Major Adverse Cardiovascular Events Events Research Articles

Machine learning approach for detection of MACE events within clinical trial data

ABSTRACT Randomized controlled trials (RCTs) are the gold standard for clinical research but may not accurately reflect the impact of medicines in real-world settings. Supplementing RCTs with insights from real-world data (RWD) can address known limitations by including more diverse patient populations, additional types of sites-of-care, and practices more representative of the care most people receive. One current challenge in using RWD is the lack of an algorithmic approach to identifying outcomes. To address this, machine learning models for identifying a frequently used outcome, Major Adverse Cardiovascular Events (MACE), were developed in Clinical Trial Data (CTD). Anonymized CTD sourced from the Medidata Enterprise Data Store were used to develop model features on the condition that they would be useful for labelling MACE events and that they could also be found in RWD. These features were used to train three random forest models to identify each component of 3-point MACE in a patient’s clinical trial journey. Performance metrics for the models are presented (recall = 0.72 [0.07], precision = 0.68 [0.12] - mean, [SD]) along with the top contributing features. We show that the models can be tuned specifically to replicate the adjudication panels’ results and present a cost–benefit analysis for deploying such models in clinical trial settings. We demonstrate the viability of using advanced algorithms for identifying clinical outcomes in prospective clinical trials. Deployment of such models could reduce the resources required to conduct RCTs. Extending such models to RWD would facilitate approval of pragmatic clinical trials for regulatory submissions.

Abstract 4135968: Radiomic features of skeletal muscle on prostate T1-Weighted MRI associated with MACE outcomes in prostate cancer patients undergoing hormonal therapy

Background: Patients with high-risk prostate cancer (PC) who undergo hormonal therapy(HT) frequently die of major adverse cardiovascular events (MACE). Skeletal muscle on abdominal T1-weighted MRI (T1W) has been shown to be associated with cardiovascular fitness. Aims: To quantify heterogeneity associated with skeletal muscle tissue composition on prostate MRI patients undergoing HT using computationally derived radiomic features and identify their association with MACE. Methods: Cohort of N=58 men diagnosed with PC who underwent a 3 Tesla pre-treatment multi-parametric MRI followed by HT and followed up for MACE events were identified. MACE is defined as a composite of cardiovascular death, atrial fibrillation, myocardial infarction, ischemic stroke, heart failure, coronary artery disease, and peripheral vascular disease. Regions of interest (ROI) of skeletal muscle, including the obturator externus, pectineus, and the adductor group of muscles, were delineated on axial T1W under the guidance of an experienced radiologist. A set of 120 radiomic features, including gray level statistics, co-occurrence, wavelet, and texture energy-based features, were extracted within the ROI which quantifies underlying subvisual texture-based heterogeneity. Radiomics associated with MACE events were identified using the Wilcoxon rank-sum test and univariate Cox-regression (p<0.05). Results: Of the N=58 patients included in this study, 18 experienced MACE. The most common MACE event was AF (8.6%). Median-time-to-MACE event was 7.3 years (6.2-8.2). 3 radiomic features (Table 1) quantifying the heterogeneity of skeletal muscle on prostate T1W were observed to be associated with MACE. Specifically, we observe that first order features have a lower response and wavelet features have a lower response in MACE patients which suggests a higher degree of local deformations and heterogeneity in skeletal tissue compared to non-MACE patients. Conclusions: Results from our study suggest that radiomics quantified texture characteristics of skeletal muscle tissue may indicate cardiovascular fitness, reflecting the likelihood of experiencing MACE following initiation of HT in PC men. Pre-treatment identification of PC patients at high risk of MACE may allow for alternative treatment options improving cardiovascular outcomes. Future studies will involve exploring larger, multi-site cohorts and machine learning modeling to determine cardiovascular risk.

Abstract 4137855: Hybrid Coronary Revascularization versus Traditional Coronary Artery Bypass Grafting for Left Main Disease

Background: The current guideline-recommended intervention for left main (LM) disease is coronary artery bypass grafting (CABG). Hybrid coronary revascularization (HCR) combines robotic coronary artery bypass and percutaneous coronary intervention (PCI) and offers a less invasive approach for patients with LM and multivessel coronary artery disease. We aim to compare clinical outcomes at 30 days, 6 months and 1 year between HCR and CABG in patients with LM disease. Methods: We retrospectively screened 761 patients who underwent bypass for LM disease between 2019 and 2023 at a single institution. A total of 118 patients who underwent either HCR (n=59) or CABG (n=59) were included after propensity matching for baseline characteristics. The primary endpoint was major adverse cardiovascular events (MACE), defined as death, myocardial infarction, repeat revascularization and stroke, at 30 days, 6 months and 1 year, which was assessed using chi-squared tests. Secondary outcomes are individual components of MACE at 30 days, 6 months and 1 year. Kaplan-Meier curves were used to visualize the difference in 1-year cumulative MACE-free survival across groups coupled with a log-rank test. Results: The mean age was 68.93±11 years for HCR patients and 68.41±10.11 years for CABG patients (p=0.394). SYNTAX score was high (> 33) for 49.1% of HCR patients and 67.3% of CABG patients (p=0.15). Hospital length of stay was shorter for HCR compared to CABG (4.07 ± 1.21 days vs. 7.58 ± 7.71 days, p<0.001). MACE events were significantly lower in the HCR group at 30 days (0% vs 10.2%; p=0.01), 6 months (0% vs 17%; p=0.002) and 1 year (2.4% vs 20.5%; p=0.01). The cumulative MACE-free survival at 1 year was significantly higher in the HCR group (p=0.007). There were no significant differences in secondary outcomes at any time point with the exception of lower repeat revascularization at 6 months in the HCR group (0% vs 10.9%; p=0.02). Conclusion: This retrospective study demonstrates that HCR is a viable alternative to CABG for LM disease. While randomized clinical trial data is still needed, this less invasive approach is a promising treatment strategy for patients with high surgical risk.

Balancing the Interactions: Assessing Antiplatelet and Antiretroviral Therapy Drug-Drug Interactions in People Living with HIV.

The clinical effect of drug-drug interactions (DDIs) between antiplatelets and antiretrovirals (ART) on bleeding, thrombosis, and other major adverse cardiovascular events (MACE) is unknown. The objective of this retrospective study was to assess the incidence of DDI at P2Y12 inhibitor (P2Y12inh) initiation and the effect of DDI on patient outcomes. Adult people living with human immunodeficiency virus (PLWH; HIV) receiving ART newly initiated on an oral P2Y12inh were included. The primary outcome was the incidence of DDI between ART and P2Y12inh at P2Y12inh initiation. Secondary outcomes included bleeding events, MACE, and switches in P2Y12inh. There were 149 PLWH included, of these, 119 (80%) were initiated on clopidogrel, 23 (15%) on ticagrelor, and 7 (5%) on prasugrel. 93 PLWH (60%) had a DDI at time of P2Y12inh initiation, with highest incidence in the clopidogrel group (n=84, 71%), followed by ticagrelor (n=9, 39%) and none with prasugrel. Within 1 year, MACE occurred in 12 PLWH, with DDI present at the time of 4 events. There were 29 bleeding events occurring within 1 year, including 17 events with DDI at time of event. However, 88% of DDI in patients with bleeding events were expected to decrease the efficacy of P2Y12inh. Though we observed high incidence of DDI between P2Y12inh and ART in PLWH, MACE and bleeding events at 1 year did not correlate with DDI. It remains unknown if DDI presence at P2Y12inh initiation with ART causes clinical outcomes of concern, or if underlying platelet reactivity in PLWH is associated with these events.

Abstract 4137991: Association of the 2022 AHA/ACC/HFSA Heart Failure Staging and Cardiovascular and Kidney Outcomes in Patients with Diabetes and Kidney Disease: A Secondary Analysis of the SCORED Trial

Introduction: The 2022 AHA/ACC/HFSA heart failure (HF) classification newly incorporates cardiac biomarkers to identify patients at risk of HF. Research Question: Given shared risk factors between HF and other cardiorenal events, the HF stages may also guide prognosis and management of cardiovascular (CV) and kidney-related events beyond HF. Aims: Examine the association of HF stage with CV and kidney events. Methods: SCORED was a randomized trial in diabetes with kidney disease comparing sotagliflozin (sota) v. placebo on CV death, hospitalizations for HF, and urgent HF visits. SCORED participants were grouped by HF stage post hoc . Stage A: No HF, normal cardiac biomarkers (NT-proBNP; <125 pg/mL, hs-cTnT; <14 ng/L) and normal cardiac structure/function by echocardiography. Stage B (pre-HF): No HF but elevated NTproBNP, hsTNT or abnormal echocardiography. Stage C/D: symptomatic HF. Endpoints of interest included the primary composite endpoint (CV death and HF-related events), major adverse CV events (MACE), and kidney-related composites (See Figure caption). Using Cox regression, we examined the association between HF stage and these endpoints, and whether the effect of sota v. placebo varied by HF stage. Results: There were 741 patients in stage A, 6560 in stage B (pre-HF) and 3283 in stage C/D (established HF). The mean NTproBNP and hs-cTnT increased with HF stage. Stepwise increases in HF stage were associated with a 2-4 fold higher incidence of the primary, MACE and kidney endpoints in the placebo group, although the incidence of the kidney-specific composite was similar in stage B and C/D (Figure). The relative risk reduction with sota v. placebo for all endpoints was similar irrespective of HF stage (p-interaction>0.05), with higher absolute benefit in each HF stage (Figure). The absolute benefit for the kidney-specific endpoint was comparable for stage B and C/D. Conclusions: Increasing HF stage is associated with higher risk of HF, MACE, and kidney events, but the risk of kidney events is similar in stage B (pre-HF) and stage C/D (established HF). Sota has similar relative benefits for all endpoints, irrespective of HF stage, with a corresponding increase in absolute benefits at higher stages.

Long-Term Impact of Pregnancy on Clinical Outcomes in Individuals With Hypertrophic Cardiomyopathy

BackgroundThe effect of pregnancy on individuals with hypertrophic cardiomyopathy (HCM) is not well investigated. ObjectivesThe purpose of this study was to assess the impact of pregnancy on all-cause mortality and clinical outcomes among individuals with HCM. MethodsUsing the TriNetX research network, we identified individuals within reproductive age (≥18-45 years) with a diagnosis of HCM between 2012 and 2022 (n = 10,936). Patients were stratified based on pregnancy history into 2 groups a) those with a history of pregnancy/high-risk pregnancy supervision and b) those without a history of pregnancy or subsequent antenatal/pregnancy supervision encounters throughout the study period. Propensity score matching resulted in 3,399 patients in each cohort. The primary outcome was all-cause mortality. Secondary outcomes include a composite of arrhythmic events (defined as sudden cardiac death, appropriate shocks, sustained ventricular tachycardia/ventricular fibrillation), major adverse cardiovascular events (MACE), and acute heart failure exacerbation during 10 years of follow-up. ResultsPregnancy in patients with HCM was associated with a comparable risk of all-cause mortality (adjusted OR: 0.89; 95% CI: 0.7-1.14; P = 0.37) at 10-year follow-up. There was no difference in MACE (adjusted OR: 1.02; 95% CI: 0.85-1.22; P = 0.80) and arrhythmic events (adjusted OR: 0.93; 95% CI: 0.73-1.18; P = 0.55) between both groups. In subgroup analysis of obstructive HCM, the findings were similar between both pregnancy and no pregnancy groups. ConclusionsPregnancy in individuals with HCM was not associated with a higher risk of adverse outcomes at long-term follow-up. Further efforts are warranted to better understand the short-term outcomes in this high-risk population.

Predicting major adverse cardiac events using radiomics nomogram of pericoronary adipose tissue based on CCTA: A multi-center study.

The evolution of coronary atherosclerotic heart disease (CAD) is intricately linked to alterations in the pericoronary adipose tissue (PCAT). In recent epochs, characteristics of the PCAT have progressively ascended as focal points of research in CAD risk stratification and individualized clinical decision-making. Harnessing radiomic methodologies allows for the meticulous extraction of imaging features from these adipose deposits. Coupled with machine learning paradigms, we endeavor to establish predictive models for the onset of major adverse cardiovascular events (MACE). To appraise the predictive utility of radiomic features of PCAT derived from coronary computed tomography angiography (CCTA) in forecasting MACE. We retrospectively incorporated data from 314 suspected or confirmed CAD patients admitted to our institution from June 2019 to December 2022. An additional cohort of 242 patients from two external institutions was encompassed for external validation. The endpoint under consideration was the occurrence of MACE after a 1-year follow-up. MACE was delineated as cardiovascular mortality, newly diagnosed myocardial infarction, hospitalization (or re-hospitalization) for heart failure, and coronary target vessel revascularization occurring more than 30days post-CCTA examination. All enrolled patients underwent CCTA scanning. Radiomic features were meticulously extracted from the optimal diastolic phase axial slices of CCTA images. Feature reduction was achieved through a composite feature selection algorithm, laying the groundwork for the radiomic signature model. Both univariate and multivariate analyses were employed to assess clinical variables. A multifaceted logistic regression analysis facilitated the crafting of a clinical-radiological-radiomic combined model (or nomogram). Receiver operating characteristic (ROC) curves, calibration, and decision curve analyses (DCA) were delineated, with the area under the ROC curve (AUCs) computed to gauge the predictive prowess of the clinical model, radiomic model, and the synthesized ensemble. A total of 12 radiomic features closely associated with MACE were identified to establish the radiomic model. Multivariate logistic regression results demonstrated that smoking, age, hypertension, and dyslipidemia were significantly correlated with MACE. In the integrated nomogram, which amalgamated clinical, imaging, and radiomic parameters, the diagnostic performance was as follows: 0.970 AUC, 0.949 accuracy (ACC), 0.833 sensitivity (SEN), 0.981 specificity (SPE), 0.926 positive predictive value (PPV), and 0.955 negative predictive value (NPV). The calibration curve indicated a commendable concordance of the nomogram, and the decision curve analysis underscored its superior clinical utility. The integration of radiomic signatures from PCAT based on CCTA, clinical indices, and imaging parameters into a nomogram stands as a promising instrument for prognosticating MACE events.

Inappropriate dosing of direct oral anticoagulants in patients with atrial fibrillation undergoing percutaneous coronary intervention

Abstract Background Underdose (inappropriate low-dose) of direct oral anticoagulants (DOAC) is sometimes prescribed due to concerns of bleeding risk in patients with atrial fibrillation (AF). In AF patients with coronary artery disease requiring percutaneous coronary intervention (PCI), careful treatment is required to prevent bleeding events because of intensive antithrombotic therapy with a combination of oral anticoagulants and antiplatelet agents. Purpose The purpose of this study was to investigate the prevalence of underdose of DOAC and its impact on clinical outcomes in AF patients with coronary artery disease undergoing PCI. Methods This multicenter observational cohort study enrolled patients with AF on DOAC undergoing PCI between January 2015 and March 2021 at 15 institutions. Appropriateness of DOAC dose was determined according to the manufacturer's labeling recommendations in Japan. Clinical outcomes within 1 year, including major adverse cardiovascular events (MACE), all-cause mortality, ischemic stroke, and major bleeding events, were evaluated. Results Of 630 patients enrolled, 168 patients (26.7%) received underdose, 227 (36.0%) received appropriate low-dose, 213 (33.8%) received appropriate standard-dose, and 22 (3.5%) received overdose. Because of the extremely small number of patients in the overdose group, the primary analysis of the present study was a comparison between the underdose group (n=168) and the appropriate dose group (appropriate low-dose and standard-dose groups) (n=440). Although the incidence of MACE, all-cause mortality, and major bleeding events was not significantly different between the 2 groups (log-rank p=0.872, p=0.170, and p=0.725), ischemic stroke more frequently occurred in the underdose group compared with the appropriate dose group (log-rank p=0.010) (Figure 1). The multivariable Cox regression analysis determined underdose of DOAC as an independent predictor for ischemic stroke (adjusted HR 3.288, 95% CI: 1.189-9.088, p=0.022). Conclusions Compared with appropriate dose of DOAC, underdose was associated with a higher incidence of ischemic stroke, despite no significant difference in MACE, all-cause mortality, and major bleeding events, in AF patients undergoing PCI.Figure 1

Comparison of cardiovascular outcomes in patients with diabetes treated with tirzepatide versus semaglutide: a multi-institutional analysis

Abstract Introduction Glucagon-like-peptide-1 (GLP-1) receptor agonists have been demonstrated to have cardiovascular benefits in patients with diabetes. Two of the most prescribed medications in this class are tirzepatide and semaglutide. Tirzepatide is a dual glucose-dependent insulinotropic polypeptide and GLP-1 receptor agonist, while semaglutide is a selective GLP-1 receptor agonist. Tirzepatide and semaglutide have previously been directly compared to assess efficacy in glycemic control as the primary endpoint. However, there is limited data directly comparing cardiovascular outcomes between the two medications in patients with diabetes. This retrospective cohort study compares the incidence of major adverse cardiovascular events (MACE) in patients with diabetes treated with tirzepatide or semaglutide. Purpose The purpose of this study is to identify differences in cardiovascular outcomes between patients with diabetes treated with tirzepatide as compared to semaglutide. Materials and Methods The TriNetX research network was used for this study. Two patient cohorts were generated using International Classification of Disease 10 (ICD-10) codes and medication codes in the TriNetX system. Both cohorts of patients had a history of diabetes (E08-E13) and no prior history of cerebral vascular accident (I63) or myocardial infarction (I21). One cohort received semaglutide and the other tirzepatide. Each cohort was prohibited from receiving the other agent. The cohorts were balanced for age, race, gender, and ethnicity by propensity score matching and the greedy nearest neighbor algorithm resulting in 36,212 patients in each arm. They were then evaluated for the 3-year outcomes of major adverse cardiovascular events (myocardial infarction, cerebral vascular accident, and death). Results Tirzepatide was associated with statistically significantly fewer MACE outcomes compared to semaglutide for each of the individual endpoints as well as the overall composite endpoint over the 3 year follow up period. Table 1. MACE events for semaglutide and tirzepatide. Table 2. Relative risks for semaglutide MACE endpoints compared to tirzepatide. Conclusions In this retrospective cohort study, tirzepatide was associated with a lower incidence of major adverse cardiovascular events compared to semaglutide in patients with diabetes. These findings suggest that tirzepatide offers superior cardiovascular protection for primary prevention compared to semaglutide and warrant further investigation in future studies and clinical trials.Table 1Table 2

Arterial stiffness for predicting major adverse cardiovascular events in post-infarcted patients

Abstract Introduction According to recent 2021 ESC prevention guidelines arterial stiffness (aortic pulse wave velocity –PWV, augmentation index - Aix) predicts future major adverse cardiovascular events (MACE). Both parameters have a prognostic relevance in different patient population (hypertension, diabetes, chronic kidney disease), however in post-infarcted, very high cardiovascular risk population the exact prognostic value for PWV and Aix needs to be clarify. Purpose We evaluated PWV and Aix cut-off values for MACE prediction and validated the prognostic relevance of high stiffness parameters in post-infarcted patients. Methods Oscillometric based pulse wave analysis method (Arteriograph) was applied for calculating arterial stiffness. We aimed to evaluate PWV and Aix cut-off values for predicting MACE (comprising all-cause death, non-fatal myocardial infarction, ischemic stroke, hospitalization for heart failure and coronary revascularization) in post-infarcted, very high cardiovascular risk patient population. 114 patients (89 male, average age: 62,5±10,5 years) were investigated in this long term, median 16,2 (IQR: 6,5-17,4) years follow-up study. Results Strong, significant correlation was found between PWV and Aix values (Spearman rho: 0,648, p<0,001). Totally 140 MACE events occurred during the 16,2 years follow-up period. Optimized PWV and Aix cut-off values for MACE prediction were calculated (PWV: 9,84 m/s, AUC: 0,754 (95% CI: 0,66-0,85), p<0,001; Aix: 34,8 %, AUC: 0,67 (95% CI: 0,57-0,77), p<0,05) by ROC analysis (Figure 1.). Kaplan-Meier analysis in both parameters showed a significantly lower event-free survival in case of high PWV and Aix values (p<0,05; Figure 2.). Multivariate Cox regression analysis revealed PWV and Aix as an independent predictor of MACE (PWV HR: 1,32 (95% CI: 1,15-1,53), p<0,001; Aix HR:1,04 (95% CI: 1,01-1,08), p<0,05). Conclusions Arterial stiffness, particularly elevated PWV predicts MACE in post-infarcted, very high cardiovascular risk patient population. All these findings emphasize the clinical relevance for the future measurement of arterial stiffness might contribute to improve individual risk stratification in patients after myocardial infarction.ROC analysis for the prediction of MACEKaplan-Meier curves for MACE

Accuracy of preoperative lung ultrasound score for the prediction of major adverse cardiac events in elderly patients undergoing HIP surgery under spinal anesthesia: The LUSHIP multicenter observational prospective study

Background and objectiveWe hypothesize that lung ultrasound scores (LUS) can help stratify the cardiac risk of elderly patients undergoing orthopedic surgery for hip fracture, adding value to the Revised Cardiac Risk Index (RCRI), the American Society of Anesthesiologists Physical Status (ASA-PS) and the National Surgical Quality Improvement Program Myocardial infarction and Cardiac arrest (NSQIP-MICA). MethodsProspective, observational multicenter study of 11 Italian hospitals on patients aged >65 years with hip fractures needing urgent surgery. Subjects with major adverse cardiovascular events (MACE) in the previous 6 months or with ongoing acute heart failure were excluded. Trained anesthesiologists obtained preoperative LUS scores during preoperative evaluation. ROC curve analysis and comparison were used to evaluate test accuracy. ResultsA total of 877 patients were enrolled in the study period. 108 MACE events occurred in 98 patients, with an overall incidence of 11.2%. LUS score was higher in complicated than non-complicated patients, 11.6 ± 6.64 vs. 4.97 ± 4.90 (p < 0.001). Preoperative LUS score ≥8 showed both better AUC (0.78) and accuracy (0.76) in predicting MACE than the RCRI scores (p < 0.001), MICA scores (p = 0.001) and ASA classes (p < 0.001). LUS sensitivity was 0.71, specificity was 0.76, negative predictive value was 0.95. LUS score ≥8 showed an OR for MACE of 5.81[95% CI 3.55–9.69] at multivariate analysis. 91 patients (10.4%) experienced postoperative pneumonia showing a preoperative LUS score higher in the non-pneumonia group, p < 0.001. ConclusionsThe preoperative LUS score, with its high negative predictive value, could improve patients’ risk stratification when used alone or add further value to the RCRI score. RegistrationRegistered at clinicaltrials.gov as NCT04074876.

The Use of Cangrelor in Cardiogenic Shock: Insights from the CAMEO Registry

Little is known about the use of cangrelor in patients with myocardial infarction (MI) presenting with cardiogenic shock (CS). CAMEO (Cangrelor in Acute MI: Effectiveness and Outcomes) is a multicenter observational registry evaluating platelet inhibition in patients with MI. We examined the duration of cangrelor infusion and the amount of time to transition from cangrelor to an oral P2Y12 inhibitor in patients with CS. We also assessed major adverse cardiovascular events (MACEs) and bleeding risks, stratified by dosage duration, time to transition and oral P2Y12 inhibitor potency. Among 2352 cangrelor-treated patients with MI, 249 patients were in CS. Among the patients with CS, 16 (6.4%) received the "bridge" infusion dose, 202 (81.1%) the PCI cangrelor infusion dose, and 30 (12.0%) had a combination of both infusion doses. Patients with CS had a median age of 66 years; 32% were women; 21% were Black patients; 35% had diabetes; 19% received thrombectomy; and 59% received mechanical circulatory support (MCS) (35% intra-aortic balloon pump, 27% Impella). The median duration of infusion was 3.9 (2-21.5 hours) in patients with CS and was 2 (1.6-3.1 hours) for all cangrelor-treated patients. The median duration of transition from cangrelor to oral P2Y12 inhibitor administration was 0.1 (-0.5-21.0 hours) for patients with CS. In multivariable modeling, chronic lung disease and the use of MCS and was associated with longer cangrelor infusions (defined as > 3.9 hours). Among cangrelor-treated patients with CS, 24.1% of these patients had a bleeding event, and 41.8% had a MACE event. After adjustment, a longer cangrelor infusion duration was associated with increased risk of bleeding (P < 0.05). The median duration of cangrelor infusion was longer for patients presenting with CS. Use of MCS was associated with longer cangrelor infusion durations in patients with CS. Further work is needed to understand the pharmacodynamics of antiplatelet agents in patients with CS.

Can incidental physical activity offset the deleterious associations of sedentary behaviour with major adverse cardiovascular events?

Incidental physical activity as part of daily living may offer feasibility advantages over traditional exercise. We examined the joint associations of incidental physical activity and sedentary behaviour with major adverse cardiovascular events (MACE) risk. Analyses included 22,368 non-exercising adults from the UK Biobank accelerometry sub-study (Median age [IQR]: 62.9 [11.6] years; 41.8% male). Physical activity and sedentary behaviour exposures were derived using a machine learning-based intensity and posture classification schema. We assessed the tertile-based joint associations of sedentary behaviour and: a) incidental vigorous (VPA), b) incidental moderate to vigorous (MVPA), c) vigorous intermittent lifestyle physical activity (VILPA; bouts lasting up to 1 minute), and d) moderate to vigorous intermittent lifestyle physical activity (MV-ILPA; bouts lasting up to 3 minutes) with MACE risk. Over an 8.0-year median follow-up, 819 MACE events occurred. Compared to the highest physical activity and lowest sedentary time, high sedentary behaviour (>11.4 hours/day) with low incidental VPA (<2.1 minutes/day) had an HR of 1.34 (95% CI: 0.98, 1.84) and low incidental MVPA (<21.8 minutes/day) had a 1.89 HR (95% CI: 1.42, 2.52) for MACE. Sedentary behaviour was not associated with MACE at medium and high levels of VPA or VILPA. Completing 4.1 minutes/day of VPA or VILPA may offset the MACE risk associated with high sedentary behaviour. Conversely, 31-65 minutes of incidental MVPA or 26-52 minutes of MV-ILPA per day largely attenuated the associations with MACE. Brief intermittent bursts of vigorous incidental physical activity may offset cardiovascular risks from high sedentary behaviour.

Long-term effects of cholinesterase inhibitors and memantine on cognitive decline, cardiovascular events, and mortality in dementia with Lewy bodies: An up to 10-year follow-up study.

We aimed to assess the impact of cholinesterase inhibitors (ChEIs) and memantine on cognition, major adverse cardiovascular events (MACE) and mortality in dementia with Lewy bodies (DLB). A total of 1,095 incident DLB patients from the Swedish Registry on cognitive/dementia disorders were included. Using an inverse probability of treatment weighting, the effect of initiating ChEI or memantine within 90 days of DLB diagnosis and nonuse was evaluated on cognitive trajectories and risks of MACE and death. The use of ChEIs significantly slowed cognitive decline at follow-ups (Mini-Mental State Examination [MMSE] -0.39 points/y; 95% confidence interval [CI], -0.96 to 0.18) compared to memantine (-2.49 points/y; -4.02 to -0.97) and nonuse (-2.50 points/y; -4.28 to -0.73). Treatment groups did not differ in MACE events. ChEI use was associated with lower risk of death in the first year after DLB diagnosis (adjusted hazard ratio [HR] 0.66, 95% CI 0.46, 0.94). Our findings illuminate the potential benefits of ChEI treatment in DLB patients. Cholinesterase inhibitors slow cognitive decline over a 5-year follow-up period when compared to both memantine treatment and nonuse in patients with dementia with Lewy bodies. Cholinesterase Inhibitors reduce risk of mortality within the initial year, but this effect is not sustained after 1 year in patients with dementia with Lewy bodies.

Assessment of perioperative cardiac risk using preoperative quantitative flow ratio in patients with coronary artery disease undergoing noncardiac surgery: a retrospective cohort study.

Quantitative flow ratio (QFR) is a novel diagnostic modality for the functional testing of coronary artery stenosis, but evidence concerning the postoperative prognostic implication of QFR in noncardiac surgery (NCS) of patients with coronary artery disease (CAD) is limited. The purpose of this study was to examine the role of QFR in perioperative risk prediction in patients with coronary heart disease. This retrospective cohort study was conducted in The First Affiliated Hospital of Wenzhou Medical University between 2013 and 2022, and consecutively included patients with CAD who had undergone NCS <1 year after coronary angiography. The primary endpoint was major adverse cardiovascular events (MACEs), which were defined as a composite of cardiovascular death, nonfatal myocardial infarction, nonfatal stroke, cardiopulmonary arrest, malignant ventricular arrhythmia (MVA), congestive heart failure, and revascularization. Univariate and multifactorial Cox regression was used to identify the independent risk factors for perioperative cardiovascular events and to construct new models. The area under the curve (AUC), net reclassification improvement (NRI), and integrated discrimination improvement (IDI) were used to compare the newly constructed model with existing traditional models. Among the 929 participants enrolled (median age 68 years; 72.0% male), the primary endpoint was met in 67 (7.2%) patients within 30 days of follow-up. There was no significant difference in the incidence of the primary endpoint between patients with QFR <0.75 and those with "gray zone" lesions (0.75≤ QFR ≤0.8) (log-rank P=0.325). Patients with QFR <0.75 and those with "gray zone" lesions (0.75≤ QFR ≤0.8) had a higher incidence of primary endpoint events compared to patients with QFR >0.8. [QFR <0.75 vs. QFR >0.8: adjusted hazard ratio (HR) =20.70, P<0.001; 0.75≤ QFR ≤0.8 vs. QFR >0.8: HR =15.99, P<0.001]. The independent predictors of MACEs events within 30 days after NCS were albumin level [HR =0.92, 95% confidence interval (CI): 0.87-0.98; P=0.008], emergency surgery (HR =4.12, 95% CI: 1.66-10.23; P=0.002), and QFR ≤0.8 (HR =15.92, 95% CI: 5.96-42.51; P<0.001). In addition, adjusting the original Revised Cardiac Risk Index (RCRI) with QFR ≤0.8 as a risk factor significantly improved the risk stratification of postoperative adverse events, with the adjusted AUC rising from 0.574 to 0.740 (P<0.001). QFR ≤0.8 could independently predict perioperative cardiovascular adverse events in patients with CAD undergoing NCS and improve the predictive value of original predictive index. Gray-zone lesions (0.75≤ QFR ≤0.8) should be actively treated.

Antithrombotic therapy at discharge and prognosis in patients with chronic coronary syndrome and atrial fibrillation who underwent PCI: a real-world study

BackgroundThis study aimed to describe the status of antithrombotic therapy at discharge and prognosis in patients with atrial fibrillation (AF) and chronic coronary syndrome (CCS) who underwent percutaneous coronary intervention (PCI).MethodsThis was an observational, prospective study. The primary endpoint was major adverse cardiovascular events (MACE), including all-cause death, myocardial infarction, stroke/transient ischemic attach (TIA), systemic embolism or ischemia-driven revascularization. Bleeding events were collected according to the Thrombolysis in Myocardial Infarction (TIMI) criteria.ResultsBetween 2017 and 2019, a cohort of 516 patients (mean age 66, [SD 9], of whom 18.4% were female) with AF and CCS who underwent PCI were evaluated, with a median followed-up time of 36 months (Interquartile range: 22–45). MACE events occurred in 13.0% of the patients, while the TIMI bleeding events were observed in 17.4%. Utilization of TAT (triple antithrombotic therapy) (P < 0.001) and oral anticoagulation (OAC) therapy (P < 0.001) increased through years. History of heart failure (HF) (Hazard ratio [HR], 1.744; 95% confidence interval [CI], 1.011–3.038) and TAT (HR, 2.708; 95%CI, 1.653–4.436) had independent associations with MACE events. OAC (HR, 10.378; 95%CI, 6.136–17.555) was identified as a risk factor for bleeding events. A higher creatine clearance (HR, 0.986; 95%CI, 0.974–0.997) was associated with a lower incidence of bleeding events.ConclusionsAntithrombotic therapy has been improved among patients with AF and CCS who underwent PCI these years. History of HF and TAT were independently associated with MACE events. Higher creatine clearance was protective factor of bleeding events, while OAC was a risk factor for TIMI bleeding events.

The predictive value of neutrophil–lymphocyte ratio combined with the Global Registry of Acute Coronary Events score for inhospital adverse cardiovascular events in patients with acute ST-elevation myocardial infarction

Background: The research explores the predictive efficacy of the neutrophil-to-lymphocyte ratio (NLR) in conjunction with the Global Registry of Acute Coronary Events (GRACEs) score for inhospital major adverse cardiovascular events (MACEs) among acute ST-segment elevation myocardial infarction (STEMI) subjects with primary percutaneous coronary intervention (PCI) history. Materials and Methods: Patients were categorized into MACE (n = 58) and non-MACE cohorts (n = 184) based on MACE occurrence events during hospitalization. The predictive value of the NLR, GRACE score, and their combination for inhospital MACE events in STEMI subjects was assessed by the receiver operating characteristic curve (ROC). Results: NLR (8.99 [5.06, 12.01] vs. 5.15 [3.13, 7.66]) and GRACE scores (159.62 ± 43.39 vs. 116.96 ± 28.15) within MACE group notably surpassed the non-MACE group (P &lt; 0.05). ROC curve analysis demonstrated that the area under the curve (AUC) for NLR in forecasting inhospital MACE events was 0. 72 (95% confidence interval [CI]: 0.645–0.795), with 0.655 sensitivity and 0.723 specificity, and optimal cutoff value as 7.01. The AUC for the GRACE score was 0.791 (95% CI: 0.717–0.865), with 0.862 sensitivity and 0.598 specificity, and the optimal cutoff value was 121.5. The combined AUC of NLR and GRACE score was 0.814 (95% CI: 0.745–0.884), with 0.707 sensitivity and 0.837 specificity. Conclusion: Both NLR and GRACE score independently predict inhospital MACE events in STEMI patients post-PCI. Integration of the NLR and GRACE score enhances accuracy in forecasting inhospital MACE event occurrences.

Pulmonary transit time is a predictor of outcomes in heart failure: a cardiovascular magnetic resonance first-pass perfusion study

BackgroundPulmonary transit time (PTT) can be measured automatically from arterial input function (AIF) images of dual sequence first-pass perfusion imaging. PTT has been validated against invasive cardiac catheterisation correlating with both cardiac output and left ventricular filling pressure (both important prognostic markers in heart failure). We hypothesized that prolonged PTT is associated with clinical outcomes in patients with heart failure.MethodsWe recruited outpatients with a recent diagnosis of non-ischaemic heart failure with left ventricular ejection fraction (LVEF) < 50% on referral echocardiogram. Patients were followed up by a review of medical records for major adverse cardiovascular events (MACE) defined as all-cause mortality, heart failure hospitalization, ventricular arrhythmia, stroke or myocardial infarction. PTT was measured automatically from low-resolution AIF dynamic series of both the LV and RV during rest perfusion imaging, and the PTT was measured as the time (in seconds) between the centroid of the left (LV) and right ventricle (RV) indicator dilution curves.ResultsPatients (N = 294) were followed-up for median 2.0 years during which 37 patients (12.6%) had at least one MACE event. On univariate Cox regression analysis there was a significant association between PTT and MACE (Hazard ratio (HR) 1.16, 95% confidence interval (CI) 1.08–1.25, P = 0.0001). There was also significant association between PTT and heart failure hospitalisation (HR 1.15, 95% CI 1.02–1.29, P = 0.02) and moderate correlation between PTT and N-terminal pro B-type natriuretic peptide (NT-proBNP, r = 0.51, P < 0.001). PTT remained predictive of MACE after adjustment for clinical and imaging factors but was no longer significant once adjusted for NT-proBNP.ConclusionsPTT measured automatically during CMR perfusion imaging in patients with recent onset non-ischaemic heart failure is predictive of MACE and in particular heart failure hospitalisation. PTT derived in this way may be a non-invasive marker of haemodynamic congestion in heart failure and future studies are required to establish if prolonged PTT identifies those who may warrant closer follow-up or medicine optimisation to reduce the risk of future adverse events.

Effect of Early Heparin Anticoagulation on Blood Flow and Cardiac Function in Patients with Acute ST Segment Elevation Myocardial Infarction Treated by Primary Percutaneous Coronary Intervention

Objective: This study aimed to investigate the effect of early administration of heparin anticoagulation on blood flow and cardiac function in patients with acute ST segment elevation myocardial infarction (STEMI) treated with primary percutaneous coronary intervention (PPCI). Methods: A retrospective analysis was conducted on 730 patients with STEMI who underwent PPCI at the Department of Cardiology of the Chengdu Fifth People's Hospital of Chengdu from December 2017 to May 2023. According to the timing of heparin administration. The patients were divided into two groups based on the timing of heparin administration: the early group (3000 U unfractionated heparin administered immediately after the diagnosis of STEMI) and the delayed group (Intravenous injection of ordinary heparin 3000 U after successful interventional catheterization following the diagnosis of STEMI). The study compared general clinical data, myocardial injury markers (initial troponin, peak troponin, and tmax troponin), interventional related indicators (preprocedural thrombolysis in myocardial infarction (TIMI) flow grade, postprocedural TIMI flow grade, stent length, and thrombus aspiration), and postoperative indexes ST segment resolution (STR), left ventricular ejection fraction (LVEF), n-terminal pro-brain natriuretic peptide (NT-proBNP), major adverse cardiovascular events (MACE), and bleeding events. Results: The early group had a lower proportion of TIMI 0–1 grade and a higher proportion of TIMI 2–3 grade compared to the delayed group (p &lt; 0.05). The early group showed better ST segment resolution (p &lt; 0.05). There was no significant difference in LVEF and NT-proBNP classification between the two groups (p &gt; 0.05). Subgroup analysis suggested an interaction between early heparin anticoagulation and left anterior descending infarct-related artery (IRA) on cardiac function. There was no significant difference in the incidence of MACE and bleeding events between the two groups (p &gt; 0.05). Logistic regression analysis revealed that early heparin anticoagulation was a predictor of immediate TIMI grade 2–3 flow, and TIMI grade 2–3 flow was negatively correlated with early heparin anticoagulation. Conclusions: Early heparin anticoagulation can improve the patency of the IRA and myocardial perfusion in patients with STEMI. Additionally, it can reduce myocardial injury and improve cardiac function without increasing the risk of in-hospital bleeding.

Coronary computed tomographic angiography-derived anatomic and hemodynamic plaque characteristics in prediction of cardiovascular events.

This study investigated the association of anatomic and hemodynamic plaque characteristics based on deep learning coronary computed tomography angiography (CCTA) with high-risk plaques that caused subsequent major adverse cardiovascular events (MACE). A retrospective analysis was conducted on patients who underwent CCTA between 1month and 3years prior to the occurrence of a MACE. Deep learning and computational fluid dynamics algorithms based on CCTA were applied to extract adverse plaque characteristics (low-attenuation plaque, positive remodeling, napkin-ring sign, and spotty calcification), and hemodynamic parameters (fractional flow reserve derived by coronary computed tomographic angiography [FFRCT], change in FFRCT across the lesion [△FFRCT], wall shear stress [WSS], and axial plaque stress [APS]). Correlation analysis, logistic regression, and Cox proportional risk analysis were conducted to understand the relationship between these measures and the occurrence of MACE and assess the value of hemodynamic parameters in predicting the incidence of MACE events and their prognosis. Our study included 86 patients with a total of 134 vessels exhibiting plaque formation and 83 culprit vessels with a subsequent coronary event. Culprit vessels had percent diameter stenosis [%DS] (0.54 ± 0.16 vs. 0.62 ± 0.13, P = 0.003), larger non-calcified plaque volume (45.8 vs. 101.7, P < 0.001), larger low-attenuation plaque volume (3.6 vs. 14.5, P < 0.001), more lesions with ≥ 3 adverse plaque characteristics (APC) (4 vs.26, P = 0.002), and worse hemodynamic features of adverse plaque. FFRCT demonstrated better visualization of maximum achievable flow in the presence of coronary stenosis and better correlation with the stenosis severity, while maximum of wall shear stress (WSSmax) was highly correlated with low-attenuation plaques and APC. The inclusion of hemodynamic parameters improved the efficacy of the predictive model, and a high WSS suggested a higher probability of MACE. Hemodynamic parameters based on CCTA are significantly correlated with plaque morphology. Importantly, integrating CCTA-derived parameters can refine the predictive performance of MACE occurrence.