Angiographic Coronary Slow Flow Is Not a Valid Surrogate for Invasively Diagnosed Coronary Microvascular Dysfunction.

BACKGROUND: Ischemia with no obstructive coronary arteries is frequently caused by coronary microvascular dysfunction (CMD). Consensus diagnostic criteria for CMD include baseline angiographic slow flow by corrected TIMI (Thrombolysis In Myocardial Infarction) frame count (cTFC), but correlations between slow flow and CMD measured by invasive coronary function testing (CFT) are uncertain. OBJECTIVES: The aim of this study was to investigate relationships between cTFC and invasive CFT for CMD. METHODS: Adults with ischemia with no obstructive coronary arteries underwent invasive CFT with thermodilution-derived baseline coronary blood flow, coronary flow reserve (CFR), and index of microcirculatory resistance (IMR). CMD was defined as abnormal CFR (<2.5) and/or abnormal IMR (≥25). cTFC was measured from baseline angiography; slow flow was defined as cTFC >25. Correlations between cTFC and baseline coronary flow and between CFR and IMR and associations between slow flow and invasive measures of CMD were evaluated, adjusted for covariates. All patients provided consent. RESULTS: Among 508 adults, 49% had coronary slow flow. Patients with slow flow were more likely to have abnormal IMR (36% vs 26%; P = 0.019) but less likely to have abnormal CFR (28% vs 42%; P = 0.001), with no difference in CMD (46% vs 51%). cTFC was weakly correlated with baseline coronary blood flow (r = -0.35; 95% CI: -0.42 to -0.27), CFR (r = 0.20; 95% CI: 0.12 to 0.28), and IMR (r = 0.16; 95% CI: 0.07-0.24). In multivariable models, slow flow was associated with lower odds of abnormal CFR (adjusted OR: 0.53; 95% CI: 0.35 to 0.80). CONCLUSIONS: Coronary slow flow was weakly associated with results of invasive CFT and should not be used as a surrogate for the invasive diagnosis of CMD.

Left ventricular free wall rupture caused by myocardial ischemia without treatable atherosclerotic coronary disease: a case series.

BACKGROUND: The clinical presentation of left ventricular free wall rupture (LVFWR) varies ranging from uneventful condition to congestive heart failure. Here we report two cases of LVFWR with different clinical presentation and notable outcome. A 53-year-old male presenting emergently with signs of myocardial infarction received immediate coronary angiography and thoracic CT-scan showing occlusion of the first marginal coronary branch without possibility of revascularization and minimal pericardial extravasation. Under ICU surveillance, LVFWR occurred 24 h later and was treated by pericardiocentesis and ECMO support followed by immediate uncomplicated surgical repair. Postoperative therapy-refractory vasoplegia and electromechanical dissociation caused fulminant deterioration and the early death of the patient. The second case is a 76-year old male brought to the emergency room after sudden syncope, clinical sings of pericardial tamponade and suspicion of a type A acute aortic dissection. Immediate CT-angiography excluded aortic dissection and revealed massive pericardial effusion and a hypoperfused myocardial area on the territory of the first marginal branch. Immediate sternotomy under mechanical resuscitation enabled removal of the massive intrapericardial clot and revealed LVFWR. After an uncomplicated surgical repair, an uneventful postoperative course, the patient was discharged with sinus rhythm and good biventricular function. One year after the operation, he is living at home, symptom free. DISCUSSION: Whereas the younger patient, who was clinically stable at hospital admission received delayed surgery and did not survive treatment, the older patient, clinically unstable at presentation, went into immediate surgery and had a flawless postoperative course. Thus, early surgical repair of LVFWR leads to best outcome and treating LVFWR as a high emergency regardless of the symptoms improve survival.

Stem Cell Therapy against Ischemic Heart Disease.

Ischemic heart disease, which is one of the top killers worldwide, encompasses a series of heart problems stemming from a compromised coronary blood supply to the myocardium. The severity of the disease ranges from an unstable manifestation of ischemic symptoms, such as unstable angina, to myocardial death, that is, the immediate life-threatening condition of myocardial infarction. Even though patients may survive myocardial infarction, the resulting ischemia-reperfusion injury triggers a cascade of inflammatory reactions and oxidative stress that poses a significant threat to myocardial function following successful revascularization. Moreover, despite evidence suggesting the presence of cardiac stem cells, the fact that cardiomyocytes are terminally differentiated and cannot significantly regenerate after injury accounts for the subsequent progression to ischemic cardiomyopathy and ischemic heart failure, despite the current advancements in cardiac medicine. In the last two decades, researchers have realized the possibility of utilizing stem cell plasticity for therapeutic purposes. Indeed, stem cells of different origin, such as bone-marrow- and adipose-derived mesenchymal stem cells, circulation-derived progenitor cells, and induced pluripotent stem cells, have all been shown to play therapeutic roles in ischemic heart disease. In addition, the discovery of stem-cell-associated paracrine effects has triggered intense investigations into the actions of exosomes. Notwithstanding the seemingly promising outcomes from both experimental and clinical studies regarding the therapeutic use of stem cells against ischemic heart disease, positive results from fraud or false data interpretation need to be taken into consideration. The current review is aimed at overviewing the therapeutic application of stem cells in different categories of ischemic heart disease, including relevant experimental and clinical outcomes, as well as the proposed mechanisms underpinning such observations.

lncRNA CCAT2 Protects Against Cardiomyocyte Injury After Myocardial Ischemia/Reperfusion by Regulating BMI1 Expression.

Myocardial ischemia/reperfusion (I/R) decreases cardiac function and efficiency. Accumulating evidence suggests that long noncoding RNAs (lncRNAs) have been linked to the cellular processes of myocardial I/R injury. The present investigation elucidated the function of lncRNA colon cancer-associated transcript 2 (CCAT2) in myocardial I/R injury and the related mechanisms.AC16 cardiomyocytes were exposed to hypoxia (16 hours) /reoxygenation (6 hours) (H/R) to mimic myocardial I/R models in vitro. CCAT2 and microRNA (miR) -539-3p expressions in AC16 cardiomyocytes were measured using real-time quantitative polymerase chain reaction. B-cell-specific Moloney murine leukemia virus insertion region 1 (BMI1) protein levels in AC16 cardiomyocytes were determined by western blotting. Cell viability, lactate dehydrogenase (LDH) leakage, reactive oxygen species (ROS) levels, mitochondrial membrane potential, and apoptosis were detected using Counting Kit-8, LDH Assay Kit, dihydroethidium assay, 5,5',6,6'-tetrachloro1,1',3,3'-tetramethylbenzimidazolylcarbocyanine iodide staining, flow cytometry, and western blotting, respectively. The interactions between the molecules were confirmed using the dual-luciferase gene reporter. The wingless/integrated/beta-catenin (Wnt/ß-catenin) pathway under the H/R condition was detected by western blotting.CCAT2 and BMI1 mRNA expressions were reduced in H/R-exposed AC16 cardiomyocytes. CCAT2 overexpression exerted protective effects against H/R-induced cardiomyocyte injury, as demonstrated by increased cell viability and mitochondrial membrane potential and decreased LDH leakage, ROS levels, and apoptosis. In addition, CCAT2 positively regulated BMI1 expression by binding to miR-539-3p. CCAT2 knockdown or miR-539-3p overexpression restrained the protective effects of BMI1 against H/R-induced cardiomyocyte injury. In addition, miR-539-3p overexpression reversed the protective effects of CCAT2. Furthermore, CCAT2 activated the Wnt/ß-catenin pathway under the H/R condition via the miR-539-3p/BMI1 axis.Overall, this investigation showed the protective effects of the CCAT2/miR-539-3p/BMI1/Wnt/ß-catenin regulatory axis against cardiomyocyte injury induced by H/R.

Association between serum beclin 1 level and cardiac valvular calcification in hemodialysis patients.

BACKGROUND: Cardiovascular calcification is a pervasive issue throughout chronic kidney disease (CKD) progression. Autophagy, a fundamental cellular process, exerts significant influence on various cardiac pathologies, including arrhythmias, atherosclerosis, heart failure, and notably, valvular, and vascular calcifications. Beclin-1, a crucial eukaryotic protein, plays a major regulatory role in autophagy as part of the phosphatidylinositol-3-kinase (PI3K) complex. Recent evidence suggests a protective role for Beclin-1-mediated autophagy in CKD vascular calcification, raising its potential as a novel therapeutic target in this context. WE AIMED TO: Investigate the association between serum Beclin 1 levels and the presence of cardiovascular valvular calcification in hemodialysis patients. RESULTS: This study evaluated a cohort of 102 hemodialysis patients, evenly divided into two groups based on echocardiographic findings. All participants underwent serum Beclin 1 measurement and transthoracic echocardiography. Patients with acute kidney injury, active malignancy, or diabetes were excluded. Our study revealed significant differences between the two groups in terms of: Serum Beclin 1 levels, all parameters of lipid profile, prevalence of ischemic heart disease, serum albumin levels and Total calcium. Echocardiography in Group 1 showed that most cases (60.78%) exhibited mild aortic valve calcification. Additionally, significant relationships were observed between Beclin 1 and: ischemic heart disease (p=0.011) Aortic valve calcification on echocardiography (p < 0.001) Interestingly, lower Beclin 1 levels were associated with more severe valve calcification. A Beclin 1 cutoff value of ≤ 35.5 ng/ml demonstrated the highest sensitivity (98%) and specificity (92%). CONCLUSION: Our findings suggest that the serum Beclin 1 level could be incorporated into a predictive model for cardiac valvular calcification in hemodialysis patients.

Shape of radiation dose response relationship for ischaemic heart disease mortality and its interpretation: analysis of the national registry for radiation workers (NRRW) cohort.

Statistically significant increases in ischemic heart disease (IHD) mortality with cumulative occupational external radiation dose were observed in the National Registry for Radiation Workers (NRRW) cohort. There were 174 541 subjects in the NRRW cohort. The start of follow up was 1955, and the end of the follow-up for each worker was chosen as the earliest date of death or emigration, their 85th birthday or 31 December 2011. The dose-response relationship showed a downward curvature at a higher dose level >0.4 Sv with the overall shape of the dose-response relationship best described by a linear-quadratic model. The smaller risk at dose >0.4 Sv appears to be primarily associated with workers who started employment at a younger age (<30 years old) and those who were employed for more than 30 years. We modelled the dose response by age-at-first exposure. For the age-at-first exposure of 30+ years old, a linear dose-response was the best fit. For age-at-first exposure <30 years old, there was no evidence of excess risk of IHD mortality for radiation doses below 0.1 Sv or above 0.4 Sv, excess risk was only observed for doses between 0.1-0.4 Sv. For this age-at-first exposure group, it was also found that the doses they received when they were less than 35 years old or greater than 50 years old did not contribute to any increased IHD risk.

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

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

Allopurinol and cardiovascular outcomes in patients with ischaemic heart disease: the ALL-HEART RCT and economic evaluation.

Background: Allopurinol is a xanthine oxidase inhibitor that lowers serum uric acid and is used to prevent acute gout flares in patients with gout. Observational and small interventional studies have suggested beneficial cardiovascular effects of allopurinol. Objective: To determine whether allopurinol improves major cardiovascular outcomes in patients with ischaemic heart disease. Design: Prospective, randomised, open-label, blinded endpoint multicentre clinical trial. Setting: Four hundred and twenty-four UK primary care practices. Participants: Aged 60 years and over with ischaemic heart disease but no gout. Interventions: Participants were randomised (1 : 1) using a central web-based randomisation system to receive allopurinol up to 600 mg daily that was added to usual care or to continue usual care. Main outcome measures: The primary outcome was the composite of non-fatal myocardial infarction, non-fatal stroke or cardiovascular death. Secondary outcomes were non-fatal myocardial infarction, non-fatal stroke, cardiovascular death, all-cause mortality, hospitalisation for heart failure, hospitalisation for acute coronary syndrome, coronary revascularisation, hospitalisation for acute coronary syndrome or coronary revascularisation, all cardiovascular hospitalisations, quality of life and cost-effectiveness. The hazard ratio (allopurinol vs. usual care) in a Cox proportional hazards model was assessed for superiority in a modified intention-to-treat analysis. Results: From 7 February 2014 to 2 October 2017, 5937 participants were enrolled and randomised to the allopurinol arm (n = 2979) or the usual care arm (n = 2958). A total of 5721 randomised participants (2853 allopurinol; 2868 usual care) were included in the modified intention-to-treat analysis population (mean age 72.0 years; 75.5% male). There was no difference between the allopurinol and usual care arms in the primary endpoint, 314 (11.0%) participants in the allopurinol arm (2.47 events per 100 patient-years) and 325 (11.3%) in the usual care arm (2.37 events per 100 patient-years), hazard ratio 1.04 (95% confidence interval 0.89 to 1.21); p = 0.65. Two hundred and eighty-eight (10.1%) participants in the allopurinol arm and 303 (10.6%) participants in the usual care arm died, hazard ratio 1.02 (95% confidence interval 0.87 to 1.20); p = 0.77. The pre-specified health economic analysis plan was to perform a 'within trial' cost-utility analysis if there was no statistically significant difference in the primary endpoint, so NHS costs and quality-adjusted life-years were estimated over a 5-year period. The difference in costs between treatment arms was +£115 higher for allopurinol (95% confidence interval £17 to £210) with no difference in quality-adjusted life-years (95% confidence interval -0.061 to +0.060). We conclude that there is no evidence that allopurinol used in line with the study protocol is cost-effective. Limitations: The results may not be generalisable to younger populations, other ethnic groups or patients with more acute ischaemic heart disease. One thousand six hundred and thirty-seven participants (57.4%) in the allopurinol arm withdrew from randomised treatment, but an on-treatment analysis gave similar results to the main analysis. Conclusions: The ALL-HEART study showed that treatment with allopurinol 600 mg daily did not improve cardiovascular outcomes compared to usual care in patients with ischaemic heart disease. We conclude that allopurinol should not be recommended for the secondary prevention of cardiovascular events in patients with ischaemic heart disease but no gout. Future work: The effects of allopurinol on cardiovascular outcomes in patients with ischaemic heart disease and co-existing hyperuricaemia or clinical gout could be explored in future studies. Trial registration: This trial is registered as EU Clinical Trials Register (EudraCT 2013-003559-39) and ISRCTN (ISRCTN 32017426). Funding: This award was funded by the National Institute for Health and Care Research (NIHR) Health Technology Assessment programme (NIHR award ref: 11/36/41) and is published in full in Health Technology Assessment; Vol. 28, No. 18. See the NIHR Funding and Awards website for further award information.

The purpose of the ALL-HEART study was to determine whether giving allopurinol to people with ischaemic heart disease (also commonly known as coronary heart disease) would reduce their risk of having a heart attack, stroke or of dying from cardiovascular disease. Allopurinol is a medication usually given to patients with gout to prevent acute gout flares. It is not currently used to treat ischaemic heart disease. We randomly allocated people aged over 60 years with ischaemic heart disease to take up to 600 mg of allopurinol daily (in addition to their usual care) or to continue with their usual care. We then monitored participants for several years and recorded any major health events such as heart attacks, strokes and deaths. We obtained most of the follow-up data from centrally held electronic hospital admissions and death records, making the study easier for participants and more cost-efficient. We asked participants in both groups to complete questionnaires to assess their quality of life during the study. We also collected data to determine whether there was any economic benefit to the NHS of using allopurinol in patients with ischaemic heart disease. There was no difference in the risk of heart attacks, strokes or death from cardiovascular disease between the participants given allopurinol and those in the group continuing their usual care. We also found no difference in the risks of other cardiovascular events, deaths from any cause or quality-of-life measurements between the allopurinol and usual care groups. The results of the ALL-HEART study suggest that we should not recommend that allopurinol be given to people with ischaemic heart disease to prevent further cardiovascular events or deaths.

MiR-181a protects the heart against myocardial infarction by regulating mitochondrial fission via targeting programmed cell death protein 4.

Worldwide, myocardial infarction (MI) is the leading cause of death and disability-adjusted life years lost. Recent researches explored new methods of detecting biomarkers that can predict the risk of developing myocardial infarction, which includes identifying genetic markers associated with increased risk. We induced myocardial infarction in mice by occluding the left anterior descending coronary artery and performed TTC staining to assess cell death. Next, we performed ChIP assays to measure the enrichment of histone modifications at the promoter regions of key genes involved in mitochondrial fission. We used qPCR and western blot to measure expression levels of relative apoptotic indicators. We report that miR-181a inhibits myocardial ischemia-induced apoptosis and preserves left ventricular function after MI. We show that programmed cell death protein 4 (PDCD4) is the target gene involved in miR-181a-mediated anti-ischemic injury, which enhanced BID recruitment to the mitochondria. In addition, we discovered that p53 inhibits the expression of miR-181a via transcriptional regulation. Here, we discovered for the first time a mitochondrial fission and apoptosis pathway which is controlled by miR-181a and involves PDCD4 and BID. This pathway may be controlled by p53 transcriptionally, and we presume that miR-181a may lead to the discovery of new therapeutic and preventive targets for ischemic heart diseases.

Ischemic heart disease-related mortality in Brazil, 2006 to 2020. A study of multiple causes of death.

CONTEXT: Both the aging of the population and the increase in noncommunicable diseases may influence the progression and outcomes culminating in death, changing the evolution of ischemic heart diseases (IHDs) and their associated causes. Using the multiple causes of death method could help understand the magnitude of these relationships and enable better targeting of investments in health. OBJECTIVES: To evaluate the mortality from IHD in Brazil between 2006 and 2020 using the method of multiple causes and identify differences in the distribution pattern of IHD mortality by sex and geographic region. METHODS: Based on information extracted from death certificates (DCs) obtained from the database of the Department of Informatics of the Unified Health System (DATASUS), we used the multiple causes method to analyze the causes of death associated with IHD when IHD was defined as the underlying cause of death (UC) and the causes of death listed as the UC when IHD was recorded in any other lines of the DC, from 2006 to 2020, in Brazil. Subsequently, the proportion of these causes of death and differences between sexes and geographic regions were evaluated, with statistical relevance analyzed using the chi-square test, and the dependence between factors illustrated using stacked bar charts and small-world network graphs. RESULTS: When IHD was listed as the UC of death, the most frequent associated causes of death were, in descending order of frequency, acute myocardial infarction (AMI), arterial hypertension (AH), chronic ischemic heart disease (CHID), heart failure (HF), and diabetes mellitus (DM). When IHD was mentioned in any line of the DC, the most frequent UCs of death were AMI followed by DM, CIHD, chronic obstructive pulmonary disease (COPD), stroke, dyslipidemia, and, in the year 2020, COVID-19. The most frequent cause of death in women were DM as the UC and associated cause of death, AH as the UC, and CIHD and Alzheimer's disease as associated causes of death, while the most frequent causes of death in men were substance dependence as the UC and associated cause of death, and cancer as an associated cause of death. The most frequent causes of death were DM and stroke in the North and Northeast, dyslipidemia and obesity in the Midwest, Alzheimer's disease in the South and Southeast, and atherosclerotic heart disease (AHD) and COPD in the South. CONCLUSIONS: Several diseases - including AMI, AH, CIHD, HF, and DM - were the most frequent associated causes of death when IHD was recorded as the UC. In contrast, AMI, DM, CIHD, COPD, and stroke were the most frequent UCs when IHD was listed as an associated cause of death. The degree of these associations varied between sexes and geographic regions.

[A prospective study on association between sleep duration and the risk of chronic obstructive pulmonary disease in adults in Suzhou].

Objective: To investigate the prospective association of sleep duration with the development of chronic obstructive pulmonary disease (COPD) in adults in Suzhou. Methods: The study used the data of 53 269 participants aged 30-79 years recruited in the baseline survey from 2004 to 2008 and the follow-up until December 31, 2017 of China Kadoorie Biobank (CKB) conducted in Wuzhong District, Suzhou. After excluding participants with airflow limitation, self-reported chronic bronchitis/emphysema/coronary heart disease history at the baseline survey and abnormal or incomplete data, a total of 45 336 participants were included in the final analysis. The association between daily sleep duration and the risk for developing COPD was analyzed by using a Cox proportional hazard regression model, and the hazard ratio (HR) values and their 95%CI were calculated. The analysis was stratified by age, gender and lifestyle factors, and cross-analysis was conducted according to smoking status and daily sleep duration. Results: The median follow-up time was 11.12 years, with a total of 515 COPD diagnoses in the follow-up. After adjusting for potential confounders, multifactorial Cox proportional hazard regression analysis showed that daily sleep duration ≥10 hours was associated with higher risk for developing COPD (HR=1.42, 95%CI: 1.03-1.97). The cross analysis showed that excessive daily sleep duration increased the risk for COPD in smokers (HR=2.49, 95%CI: 1.35-4.59, interaction P<0.001). Conclusion: Longer daily sleep duration (≥10 hours) might increase the risk for COPD in adults in Suzhou, especially in smokers.

Unveiling macrophage diversity in myocardial ischemia-reperfusion injury: identification of a distinct lipid-associated macrophage subset.

Background and objective: Macrophages play a crucial and dichotomous role cardiac repair following myocardial ischemia-reperfusion, as they can both facilitate tissue healing and contribute to injury. This duality is intricately linked to environmental factors, and the identification of macrophage subtypes within the context of myocardial ischemia-reperfusion injury (MIRI) may offer insights for the development of more precise intervention strategies. Methods: Specific marker genes were used to identify macrophage subtypes in GSE227088 (mouse single-cell RNA sequencing dataset). Genome Set Enrichment Analysis (GSEA) was further employed to validate the identified LAM subtypes. Trajectory analysis and single-cell regulatory network inference were executed using the R packages Monocle2 and SCENIC, respectively. The conservation of LAM was verified using human ischemic cardiomyopathy heart failure samples from the GSE145154 (human single-cell RNA sequencing dataset). Fluorescent homologous double-labeling experiments were performed to determine the spatial localization of LAM-tagged gene expression in the MIRI mouse model. Results: In this study, single-cell RNA sequencing (scRNA-seq) was employed to investigate the cellular landscape in ischemia-reperfusion injury (IRI). Macrophage subtypes, including a novel Lipid-Associated Macrophage (LAM) subtype characterized by high expression of Spp1, Trem2, and other genes, were identified. Enrichment and Progeny pathway analyses highlighted the distinctive functional role of the SPP1+ LAM subtype, particularly in lipid metabolism and the regulation of the MAPK pathway. Pseudotime analysis revealed the dynamic differentiation of macrophage subtypes during IRI, with the activation of pro-inflammatory pathways in specific clusters. Transcription factor analysis using SCENIC identified key regulators associated with macrophage differentiation. Furthermore, validation in human samples confirmed the presence of SPP1+ LAM. Co-staining experiments provided definitive evidence of LAM marker expression in the infarct zone. These findings shed light on the role of LAM in IRI and its potential as a therapeutic target. Conclusion: In conclusion, the study identifies SPP1+ LAM macrophages in ischemia-reperfusion injury and highlights their potential in cardiac remodeling.

Transcatheter Treatment of Mitral Valve Regurgitation in the Setting of Concomitant Coronary or Multivalvular Heart Disease: A Focused Review.

Treatment for mixed valve disease has historically been limited, often surgery being the only option. With the recent advancement of transcatheter therapies, percutaneous approaches are quickly becoming viable therapeutic considerations in inoperable or high-risk patients, also offering the option for a staged or same-session treatment. Guidelines are primarily focused on single-valve disease. However, patients often present with multiple pathologies. This review summarizes the data and literature on transcatheter treatment of patients with mitral regurgitation who concomitantly have aortic stenosis or regurgitation, tricuspid regurgitation, or ischemic cardiomyopathy. Pathophysiology, hemodynamics, available therapies as well as order and timing of interventions are discussed.

Positive effects of low-dose S-ketamine on preventing myocardial injury after thoracoscopic lobectomy in patients aged 70 to 85.

OBJECTIVE: To investigate the effects of low-dose S-ketamine on marker of myocardial injury (BNP, hs-cTnT and HFABP) after thoracoscopic lobectomy in patients aged 70 to 85. METHODS: One hundred patients (four cases excluded) aged 70-85 years, with body mass index 18-24 kg·m-2 and American Society of Anesthesiologists physical status II-III, scheduled for elective lobectomy from April 2022 to April 2023, were selected. The patients were divided into two groups by a random number table method, namely, the low-dose S-ketamine combined with GDFT group (group S) and the control group (group C), with 48 cases in each group. In group S, a low dose of S-ketamine (0.2 mg/kg) was given 1 min before intubation, and the maintenance dose was 0.12 mg·kg-1·h-1. Fluid therapy, guided by cardiac index (CI), changes in stroke volume (△SV), and other dynamic indicators, was used for rehydration during the operation. Group C was given the same amount of normal saline (0.2 mg/kg) 1 min before intubation, and the same rehydration therapy was adopted during the operation. The mean arterial pressure (MAP) and heart rate (HR) of the two groups were observed and recorded immediately after entering the operating room (T0), immediately after intubation (T1), immediately after the beginning of one-lung ventilation (OLV) (T2), immediately after the beginning of surgery (T3), immediately after the end of OLV (T4), and at the end of surgery (T5). The intraoperative fluid intake and output and the use of vasoactive drugs were recorded. The plasma levels of heart-type fatty acid-binding protein (HFABP), high-sensitivity troponin T (hs-cTnT), brain natriuretic peptide (BNP), interleukin-6 (IL-6), interleukin-8 (IL-8), and tumor necrosis factor-α (TNF-α) were recorded 24 h before operation and 24 and 48 h after operation. Visual analogue scale (VAS) pain scores at rest were recorded at 2 (V1), 6 (V2), 12 (V3), 24 (V4), and 48 h (V5) after operation, and the occurrence of myocardial ischemia during hospitalization was noted. RESULTS: Compared with group C, MAP was significantly higher at T1-T5 in group S (P < 0.05), and the plasma concentrations of IL-6, IL-8, TNF-α, BNP, hs-cTnT, and HFABP were significantly lower at 24 and 48 h after operation (P < 0.05). The VAS pain scores at 2, 6, 12, 24, and 48 h after operation, the number of effective patient-controlled intravenous analgesia (PCIA) compressions, and the total number of PCIA compressions within 48 h after operation were significantly decreased (P < 0.05). Compared with group C, The hospitalization days, and the incidence of postoperative myocardial ischemia in group S were lower (P < 0.05). There were no significant intergroup differences in urine volume, extubation time, the incidence of postoperative atrial fibrillation, bleeding volume, colloid infusion volume, total fluid infusion volume, and the incidence of rescue analgesia. CONCLUSIONS: Low-dose S-ketamine can reduce the levels of hs-cTnT, HFABP, and BNP in older patients after pulmonary lobectomy, which has a positive effect on preventing myocardial injury. TRIAL REGISTRATION: This study was registered on CHICTR (registration No. ChiCTR2300074475). Date of registration: 08/08/2023.

Blood group AB is associated with reduced blood loss but also elevated cardiovascular mortality in aortocoronary bypass surgery.

Patient blood group (BG) is predictive for von-Willebrand-factor (VWF) and Factor VIII variation. The clinical impact of this ABO-effect on blood loss, cardiovascular complications and outcome has been described for several patient cohorts. The aim of this study was to investigate the impact of patient BG on blood loss and outcome after coronary artery bypass surgery (CABG). Patient records, intraoperative data and perioperative transfusion records of 5713 patients receiving an on-pump CABG procedure between 05/2004 and 12/2018 were analyzed. A logistic regression model for death due to perioperative myocardial ischaemia (PMI) was developed from initially 24 variables by using an univariate and multivariate selection process. BG AB patients required less blood transfusions as compared to the other blood groups, especially in case of emergency operations. However, BG AB patients also had a higher mortality which was due to secondary cardiovascular complications. The impact of blood type on the rate of cardiovascular mortality was confirmed in the logistic regression model. BG AB patients have a worse outcome after CABG surgery due to an increased incidence of fatal cardiovascular complications. As perioperative myocardial ischemia due to graft occlusion appears to be the most likely explanation, stricter anticoagulation for BG AB patients should be discussed.

Human papillomavirus infection and cardiovascular mortality: a cohort study.

BACKGROUND AND AIMS: High-risk human papillomavirus (HR-HPV) infection-a well-established risk factor for cervical cancer-has associations with cardiovascular disease (CVD). However, its relationship with CVD mortality remains uncertain. This study examined the associations between HR-HPV infection and CVD mortality. METHODS: As part of a health examination, 163 250 CVD-free Korean women (mean age: 40.2 years) underwent HR-HPV screening and were tracked for up to 17 years (median: 8.6 years). National death records identified the CVD mortality cases. Hazard ratios (HRs) and 95% confidence intervals (CIs) for CVD mortality were estimated using Cox proportional hazard regression analyses. RESULTS: During 1 380 953 person-years of follow-up, 134 CVD deaths occurred, with a mortality rate of 9.1 per 105 person-years for HR-HPV(-) women and 14.9 per 105 person-years for HR-HPV(+) women. After adjustment for traditional CVD risk factors and confounders, the HRs (95% CI) for atherosclerotic CVD (ASCVD), ischaemic heart disease (IHD), and stroke mortality in women with HR-HPV infection compared with those without infection were 3.91 (1.85-8.26), 3.74 (1.53-9.14), and 5.86 (0.86-40.11), respectively. The association between HR-HPV infection and ASCVD mortality was stronger in women with obesity than in those without (P for interaction = .006), with corresponding HRs (95% CI) of 4.81 (1.55-14.93) for obese women and 2.86 (1.04-7.88) for non-obese women. CONCLUSIONS: In this cohort study of young and middle-aged Korean women, at low risks for CVD mortality, those with HR-HPV infection had higher death rates from CVD, specifically ASCVD and IHD, with a more pronounced trend in obese individuals.

p53 Acetylation Exerts Critical Roles in Pressure Overload-Induced Coronary Microvascular Dysfunction and Heart Failure in Mice.

BACKGROUND: Coronary microvascular dysfunction (CMD) has been shown to contribute to cardiac hypertrophy and heart failure (HF) with preserved ejection fraction. At this point, there are no proven treatments for CMD. METHODS: We have shown that histone acetylation may play a critical role in the regulation of CMD. By using a mouse model that replaces lysine with arginine at residues K98, K117, K161, and K162R of p53 (p534KR), preventing acetylation at these sites, we test the hypothesis that acetylation-deficient p534KR could improve CMD and prevent the progression of hypertensive cardiac hypertrophy and HF. Wild-type and p534KR mice were subjected to pressure overload by transverse aortic constriction to induce cardiac hypertrophy and HF. RESULTS: Echocardiography measurements revealed improved cardiac function together with a reduction of apoptosis and fibrosis in p534KR mice. Importantly, myocardial capillary density and coronary flow reserve were significantly improved in p534KR mice. Moreover, p534KR upregulated the expression of cardiac glycolytic enzymes and Gluts (glucose transporters), as well as the level of fructose-2,6-biphosphate; increased PFK-1 (phosphofructokinase 1) activity; and attenuated cardiac hypertrophy. These changes were accompanied by increased expression of HIF-1α (hypoxia-inducible factor-1α) and proangiogenic growth factors. Additionally, the levels of SERCA-2 were significantly upregulated in sham p534KR mice, as well as in p534KR mice after transverse aortic constriction. In vitro, p534KR significantly improved endothelial cell glycolytic function and mitochondrial respiration and enhanced endothelial cell proliferation and angiogenesis. Similarly, acetylation-deficient p534KR significantly improved coronary flow reserve and rescued cardiac dysfunction in SIRT3 (sirtuin 3) knockout mice. CONCLUSIONS: Our data reveal the importance of p53 acetylation in coronary microvascular function, cardiac function, and remodeling and may provide a promising approach to improve hypertension-induced CMD and to prevent the transition of cardiac hypertrophy to HF.