IL6/adiponectin/HMGB1 feedback loop mediates adipocyte and macrophage crosstalk and M2 polarization after myocardial infarction.

Background: Differences in border zone contribute to different outcomes post-infarction, such as left ventricular aneurysm (LVA) and myocardial infarction (MI). LVA usually forms within 24 h of the onset of MI and may cause heart rupture; however, LVA surgery is best performed 3 months after MI. Few studies have investigated the LVA model, the differences in border zones between LVA and MI, and the mechanism in the border zone. Methods: The LVA, MI, and SHAM mouse models were used. Echocardiography, Masson's trichrome staining, and immunofluorescence staining were performed, and RNA sequencing of the border zone was conducted. The adipocyte-conditioned medium-treated hypoxic macrophage cell line and LVA and MI mouse models were employed to determine the effects of the hub gene, adiponectin (ADPN), on macrophages. Quantitative polymerase chain reaction (qPCR), Western blot analysis, transmission electron microscopy, and chromatin immunoprecipitation (ChIP) assays were conducted to elucidate the mechanism in the border zone. Human subepicardial adipose tissue and blood samples were collected to validate the effects of ADPN. Results: A novel, simple, consistent, and low-cost LVA mouse model was constructed. LVA caused a greater reduction in contractile functions than MI owing to reduced wall thickness and edema in the border zone. ADPN impeded cardiac edema and promoted lymphangiogenesis by increasing macrophage infiltration post-infarction. Adipocyte-derived ADPN promoted M2 polarization and sustained mitochondrial quality via the ADPN/AdipoR2/HMGB1 axis. Mechanistically, ADPN impeded macrophage HMGB1 inflammation and decreased interleukin-6 (IL6) and HMGB1 secretion. The secretion of IL6 and HMGB1 increased ADPN expression via STAT3 and the co-transcription factor, YAP, in adipocytes. Based on ChIP and Dual-Glo luciferase experiments, STAT3 promoted ADPN transcription by binding to its promoter in adipocytes. In vivo, ADPN promoted lymphangiogenesis and decreased myocardial injury after MI. These phenotypes were rescued by macrophage depletion or HMGB1 knockdown in macrophages. Supplying adipocytes overexpressing STAT3 decreased collagen disposition, increased lymphangiogenesis, and impaired myocardial injury. However, these effects were rescued after HMGB1 knockdown in macrophages. Overall, the IL6/ADPN/HMGB1 axis was validated using human subepicardial tissue and blood samples. This axis could serve as an independent factor in overweight MI patients who need coronary artery bypass grafting (CABG) treatment. Conclusion: The IL6/ADPN/HMGB1 loop between adipocytes and macrophages in the border zone contributes to different clinical outcomes post-infarction. Thus, targeting the IL6/ADPN/HMGB1 loop may be a novel therapeutic approach for cardiac lymphatic regulation and reduction of cell senescence post-infarction.

Glycated serum protein is independently associated with progressive infarction in patients with acute ischemic stroke.

OBJECTIVE: This study investigated the relationship between glycated serum protein (GSP) and progressive infarction (PI). METHODS: From April 2017 to December 2020, we recruited 477 patients within 48 hours after the onset of acute ischemic stroke into this case-control study. Demographic characteristics, clinical information, and laboratory and neuroimaging data were recorded after admission. RESULTS: PI occurred in 144 (30.8%) patients. Patients with PI had higher initial National Institute of Health Stroke Scale (NIHSS) scores, higher discharge NIHSS scores, higher modified Rankin scale scores at 3 months after onset, higher GSP levels, lower prothrombin times, and lower creatinine levels than patients without PI. The likelihood of PI increased with increases in the GSP quartile. Multiple regression analysis revealed that high GSP levels (>2.14 mmol/L) were independently associated with PI. Subgroup analyses identified high GSP levels as an independent predictor of PI in patients with large artery atherosclerosis (third quartile: odds ratio [OR] = 3.793; 95% confidence interval [CI] = 1.555-9.250; fourth quartile: OR = 2.675; 95% CI = 1.056-6.776) and anterior circulation small vessel occlusion (fourth quartile: OR = 13.859; 95% CI = 2.024-94.885). CONCLUSIONS: GSP might be an independent predictor for PI in certain patients with acute ischemic stroke.

Nutritional Status and Recurrent Major Cardiovascular Events Following Acute Myocardial Infarction-A Follow-Up Study in a Primary Percutaneous Coronary Intervention Center.

BACKGROUND: Acute myocardial infarction is often accompanied by malnutrition, which is associated with an imbalance between catabolic and anabolic processes. This ultimately leads to cardiac cachexia, which worsens the patient's prognosis. We aimed to assess the correlation between nutritional status, assessed using the controlling nutritional status (CONUT) score, and the rate of major cardiovascular adverse events (MACE). METHODS: The present investigation was a non-randomized, prospective, observational study in which 108 patients with acute myocardial infarction were included. Nutritional status was assessed using the CONUT score. Based on the CONUT score, the patients were divided as follows: Group 1-normal or mild nutritional status (CONUT < 3 points, n = 76), and Group 2-moderate to severe nutritional deficiency (CONUT ≥ 3 points, n = 32). Demographic, echocardiographic, and laboratory parameters were obtained for all patients, as well as the MACE rate at 1 and 3 months of follow-up. RESULTS: The MACE occurred more frequently in patients with impaired nutritional status at both 1-month follow-up (46.9% versus 9.2%; p < 0.0001) and 3-month follow-up (68.8% versus 10.5%; p < 0.0001). In terms of cardiovascular events, patients with poor nutritional status, with a CONUT score ≥ 3, presented more frequent non-fatal myocardial infarction, stroke, revascularization procedure, and ventricular arrhythmia. Also, the number of cardiovascular deaths was higher in the undernourished group. CONCLUSIONS: This study found that patients with poor nutritional status experienced inflammatory status, frailty, and cardiovascular events more often than those with normal nutritional status at 1-month and 3-month follow-up after an acute myocardial infarction.

Predictors of periprocedural myocardial infarction after rotational atherectomy.

Introduction: Rotational atherectomy (RA) presents superior efficacy over traditional balloon angioplasty in managing calcified plaques, albeit being associated with a perceived heightened aggressiveness and increased risk of periprocedural complications. Aim: To assess the frequency and predictive factors of periprocedural myocardial infarction (MI) following RA. Material and methods: This was a retrospective observational study, encompassing 534 patients. The definition of periprocedural MI was consistent with the 4th universal definition of MI. Results: Periprocedural MI occurred in 45 (8%) patients. This subset tended to be older (74.6 ±8.2 vs. 72 ±9.3%; p = 0.04) with SYNTAX Score (SS) > 33 points (p = 0.01), alongside elevated rates of no/slow flow (p = 0.0003). These patients less often fulfilled the indication for RA, which is a non-dilatable lesion. The incidence of traditional risk factors was similar in both groups. Univariable logistic regression models revealed: male gender (OR = 0.54; p = 0.04), non-dilatable lesion (OR = 0.41; p = 0.01), prior coronary artery bypass grafting (CABG) (OR = 0.07; p = 0.01) as negative and SS > 33 (OR = 2.8; p = 0.02), older age (OR = 1.04; p = 0.04), no/slow flow (OR = 7.85; p = 0.002) as positive predictors. The multivariable model showed that occurrence of no/slow flow (OR = 6.7; p = 0.02), SS > 33 (OR = 2.95; p = 0.02), non-dilatable lesion (OR = 0.42; p = 0.02), and prior CABG (OR = 0.08; p = 0.02) were independent predictors of periprocedural MI. Conclusions: Periprocedural MI after RA was not an uncommon complication, occurring in nearly one-twelfth of patients. Our analysis implicated female gender, older age, and more severe coronary disease in its occurrence. As expected, the presence of no/slow flow amplified the risk of periprocedural MI, whereas prior CABG and non-dilatable lesions mitigated this risk.

Concurrent myocardial infarction in the setting of thrombotic thrombocytopenic purpura secondary to systemic lupus erythematosus: A case report.

Key Clinical Message: In acute thrombotic thrombocytopenic purpura (TTP), apart from urgent treatment, assessing the patient's medical history, especially conditions like systemic lupus erythematosus that could trigger TTP, is crucial. Rarely, TTP patients may experience cardiac conditions as severe as a myocardial infarction. Abstract: A 45-year-old woman manifested severe and acute thrombotic thrombocytopenic purpura (TTP) of unknown origin. The patient's symptoms, the laboratory data, the detection of the reduction in ADAMTS13 activity, and the presence of schistocytes on the peripheral smear confirmed the diagnosis. The patient was then planned for therapeutic plasma exchange (TPE). Prior to the scheduled TPE, she suddenly experienced extreme shortness of breath and chest pain. An electrocardiogram was obtained immediately after reporting signs of an inferior myocardial infarction. Further examinations to acquire information about the patient's underlying medical conditions in order to study the secondary causes of TTP, combined with the results of the laboratory tests, resulted in the patient being diagnosed with systemic lupus erythematosus.

Assessing right ventricular peak strain in myocardial infarction patients with mitral regurgitation by cardiac magnetic resonance feature tracking.

Background: Although it is known that mitral regurgitation (MR) in patients with myocardial infarction (MI) may increase the right ventricular (RV) afterload, leading to RV dysfunction, the exact detrimental effects on RV function and myocardial peak strain remain unresolved. In this study, we assessed the impact of MR on the impairment of RV myocardial deformation in patients with MI and explored the independent influential factors of RV peak strain. Methods: A total of 199 MI participants without or with MR were retrospectively assessed in this study. The cardiovascular magnetic resonance examination protocol included a late gadolinium-enhanced (LGE) imaging technique and a cine-balanced steady-state free precession sequence. Statistical tests, including two independent sample t-test or Mann-Whitney U-test, analysis of variance, Kruskal-Wallis test, and multiple linear regression analysis models were performed. Results: The MI (MR+) group exhibited significantly lower RV strain parameters in the radial, circumferential and longitudinal directions when compared to the control and the MI (MR-) groups (both P<0.05). The RV global longitudinal peak strain (GLPS) in the MI group significantly decreased when compared with that in the control group (P<0.05). As moderate-severe MR worsened in patients with MI, RV myocardial global peak strain and the peak systolic strain rate (PSSR) gradually decreased. Multiple linear regression analysis revealed that left ventricular (LV) GLPS, triglycerides, and age were independently correlated with RV GLPS (all P<0.05). RV end-systolic volume (RVESV) acted as an independent association factor for RV global peak strain. Conclusions: MR may exacerbate the impairment of RV peak strain and functions in patients with MI. LV GLPS was positively correlated with RV GLPS. However, RVESV, triglycerides, and age acted as independent risk factors associated with worsening RV GLPS.

Association between the insufficient improvement of the quantitative flow ratio and worsening outcomes in ST-segment elevated myocardial infarction: a multicentre prospective cohort study.

Background: Improved coronary physiological function after percutaneous coronary intervention (PCI) has been shown to improve prognosis in stable ischaemic heart disease, but has not yet been explored in ST-segment elevated myocardial infarction (STEMI). The study sought to determine whether an improvement in the quantitative flow ratio (QFR) could improve the prognosis of STEMI patients undergoing primary PCI. Methods: Patients diagnosed with STEMI who were receiving primary PCI were recruited for the study. Those with thrombolysis in myocardial infarction (TIMI) flow <2 after wiring were excluded. The ΔQFR was calculated using the following formula: ΔQFR = post-PCI QFR - pre-stent QFR. The primary endpoint was the composite event, including recurrent myocardial infarction (MI) and acute heart failure (AHF). Results: In total, 515 STEMI patients with a median follow-up of 364 days were enrolled in the study. Based on the cut-off value from the receiver operator characteristic (ROC) curve, the patients were divided into the following two groups: the lower ΔQFR group (≤0.25, N=332); and the normal ΔQFR group (>0.25, N=183). Patients with a lower ΔQFR had a relatively higher rate of MI/AHF (10.5% vs. 4.4%, P=0.019) and AHF (7.2% vs. 2.7%, P=0.044). A lower ΔQFR was significantly associated with a higher incidence of MI/AHF [hazard ratio (HR) =2.962, 95% confidence interval (CI): 1.358-6.459, P=0.006, respectively] after adjusting for potential confounders. Pre-stent angiographic microvascular resistance [odds ratio (OR) =1.027, 95% CI: 1.022-1.033, P<0.001] and the stent-to-vessel diameter ratio <1.13 (OR =1.766, 95% CI: 1.027-3.071, P=0.04) were independent predictors of a lower ΔQFR. Conclusions: An insufficient improvement in the QFR contributes to worsening outcomes and might be a useful tool for risk stratification in STEMI.

Optogenetic Stimulation of the Cardiac Vagus Nerve to Promote Heart Regenerative Repair after Myocardial Infarction.

Background: It had been shown that selective cardiac vagal activation holds great potential for heart regeneration. Optogenetics has clinical translation potential as a novel means of modulating targeted neurons. This study aimed to investigate whether cardiac vagal activation via optogenetics could improve heart regenerative repair after myocardial infarction (MI) and to identify the underlying mechanism. Methods: We used an adeno-associated virus (AAV) as the vector to deliver ChR2, a light-sensitive protein, to the left nodose ganglion (LNG). To assess the effects of the cardiac vagus nerve on cardiomyocyte (CM) proliferation and myocardial regeneration in vivo, the light-emitting diode illumination (470 nm) was applied for optogenetic stimulation to perform the gain-of-function experiment and the vagotomy was used as a loss-of-function assay. Finally, sequencing data and molecular biology experiments were analyzed to determine the possible mechanisms by which the cardiac vagus nerve affects myocardial regenerative repair after MI. Results: Absence of cardiac surface vagus nerve after MI was more common in adult hearts with low proliferative capacity, causing a poor prognosis. Gain- and loss-of-function experiments further demonstrated that optogenetic stimulation of the cardiac vagus nerve positively regulated cardiomyocyte (CM) proliferation and myocardial regeneration in vivo. More importantly, optogenetic stimulation attenuated ventricular remodeling and improved cardiac function after MI. Further analysis of sequencing results and flow cytometry revealed that cardiac vagal stimulation activated the IL-10/STAT3 pathway and promoted the polarization of cardiac macrophages to the M2 type, resulting in beneficial cardiac regenerative repair after MI. Conclusions: Targeting the cardiac vagus nerve by optogenetic stimulation induced macrophage M2 polarization by activating the IL-10/STAT3 signaling pathway, which obviously optimized the regenerative microenvironment and then improved cardiac function after MI.

Carbon Dots Derived from Curcumae Radix and Their Heartprotective Effect.

Background: Acute myocardial infarction (AMI) is a common cardiovascular disease in clinic. Currently, there is no specific treatment for AMI. Carbon dots (CDs) have been reported to show excellent biological activities, which hold promise for the development of novel nanomedicines for the treatment of cardiovascular diseases. Methods: In this study, we firstly prepared CDs from the natural herb Curcumae Radix Carbonisata (CRC-CDs) by a green, simple calcination method. The aim of this study is to investigate the cardioprotective effect and mechanism of CRC-CDs on isoproterenol (ISO) -induced myocardial infarction (MI) in rats. Results: The results showed that pretreatment with CRC-CDs significantly reduced serum levels of cardiac enzymes (CK-MB, LDH, AST) and lipids (TC, TG, LDL) and reduced st-segment elevation and myocardial infarct size on the ECG in AMI rats. Importantly, cardiac ejection fraction (EF) and shortening fraction (FS) were markedly elevated, as was ATPase activity. In addition, CRC-CDs could significantly increase the levels of superoxide dismutase (SOD), reduced glutathione (GSH), catalase (CAT), and reduce the levels of malondialdehyde (MDA) and reactive oxygen species (ROS) in myocardial tissue, thereby exerting cardioprotective effect by enhancing the antioxidant capacity of myocardial tissue. Moreover, the TUNEL staining image showed that positive apoptotic cells were markedly declined after CRC-CDs treatment, which indicate that CRC-CDs could inhibit cardiomyocyte apoptosis. Importantly, The protective effect of CRC-CDs on H2O2 -pretreated H9c2 cells was also verified in vitro. Conclusion: Taken together, CRC-CDs has the potential for clinical application as an anti-myocardial ischemia drug candidate, which not only provides evidence for further broadening the biological application of cardiovascular diseases, but also offers potential hope for the application of nanomedicine to treat intractable diseases.

Dapagliflozin ameliorates myocardial infarction injury through AMPKα-dependent regulation of oxidative stress and apoptosis.

Dapagliflozin (DAPA) has been demonstrated to reduce cardiovascular mortality and heart failure hospitalization rates in diabetic patients. However, the mechanism underlying its cardio-protective effect in non-diabetic patients remains unclear. Our study aimed to explore the cardio-protective impact of DAPA on myocardial infarction in non-diabetic mice. We induced myocardial infarction in C57BL/6 mice by ligating the descending branch of the left coronary artery. After surgery, the animals were randomly treated with either saline or DAPA. We employed echocardiography, Western blot analysis, and tissue staining to assess post-infarction myocardial injury. Additionally, we investigated the mechanism of action through cell experiments. Compared to the myocardial infarction group, DAPA treatment significantly attenuated ventricular remodeling and improved cardiac function. By mitigating myocardial oxidative stress and apoptosis, DAPA may activate the AMPKα signaling pathway, thereby exerting a protective effect. These findings suggest that DAPA could serve as a novel therapeutic approach for patients with cardiac infarction.

Ceruloplasmin, Vitamin C, and Uric Acid Levels in Patients With Myocardial Infarction: A Comparative Cross-Sectional Study.

INTRODUCTION: Global mortality is significantly influenced by myocardial infarction. Scientists have examined the role of the copper-containing protein ceruloplasmin in heart attacks. It helps to regulate oxidative stress, iron metabolism, and inflammation. Vitamin C's antioxidative qualities lend credence to the idea that it could help prevent cardiovascular disease. Several studies have shown that elevated uric acid levels are related to a higher risk of myocardial infarction. With this background, we conducted this study to estimate levels of ceruloplasmin, vitamin C, and uric acid in patients with myocardial infarction. MATERIALS AND METHODS: A tertiary care hospital in central India carried out this comparative cross-sectional study. The study was conducted between December 2022 and April 2023. Patients of any gender with newly diagnosed myocardial infarction who received admission to the intensive care unit and had ST-segment elevation of at least 2 mm in two or more consecutive electrocardiogram leads were included in the patient group. The control group consisted of individuals who did not exhibit any changes associated with myocardial infarction. Based on sex, age, and body mass index, the 75 control and 75 patients were matched. Ceruloplasmin, vitamin C, and uric acid were analyzed and compared. RESULTS: The uric acid levels among the patient group were 10.34 ± 3.23 mg/dL, and among the controls, they were 3.45 ± 1.12 mg/dL (p<0.001). The ceruloplasmin levels among the patient group were 64.34 ± 4.21 mg/dL, and among the controls, they were 29.23 ± 3.82 mg/dL (p<0.001). The vitamin C levels among the patient group were 13.80 ± 0.94 µmol/L, and among the controls, they were 45.62 ± 4.34 µmol/L (p<0.001). CONCLUSION: The patients with myocardial infarction demonstrated significantly elevated levels of ceruloplasmin and uric acid, while their vitamin C levels were lower in comparison. It is crucial to comprehend the underlying mechanisms through which these parameters influence the development of myocardial infarction.

A Rare Case of Streptococcus agalactiae Ventriculitis and Endocarditis.

Streptococcus agalactiae infection is typically seen in specific populations, including neonates, pregnant women, and the elderly. These patients have immature, lower, and waning immune systems, which makes them more susceptible to infections. Typical S. agalactiae infections manifest as cellulitis, bacteremia, endocarditis, meningitis, ventriculitis (a rare complication of meningitis), and osteomyelitis. In rare cases, a patient can present with two or more of these typical infection manifestations. The authors present a case of a 48-year-old female with a past medical history of hypothyroidism and chronic back pain who presented to the emergency department with altered mental status. The patient developed nausea and vomiting two days prior to presentation after a family gathering, followed by occipital headache and agitation. On arrival at the emergency department, the patient did not follow commands and was drowsy. The initial examination showed positive for Brudzinski and Kernig signs. The patient was tachycardic, tachypneic, and hypertensive. Initial computed tomography (CT) head without contrast was negative for any acute pathology. Neurology was consulted, and a bedside lumbar puncture was performed, which was significant for elevated opening pressure of 32 cm H2O. The patient was initially started on ceftriaxone, ampicillin, vancomycin, acyclovir, and dexamethasone. Magnetic resonance imaging (MRI) of the brain with and without contrast showed acute ventriculitis, mild leptomeningeal enhancement, and a right posterior corona radiata acute lacunar infarct. Meningitis panel, BioFire (BioFire Diagnostics, Salt Lake City, UT), was positive for S. agalactiae, and the patient was de-escalated to ceftriaxone. Cerebrospinal fluid and blood cultures returned positive for S. agalactiae. A transthoracic echocardiogram was negative for endocarditis, but a transesophageal echocardiogram was significant for a 0.7 × 0.4 cm mobile echodensity attached to the posterior leaflet of the mitral valve (P1/P2 scallop). Repeat blood cultures, additional cerebrospinal fluid analysis, and infectious workup remained negative. Cardiology was consulted and recommended medical treatment. The patient improved clinically, continued ceftriaxone, and was discharged to complete a total of six weeks of treatment with outpatient follow-up evaluations. This case depicts a rare presentation of endocarditis, meningitis, and ventriculitis S. agalactiae infection and the need for a definite treatment algorithm in the management of complicated conditions such as the one presented.

Hepatic Infarction in Pregnancy: A Systematic Review.

OBJECTIVE: Hepatic infarction is a rare complication of pregnancy most often associated with hemolysis, elevated liver enzymes, low platelets (HELLP) syndrome. The objective of this review is to identify risk factors, presenting signs and symptoms, methods of diagnosis, and best management practices based on published case reviews. DATA SOURCES: PUBMED and MEDLINE: OVID databases were searched for citations regarding hepatic infarction in pregnancy or the postpartum period since database inception until the study date of December 18, 2023. Keywords included "liver infarction" OR "hepatic infarction," AND "pregnancy" OR "obstetrics." STUDY ELIGIBILITY: Case reviews or case series published in the English language were included. Our study was registered with PROSPERO (#CRD42023488176) and was conducted in accordance with published PROSPERO and MOOSE guidelines. STUDY APPRAISAL: Included papers were evaluated for bias using a previously published tool by Murad et al (2018). RESULTS: A total of 38 citations documenting 50 pregnancies published between 1979 - 2023 were included. Of these, 34% had a history of hypertensive disease, 26% had antiphospholipid syndrome (APS), and 22% had a history of thrombus. Of those without a pre-existing diagnosis of APS, 24% tested positive during hospitalization. Most patients presented with epigastric or right upper quadrant pain (78%) and 32% and 16% had severe blood pressure (BP) or mild BP, respectively. Sixty-four percent of patients presented with transaminitis. Forty-six percent of patients delivered preterm and 32% of pregnancies ended in intrauterine fetal demise, abortion, or early termination of pregnancy for maternal benefit. CT scan was used to confirm diagnosis of hepatic infarction in 58% of cases, MRI in 14%, and ultrasound in 6%. In cases that described management, treatment was always multimodal, including antihypertensives (18%), therapeutic anticoagulation (45%), blood product transfusion (36%), plasma exchange or intravenous immunoglobulin (20%), and steroids (39%). Transfer to the intensive care unit was required in 20% of cases. CONCLUSIONS: Hepatic infarction should be considered in all cases of HELLP, but specifically in patients with a history of APS who present with epigastric or right upper quadrant pain. The diagnosis can usually be confirmed with CT scan alone, and management should be prompt with supportive care, therapeutic anticoagulation, and steroids.

Multimodal ultrasound diagnosis of epididymo-orchitis with secondary testicular infarction: A case report.

We report a case of a 48-year-old man with testicular infarction caused by epididymo-orchitis (EO). Multimodal ultrasound showed extensive necrosis of the testis, and the patient underwent right orchiectomy. Postoperative pathology confirmed extensive necrosis of the testis. After 3 months of follow-up, the examination of scrotal ultrasound showed that the left testis and epididymis had no obvious abnormality.

Pressure-Controlled Intermittent Coronary Sinus Occlusion (PiCSO) in Acute Myocardial Infarction: The PiCSO-AMI-I Trial.

BACKGROUND: Primary percutaneous coronary intervention (pPCI) has improved clinical outcomes in patients with ST-segment-elevation myocardial infarction. However, as many as 50% of patients still have suboptimal myocardial reperfusion and experience extensive myocardial necrosis. The PiCSO-AMI-I trial (Pressure-Controlled Intermittent Coronary Sinus Occlusion-Acute Myocardial Infarction-I) evaluated whether PiCSO therapy can further reduce myocardial infarct size (IS) in patients undergoing pPCI. METHODS: Patients with anterior ST-segment-elevation myocardial infarction and Thrombolysis in Myocardial Infarction flow 0-1 were randomized at 16 European centers to PiCSO-assisted pPCI or conventional pPCI. The PiCSO Impulse Catheter (8Fr balloon-tipped catheter) was inserted via femoral venous access after antegrade flow restoration of the culprit vessel and before proceeding with stenting. The primary end point was the difference in IS (expressed as a percentage of left ventricular mass) at 5 days by cardiac magnetic resonance. Secondary end points were the extent of microvascular obstruction and intramyocardial hemorrhage at 5 days and IS at 6 months. RESULTS: Among 145 randomized patients, 72 received PiCSO-assisted pPCI and 73 conventional pPCI. No differences were observed in IS at 5 days (27.2%±12.4% versus 28.3%±11.45%; P=0.59) and 6 months (19.2%±10.1% versus 18.8%±7.7%; P=0.83), nor were differences between PiCSO-treated and control patients noted in terms of the occurrence of microvascular obstruction (67.2% versus 64.6%; P=0.85) or intramyocardial hemorrhage (55.7% versus 60%; P=0.72). The study was prematurely discontinued by the sponsor with no further clinical follow-up beyond 6 months. However, up to 6 months of PiCSO use appeared safe with no device-related adverse events. CONCLUSIONS: In this prematurely discontinued randomized trial, PiCSO therapy as an adjunct to pPCI did not reduce IS when compared with conventional pPCI in patients with anterior ST-segment-elevation myocardial infarction. PiCSO use was associated with increased procedural time and contrast but no increase in adverse events up to 6 months. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT03625869.

Differential impact of fentanyl and morphine doses on ticagrelor-induced platelet inhibition in ST-segment elevation myocardial infarction: a subgroup analysis from the PERSEUS randomized trial.

Introduction: Among patients with ST-segment elevation myocardial infarction (STEMI) treated with primary percutaneous coronary intervention (PCI), intravenous fentanyl does not enhance ticagrelor-induced platelet inhibition within 2 h compared to morphine. The impact of the total dose of fentanyl and morphine received on ticagrelor pharmacodynamic and pharmacokinetic responses in patients with STEMI remains however undetermined. Materials and methods: We performed a post-hoc subanalysis of the prospective, open-label, single-center, randomized PERSEUS trial (NCT02531165) that compared treatment with intravenous fentanyl vs. morphine among symptomatic patients with STEMI treated with primary PCI after ticagrelor pretreatment. Patients from the same population as PERSEUS were further stratified according to the total dose of intravenous opioids received. The primary outcome was platelet reactivity using P2Y12 reaction units (PRU) at 2 h following administration of a loading dose (LD) of ticagrelor. Secondary outcomes were platelet reactivity and peak plasma levels of ticagrelor and AR-C124910XX, its active metabolite, at up to 12 h after ticagrelor LD administration. Generalized linear models for repeated measures were built to determine the relationship between raw and weight-weighted doses of fentanyl and morphine. Results: 38 patients with STEMI were included between December 18, 2015, and June 22, 2017. Baseline clinical and procedural characteristics were similar between low- and high-dose opioid subgroups. At 2 h, there was a significant correlation between PRU and both raw [regression coefficient (B), 0.51; 95% confidence interval (CI), 0.02-0.99; p = 0.043] and weight-weighted (B, 0.54; 95% CI, 0.49-0.59; p < 0.001) doses of fentanyl, but not morphine. Median PRU at 2 h was significantly lower in patients receiving low, as compared to high, doses of fentanyl [147; interquartile range (IQR), 63-202; vs. 255; IQR, 183-274; p = 0.028], whereas no significant difference was found in those receiving morphine (217; IQR, 165-266; vs. 237; IQR, 165-269; p = 0.09). At 2 h, weight-weighted doses of fentanyl and morphine were significantly correlated to plasma levels of ticagrelor and AR-C124910XX. Conclusion: In symptomatic patients with STEMI who underwent primary PCI after ticagrelor pretreatment and who received intravenous opioids, we found a dose-dependent relationship between the administration of intravenous fentanyl, but not morphine, and ticagrelor-induced platelet inhibition.

Reading and writing from right to left after anterior cerebral artery stroke.

This is the case report of a woman who started to write and read from right to left after anterior cerebral artery stroke, affecting the left supplementary motor area. No cases were found in the literature with exactly the same characteristics. She has been able to read and write faster after rehabilitation approach at Sarah Network of Rehabilitation Hospitals, in the Belo Horizonte city unit, Brazil, despite the maintenance of the inversion. She returned to her previous activities in an adaptive way. It was discussed how the dysfunction in this cerebral area and its connections may disturb the reading strategy and direction.

Relato do caso de uma mulher que passou a escrever e ler da direita para a esquerda após um acidente vascular encefálico isquêmico de artéria cerebral anterior, acometendo área motora suplementar esquerda. Não foram encontrados casos na literatura exatamente com as mesmas características. Durante a participação da paciente no programa de reabilitação neurológica da Rede Sarah de Hospitais de Reabilitação, unidade Belo Horizonte, foram observados ganhos na agilidade de leitura e escrita, ainda que mantendo a inversão, e retorno às suas atividades de forma adaptada. Realizou-se discussão de como o comprometimento dessa área e de suas conexões pode perturbar a estratégia de leitura e sua direção.

The involvement of soluble epoxide hydrolase in the development of cardiovascular diseases through epoxyeicosatrienoic acids.

Arachidonic acid (AA) has three main metabolic pathways: the cycloxygenases (COXs) pathway, the lipoxygenases (LOXs) pathway, and the cytochrome P450s (CYPs) pathway. AA produces epoxyeicosatrienoic acids (EETs) through the CYPs pathway. EETs are very unstable in vivo and can be degraded in seconds to minutes. EETs have multiple degradation pathways, but are mainly degraded in the presence of soluble epoxide hydrolase (sEH). sEH is an enzyme of bifunctional nature, and current research focuses on the activity of its C-terminal epoxide hydrolase (sEH-H), which hydrolyzes the EETs to the corresponding inactive or low activity diol. Previous studies have reported that EETs have cardiovascular protective effects, and the activity of sEH-H plays a role by degrading EETs and inhibiting their protective effects. The activity of sEH-H plays a different role in different cells, such as inhibiting endothelial cell proliferation and migration, but promoting vascular smooth muscle cell proliferation and migration. Therefore, it is of interest whether the activity of sEH-H is involved in the initiation and progression of cardiovascular diseases by affecting the function of different cells through EETs.

Mast cells: a novel therapeutic avenue for cardiovascular diseases?

Mast cells are tissue-resident immune cells strategically located in different compartments of the normal human heart (the myocardium, pericardium, aortic valve and close to nerves) as well as in atherosclerotic plaques. Cardiac mast cells produce a broad spectrum of vasoactive and proinflammatory mediators, which have potential roles in inflammation, angiogenesis, lymphangiogenesis, tissue remodeling and fibrosis. Mast cells release preformed mediators (e.g., histamine, tryptase, chymase) and de novo synthesized mediators [e.g., cysteinyl leukotriene C4 (LTC4) and prostaglandin D2 (PGD2)], as well as cytokines and chemokines, which can activate different resident immune cells (e.g., macrophages) and structural cells (e.g., fibroblasts, endothelial cells) in the human heart and aorta. The transcriptional profiles of various mast cell populations highlight their potential heterogeneity and distinct gene and proteome expression. Mast cell plasticity and/or heterogeneity enable these cells the potential for performing different, even opposite, functions in response to changing tissue contexts. Human cardiac mast cells display significant differences compared to mast cells isolated from other organs. These characteristics make cardiac mast cells intriguing, given their dichotomous potential roles of inducing or protecting against cardiovascular diseases. Identification of cardiac mast cell subpopulations represents a prerequisite for understanding their potential multifaceted roles in health and disease. Several new drugs specifically targeting human mast cell activation are under development or in clinical trials. Mast cells and/or their subpopulations can potentially represent novel therapeutic targets for cardiovascular disorders.

Increased cardiovascular risks and mortality in prurigo nodularis: a global cohort study.

BACKGROUND: Prurigo nodularis (PN) presents with intensely itchy hard nodules. Despite being limited to the skin, PN was noted to be associated with systemic diseases including diabetes and chronic renal failure. In previous smaller retrospective studies, several cardiac and vascular diseases were found more frequently in patients with PN. However, small cohort sizes, partially discrepant outcomes, missing data, and incomplete risk assessment limit these findings. METHODS: Electronic health records (EHR)s of 64,801 patients (59.44% females) with PN and an equal sized propensity-matched control group were retrieved. In these cohorts, the risks to develop cardiac and vascular diseases and mortality following the diagnosis of PN were determined. Sub-analyses included stratification for sex, ethnicity, and treatments. FINDINGS: PN was associated with a higher risk for a broad range of acute cardiac events including heart failure and myocardial infarction. For example, the hazard ratio of myocardial infarction was 1.11 (95%-CI: 1.041-1.184, p = 0.0015) following PN diagnosis. Also, all-cause mortality was higher in patients with PN. Further, chronic vascular as well as structural heart diseases, e.g., peripheral arterial disease, chronic ischaemic heart disease and valval disorders were found more frequently following a PN diagnosis. Risks were more pronounced in white and female patients. Having established an increased risk for death and cardiovascular disease, we next addressed if dupilumab that has been recently licenced for use in this indication can modulate these risks. The risk of death but not of any cardiovascular disease was slightly reduced in patients with PN treated with dupilumab as opposed to those treated with systemic therapies other than dupilumab. The study is limited by retrospective data collection and reliance on ICD10-disease classification. INTERPRETATION: PN is associated with higher mortality and an increased risk for the development of a wide range of cardiac and vascular diseases. Health care professionals should take this into account when managing patients with PN. FUNDING: This work was supported by the University of Lübeck, the Deutsche Forschungsgemeinschaft and the State of Schleswig-Holstein.