion injury by linarin treatment in stroke.

Norepinephrine boluses for the prevention of post-reperfusion syndrome in living donor liver transplantation: A prospective, open-label, single-arm feasibility trial.

Post-reperfusion syndrome (PRS) is a serious haemodynamic event during liver transplantation (LT), which increases early graft dysfunction and mortality. This study aimed to test the efficacy and safety of norepinephrine (NE) boluses to prevent PRS during orthotopic LT. This feasibility phase II trial prospectively recruited a single arm of 40 patients undergoing living donor LT. The intervention was an escalated protocol of NE boluses starting at 20 µg. The primary outcome was the incidence of PRS. The secondary outcomes were arrhythmia, electrocardiographic (EKG) ischaemic changes, mean pulmonary pressure after reperfusion, 3-month survival and 1-year survival. PRS occurred in 28 (70%) cases [95% confidence interval (CI) 54% to 83%, P < 0.001], with a relative risk reduction of 0.22 when compared to our previous results (90%). Twelve cases developed transient EKG ischaemic changes. All EKG ischaemic changes returned to baseline after correction of hypotension. There was no significant arrhythmia or bradycardia (95% CI 0 to 0.9). After reperfusion, the mean pulmonary artery pressure was not significantly higher than the normal limit (20 mmHg) (P = 0.88). The 3-month survival was 0.95 (95% CI 0.83 to 0.99), and the 1-year survival was 0.93 (95% CI 0.8 to 0.98). Our findings suggest that NE boluses starting with 20 μg is feasible and effective in lowering the risk of PRS during living donor LT. Additionally, NE boluses were not associated with significant myocardial ischaemic events, arrhythmia or a rise in pulmonary pressure.

The protective effects of uric acid against myocardial ischemia via the Nrf2 pathway

Uric acid (UA) possesses both pro- and anti-oxidative properties in ischemic heart disease, but the underlying mechanism remains unclear. We aimed to investigate UA’s protective effect on myocardial ischemia by examining its effects on ECG Ischemic Alterations (EIA) and H2O2-induced oxidative stress in H9C2 myocardial cells. The incidence of EIA decreased over time and was more prevalent among women than men. A U-shaped relationship was observed between UA levels and EIA incidence, with the third quartile exhibiting a protective association. Addition of 237.9 μmol/L UA improved cellular damage and oxidative stress in H2O2-treated H9C2 cells, as determined by cell viability, LDH release, ROS levels, and total antioxidant capacity assays. UA activated the Nrf2 pathway, evidenced by increased expression of Nrf2, GCLC, and HO-1 proteins. By reversing cell cycle blockage, promoting wound healing ability, improving colony-forming capacity, and increasing angiogenesis in H2O2-treated cells, UA exhibited positive effects on cardiomyocyte growth characteristics. Additionally, use of Nrf2 inhibitor ML385 confirmed the involvement of the Nrf2 pathway by negating UA’s effects on oxidatively damaged cardiomyocytes. Our findings suggest that UA induces downstream antioxidant factors to ameliorate oxidative stress by activating the Nrf2 pathway, which could be one of the targets responsible for UA’s beneficial effects in myocardial ischemia.

Coronary No-Reflow after Primary Percutaneous Coronary Intervention-Current Knowledge on Pathophysiology, Diagnosis, Clinical Impact and Therapy.

Coronary no-reflow (CNR) is a frequent phenomenon that develops in patients with ST-segment elevation myocardial infarction (STEMI) following reperfusion therapy. CNR is highly dynamic, develops gradually (over hours) and persists for days to weeks after reperfusion. Microvascular obstruction (MVO) developing as a consequence of myocardial ischemia, distal embolization and reperfusion-related injury is the main pathophysiological mechanism of CNR. The frequency of CNR or MVO after primary PCI differs widely depending on the sensitivity of the tools used for diagnosis and timing of examination. Coronary angiography is readily available and most convenient to diagnose CNR but it is highly conservative and underestimates the true frequency of CNR. Cardiac magnetic resonance (CMR) imaging is the most sensitive method to diagnose MVO and CNR that provides information on the presence, localization and extent of MVO. CMR imaging detects intramyocardial hemorrhage and accurately estimates the infarct size. MVO and CNR markedly negate the benefits of reperfusion therapy and contribute to poor clinical outcomes including adverse remodeling of left ventricle, worsening or new congestive heart failure and reduced survival. Despite extensive research and the use of therapies that target almost all known pathophysiological mechanisms of CNR, no therapy has been found that prevents or reverses CNR and provides consistent clinical benefit in patients with STEMI undergoing reperfusion. Currently, the prevention or alleviation of MVO and CNR remain unmet goals in the therapy of STEMI that continue to be under intense research.

Role of Neck Vessel Doppler in Correlation with Coronary CT Angiography for Assessing Coronary Artery Disease Burden in Diabetic Women and Men

Objectives: With an incidence of 4.1 for women and 6.4 for men/1000 person-years, cardiovascular disease is the primary cause of morbidity and mortality for both men and women worldwide.[1] In asymptomatic patients, subclinical atherosclerosis has been detected utilising several non-invasive methods, such as computed tomography (CT) coronary angiography and Neck Vessel Doppler (NVD) to test coronary calcification. The goal of the present study was to assess the role of NVD in correlation with coronary CT angiography (CCTA) in assessing the coronary artery disease (CAD) burden in diabetic women and men patients. Materials and Methods: This study was conducted on 30 female patients and 30 male patients aged 40–60 years, who were referred for CCTA for suspected CAD at Nizam’s Institute of Medical Sciences Hospital, Hyderabad. This study was an observational and prospective study of diabetes mellitus patients. All subjects underwent NVD and CCTA scan on the same day. Carotid intimal media thickness (CIMT) was considered the largest of the two separate values (left and right CIMT). The analysis examined factors associated with coronary artery calcification defined as a coronary artery calcium (CAC) score &gt;0. Results: The mean age at assessment was 52.6 years in the diabetic male group and 53.7 in the diabetic female group. 63% of the study population was also hypertensive in the male group and 77% of the study population was also hypertensive in the female group. Mean CIMT was 1.01 mm in the diabetic male group and 1.02 mm in the diabetic female group. Twenty-two (73.3%) patients in the diabetic male group had a CAC score &gt;0, of which 4 (18.18%) had severe coronary artery calcification (CAC score &gt;400 Au), 7 (31.81%) had moderate coronary artery calcification (CAC score 100–400 Au), 11 (50%) had mild coronary artery calcification (CAC score 1-99 Au), and 8 out of 30 (26.67%) had no coronary artery calcification (CAC score &lt;0 Au). Twenty (66.67%) patients in the diabetic female group had a CAC score &gt;0, of which 2 (10%) had severe coronary artery calcification (CAC score &gt;400 Au), 7 (35%) had moderate coronary artery calcification (CAC score 100–400 Au), 11 (55%) had mild coronary artery calcification (CAC score 1-99Au) and 10 out of 30 (33.33%) had no coronary artery calcification (CAC score &lt;0 Au). Mean CIMT and carotid plaque were significantly associated with CAC (P = 0.046 and P = 0.026, respectively, in the diabetic male’s group and P = 0.008 and P = 0.011, respectively, in the diabetic female’s group). The significance was more profound in the diabetic female group when compared to the diabetic male group. Conclusion: NVD giving various surrogate parameters such as CIMT and plaque, in correlation with CCTA (CAC score), can play a significant role in assessing the CAD burden in men and women with diabetes and hypertension, thereby helping the clinician to assess the future risk for stroke or myocardial ischemic events to take active interventions.

Purtscher-like retinopathy following coronary artery bypass grafting in an antiphospholipid syndrome patient: a case report

BackgroundPurtscher retinopathy is a rare occlusive microangiopathy comprising a constellation of retinal signs including cotton wool spots, retinal hemorrhages and Purtscher flecken. While classical Purtscher must be antedated by a traumatic incident, Purtscher-like retinopathy is used to refer to the same clinical syndrome in the absence of trauma. Various non-traumatic conditions have been associated with Purtscher-like retinopathy e.g. acute pancreatitis, preeclampsia, parturition, renal failure and multiple connective tissue disorders. In this case study, we report the occurrence of Purtscher-like retinopathy following coronary artery bypass grafting in a female patient with primary antiphospholipid syndrome (APS).Case presentationA 48-year-old Caucasian female patient presented with a complaint of acute painless diminution of vision in the left eye (OS) that occurred approximately two months earlier. Clinical history revealed that the patient underwent coronary artery bypass grafting (CABG) two months earlier and that visual symptoms started 4 days thereafter. Furthermore, the patient reported undergoing percutaneous coronary intervention (PCI) one year before for another myocardial ischemic event. Ophthalmological examination revealed multiple yellowish-white superficial retinal lesions i.e. cotton-wool spots, exclusively in the posterior pole and predominantly macular within the temporal vascular arcades only OS. Fundus examination of the right eye (OD) was normal and the anterior segment examination of both eyes (OU) was unremarkable. A diagnosis of Purtscher-like retinopathy was made based on clinical signs, suggestive history and consolidated by fundus fluorescein angiography (FFA), spectral domain optical coherence tomography (SD-OCT) and optical coherence tomography angiography (OCTA) of macula, optic nerve head (ONH) according to the diagnostic guidelines of Miguel. The patient was referred to a rheumatologist to identify the underlying systemic cause and was diagnosed with primary antiphospholipid syndrome (APS).ConclusionsWe report a case of Purtscher-like retinopathy complicating primary antiphospholipid syndrome (APS) following coronary artery bypass grafting. This conveys a message to clinicians that patients presenting with Purtscher-like retinopathy should undergo meticulous systemic work-up in order to identify potentially life-threatening underlying systemic diseases.

5597164 BURDEN AND RISK FACTOR TO ACUTE MYOCARDIAL ISCHAEMIA IN CHILDREN WITH SICKLE CELL ANAEMIA

Introduction: Sickle cell anaemia (SCA) is a genetic disorder of haemoglobin synthesis with multi-organ manifestations. Myocardial ischaemia (MI) and infarction as a result of sickling are not commonly reported, often overshadowed by the more dramatic presentation of musculoskeletal pain. Studies have postulated that sudden deaths during vaso-occlusive crisis (VOC) may be secondary to the arrhythmogenic effect of severe MI. Aim: This study compared the prevalence of MI and associated risk factor in children with SCA aged 6 months to 18 years in VOC and steady state at the Lagos University Teaching Hospital using both cardiac troponin T (cTnT) and electrocardiography (ECG) as recommended by the fourth universal definition of MI (2018). Methodology: A cross-sectional comparative study conducted over 10months (March and December 2019). The participants were 250 children (125 age and gender-matched children with SCA in VOC and steady state respectively). Informed consent was obtained from the parents or caregivers while assent was obtained from children 10 years and above. Socio-demographic data and relevant history were obtained using an interviewer-administered questionnaire. Targeted clinical examination with focus on the cardiovascular system was done. All study participants had ECG performed and blood samples taken for cTnT, full blood count, electrolyte, urea, and creatinine. Myocardial ischaemia was defined as cTnT level greater than 100ng/L which is the 99th percentile and abnormal ECG findings indicative of MI (wide Q wave, ST-segment elevation or prolonged QT interval corrected for heart rate with accompanying Q wave abnormalities). Statistical package for social sciences (SPSS) software version 20 was used for analysis, statistical association was declared significant if the p-value was <0.05. Results: The prevalence of MI using cTnT alone in children with SCA in VOC and steady state was 42.4% (53) and 23.2% (29) respectively while with ECG alone, the prevalence of MI in children with SCA in VOC and steady state was 40.8% (51) and 20.8% (26) respectively. The prevalence of MI using both cTnT and ECG in children with SCA in VOC and steady state was 38.4% and 20% respectively and this was statistically significant (p-valve 0.001). In relation to VOC, the mean age (10.0±4.1), mean WBC (20,131.2±7,268.0), mean platelet count (461,208.0±143,956.8) and pain score of children with MI was significantly higher compared to those without MI. Among the steady state children, higher mean age (11.6±3.5), lower mean PCV (22.3±3.7) and higher mean platelet count (446,240.0±140,841.0) was significant in children in steady state with MI compared to those without MI. Furthermore, on multivariate analysis, the mean age & mean platelet count; mean age & low PCV; were significantly associated with MI in children with VOC and steady state respectively. The older age group in both study participants had a higher prevalence of MI. Combining both cTnT and ECG in the diagnosis of MI gave similar prevalence compared to using either cTnT or ECG alone. Conclusion: Myocardial ischaemia (MI) is prevalent in children with SCA. Children with SCA should routinely be screened for MI during VOC and steady state especially adolescents with SCA for early intervention.

EFFECT OF SEVERITY OF ISCHEMIA ON QT DISPERSION IN PATIENTS WITH CORONARY ARTERY DISEASE

Background: Coronary artery disease (CAD) is the most prevalent cause of death due to myocardial ischemia. QT dispersion is a marker of increased risk for myocardial ischemia events. The objective of this study was to find out the effect of severity of ischemia on ventricular repolarization heterogeneity by measuring and comparing QT dispersion in single, double and triple coronary artery disease patients. Methods: This cross-sectional comparative study was conducted in the Department of Physiology, Army Medical College (AMC) in collaboration with Electrophysiology Department, Armed Forces Institute of Cardiology (AFIC). Forty patients aged 55±8 Yrs with CAD were included in the study. Holter monitors were used to attain ECG recordings digitally with ten electrodes. For exploration of digital QT dispersion data CardioScan Luxury version was used. Results: Out of 40 patients 18 (45%) had single, 16 (40%) double, and 6 (15%) had triple vessel disease. A significant difference was noted on comparison across mean values of QT dispersion in three groups with single, double and triple vessels coronary artery disease (p=0.01). There was also a remarkable difference of QT dispersion between single and triple vessel disease patients (p=0.007). Conclusion: Ventricular repolarization heterogeneity increases with the ischemia. Patients with triple vessel disease are more prone to risk of developing life threatening arrhythmias. Pak J Physiol 2022;18(4):11-3

Metabolites Analysis of Anti-Myocardial Ischemia Active Components of Saussurea involucrata Based on Gut Microbiota-Drug Interaction.

Saussurea involucrata has been reported to have potential therapeutic effects against myocardial ischemia. The pharmacological effects of oral natural medicines may be influenced by the participation of gut microbiota. In this study, we aimed to investigate the bidirectional regulation of gut microbiota and the main components of Saussurea involucrata. We first established a quantitative method for the four main components (chlorogenic acid, syringin, acanthoside B, rutin) which were chosen by fingerprint using liquid chromatography tandem mass spectrometry (LC-MS/MS), and found that gut microbiota has a strong metabolic effect on them. Meanwhile, we identified five major rat gut microbiota metabolites (M1–M5) using liquid chromatography tandem time-of-flight mass spectrometry (LC/MSn-IT-TOF). The metabolic properties of metabolites in vitro were preliminarily elucidated by LC-MS/MS for the first time. These five metabolites of Saussurea involucrata may all have potential contributions to the treatment of myocardial ischemia. Furthermore, the four main components (10 μg/mL) can significantly stimulate intestinal bacteria to produce short chain fatty acids in vitro, respectively, which can further contribute to the effect in myocardial ischemia. In this study, the therapeutic effect against myocardial ischemia of Saussurea involucrata was first reported to be related to the intestinal flora, which can be useful in understanding the effective substances of Saussurea involucrata.

Epidemiology of Atrial Fibrillation and Related Myocardial Ischemia or Arrhythmia Events in Chinese Community Population in 2019.

BackgroundAtrial fibrillation (AF) is the most common arrhythmia, and the incidence increases rapidly all over the world. The global prevalence of AF (age-adjusted) is 0.60% for men and 0.37% for women and the prevalence of AF in China is 0.65%. It is expected that the number of patients with AF will continue to rise in the future worldwide due to population aging.ObjectiveTo explore the prevalence of AF in Chinese community population in 2019 and clarify the prevalence of AF complicated with other arrhythmias and myocardial ischemia (MI) events.MethodsThe remote electrocardiogram (ECG) diagnosis system of Xinhua Hospital was assessed to the screen participants with ECG evidence of AF between January 1 and December 31, 2019. The prevalence rates of AF and its association with other arrhythmias and MI events were analyzed and subgroup analysis was performed between different sexes and age groups.ResultsA total of 22,016 AF cases were identified out of all ECGs derived from the remote ECG diagnosis system in 2019. It is estimated that AF was presented in nearly 10.15 million people in China (age-adjusted standardized rate 0.72%, 95% CI 0.20–1.25%) in 2019 and 62% of the AF cases (6.27 million) affected people aged 65 years and above (age-adjusted standardized rate 3.56%, 95% CI 3.28–3.85%). The prevalence rate of AF in males was higher than that in females (p < 0.001), and the ventricular rate of AF patients was faster in females (p < 0.001) and younger patients (p < 0.001). AF patients with lower ventricular rate (under 60 beats per min) were associated with increased prevalence of ventricular escape/escape rhythm [p < 0.001, odds ratio (OR) 5.14] and third-degree atrioventricular block (p < 0.001, OR 32.05).ConclusionThe prevalence of AF is higher in the Chinese community population than that was previously reported. AF patients complicated with ECG patterns suggesting myocardial infarction is common in men, and stricter measures should be taken to control the common risk factors of AF and coronary heart disease. It is also important that more attention should be paid to recognize fatal arrhythmias, especially in elderly male patients with AF.

Trimetazidine Alleviates Postresuscitation Myocardial Dysfunction and Improves 96-Hour Survival in a Ventricular Fibrillation Rat Model.

BackgroundMyocardial dysfunction is a critical cause of post‐cardiac arrest hemodynamic instability and circulatory failure that may lead to early mortality after resuscitation. Trimetazidine is a metabolic agent that has been demonstrated to provide protective effects in myocardial ischemia. However, whether trimetazidine protects against postresuscitation myocardial dysfunction is unknown.Methods and ResultsCardiopulmonary resuscitation was initiated after 8 minutes of untreated ventricular fibrillation in Sprague‐Dawley rats. Animals were randomized to 4 groups immediately after resuscitation (n=15/group): (1) normothermia control (NTC); (2) targeted temperature management; (3) trimetazidine‐normothermia; (4) trimetazidine‐targeted temperature management. TMZ was administered at a single dose of 10 mg/kg in rats with trimetazidine. The body temperature was maintained at 34.0°C for 2 hours and then rewarmed to 37.5°C in rats with targeted temperature management. Postresuscitation hemodynamics, 96‐hours survival, and pathological analysis were assessed. Heart tissues and blood samples of additional rats (n=6/group) undergoing the same experimental procedure were collected to measure myocardial injury, inflammation and oxidative stress‐related biomarkers with ELISA‐based quantification assays. Compared with normothermia control, tumor necrosis factor‐α, and cardiac troponin‐I were significantly reduced, whereas the left ventricular ejection fraction and 96‐hours survival rates were significantly improved in the 3 experimental groups. Furthermore, inflammation and oxidative stress‐related biomarkers together with collagen volume fraction were significantly decreased in rats undergoing postresuscitation interventions.ConclusionsTrimetazidine significantly alleviates postresuscitation myocardial dysfunction and improves survival by decreasing oxidative stress and inflammation in a ventricular fibrillation rat model. A single dose of trimetazidine administrated immediately after resuscitation can effectively improve cardiac function, whether used alone or combined with targeted temperature management.

Thrombosis and Major Bleeding Risk After Primary PCI Among Patients With Multivessel Coronary Artery Disease.

Background and AimThis study aimed to develop and validate separate risk prediction models for thrombosis events (TEs) and major bleeding (MB) in patients with multivessel coronary artery lesions who had undergone primary percutaneous coronary intervention (PCI).Methods and ResultsThrombosis events (TEs) were defined as the composite of myocardial infarction recurrence or ischemic cerebrovascular events, whereas MB was defined as the occurrence of bleeding academic research consortium (BARC) three or five bleeding. The derivation and validation cohorts comprised 2,976 patients who underwent primary PCI between January 2010 and June 2017. At a median follow-up of 3.07 years (1,122 days), TEs and MB occurred in 167 and 98 patients, respectively. Independent predictors of TEs were older age, prior PCI, non-ST elevated MI (NSTEMI), and stent thrombosis (ST). Independent predictors of MB were triple therapy at discharge, coronary artery bifurcation lesions, lesion restenosis, target lesion of the left main coronary artery, stent thrombosis, non-use of IABP during primary PCI, type A/B according to the American College of Cardiology classification of the coronary lesion, and PTCA. In the derivation and validation cohorts, the areas under the curve were 0.817 and 0.82 for thrombosis and 0.886 and 0.976 for bleeding, respectively. In the derivation cohort, high thrombotic risk (n = 755) was associated with higher 3-year incidence of TEs, major adverse cardiovascular events (MACEs), and all-cause death compared to low risk (n = 1,275) (p = 0.0022, 0.019, and 0.012, respectively). High bleeding risk (n = 1,675) was associated with higher incidence of bleeding, MACEs, and cardiac death compared to low risk (n = 355) (p < 0.0001).ConclusionSimple risk scores can be useful in predicting risks of ischemic and bleeding events after primary PCI, thereby stratifying thrombotic or MB risks and facilitating clinical decisions.

Thrombosis and major bleeding risk after primary percutaneous coronary intervention among patients with multi-vessels coronary artery disease

Abstract Background and aims The present study aimed to develop and validate separate risk prediction models for thrombosis events (TEs) and major bleeding (MB) in patients with multi-vessel coronary artery lesions who had undergone primary percutaneous coronary intervention (PCI). Methods and results TEs were defined as the composite of myocardial infarction recurrence or ischemic cerebrovascular events, whereas MB was defined as the occurrence of bleeding academic research consortium (BARC) 3 or 5 bleeding. The derivation and validation cohorts comprised 2976 patients who underwent primary PCI between January 2010 and June 2017. At a median follow-up of 3.07 years (1122 days), TEs and MB occurred in 167 and 98 patients, respectively. Independent predictors of TEs were older age, prior PCI, non-ST elevated MI (NSTEMI), and stent thrombosis (ST). Independent predictors of MB were triple therapy at discharge, coronary artery bifurcation lesions, lesion restenosis, target lesion of the left main coronary artery, and PTCA. In the derivation and validation cohorts, the areas under the curve were 0.817 and 0.820 for thrombosis and 0.886 and 0.976 for bleeding, respectively. In the derivation cohort, high thrombotic risk (n=755) was associated with a higher 3-year incidence of TEs, major adverse cardiovascular events (MACEs), and all-cause death, compared to low risk (n=1275) (p=0.0022, 0.019, 0.012, respectively). High bleeding risk (n=1675) was associated with a higher incidence of bleeding, MACEs, cardiac death, compared to low risk (n=355) (p&amp;lt;0.0001). Conclusion Simple risk scores can be useful in predicting the risks of ischemic and bleeding events after primary PCI, thereby stratifying thrombotic or MB risks and facilitating clinical decisions. Funding Acknowledgement Type of funding sources: Foundation. Main funding source(s): This study was supported by the Chinese Academy of Medical Sciences Innovation Fund for Medical Sciences (2016-I2M-1–009), National Natural Science Funds (number: 81970308) and the Fund of “Sanming” Project of Medicine in Shenzhen (number: SZSM201911017). Figure 2Figure 3

Association of renal transplantation with reduced risk of myocardial infarction and ischemic stroke in ANCA-associated vasculitis: An observational cohort study

ObjectiveMyocardial infarction and ischemic stroke are leading causes of cardiovascular (CV) morbidity and mortality in ANCA-associated vasculitis (AAV), especially for the 20% with end-stage renal disease (ESRD). We assessed the impact of renal transplantation on the risk of myocardial infarction and stroke among patients with ESRD due to AAV. MethodsWe identified patients from the United States Renal Data System with ESRD due to AAV between 2000 and 2016. We examined the association between renal transplantation and the risk of non-fatal and fatal myocardial infarction or ischemic stroke among waitlisted patients using Medicare claims and death data through 2017. We used time-varying Cox proportional hazards models with age as the time scale to estimate hazard ratios (HR) and 95% confidence intervals (CIs) for myocardial infarction and ischemic stroke events among patients who received a renal transplant compared to those who remained on the waitlist. ResultsOf 1029 waitlisted patients, 593 (58%) were transplanted over a mean of 5.7 years. There were 17 events (4.6/1,000 person-years) in the transplanted group and 40 events (13.7/1,000 person-years) in the group that remained waitlisted. A renal transplant was associated with a 78% lower risk of myocardial infarction or ischemic stroke (HR=0.22, 95% CI 0.11 to 0.47). These findings persisted across sex and age groups and when censoring patients after living donor transplantation. ConclusionsAmong AAV patients with ESRD, renal transplantation can substantially reduce the risk of myocardial infarction and ischemic stroke. Improving access to transplantation for this population may further improve outcomes.

Ultrafiltration Volume: Surrogate Marker of the Extraction Ratio, Determinants, Clinical Correlates and Relationship with the Dialysis Dose

The ultrafiltration volume, a surrogate maker of inter-dialytic weight gain and extraction ratio plays a significant contributory role in the dialysis dose but in very large amount can lead to intradialysis hypotension and its consequences of myocardial ischemia and stunning and further diminution of kidney function. Measures are needed to prescribe the optimal quantity for each session.

Early Outcomes of Carotid Revascularization in Retrospective Case Series.

Background: Most data in carotid stenosis treatment arise from randomized control trials (RCTs) and cohort studies. The aim of this meta-analysis was to compare 30-day outcomes in real-world practice from centers providing both modalities. Methods: A data search of the English literature was conducted, using PubMed, EMBASE and CENTRAL databases, until December 2019, using the Preferred Reporting Items for Systematic Reviews and Meta-Analysis statement (PRISMA) guidelines. Only studies reporting on 30-day outcomes from centers, where both techniques were performed, were eligible for this analysis. Results: In total, 15 articles were included (16,043 patients). Of the patients, 68.1% were asymptomatic. Carotid artery stenting (CAS) did not differ from carotid endarterectomy (CEA) in terms of stroke (odds ratio (OR) 0.98; 0.77–1.25; I2 = 0%), myocardial ischemic events (OR 1.03; 0.72–1.48; I2 = 0%) and all events (OR 1.0; 0.82–1.21; I2 = 0%). Pooled stroke incidence in asymptomatic patients was 1% (95% CI: 0–2%) for CEA and 1% for CAS (95% CI: 0–2%). Pooled stroke rate in symptomatic patients was 3% (95% CI: 1–4%) for CEA and 3% (95% CI: 1–4%) for CAS. The two techniques did not differ in either outcome both in asymptomatic and symptomatic patients. Conclusion: Carotid revascularization, performed in centers providing both CAS and CEA, is safe and effective. Both techniques did not differ in terms of post-procedural neurological and cardiac events, both in asymptomatic and symptomatic patients. These findings reiterate the importance of a tailored therapeutic strategy and that “real-world” outcomes may only be valid from centers providing both treatments.