Impact of Isolated Coronary Microvascular Disease Diagnosed Using Various Measurement Modalities on Prognosis: An Updated Systematic Review and Meta-Analysis.

INTRODUCTION: The main aim of this study was to investigate the impact of isolated coronary microvascular disease (CMD) as diagnosed via various modalities on prognosis. METHODS: A systematic literature review of PubMed, Embase, and Cochrane Library databases was conducted to identify relevant studies published up to March 2023. Included studies were required to measure coronary microvascular function and report outcomes in patients without obstructive coronary artery disease (CAD) or any other cardiac pathological characteristics. The primary endpoint was all-cause mortality, and the secondary endpoint was a major adverse cardiac event (MACE). Pooled effects were calculated using random effects models. RESULTS: A total of 27 studies comprising 18,204 subjects were included in the meta-analysis. Indices of coronary microvascular function measurement included coronary angiography-derived index of microcirculatory resistance (caIMR), hyperemic microcirculatory resistance (HMR), coronary flow reserve (CFR), and so on. Patients with isolated CMD exhibited a significantly higher risk of mortality (OR: 2.97, 95% CI, 1.91-4.60, p < 0.0001; HR: 3.38, 95% CI, 1.77-6.47, p = 0.0002) and MACE (OR: 5.82, 95% CI, 3.65-9.29, p < 0.00001; HR: 4.01, 95% CI, 2.59-6.20, p < 0.00001) compared to those without CMD. Subgroup analysis by measurement modality demonstrated consistent and robust pooled effect estimates in various subgroups. CONCLUSION: CMD is significantly associated with an elevated risk of mortality and MACE in patients without obstructive CAD or any other identifiable cardiac pathologies. The utilization of various measurement techniques may have potential advantages in the management of isolated CMD.

Predictability of noninvasive liver fibrosis score for cardiac events in patients with nonalcoholic fatty liver disease.

BACKGROUND AND AIMS: Patients with nonalcoholic fatty liver disease (NAFLD) have a higher risk of cardiac events. However, although the severity of liver fibrosis is related to worsening prognosis in patients with NAFLD, it is unclear whether the noninvasive liver fibrosis score has a predictive value for cardiac events. METHODS AND RESULTS: We evaluated 4071 patients with NAFLD diagnosed using ultrasonography. Liver fibrosis was assessed and divided into three groups based on the Fibrosis-4 (FIB4) index and NAFLD fibrosis score (NFS). The primary outcome of this study was major adverse cardiac events (MACE), including cardiac death, nonfatal myocardial infarction, and revascularization due to coronary artery disease. The median age of the evaluated patients was 61 (52-69) years, and 2201 (54.1%) were male. During the median follow-up period of 6.6 years, 179 (4.4%) patients experienced MACE. Kaplan-Meier survival analysis demonstrated that MACE increased progressively with the FIB4 index (log-rank, p < 0.001) and NFS (log-rank, p < 0.001). Multivariable analysis showed that the higher the FIB4 index, the higher the risk for MACE (low group as reference vs. intermediate group, hazard ratio [HR]: 1.860 [95% confidence interval (CI), 1.326-2.610; p < 0.001]; vs. high group, HR:3.325 [95% CI, 2.017-5.479; p < 0.001]), as well as NFS (low NFS group as reference vs. intermediate group, HR: 1.938 [95% CI, 1.391-2.699; p < 0.001]; vs. high group, HR: 3.492 [95% CI, 1.997-6.105; p < 0.001]). CONCLUSIONS: The FIB4 index and NFS are associated with the probability of MACE in patients with NAFLD. CLINICAL TRIALS: The study design was approved by the ethics review board of Ogaki Municipal Hospital (approval number: 20221124-12, registration date: November 28th, 2022). https://www.ogaki-mh.jp/chiken/kenkyu.html.

The ability and optimal cutoff value of serum cell division cycle 42 in estimating major adverse cardiac event in STEMI patients treated with percutaneous coronary intervention.

Cell division cycle 42 (CDC42) regulates cholesterol efflux, chronic inflammation, and reendothelialization in various atherosclerotic diseases. This study aimed to investigate the correlation of serum CDC42 with myocardial injury indicators and major adverse cardiac event (MACE) in ST-elevation myocardial infarction (STEMI) patients who were treated with percutaneous coronary intervention (PCI). In 250 STEMI patients about to receive PCI, serum samples were collected at enrollment before PCI treatment, and the serum samples were also obtained from 100 healthy controls (HCs) at enrollment. Serum CDC42 was detected by enzyme-linked immunosorbent assay. Serum CDC42 was decreased (versus HCs, P < 0.001) and negatively correlated with diabetes mellitus (P = 0.017), multivessel disease (P = 0.016), cardiac troponin I (P < 0.001), creatine kinase MB (P = 0.012), stent diameter ≥ 3.5 mm (P = 0.039), white blood cell (P < 0.001), low-density lipoprotein cholesterol (P = 0.049), and C-reactive protein (P < 0.001) in STEMI patients. Besides, 29 (11.6%) STEMI patients experienced MACE. The 1-year, 2-year, and 3-year accumulating MACE rates were 7.5%, 17.3%, and 19.3%, accordingly. Serum CDC42 was reduced in STEMI patients who experienced MACE compared to those who did not (P = 0.001). Serum CDC42 ≥ 250 pg/mL, ≥ 400 pg/mL, ≥ 700 pg/mL (cut by near integer value of 1/4th quartile, median, and 3/4th quartile) were associated with decreased accumulating MACE rates in STEMI patients (all P < 0.050). Notably, serum CDC42 ≥ 250 pg/mL (hazard ratio = 0.435, P = 0.031) was independently related to reduced accumulating MACE risk in STEMI patients. A serum CDC42 level of ≥ 250 pg/mL well predicts decreased MACE risk in STEMI patients who are treated with PCI.

Assessing risk of major adverse cardiac events among patients with chest pain and cocaine use using the HEART score.

INTRODUCTION: Chest pain (CP), a common presentation in the emergency department (ED) setting, is associated with significant morbidity and mortality if emergency clinicians miss the diagnosis of acute coronary syndrome (ACS). The HEART (History, Electrocardiogram, Age, Risk Factors, Troponin) score had been validated for risk-stratification patients who are at high risk for ACS and major adverse cardiac events (MACE). However, the use of cocaine as a risk factor of the HEART score was controversial. We hypothesized that patients with cocaine-positive (COP) would not be associated with higher risk of 30-day MACE than cocaine-negative (CON) patients. METHODS: This retrospective study included adult patients who presented to 13 EDs of a University's Medical System between August 7, 2017 to August 19, 2021. Patients who had CP and prospectively calculated HEART scores and urine toxicology tests as part of their clinical evaluation were eligible. Areas Under The Receiver Operating Curve (AUROC) were calculated for the performance of HEART score and 30-day MACE for each group. RESULTS: This study analyzed 46,210 patients' charts, 663 (1.4%) were COP patients. Mean age was statistically similar between groups but there were fewer females in the COP group (26.2% vs 53.2%, p < 0.001). Mean (+/- SD) HEART score was 3.7 (1.4) comparing to 3.1 (1.8, p < 0.001) between COP vs CON groups, respectively. Although more COP patients (54%) had moderate HEART scores (4-6) vs. CON group (35.2%, p < 0.001), rates of 30-day MACE were 1.1% for both groups. HEART score's AUROC was 0.72 for COP and 0.78 for CON groups. AUROC for the Risk Factor among COP patients, which includes cocaine, was poor (0.54). CONCLUSION: This study, which utilized prospective calculated HEART scores, demonstrated that overall performance of the HEART score was reasonable. Specifically, our analysis showed that the rate of 30-day MACE was not affected by cocaine use as a risk factor. We would recommend clinicians to consider the HEART score for this patient group.

Prior electrocardiograms not useful for machine learning predictions of major adverse cardiac events in emergency department chest pain patients.

At the emergency department (ED), it is important to quickly and accurately determine which patients are likely to have a major adverse cardiac event (MACE). Machine learning (ML) models can be used to aid physicians in detecting MACE, and improving the performance of such models is an active area of research. In this study, we sought to determine if ML models can be improved by including a prior electrocardiogram (ECG) from each patient. To that end, we trained several models to predict MACE within 30 days, both with and without prior ECGs, using data collected from 19,499 consecutive patients with chest pain, from five EDs in southern Sweden, between the years 2017 and 2018. Our results indicate no improvement in AUC from prior ECGs. This was consistent across models, both with and without additional clinical input variables, for different patient subgroups, and for different subsets of the outcome. While contradicting current best practices for manual ECG analysis, the results are positive in the sense that ML models with fewer inputs are more easily and widely applicable in practice.

Recurrent events of acute coronary syndrome in young adult patients after Kawasaki disease.

OBJECTIVE: I encountered three adult patients with major coronary artery occlusion after Kawasaki disease in childhood, who had developed again acute coronary syndrome of adults in the peripheral branches, such as the 4th segments, the atrioventricular node artery, and the posterior descending artery, of the right coronary artery. METHODS: I reviewed their clinical course and coronary angiograms. RESULTS: Their age at onset of acute coronary syndrome ranged from 29 to 33 years. The male patient with a previous anteroseptal myocardial infarction in children had a symptomatic occlusion of the branch of the 4th posterior descending artery at 32 years of age. Acute coronary syndrome occurred in the area of 4th atrioventricular node artery in two female patients. The collateral arteries from the circumflex artery to the 4th atrioventricular node arteries were not clearly injected. It was suspected that they had developed bilateral giant aneurysms after acute Kawasaki disease. Two patients had an acute myocardial infarction due to thrombotic occlusion in a giant aneurysm of the right coronary artery or the left anterior descending artery, and one patient had an asymptomatic coronary occlusion of the right coronary artery and left anterior descending artery in children. CONCLUSION: Occlusion of peripheral coronary arteries in adulthood can occur in patients with multi-vessel disease caused by Kawasaki disease. Recurrent events of acute coronary syndrome can occur in adults, although its prevalence may be low. Careful follow-up in adults is also needed in this population.

Association between Immune Checkpoint Inhibitors and Atherosclerotic Cardiovascular Disease Risk: Another Brick in the Wall.

In recent years, immune checkpoint inhibitors have significantly changed the field of oncology, emerging as first-line treatment, either alone or in combination with other regimens, for numerous malignancies, improving overall survival and progression-free survival in these patients. However, immune checkpoint inhibitors might also cause severe or fatal immune-related adverse events, including adverse cardiovascular events. Initially, myocarditis was recognized as the main immune checkpoint inhibitor-related cardiac event, but our knowledge of other potential immune-related cardiovascular adverse events continues to broaden. Recently, preclinical and clinical data seem to support an association between immune checkpoint inhibitors and accelerated atherosclerosis as well as atherosclerotic cardiovascular events such as cardiac ischemic disease, stroke, and peripheral artery disease. In this review, by offering a comprehensive overview of the pivotal role of inflammation in atherosclerosis, we focus on the potential molecular pathways underlying the effects of immune checkpoint inhibitors on cardiovascular diseases. Moreover, we provide an overview of therapeutic strategies for cancer patients undergoing immunotherapy to prevent the development of cardiovascular diseases.

Getting to the HEART of Major Adverse Cardiac Events.

How to cite this article: Samavedam S. Getting to the HEART of Major Adverse Cardiac Events. Indian J Crit Care Med 2024;28(8):724-725.

Age-Related Association between Sex and Postoperative Atrial Fibrillation in Non-Cardiac Surgery Patients: Observational Cohort Study.

Background: Postoperative atrial fibrillation (POAF) is a common complication that has shown conflicting results regarding sex differences. The potential effect of age on this association has not been adequately explored. We hypothesized that younger males would have a higher risk of POAF than females and that this difference would vary by age group. Methods: In this observational cohort study, we enrolled consecutive patients who underwent non-cardiac surgery between January 2011 and June 2019 at our institution and excluded those with preoperative atrial fibrillation and those undergoing sex-specific surgery. We stratified the patients into four groups based on their sex and age: females younger than 50 years, females older than 50 years, males younger than 50 years, and males older than 50 years. The primary outcome was the incidence of POAF. Results: Of the 141,337 patients included in the study, 6414 (4.5%) were treated for POAF. The incidence of POAF was highest in males older than 50 years (7.4%), followed by females older than 50 years (4.6%), males younger than 50 years (2.1%), and females younger than 50 years (1.9%). After adjusting for potential confounding factors, the risk of POAF was significantly increased in all groups compared with females younger than 50 years, with an odds ratio (OR) of 2.43 (95% confidence interval [CI]: 2.17-2.73, p < 0.001) for females older than 50 years, 1.19 (95% CI: 1.05-1.35, p = 0.01) for males younger than 50 years, and 4.39 (95% CI: 3.91-4.94, p < 0.001) for males older than 50 years. The OR for POAF risk according to sex peaked between 60 and 70 years old and decreased gradually thereafter. Conclusions: Our study suggests that sex and age are important factors associated with the risk of POAF in non-cardiac surgery patients and that sex-specific and age-specific risk stratification and interventions might be needed to prevent and manage POAF in non-cardiac surgery patients. Further studies are needed to better understand the underlying mechanisms of sex and age differences in POAF and to develop more targeted and effective interventions to reduce the incidence of this common postoperative complication.

Prognostic Significance of Biventricular and Biatrial Strain in Dilated Cardiomyopathy: Strain Analysis Derived from Cardiovascular Magnetic Resonance.

Background: Dilated cardiomyopathy (DCM) has a poor prognosis and high mortality. The relationship between the deformation capacity of the biatrial and biventricular regions in patients with DCM remains unclear. Methods: This retrospective study used cardiovascular magnetic resonance (CMR) to assess patient enrollment between September 2020 to May 2022. Feature tracking (FT) was used to evaluate biventricular global radial strain (GRS), global circumferential strain (GCS) and global longitudinal strain (GLS). Fast long-axis method was used to evaluate biatrial GLS by analyzing balanced steady-state free precession cine images. The median follow-up period was 362 days (interquartile range: 234 to 500 days). DCM patients were divided into two groups based on the occurrence or non-occurrence of major adverse cardiac event (MACE). The primary endpoint was defined as all-cause death, heart transplantation, and adverse ventricular arrhythmia. The secondary end point included hospitalizations due to heart failure. Cox regression analysis was utilized for variables and Kaplan-Meier survival was utilized for clinical outcomes. Results: There were 124 DCM patients (52.82 ± 12.59 years, 67.74% male) and 53 healthy volunteers (53.17 ± 14.67 years, 52.83% male) recruited in this study. Biventricular GRS, GCS, GLS, and biatrial GLS were significantly impaired in the DCM group compared with the healthy group. In receiver-operating characteristic curve, biatrial GLS and biventricular GRS, GCS, and GLS showed significant prognostic value in predicting MACEs (all p < 0.05). In multivariate Cox regression analysis, left ventricular (LV) GLS offered a significant and independent prognostic value surpassing other CMR parameters in predicting MACE. In Kaplan-Meier analysis, patients with a LV GLS > -4.81% had a significantly higher rate of MACE (Log-rank p < 0.001). Conclusions: LV GLS was independently associated with MACEs in DCM patients by using FT and fast long-axis method derived from CMR. Comprehensive CMR examination including biatrial and biventricular functions should be systematically performed, to understand disease characteristics, as well as improve the risk stratification and therapeutic management for patients with DCM.

Assessment of the Prognostic Value of MRI Left Ventricular Global Function Index (LVGFI) in Patients With End-Stage Renal Disease Under Maintenance Dialysis.

BACKGROUND: Left ventricular global function index (LVGFI) integrates LV volumetric and functional parameters. In patients with end-stage renal disease (ESRD), cardiac injury manifests as LV hypertrophy and dysfunction. However, the prognostic value of LVGFI in this population remains unclear. PURPOSE: To investigate the association of LVGFI with major adverse cardiac events (MACE) in patients with ESRD. STUDY TYPE: Prospective. POPULATION: One hundred fifty-eight ESRD patients (mean age: 54.1 ± 14.4 years; 105 male) on maintenance dialysis. FILED STRENGTH/SEQUENCE: 3.0 T, balanced steady-state free precession (bSSFP) cine and modified Look-Locker inversion recovery (MOLLI) sequences. ASSESSMENT: LV volumetric and functional parameters were determined from bSSFP images. LVGFI was calculated as the ratio of stroke volume to global volume and native T1 was determined from MOLLI T1 maps. MACE was recorded on follow up. Models were developed to predict MACE from conventional risk factors combined with LVGFI, GLS, native T1, and LV mass index (LVMI), respectively. Subgroup analyses were further performed in participants with LVEF above median. STATISTICAL TESTS: Cox proportional hazard regression and log-rank test were used to investigate the association between LVGFI and MACE. The predictive models were evaluated and compared using Harrell's C-statistics and DeLong tests. A P value <0.05 was considered statistically significant. RESULTS: Thirty-four MACE occurred during the median follow-up period of 26 months. The hazard of MACE increased by 114% for each 10% decrease in LVGFI in univariable analysis. The predictive model consisting of LVGFI (C-statistic: 0.724) had significantly better predictive performance than the others (all P < 0.001). These results were consistent in patients (N = 79) with LVEF > median (63.54%). DATA CONCLUSION: LVGFI is a novel marker for MACE risk stratification in patients with ESRD and was better able to predict MACE than native T1 mapping and GLS. EVIDENCE LEVEL: 2 TECHNICAL EFFICACY: Stage 3.

Residual risks and evolving atherosclerotic plaques.

Atherosclerotic disease of the coronary and carotid arteries is the primary global cause of significant mortality and morbidity. The chronic occlusive diseases have changed the epidemiological landscape of health problems both in developed and the developing countries. Despite the enormous benefit of advanced revascularization techniques, use of statins, and successful attempts of targeting modifiable risk factors, like smoking and exercise in the last four decades, there is still a definite "residual risk" in the population, as evidenced by many prevalent and new cases every year. Here, we highlight the burden of the atherosclerotic diseases and provide substantial clinical evidence of the residual risks in these diseases despite advanced management settings, with emphasis on strokes and cardiovascular risks. We critically discussed the concepts and potential underlying mechanisms of the evolving atherosclerotic plaques in the coronary and carotid arteries. This has changed our understanding of the plaque biology, the progression of unstable vs stable plaques, and the evolution of plaque prior to the occurrence of a major adverse atherothrombotic event. This has been facilitated using intravascular ultrasound, optical coherence tomography, and near-infrared spectroscopy in the clinical settings to achieve surrogate end points. These techniques are now providing exquisite information on plaque size, composition, lipid volume, fibrous cap thickness and other features that were previously not possible with conventional angiography.

Potential utility of B-type natriuretic peptides in secondary prevention following percutaneous coronary intervention in remote communities of Western Australia.

INTRODUCTION: A third of all acute coronary events that present in the Australian population occur in patients with established coronary heart disease. This study assessed the prognostic value of combined B-type natriuretic peptides (BNP) measurement and quantitative myocardial perfusion scan (MPS) data for cardiac events (CE). MATERIAL AND METHODS: This retrospective cohort study involved 133 patients from rural Western Australia. The cut-off for normality was 6.0 for qualitative summed difference scores (SDS) of MPS and 400 pg/mL for BNP. RESULTS: Patients with no CE had a mean SDS and BNP (1.52 with a 95% CI of 0.34 to 2.69), (175.9 with a 95% CI of 112.7-239.1) that was lower than patients with CE (6.54 with 95% CI 4.18-9.89) (P = 0.0003), (669.1 with 95% CI 543.9-794.3) (P < 0.0001). The sensitivity and specificity of combined testing for predicting CE respectively were 79.6% and 86.3% for SDS, 84.6% and 94.1% for BNP, and 100% and 92.7% for SDS and BNP combined. DISCUSSION AND CONCLUSION: Elevated BNP is marginally superior to MPS in predicting CEs in patients who have previously undergone percutaneous coronary intervention (PCI); however, MPS can identify the region of myocardium most at risk. Routine BNP monitoring in this subgroup may serve as secondary prevention by identifying subclinical disease.

Rural communities are disproportionately affected by preventable coronary heart disease-related deaths and access to cardiac imaging techniques can be infrequent or unavailable.Secondary prevention strategies can reduce hospital readmissions and contribute to improving the management of chronic conditions.This study demonstrated that elevated B-type natriuretic peptides levels were marginally superior to myocardial perfusion scans in predicting cardiac events in patients with prior percutaneous coronary intervention.Monitoring BNP levels in rural patients with prior percutaneous coronary interventions is a relatively non-invasive and inexpensive, and may lead to improved risk estimation, identify the subclinical disease and provoke further investigation as clinically appropriate.

Prognostic Value of Novel Natriuretic Peptide Index After Percutaneous Coronary Intervention.

BACKGROUND: The predictive value of both atrial natriuretic peptide (ANP) and B-type natriuretic peptide (BNP) is well known. This study evaluated the prognostic value of a novel natriuretic peptide index (NPI) combining ANP and BNP. Methods and Results: This study included 849 consecutive patients with coronary artery disease who underwent successful percutaneous coronary intervention (PCI). Patients were followed up clinically for up to 3 years or until the occurrence of major adverse cardiac events (MACE). The primary endpoint was a composite of all-cause death and non-fatal myocardial infarction. The NPI (pg/mL) was defined as √ANP×BNP. MACE occurred in 73 patients (8.6%) during the follow-up period. Receiver operating characteristic curve analysis showed the highest area under the curve for NPI (0.779) compared with ANP and BNP (0.773 and 0.755, respectively). A risk analysis of MACE occurrence adjusted for the multivariable model showed the highest hazard ratio (HR) for NPI (1.33; 95% confidence interval [CI] 1.18-1.51; P<0.001) compared with ANP and BNP (HR 1.25 [95% CI 1.13-1.39] and 1.30 [95% CI 1.13-1.49], respectively; P<0.001). The NPI was a significant independent predictor of MACE, among other clinical parameters, in the multivariable analysis. CONCLUSIONS: Compared with ANP and BNP, the NPI was more effective in predicting future adverse events after PCI.

Performance analysis considering endpoints for three accelerated diagnostic protocols for chest pain.

INTRODUCTION: The modified accelerated diagnostic protocol (ADP) to assess patients with chest pain symptoms using troponin as the only biomarker (mADAPT), the History, ECG, Age, Risk factors, and Troponin (HEART) pathway, and the Emergency Department Assessment of Chest Pain Rule (EDACS)-ADP, are the three most well-known ADPs for patients with chest pain. These ADPs define major adverse cardiac event (MACE) as components of acute myocardial infarction, revascularization, and death; unstable angina is not included as an endpoint. METHODS: We performed a single-center prospective observational study comparing the performance of these 3 ADPs for patients with 30-day MACE with and without unstable angina. We hypothesized that these ADPs will have high sensitivities for MACE without unstable angina, a definition used for score derivation studies. However, when unstable angina is included in the MACE, their performances would be lower than the acceptable rate of >99% sensitivity. RESULTS: A total of 1,214 patients were included in the analysis. When unstable angina was not included in the endpoint, sensitivities for MACE were 99.1% (95% confidence interval [CI]: 96.7-99.9%), 99.5% (95% CI: 97.4-100%), and 100% (95% CI: 98.3-100%) for mADAPT, EDACS-ADP, and HEART pathway, respectively. The HEART pathway had the highest proportion of patients classified as low risk (39.2%, 95% CI: 35.8-42.9%), followed by EDACS-ADP (31.3%, 95% CI: 28.2-34.6%) and mADAPT (29.3%, 95% CI: 26.4-32.5%). However, when unstable angina was included in the MACE, sensitivities were 96.6% (95% CI: 94.4-98.1%) for mADAPT, 97.3% (95% CI: 95.3-98.6%) for EDACS-ADP, and 97.3% (95% CI: 95.3-98.6%) for the HEART pathway, respectively. There were 15 false-negative cases with mADAPT, and 12 false-negative cases each for EDACS-ADP and HEART pathway. CONCLUSION: All three ADPs-mADAPT, EDACS-ADP, and HEART pathway-were similarly accurate in their discriminatory performance for the risk stratification of ED patients presenting with possible ACS when unstable angina was not included in the endpoint. The HEART pathway showed the best combination of sensitivity and proportion of patients that can be classified as safe for early discharge. However, when unstable angina was added to the endpoint, all three ADPs did not show appropriate safety levels and their performances were lower than the acceptable risk of MACE.

Circulating tumor necrosis factor-α, interleukin-1ß, and interleukin-17A estimates increased major adverse cardiac event risk in acute myocardial infarction patients.

BACKGROUND: Inflammatory cytokines are implicated in the development of atherosclerosis and cardiomyocyte injury during acute myocardial infarction (AMI). This study aimed to investigate the correlation of eight common inflammatory cytokines with major adverse cardiac event (MACE) risk and further establish a prognostic model in AMI patients. METHODS: Serum samples of 210 AMI patients and 20 angina pectoris patients were, respectively, collected at admission, to detect tumor necrosis factor-alpha (TNF-α), interleukin (IL)-1ß, IL-6, IL-8, IL-10, IL-17A, vascular cell adhesion molecule-1 (VCAM-1), and intercellular adhesion molecule 1 (ICAM-1) via enzyme-linked immunosorbent assay. RESULTS: TNF-α, IL-6, IL-8, IL-17A, VCAM-1, and ICAM-1 were elevated (all p < 0.050); IL-10 (p = 0.009) was declined; IL-1ß (p = 0.086) was not varied in AMI patients compared with angina pectoris patients. TNF-α (p = 0.008), IL-17A (p = 0.003), and VCAM-1 (p = 0.014) were elevated in patients with MACE occurrence compared to patients without MACE occurrence; meanwhile, they possessed a relatively good value for identifying MACE risk via receiver-operating characteristic (ROC) analysis. Subsequent multivariate logistic regression analysis revealed that the independent risk factors for MACE contained TNF-α (odds ratio (OR) = 1.038, p < 0.001), IL-1ß (OR = 1.705, p = 0.044), IL-17A (OR = 1.021, p = 0.009), history of diabetes mellitus (OR = 4.188, p = 0.013), history of coronary heart disease (OR = 3.287, p = 0.042), and symptom-to-balloon time (OR = 1.064, p = 0.030), whose combination disclosed a satisfying prognostic value for MACE risk (area under the curve: 0.877, 95% CI: 0.817-0.936). CONCLUSION: Elevated levels of serum TNF-α, IL-1ß, and IL-17A independently correlated with MACE risk in AMI patients, which perhaps provide novel auxiliary for AMI prognostic prediction.

Evaluation of Risk of Cardiac or Cerebrovascular Events in Romosozumab Users Focusing on Comorbidities: Analysis of the Japanese Adverse Drug Event Report Database.

Background: Romosozumab is associated with an increased risk of cardiac or cerebrovascular events. Identifying the risk factors for these events could contribute to the safe use of romosozumab. Objective: This study aimed to investigate risk factors for cardiac or cerebrovascular events in romosozumab users. Methods: First, disproportionality analysis was performed to compare the frequency of cardiac or cerebrovascular events, using data from the Japanese Adverse Drug Event Report database. Next, multivariate logistic analysis was performed to investigate risk factors for cardiac or cerebrovascular events in romosozumab users. Results: In total, 859 romosozumab users were identified. A disproportionality of both cardiac and cerebrovascular events was observed in only romosozumab users. Multivariate logistic analysis revealed that the risk of cardiac events in romosozumab users was significantly increased in patients with cardiac disease (odds ratio [OR]: 5.9, 95% confidence interval [CI] 3.5-9.9; P < 0.01) and hypertension (OR: 1.6, 95% CI 1.0-2.7; P = 0.047). In addition, the risk of cerebrovascular events in romosozumab users was significantly increased in the presence of cerebrovascular disease (OR: 2.7, 95% CI 1.2-6.2; P = 0.02) and hypertension (OR: 2.6, 95% CI 1.7-3.9; P < 0.01). Conclusion: Our findings suggest that hypertension may increase the risk of cardiac or cerebrovascular events in romosozumab users. Although additional studies are needed to assess other associated factors, these findings may contribute to the appropriate use of romosozumab and limit adverse events.

Association of NFKB1 gene rs28362491 mutation with the occurrence of major adverse cardiovascular events.

BACKGROUND: Several studies have reported that NFKB1 gene rs28362491 polymorphism was associated with susceptibility to coronary heart disease in populations of different genetic backgrounds. To date, there have been no studies on the association between NFKB1 gene rs28362491 polymorphism and the occurrence of major adverse cardiac and cerebrovascular event (MACCE). The present study was to explore the relationship between NFKB1 gene rs28362491 polymorphism and MACCEs to investigate whether identifying NFKB1 gene polymorphism is beneficial to evaluating MACCE risks and patients' prognoses. METHODS: We recruited 257 high-risk of cardiovascular disease patients with chest pain or precordial discomfort. The SNPscan™ were used to analyze the NFKB1 gene rs28362491 polymorphism. All patients were followed up in the clinic or by telephone interview for MACCEs. RESULTS: During the followed-up time (mean: 30.1 months) 49 patients had MACCEs (19.1%). Patients with the different genotypes of NFKB1 rs28362491 had different incidence rate of MACCE. The incidence of MACCE in patients carried II, ID and DD genotype was 16.5%, 15.9%, 32.6%, respectively. Log-rank analysis showed that the survival rate in patients with NFKB1 rs28362491 DD genotype was much lower than that in II or ID genotype carriers (P = 0.034). After excluding the influence of traditional risk factors of MACCEs, Cox regression showed that the DD genotype carriers had 2.294-fold relative risk of MACCEs comparing with patients carried II or ID genotype. CONCLUSION: The NFKB1 gene rs28362491 mutant was an independent predictor of worse long-term prognosis for MACCEs. Therefore, identifying NFKB1 gene rs28362491 mutant may be used as a good way for guiding the standardized management of patients with high-risk of cardiovascular diseases.

Reconsidering treatment guidelines for acute myocardial infarction during the COVID-19 pandemic.

BACKGROUND: COVID-19 affects healthcare resource allocation, which could lead to treatment delay and poor outcomes in patients with acute myocardial infarction (AMI). We assessed the impact of the COVID-19 pandemic on AMI outcomes. METHODS: We compared outcomes of patients admitted for acute ST-elevation MI (STEMI) and non-STEMI (NSTEMI) during a non-COVID-19 pandemic period (January-February 2019; Group 1, n = 254) and a COVID-19 pandemic period (January-February 2020; Group 2, n = 124). RESULTS: For STEMI patients, the median of first medical contact (FMC) time, door-to-balloon time, and total myocardial ischemia time were significantly longer in Group 2 patients (all p < 0.05). Primary percutaneous intervention was performed significantly more often in Group 1 patients than in Group 2 patients, whereas thrombolytic therapy was used significantly more often in Group 2 patients than in Group 1 patients (all p < 0.05). However, the rates of and all-cause 30-day mortality and major adverse cardiac event (MACE) were not significantly different in the two periods (all p > 0.05). For NSTEMI patients, Group 2 patients had a higher rate of conservative therapy, a lower rate of reperfusion therapy, and longer FMC times (all p < 0.05). All-cause 30-day mortality and MACE were only higher in NSTEMI patients during the COVID-19 pandemic period (p < 0.001). CONCLUSIONS: COVID-19 pandemic causes treatment delay in AMI patients and potentially leads to poor clinical outcome in NSTEMI patients. Thrombolytic therapy should be initiated without delay for STEMI when coronary intervention is not readily available; for NSTEMI patients, outcomes of invasive reperfusion were better than medical treatment.

CPAP telemonitoring can track Cheyne-Stokes respiration and detect serious cardiac events: The AlertApnée Study.

BACKGROUND AND OBJECTIVE: Case reports have suggested that continuous positive airway pressure (CPAP) telemonitoring can detect the onset of acute cardiac events such as decompensated heart failure (HF) or atrial fibrillation through an increase in the apnoea-hypopnoea index (AHI) and onset of Cheyne-Stokes Respiration (CSR). This study addressed whether long-term remote CPAP treatment telemonitoring revealing CSR can help detect serious cardiac events (SCEs) in obstructive sleep apnoea (OSA) patients. METHODS: This monocentric prospective cohort study included adults receiving CPAP therapy for OSA with daily telemonitoring. Any sudden increase in AHI generated an alert for the home healthcare provider to download CPAP data to identify CSR. A medical consultation was scheduled if CSR was detected. RESULTS: We included 555 adults (412 men; 57% with known cardiovascular comorbidities). During the 1-year follow-up, 78 CSR episodes were detected in 74 patients (CSR+). The main conditions associated with incident CSR were HF (24 patients [30.8%]), ventilatory instability (21, 26.9%), leaks (13, 16.7%), medications inducing central apnoeas (baclofen, ticagrelor, opioids) (7, 9.0%), arrhythmias (6, 7.7%) and renal failure (2, 2.6%). Fifteen (20.3%) CSR+ patients had a confirmed SCE. In univariable analysis, a CSR episode increased the risk of an SCE by 13.8-fold (5.7-35.6) (p < 0.0001), with an adjusted OR of 5.7 (2.0-16.8) in multivariable analysis. CONCLUSION: Long-term telemonitoring of patients on CPAP treatment can alert CSR episodes and allows early detection of SCEs in patients with or without known cardiac comorbidities.