Occurrence Of Major Adverse Cardiovascular Events Research Articles

The prognostic value of cartilage intermediate layer protein 1 (CILP1) in patients with diabetic cardiomyopathy.

To measure the plasma levels of human cartilage intermediate layer protein 1 (CILP1) in patients with diabetic cardiomyopathy (DCM), and to investigate its association with the occurrence of major adverse cardiovascular events (MACE) in DCM. A total of 336 diabetic patients were enrolled and assigned into two groups based on the presence or absence of DCM (DCM group and N-DCM group). The baseline clinical data including glutamic-pyruvic transaminase (ALT), glutamic oxaloacetic acid transferase (AST), albumin, serum creatinine, glycosylated hemoglobin (HbA1c), C-reactive protein (CRP), and N-terminal pro brain natriuretic peptide (NT-proBNP) were recorded. Subsequently, plasma levels of CILP1 at admission were detected by the enzyme linked immunosorbent assay (ELISA) method. Echocardiographic parameters were also acquired for all patients. The association of CILP1 with LVEF, LVDD and CRP was determined. In addition, the occurrence of MACE was examined during the 12-month follow-up in the DCM group. The concentration of CILP1 in the DCM group was higher than in the N-DCM group [1329.97 (1157.14, 1494.36) ng/L vs. 789.00 (665.75, 937.06) ng/L, P < 0.05], higher in the MACE group than in the non-MACE group [1777.23 (1532.83, 2341.26)ng/L vs. 885.00 (722.40, 1224.91) ng/L, P < 0.05). Correlation analysis revealed that CILP1 expression was associated with LVEF, CRP and LVDD (r = -0.58, 0.29 and 0.44, respectively, P < 0.05). Analysis of a nomogram demonstrated that CILP1, sex, age, BMI, LVEF and LVDD could predict the occurrence of MACE in DCM patients at 12months (P < 0.05). The plasma levels of CILP1 were independently associated with a stronger discriminating power for DCM. Furthermore, inclusion of CILP1 as a covariate in the model caused a significant improvement in risk estimation compared with traditional risk factors for DCM [BASIC: AUC: 0.556, 95%CI: 0.501-0.610; BASIC + CILP1: AUC: 0.913, 95%CI: 0.877-0.941, P < 0.05] and MACE [BASIC: AUC: 0.710, 95%CI: 0.616-0.792; BASIC + CILP1: AUC: 0.871, 95%CI: 0.794-0.928, P < 0.05]. The serum concentration of CILP1 was increased in DCM patients. Elevated fasting plasma CILP1 levels was a robust diagnostic marker of DCM and was independently associated with an increased risk of MACE.

Abstract 4113890: Impact of blood pressure management on cardiovascular events among patients with familial hypercholesterolemia

Background: Hypertension status has been associated with worse outcomes among patients with familial hypercholesterolemia (FH). We aimed to determine clinical impact of management of blood pressure in development of major adverse cardiovascular events (MACE). Methods: Patients with clinically diagnosed heterozygous FH (HeFH) (N=1,273, male/female=614/659) with blood pressure data were assessed. We divided the patients into 4 groups (group 1: patients without hypertension from baseline to their follow-up, group 2: patients without hypertension at baseline, but developed hypertension at follow-up, group 3: patients with hypertension at baseline, but well-controlled at follow-up, group 4: patients with hypertension from baseline and uncontrolled at their follow-up). Cox proportional hazards models were used to assess factors associated with MACE, including cardiovascular death and any coronary events. Results: The median follow-up period was 10.9 years. During the follow-up period, 142 MACEs were observed. We found that the management of blood pressure was significantly associated with the occurrence of MACE (hazard ratio (HR): 2.50; 95% confidence interval (CI): 1.30–3.70; p&lt;0.001, HR: 4.18; 95% CI: 2.08–6.28; p&lt;0.001, HR: 10.96; 95% CI: 6.10–17.58; p&lt;0.001, in group 2, group 3, and group 4, respectively when group 1 was considered as reference). Conclusions: Blood pressure management appears to be very important among patients with HeFH.

Abstract 4136498: Analysis of Cardiovascular Events in Cancer Survivors: A Comparative Study of Solid Tumors and Hematologic Malignancies at a Tertiary Cardiovascular Center

Background: Cardiovascular disease (CVD) and cancer represent the leading contributors of death worldwide. Although advancements in antineoplastic therapies have notably enhanced prognoses, CVD now emerges as the primary cause of mortality in this population. Ojective: To assess the occurrence of CVD in cancer survivors and investigate disparities based on their previous cancer diagnosis, categorized into solid tumors or hematological malignancies. Methods: A cross-sectional study was conducted, including adult oncology survivors who had previously undergone oncological treatment and were referred to our center between 2010 and 2023 due to the presentation of major adverse cardiovascular events (MACE). They were categorized into two groups: those with hematological cancer and those with solid tumors. We used Chi2 test to assess differences between categorical variables and the Wilcoxon rank-sum test to evaluate differences in continuous parameters. Statistical analysis was performed using R 4.0 and StataMP 14.1. Results: A total of 214 oncological patients were included (median age: 69 [IQR: 55-80], women: 53%), comprising 164 (76.6%) with solid tumors and 50 (23.4%) with hematological cancer. Baseline characteristics were mostly similar between the groups (Table 1), with diabetes being more prevalent in patients with solid tumors (26% vs 12%, p=0.036). The prevalence of heart failure was predominantly NYHA I and II in solid tumors and NYHA III in hematological cancer (p=0.002) (Table 2). The incidence of coronary artery disease (CAD) was the most common MACE in solid tumors (39% vs 34%), but this was not statistically significant (p=0.04). In hematological cancer, the most frequent MACE was myocardial dysfunction, showing a significant difference (46% vs 24%, p=0.002). Similarly, valvular heart disease (VHD) appeared more frequently in this group (38% vs 20%, p=0.01). The remaining MACEs did not show significant differences, nor did the count of MACEs upon hospital arrival. Conclusion: Myocardial dysfunction and VHD exhibited a higher incidence in hematological cancer compared to solid tumors. Conversely, the incidence of CAD was higher in the solid tumor group; however, similar to the occurrence of other MACEs, there was no significant difference between the two groups. These findings could emphasize the importance of closely monitoring specific cancer types to enhance prevention strategies but still need further analysis to also determine the exact etiologies.

Abstract 4148096: Discrimination Abilities of Euroscore and SYNTAX score for Prognostic Outcomes in patients with Stable Coronary Artery Disease: A Systematic Review and Meta-analysis

Introduction: There is a lack of good risk prediction models in patients with stable coronary artery disease (SCAD). We conducted a meta-analysis of validation studies to compare and determine the discrimination abilities of Euroscore (ES) and Syntax score (SS) for prognostic outcomes in patients with SCAD. Methods: A comprehensive literature search was conducted across MEDLINE, Cochrane and Embase from inception till May 2024. All studies that reported C-statistic/AUC for predicting all cause mortality, cardiac death or Major adverse cardiovascular events (MACE) for patients with stable coronary artery disease (SCAD) were included in the analysis. Studies lacking confidence intervals (CI) for C-statistic or those which reported C-statistics in patients with acute coronary syndromes or mixed SCAD and ACS patients were excluded. A generic inverse variance method was used to pool C-statistics and their corresponding standard errors (SEs). The SEs were calculated from CI wherever needed. A pooled C statistic of &gt;0.8 was considered to be a good discrimination ability. Results: A total of 5 studies with a patient population of 5903 were included in the meta-analysis. For ES, the pooled C-statistic for all cause mortality (n=2666) was 0.69[0.51-0.87] while for cardiac death (n=2666) it was 0.77[0.60-0.71]. The discrimination ability of ES for MACE as reported by one study (n=305) was 0.54[0.49-0.60]. For SS, the summary AUC for all cause mortality (n=2936) was 0.77[0.69-0.85] while for cardiac death (n=305) it was 0.52[0.46-0.57]. The pooled AUC of SS for occurrence of MACE(n=2666) was 0.56[0.45-0.66]. Conclusion: None of the two scores have a a good discrimination ability for risk stratification in SCAD patients. The predictive accuracy of SS is comparatively better than ES for all cause mortality. However, ES performs better for predicting cardiac death. Better risk prediction models with large scale external validations are needed.

The cardio-protective effect of cardiomyopeptidin in critically ill patients with myocardial injury: a retrospective cohort study

In order to investigate the association between the use of cardiomyopeptidin (CMP) and outcomes in critically ill patients with myocardial injury, we conducted a retrospective cohort study in Nanfang hospital, Southern Medical University. Clinical data of patients with myocardial injury were collected retrospectively and adjusted for possible confounders by propensity score weighting. The main outcome was the in-hospital mortality. Secondary outcomes included the major adverse cardiovascular events (MACE) occurring during the hospital, the individual components of MACEs, changes in high sensitive troponin T (hsTnT) levels, length of stay (LOS) in ICU and hospital. A Cox proportional hazards model was constructed to examine the association between the application of CMP and in-hospital mortality. Logistic regression and linear regression are used to analyze secondary outcomes. In total, 339 critically ill patients with myocardial injury were included in the analysis. After inverse probability of treatment weighting (IPTW), the use of CMP was associated with reduced in-hospital mortality (HR: 0.64, 95%CI: 0.43–0.96, P = 0.03). No significant differences were found in change of hsTnT, the occurrence of MACE and LOS in ICU as well as hospital after IPTW. The association was more significant in the subgroup with hsTnT > 3URL (HR: 0.41, 95%CI: 0.23–0.71, P < 0.001) and APACHE II score < 25 (HR: 0.13, 95%CI: 0.17–0.59, P < 0.001). Cardiomyopeptidin was associated with reduced in-hospital mortality in critically ill patients with myocardial injury. Our study provides initial clinical basis for the application of CMP with cardio-protective effect in critically ill patients. These results need to be confirmed in future randomized controlled trails.

Prognostic Value of Systemic Inflammation Response Index and N-Terminal Pro-B-Type Natriuretic Peptide in Patients with Myocardial Infarction with Nonobstructive Coronary Arteries- A Retrospective Study.

The Systemic Inflammation Response Index (SIRI) and N-terminal Pro-B-type natriuretic peptide (NT-proBNP) have been proposed as reliable predictors of poor prognosis in cardiovascular disease and all-cause mortality, However, their validity has not been extensively evaluated in patients with myocardial infarction with nonobstructive coronary arteries (MINOCA). 259 patients diagnosed with MINOCA were enrolled in this study from January 2015 to December 2022, and serum levels of SIRI and NT-proBNP were detected. The primary endpoints were major adverse cardiovascular events (MACE). According to the occurrence of MACE during the follow-up period, patients were grouped into MACE and Non-MACE groups, and divided by the median values for SIRI and NT-proBNP into groups: low SIRI, high SIRI, low NT-proBNP, and high NT-proBNP. A statistically significant difference in the levels of SIRI and NT-proBNP was observed between the MACE group and the non-MACE group. Kaplan-Meier survival curve analysis revealed that patients with high SIRI and high NT-proBNP had a significantly higher risk of MACE (log-rank P < 0.001). Furthermore, even after adjusting for covariates, the high SIRI and high NT-proBNP were associated with an increased risk of MACE (P<0.001, HR: 3.188, 95% CI 1.940-5.241; P<0.001, HR: 2.245, 95% CI 1.432-3.519). Additionally, the combined prognosis prediction of SIRI and NT-proBNP was superior to a single prediction, and adding SIRI and NT-proBNP to the traditional risk factor model improved the model's predictive value. High levels of SIRI and NT-proBNP exhibit a significant correlation with an increased risk of MACE, thereby suggesting that SIRI can be used as a reliable inflammatory indicator for predicting the risk in MINOCA patients, with significantly improved prognostic value when combined with NT-proBNP.

Predicting major adverse cardiovascular events in angina patients using radiomic features of pericoronary adipose tissue based on CCTA.

This study aims to evaluate whether radiomic features of pericoronary adipose tissue (PCAT) derived from coronary computed tomography angiography (CCTA) can better predict major adverse cardiovascular events (MACE) in patients with angina pectoris. A single-center retrospective study included 239 patients with angina pectoris who underwent coronary CT examinations. Participants were divided into MACE (n = 46) and non-MACE (n = 193) groups based on the occurrence of MACE during follow-up, and further allocated into a training cohort (n = 167) and a validation cohort (n = 72) at a 7:3 ratio. Automatic segmentation of PCAT surrounding the proximal segments of the left anterior descending artery (LAD), left circumflex coronary artery (LCX), and right coronary artery (RCA) was performed for all patients. Radiomic features of the coronary arteries were extracted, screened, and integrated while quantifying the fat attenuation index (FAI) for the three vessels. Univariate and multivariate logistic regression analyses were utilized to select clinical predictors of adverse cardiovascular events. Subsequently, machine learning techniques were employed to construct models based on FAI, clinical features, and radiomic characteristics. The predictive performance of each model was assessed and compared using receiver operating characteristic (ROC) curves, calibration plots, and decision curve analysis for clinical utility. The radiomics model demonstrated superior performance in predicting MACE in patients with angina pectoris within both the training and validation cohorts, yielding areas under the curve (AUC) of 0.83 and 0.71, respectively, which significantly outperformed the FAI model (AUC = 0.71, 0.54) and the clinical model (AUC = 0.81, 0.67), with statistically significant differences in AUC (p < 0.05). Calibration curves for all three predictive models exhibited good fit (all p > 0.05). Decision curve analysis indicated that the radiomics model provided higher clinical benefit than the traditional clinical and FAI models. The CCTA-based PCAT radiomics model is an effective tool for predicting MACE in patients with angina pectoris, assisting clinicians in optimizing risk stratification for individual patients. The CCTA-based radiomics model significantly surpasses traditional FAI and clinical models in predicting major adverse cardiovascular events in patients with angina pectoris.

Predictive value of Type D personality combined with unhealthy cardiovascular behaviors for the long-term adverse cardiovascular events in ACS patients

Abstract Background Acute coronary syndrome (ACS) has become a major public health problem worldwide due to its high morbidity and mortality. In addition to traditional risk factors, psychosocial factors play an important role in the development of ACS.Type D personality, as a combination of social inhibition and negative affect, has been defined as a psychological risk factor for coronary heart disease by the European Society of Cardiology.Meanwhile, ACS patients with Type D personality may have behaviors such as unhealthy dietary behaviors, less regular physical activity, and poorer self-management behaviors. Then, whether the combination of Type D personality and poor cardiovascular health behaviors can increase the risk of poor prognosis in patients with ACS requires further research. Purpose The aim of this study was to investigate the effect of Type D personality combined with poor cardiovascular health behaviors on long-term major adverse cardiovascular events(MACE) in patients with ACS. Methods A total of 18631 patients diagnosed with ACS between January 2017 and July 2023 were included in this study. Type D personality, cardiovascular health behaviors (smoking cessation, physical activity, average sleep duration at night, dietary assessment index, BMI, lipids, blood glucose, blood pressure) were assessed during the admission period, and were divided into poor, general, and ideal cardiovascular health with a cut-off score of 50 and 80.The binary logistic regression analysis was used to assese the effect of Type D personality combined with cardiovascular health score on the occurrence of MACE (stroke, reinfarction, revascularization, all-cause death). Results The median follow-up in this study was 37 months, and we found that a total of 3750 people had MACE during the follow-up period. The logistic regression result showed that compared with Type D personality (-) and cardiovascular health behaviors (poor) group, Type D personality (+) and cardiovascular health behaviors (poor) group (OR=1.451, 95%CI=1.055-1.995,P=0.022), Type D personality (+) and cardiovascular health behaviors (general) group (OR=1.425, 95%CI=1.092-1.858,P=0.009), Type D personality (-) cardiovascular health behavior (poor) group (OR=1.301, 95%CI=1.013-1.670, P=0.039) were independent risk factors for the occurrence of further adverse cardiovascular events. Conclusion Type D personality combined with unhealthy cardiovascular behavior individuals may be at high risk for MACE. Therefore, early assessment of Type D personality and cardiovascular health behaviors are needed, thereby reducing the incidence of MACE in ACS patients.

Is the HNF4A gene variant paradoxically associated with better prognostic in CAD patients?

Abstract Background The Hepatocyte nuclear factor 4 A (HNF4A) gene was considered to be associated with susceptibility to atherosclerosis and coronary artery disease (CAD). It encodes a protein HNF4α, a genetic transcription factor regulating the genetic expression of thousands of genes playing essential roles in glucose and lipid metabolism. Its abnormal expression is emerging as a critical factor in diabetes, dyslipidemia, and cancer. Loss of function of specific mutations could attenuate its role in CAD pathogenesis and the progression of atherosclerosis. Aim To investigate whether a genetic variant (HNF4α rs1884613 C&amp;gt;G) could be associated with a low genetic function and, paradoxically, a better prognostic in CAD patients. Methods A cohort of 1,718 patients with coronary angiography (&amp;gt;70% stenosis of at least one main coronary vessel) from the GENEMACOR Study was investigated. Thirty-three genetic variants were genotyped using TaqMan assay methodology and HNF4A rs1884613 C&amp;gt;G genotype models were individually studied regarding the occurrence of Major Adverse Cardiovascular Events (MACEs). We used bivariate analysis to evaluate genotypic and allelic differences. Multivariate Cox regression analysis estimated variables independently associated with MACE, and Kaplan-Meier estimate methodology assessed the survival. Results Of the 1,718 CAD patients with the CC wild type, 73.4% had MACE, compared with 66.5% without. CG had 25.2% compared with 30.5% without. Finally, in the GG genotype, only 1.4% had events compared with 3.0% without (p=0.004). Cox regression analysis showed that GG genotype (mutated) is significantly and independently associated with 56% of MACE protection with a hazard ratio (HR) of 0.436; p=0.014. Physical inactivity and type-2 Diabetes remained independently associated with MACE occurrence (Fig.1). Kaplan-Meier cumulative event analysis disclosed that the carriers of the GG genotype were significantly associated with a better event-free time, and CC discloses a worse event-free time (Breslow test, p=0.001) (Fig.2). Conclusions The rs1884613 genetic variant of HNF4A is associated with a better CAD prognosis. This variant could probably induce gene downregulation and HNF4A gene function loss. Modifying and modulating hepatic lipase and lipid metabolism positively affected atherosclerosis progression. Future bioactive modulators for HNF4A variants could raise the possibility that diseases involving diabetes, lipid disorders, and cancer might be amenable to pharmacologic intervention.

Left atrial strain predicts adverse events in hypertrophic cardiomyopathy: preliminary results from a CMR study

Abstract Background Hypertrophic cardiomyopathy (HCM) is associated with an increased risk of major adverse cardiovascular events (MACE), however, current risk stratification methods are imperfect. Left atrial global longitudinal strain (LA GLS) is an increasingly acknowledged predictive parameter, yet its potential role in HCM is not well defined. Purpose This study aims to investigate the prognostic role of cardiac magnetic resonance (CMR)-derived LA GLS for the occurrence of MACE in patients with HCM. Methods A retrospective, single-centre, CMR study of HCM patients was conducted. Clinical data was collected from electronic medical record and CMR images were analysed by two blinded investigators. LA GLS was derived from CMR two-chamber cine images by a semiautomatic method, and was categorized according to its median value. The endpoint was a composite of MACE, including all-cause death, sudden cardiac death (SCD), sustained and non-sustained ventricular tachycardias (VT), appropriate implantable cardiac defibrillator (ICD) shocks, heart failure (HF) hospitalization, and new-onset atrial fibrillation (AF). Cox regression analysis was performed. The preliminary results of the study are now reported. Results A total of 54 HCM patients were included, mean age was 58.5 years ± 15.9 and 38.9% were female. Average maximal wall thickness (MWT) was 18.0 mm ± 3.9, 37% had left ventricular outflow obstruction (LVOTO) and 45.1% had positive late gadolinium enhancement (LGE). After a mean follow-up of 6.9 ± 3.0 years, 26 patients (48.1%) experienced the composite endpoint. Figure 1 shows the clinical and CMR differences according to the occurrence of MACE. LA GLS was significantly lower in patients with MACE compared to those without (26.5 ± 19% vs 36.7 ± 13%, p=0.026), with a moderate predictive value (AUC = 0.68, Figure 2A). Multivariate Cox regression analysis revealed that a decrease in LA GLS (HR 1.09 per each 1% decrease, 95% CI 1.03-1.15, p=0.002), the presence of LGE (HR 6.9, 95% CI 1.7-28, p=0.007), the presence of LVOTO (HR 3.4, 95% CI 1.12-10.2, p=0.031) and an increase in MWT (HR 1.23 per each 1mm increase, 95% CI 1.05-1.45, p=0.011) were independently associated with MACE. Among low-risk HCM patients (absence of LGE or LVOTO, or MWT below our median value), LA GLS had an additional prognostic role, and those with an LA GLS above the median value (LA GLS&amp;gt;29.7%) presented a remarkably favourable prognosis (Figure 2B-D). Conclusions CMR-derived LA GLS is a predictor of outcomes in HCM beyond established imaging prognostic factors. Particularly, LA GLS appears to be useful in risk-stratifying low-risk HCM patients: those with normal LA GLS show an excellent prognosis. If confirmed in larger studies, LA GLS could be used to individualise HCM management.Figure 2

Impact of changes of Achilles tendon thickening on cardiovascular events among patients with familial hypercholesterolemia

Abstract Backgrounds Achilles tendon thickening (ATT) can be regressed through LDL-lowering in patients with familial hypercholesterolemia (FH). The Japan Atherosclerosis Society (JAS) determined the threshold of ATT as ≥8.0 mm in male and ≥7.5 mm in female. Purpose We aimed to determine clinical impact of changes of ATT in development of major adverse cardiovascular events (MACE). Methods Patients with clinically diagnosed FH (N=1,273, male/female=614/659) with ATT data using X-ray were assessed. We divided the patients into 4 groups (group 1: patients without ATT from baseline to their follow-up, group 2: patients without ATT at baseline, but developed ATT at follow-up, group 3: patients with ATT at baseline, but regressed at follow-up, group 4: patients with ATT from baseline to their follow-up). Cox proportional hazards models were used to assess factors associated with MACE, including cardiovascular death and any coronary events. Results The median follow-up period was 10.9 years. During the follow-up period, 142 MACEs were observed, and median ATT was regressed from 7.8 to 7.6 mm. We found that there was more significant positive correlation between cholesterol-year score and ATT among patients with and without MACE (p &amp;lt;0.001; Spearman’s r=0.33, and p &amp;lt;0.001; Spearman’s r=0.35, respectively). Under these circumstances, changes of ATT were significantly associated with the occurrence of MACE (hazard ratio (HR): 2.73; 95% confidence interval (CI): 1.33–4.13; p&amp;lt;0.001, HR: 2.18; 95% CI: 1.08–3.28; p&amp;lt;0.001, HR: 6.34; 95% CI: 3.10–9.58; p&amp;lt;0.001, in group 2, group 3, and group 4, respectively when group 1 was considered as reference). Conclusion Assessments of ATT condition represent diagnostic values and risk stratification information among patients with FH.

Is the obesity paradox leading to a less stringent secondary prevention strategy in post-acute coronary syndrome patients?

Abstract Introduction Patients with acute coronary syndrome (ACS) are at very high risk of recurrent cardiovascular (CV) events. Despite being a major CV risk factor, obesity was associated with best survival in patients with ACS, the so-called "obesity paradox". It is uncertain if this finding is leading to a less stringent secondary prevention strategy in this group of patients, and whether it influences prognosis. Purpose To analyze the impact of obesity on outcomes after ACS and on other CV risk factor management. Methods Single-center, retrospective observational study that included all consecutive post-ACS patients enrolled in a phase 2 cardiac rehabilitation (CR) program in 2017, with a follow-up of 24 months. Patients were classified in 2 groups according to body mass index (BMI) at baseline: Group 1 (G1) were obese patients (BMI≥30 kg/m2), and Group 2 (G2) were non-obese patients (BMI&amp;lt;30kg/m2). Major adverse cardiovascular events (MACE) were defined as a composite of death, non-fatal ACS, non-fatal stroke, and unplanned revascularization. Results 198 patients were included (mean age of 60.3±10.7 years, 82% male) with a mean BMI of 27.7±4.2 kg/m2. Forty-seven patients (23.7%) had a BMI≥30 kg/m2. Patients in G1 were more likely to have hypertension (79% vs 55%; p=0.003) and diabetes (36% vs 20%; p=0.022). CR program was associated with smoking cessation, significant BMI (G1: -0.69 (95%CI: -0.40 to -0.10); G2: -0.39 (95%CI: -0.20 to -0.57) and LDL-Cholesterol (LDL-C) reduction (G1: -38 (95%CI: -25 to -50); G2: -29 (95%CI: -22 to -36), and functional capacity improvement (G1: +1.2 METs (95%CI: +0.9 to +1.5); G2: +1.1 METs (95%CI: +1.0 to +1.4) in both groups at 3 months, with similar magnitude of improvement. At 24 months, BMI had returned to baseline values in both groups, while the improvement in smoking status, LDL-C and functional capacity persisted. At 24 months, MACE occurrence was numerically increased in obese group (G1: 26.1% vs. G2: 17.2%, p=0.182), with a statistically significant higher incidence of non-fatal recurrent ACS in G1 (17% vs. 7.3%, p=0.048). Conclusions ACS patients with obesity have worse prognosis, despite the similar improvement in CV risk profile. Our data also suggests that, despite the short-term improvement in BMI, current treatment strategies are not effective at achieving a persistent weight control over 24-months.

Outcomes of post-acute coronary syndrome patients enrolled in a phase 2 cardiac rehabilitation program

Abstract Introduction Cardiac rehabilitation (CR) is a class I recommendation in the management of patients with acute coronary syndrome (ACS), namely ST-elevation myocardial infarction (STEMI) and non-ST acute coronary syndrome (NST-ACS). Reported mortality and recurrent cardiovascular (CV) events are still unacceptably high in these patients. Purpose To assess CV outcomes of patients enrolled in a CR program and its association with ACS presentation. Methods Single-center, retrospective observational study that included all consecutive post-ACS patients enrolled in a phase 2 CR program in 2017, with a follow-up of 24 months. Group 1 were patients with STEMI; group 2 were patients with NST-ACS. Major adverse cardiovascular events (MACE) were defined as a composite of death, non-fatal ACS, non-fatal stroke, and unplanned revascularization. Results Of the 202 ACS patients who attended the CR program in 2017, 4 were excluded due to missing data. Of the 198 patients analyzed (age 60.3±10.7 years, 82% male), 101 patients had a STEMI and 97 NST-ACS. STEMI patients were significantly younger (57±9.5 vs. 63±10, p&amp;lt;0.001), with fewer CV risk factors (diabetes 16% vs. 32%, p=0.008; hypertension 51% vs. 72%, p=0.002; obesity 17% vs. 31%, p=0.020; dyslipidemia 54% vs. 77%, p&amp;lt;0.001), except for active smoking (53% vs. 29%, p=0.001), and were less likely to have previous history of coronary artery disease (9% vs. 31%, p&amp;lt;0.001). During the 3-month CR program, both groups achieved significant reduction in body mass index, LDL-Cholesterol, functional capacity, and smoking cessation rates. At 3-, 12-, and 24-months evaluation, both groups showed no differences in risk factor management, nor differences in lipid-lowering therapy, namely percentage of high-intensity statin and ezetimibe use. STEMI patients were treated more frequently with ticagrelor (86% vs. 67%, p=0.001) at baseline. MACE occurrence was significantly lower in STEMI patients (11% vs. 28%, p=0.003), driven mainly by recurrent ACS (4% vs. 15%, p=0.006). Conclusions In our study, NST-ACS patients had significantly higher CV disease burden and worse outcomes at 24-month follow-up. Despite the heightened CV risk in this group, secondary prevention treatment intensity was similar in both groups.

Long-term clinical outcomes informed by artificial intelligence-enabled single-lead ECG detection of reduced ejection fraction

Abstract Background * Reduced left ventricular ejection fraction (LVEF) is linked to poor clinical outcomes (1, 2). * Despite its increasing prevalence, reduced LVEF is often undetected due to resource-limited echocardiography and lack of suitable point-of-care diagnostic tools. * Previous studies have shown that an artificial intelligence-enabled electrocardiogram (AI-ECG) algorithm can accurately identify patients with reduced LVEF, but may also offer novel insights on long-term prognosis (3, 4). Purpose We aimed to determine if an AI-ECG algorithm designed for detecting reduced LVEF can also independently predict 2-year major adverse cardiovascular events (MACE) and all-cause mortality. Method * A retrospective multicentre observational study investigating the ability of AI-ECG to predict long-term clinical outcomes (i.e. over two years' follow up). * Analysis included a total of 1,007 consecutive unselected patients attending for routine echocardiography, with a single-lead ECG recording performed at the same time. * An AI-ECG algorithm, designed to identify impaired LVEF, was applied to each single-lead ECG. * Occurrence of MACE and all-cause mortality associated with AI-ECG results (Figure 1) was investigated using Cox regression; evaluating performance of AI-ECG results as a classifier (0 or 1) and as a probability score (0 to 1). * The study was approved by the UK Health Research Authority (reference 21/LO/0051). Results * The mean age was 62.3 years. 52.4% of patients were male and 57.5% of patients were White. * Appropriately, patients with a positive AI-ECG had a higher MACE rate compared to those with a negative AI-ECG (34.2% vs. 11.9%; adjusted hazard ratio (aHR) 2.02; 95% CI, 1.46 – 2.81; p &amp;lt; 0.005), primarily driven by increased mortality (23% vs. 9.6%; p &amp;lt; 0.0001; aHR 1.65; 95% CI, 1.12 – 2.43) and heart failure hospitalization (14.5% vs. 1%; p &amp;lt; 0.0001) – Figure 2. * AI-ECG probability score (per 10% increase) was significantly associated with MACE (aHR 1.17; 95% CI, 1.09 – 1.25; p &amp;lt; 0.005) and all-cause mortality (aHR 1.11; 95% CI, 1.02 – 1.20; p = 0.01). * Importantly, sub-analysis of AI-ECG for those who have a normal LVEF (i.e. ≥50%) continued to show association between positive AI-ECG and MACE (27.2% vs. 11.9%; p &amp;lt; 0.0001; aHR 1.70, 95% CI 1.17 – 2.48) and all-cause mortality (20.4% vs. 9.6%; p &amp;lt; 0.0001; aHR 1.53, 95% CI 1.00 – 2.36). Conclusion An AI-ECG algorithm designed to identify impaired LVEF can identify patients at risk of MACE and all-cause mortality from single-lead ECG screening – regardless of their LVEF. Such results may enable further risk stratification for cardiovascular investigations through the simple addition of single-lead ECG recording.

Plasma cytokines are associated with major adverse cardiovascular events in follow-up of patients undergoing carotid endarterectomy

Abstract Background Patients with carotid artery disease undergoing carotid endarterectomy (CEA) have a high risk of experiencing Major Adverse Cardiovascular Events (MACE) after surgery. The occurrence of MACE in CEA-treated patients is not predicted by common cardiovascular (CV) risk factors. Purpose We aimed to identify the association between plasma and plaque inflammatory cytokines and the incidence of MACE in the follow-up after CEA. We hypothesized that MACE is related to a higher level of circulating inflammatory cytokines at the time of surgery. Methods We prospectively enrolled patients with carotid artery disease undergoing CEA. Plasma and carotid plaques were collected during the surgery. Inflammatory cytokines (MCP-1/CCL2, IL-8/CXCL8, IFN-gamma, IL-10, IL-1beta/IL-1F2, IL-6, PDGF-AA, PDGF-AB/BB, TNF-alpha, VEGF) were measured in plasma and tissue homogenates using a customized 10-plex Luminex assay. Baseline demographics and clinical data for all the patients were extracted from electronic health records. MACE after CEA was defined as a composite measure of nonfatal cardiac events such as myocardial infarction with or without revascularization, cerebrovascular events (ischemic stroke, TIA, and amaurosis fugax), and all-cause mortality. Results Of 107 patients who underwent CEA with a median age of 73 (67-78) years, 57 (53.2%) experienced MACE during a median follow-up of 5.2 [2.2-9.3] years: 23 (40.3%) cardiac events, 9 (15.7%) CVA, and 25 (43.8%) all-cause mortality. Plaque cytokines levels did not differ between the groups with and without MACE in the follow-up after CEA. Instead, plasma cytokines were associated with MACE in the follow-up after CEA, as summarized in Figure 1. In the logistic regression analysis, plasma levels of MCP-1/CCL2, IFN-gamma, and TNF-alpha were independent predictors of MACE in follow-up post-CEA in univariate and multivariable models adjusted for CV risk factors such as age, BMI, systolic and diastolic blood pressure, low-density lipoprotein, high-density lipoprotein, and glucose level: MCP1/CCL2 (HR 1.009 [1.002-1.015]; p=0.007), IFN-gamma (HR 1.368 [1.014-1.845]; p=0.040), and TNF-alpha (HR 1.121 [1.022-1.228]; p=0.015) (Table 1). Conclusions Plasma levels of CCL2, IFN-gamma, and TNF-alpha are associated with the high incidence of MACE in the follow-up after CEA, indicating that these are potential biomarkers of MACE in this patient population and potential therapeutic targets in patients' progression of systemic atherosclerosis.Plasma cytokines and MACE after CEACytokines logistic regression analysis

Adverse cardiovascular events in patients with cancer: a biomarker-enhanced clinical risk score

Abstract Background/Introduction Continuously improving cancer-specific survival puts a growing proportion of cancer patients at risk of major adverse cardiovascular events (MACE), but reliable tools for cardiovascular risk prediction remain unavailable (1). Purpose To assess a broad panel of cardiovascular biomarkers and clinical risk factors and to provide a novel risk score for the prediction of MACE in cancer patients. Methods Among 2’192 patients with newly diagnosed or recurrent cancer, a broad panel of cardiovascular biomarkers, including NT-proBNP, P-/E-/L-selectins, ICAM-1, VCAM-1, sLOX-1, CRP, and Lp(a) were measured by blinded study personnel. Patients were followed prospectively for the occurrence of 2-year MACE and 5-year cardiovascular death (2,3). Uni- and multivariable competing risk models were fit to assess independent associations of cardiovascular risk factors and biomarkers with MACE, and a risk score was developed. Results Beyond clinical risk factors, ICAM-1, P-/E-/L-selectins and NT-proBNP levels were independently linked to 2-year MACE risk, though shape of associations differed markedly. A clinical risk score was derived, assigning +1 point for male sex, smoking, and age ≥60 years, and +2 points for ASCVD history, yielding a bootstrapped C-statistic of 0.76 (95%CI:0.71-0.81). Implementation of cardiovascular biomarkers conferred improved performance (0.83, 95%CI:0.78-0.88). A simplified model, solely informed by clinical variables and readily available NT-proBNP (+1 point for NT-proBNP≥230pg/mL), achieved similar performance (0.80, 95%CI:0.74-0.86), with a cumulative 2-year MACE incidence of 0% in low- and 11.0% in high-risk patients. Conclusions Cancer patients are at substantial MACE risk. The herein presented first-of-its-kind risk score, integrating traditional cardiovascular risk factors and biomarkers, including NT-proBNP, effectively predicts 2-year MACE and 5-year cardiovascular death.

Predictors of adverse cardiac events in a large cohort of patients with antiphospholipid syndrome

Abstract Background Non-valvular cardiac disease in antiphospholipid syndrome (APS) has been modestly evaluated. Aim We wanted to assess the prevalence and evolution of major adverse cardiovascular events(MACE) in a cohort of APS patients. Material and Methods From a large cohort of 181 APS patients included in a study from 2011-2012.year data for the occurrence of MACE in 10 years of follow-up were evaluated in 82 patients (86.6% females, 62.2% with primary (PAPS), and 37.8% patients with APS associated with systemic lupus erythematosus (SLE) (sAPS)). At the inclusion in all patients, a transthoracic echocardiography study for the assessment of dimensions and functionality of the left and right heart along with valvular functions and morphology. Standard atherosclerotic risk factors prevalence was analyzed. Antiphospholipid antibodies(aPL) analysis included the detection of aCL (IgG/IgM), ß2GPI (IgG/IgM), and LA, and all patients were treated according to the valid guidelines by the rheumatologist. Data regarding the occurrence of new myocardial infarction (MI), cerebrovascular events (CVI), arterial and/or venous thrombosis, heart failure (HF), and cardiovascular death (considered as MACE) have been collected 10 years after inclusion. Results The prevalence of standard atherosclerotic risk factors was less than 40% in both study groups. Left ventricle ejection fraction(LVEF) was over 45% in more than 90% of patients in both groups (p=0.246) with valvular dysfunction present in 49% of PAPS and 58.1% of sAPS patients (p=0.426). 9.8% PAPS and 12.9% sAPS had coronary artery disease(CAD) (p=0.724) and HF was present in 7.8% PAPS and 3.2% sAPS (p=0.645). MACE occurred in 17.6% of PAPS and 22.6% of sAPS (p=0.585). The new MI occurred in 9.8% of PAPS and 9.7% of sAPS (p=1.000), CVI in 5.9% of PAPS and 3.2% of sAPS (p=1.000), HF in 5.9% of PAPS and 3.2% of sAPS (p=1.000) and cardiovascular death in 9.8% of PAPS and 12.9% of sAPS (p=0.724). New thrombotic events (arterial and/or venous) occurred in 15.7% of PAPS and 17.2% of sAPS (p=1.000). During the follow-up period, 66.7% of PAPS and 55.2% of SAPS (p=0.313) were treated with aspirin, 25.5% of PAPS and 25.0% of sAPS with warfarin, and chloroquine was administered in 46.8% of PAPS and 53.6% of sAPS (p=0.571). Age (p=0.008), gender (p=0.034), thrombotic APS (p=0.033), hypertension (p=0.003), diabetes mellitus (p=0.043), and cardiovascular manifestations present at the time of APS diagnosis (p=0.035), namely CAD (p=0.001) and HF (p=0.005) were significantly associated with 10y MACE. aPL type and category were not associated with 10y MACE. In a multivariate logistic model, age. hypertension, and HF were independent predictors for 10y MACE. Conclusions APS patients develop new cardiovascular events despite optimal medical therapy. Cardiovascular evaluation at the time of diagnosis and proper cardiologist follow-up with the rigorous treatment of standard atherosclerotic risk factors is of utmost importance.

Can the presence of aortic or coronary artery calcifications in the standard of care baseline CT or PET-CT scan of patients with Hodgkin or non-Hodgkin lymphoma be used as a predictor of MACE?

Abstract Background Major adverse cardiovascular events (MACE), commonly defined as acute myocardial infarction, acute coronary syndrome/ischemic heart disease requiring revascularization, stroke, and heart failure, represent a significant cause of mortality among patients with cancer. With increased rates of both cancer and cancer survivorship, the identification of new predictive markers for the development of MACE in this population is crucial for implementing effective preventive and risk-mitigation strategies. Purpose To determine whether the presence of calcifications in the coronary arteries (CAC) or aorta (CA) of lymphoma patients, as reported in standard-of-care PET-CT (Positron Emission Tomography-Computed Tomography) or chest CT (Computed Tomography) scan, can predict the occurrence of MACE. Methods A Retrospective analysis was conducted on a cohort of patients diagnosed with Hodgkin or non-Hodgkin lymphoma and treated with anthracycline-based chemotherapy. Patients were diagnosed from January 1, 2013, and followed through to June 30, 2023. The reference point for the study was the radiologist’s report of the PET-CT or chest CT conducted before the initiation of anthracycline therapy. Patients who did not undergo a PET-CT or CT before the start of treatment, and/or developed MACE before treatment initiation were excluded. Univariate and multivariate adjusted Cox regression models were employed to assess whether the presence of CA and CAC was associated with the development of MACE. Associations with outcomes were evaluated using the Kaplan-Meier method and Cox regression. Results 326 patients were included with a mean age of 55 years (range: 52-60), predominantly male 201 (61%) and white 314 (96%), CAC was reported in 75 patients (23%) and CA in 18 (6%). In the univariate regression model, a statistically significant association was found between the presence of both CA and CAC with the risk of MACE. CAC showed a stronger association with the development of MACE than CA (HR: 3.7 [1-7.9], p=0.0005 vs HR: 2.9 [1- 8.5], p=0.050). In multivariable analysis CAC emerged as the strongest predictor of MACE (HR: 2.9 [1.3 – 6.4], p=0.01), after accounting for hypertension, diabetes, dyslipidemia, and GFR &amp;lt;60 (Table 1), while the association with CA attenuated (HR: 2.01 [0.7-6.5], p=0.2010) and was no longer significant (Table 2). Conclusion CAC in the standard-of-care PET/-CT scans was a predictor of MACE in lymphoma patients treated with anthracyclines, while the association with CA weakened in multivariable analyses and was likely underpowered given the small number of patients with CA. If replicated, this finding warrants closer surveillance of this group of patients and can be considered as a non-invasive cardiovascular risk marker.

Machine learning model using cardiovascular magnetic resonance to predict cardiovascular events in asymptomatic patients with known CAD

Abstract Background Despite declining rates, recurrent cardiovascular events continue to pose significant mortality and morbidity risks in patients with obstructive coronary artery disease (CAD). Traditional prognostic assessments in these patients rely on limited clinical and imaging data. Although several studies have shown the strong prognostic value of stress cardiovascular magnetic resonance (CMR) in asymptomatic patients with known CAD, no dedicated score using CMR was established. Machine learning (ML) methods present an opportunity to leverage a wider array of variables to address this gap. Purpose This study sought to investigate the feasibility and accuracy of ML using stress CMR and clinical data to predict major adverse cardiovascular events (MACE) over a 10-year period in patients with known obstructive CAD, comparing its performance with traditional statistical methods. Methods Between 2009 and 2011, consecutive asymptomatic patients with known obstructive CAD referred for vasodilator stress CMR in two independent centres were followed for the occurrence of MACE defined by cardiovascular mortality or recurrent non-fatal myocardial infarction (MI). Known obstructive CAD was defined by a history of percutaneous coronary intervention, coronary artery bypass surgery, or MI. The first center (N=866) was designated as the derivation cohort for variable selection and model building. The second center (N=224) was used as the validation cohort to evaluate the performance of the final ML-model. Various feature selection methods (Random Forest [RF], XGBoost, and Boruta) were employed to identify robust and informative variables. A final RF model was trained on the derivation cohort and evaluated on the validation cohort. Performance was compared with a standard generalized logistic regression model (GLM), utilizing the receiver operating characteristics (ROC) and the precision-recall (PR) curves as well as the area under the curves (AUC). Results In the derivation cohort (age 67±7 years, LVEF 43±8%, 81% male), 243 (28%) out of 866 patients encountered MACE during the 10-year follow-up period while in the validation cohort (age 67±7 years, LVEF 43±7%, 84% male), 53 (24%) out of 224 patients experienced MACE. Through feature selection method in the derivation cohort, one clinical and four CMR variables emerged as key predictors: number of ischemic segments, number of late gadolinium enhancement (LGE) segments, left ventricular ejection fraction, left ventricular end-diastolic diameter indexed, and age (Figure 1). Using those 5 variables, the RF model significantly outperformed the GLM, demonstrating superior predictive accuracy (AUROC: 0.89 vs. 0.73; PRAUC: 0.78 vs. 0.58, all p&amp;lt;0.001) in the validation cohort (Figure 2). Conclusions A supervised machine learning model using RF, integrating age and stress-CMR data, outperformed traditional statistical methods in predicting 10-year MACE for asymptomatic patients with known CAD.Figure1:Variable selectionFigure2:Models performance on validatio

Platelet Reactivity with MACE in Acute Coronary Syndrome Patients Post-PCI under Dual Antiplatelet Therapy: A Meta-Analysis.

Aim/Background Acute coronary syndrome (ACS), a condition characterized by acute cardiac ischemia, is among the major causes of death from cardiovascular diseases (CVD). However, whether there is a correlation between platelet reactivity and major adverse cardiovascular events (MACE) remains debatable, and whether platelet function tests should be tailored for ACS patients after percutaneous coronary intervention (PCI) is still under discussion. This study aims to investigate the relationship between platelet reactivity and the occurrence of MACE in ACS patients post-PCI and to discuss the implications of these findings. Methods Clinical studies on 'PCI, ACS, dual antiplatelet therapy (DAPT), platelet reactivity, major adverse cardiovascular events (MACE)' up to 31 October 2023, were systematically collected from Embase, PubMed, and the Cochrane Library. Twelve articles meeting predefined criteria were selected. Meta-analysis was performed using Review Manager 5.4 (Cochrane, London, UK) and Stata 15.0 (StataCorp LLC, College Station, TX, USA) to compute pooled effect sizes, assess heterogeneity, explore sources of heterogeneity, and evaluate publication bias. Results Twelve articles consisting of 9297 patients were included. The meta-analysis showed that ACS patients with high platelet reactivity (HPR) who received PCI and used DAPT for 1-2 years had a greater risk of MACE (risk ratio (RR) = 1.79, 95% confidence interval (CI): 1.30-2.46) compared to those with low platelet reactivity. Moreover, greater platelet reactivity was associated independently with all-cause mortality (RR = 2.26, 95% CI: 1.63-3.12), cardiac mortality (RR = 2.87, 95% CI: 2.16-3.8), myocardial infarction (RR = 1.98, 95% CI: 1.53-2.5), in-stent restenosis (RR = 1.87, 95% CI: 1.22-2.87), as well as stroke (RR = 1.62, 95% CI: 1.02-2.57), but not with coronary revascularization events (RR = 0.99, p = 0.96, 95% CI: 0.80-1.24). On the other hand, meta-regression revealed that region (p = 0.99), type of ACS patient (p = 0.16), drug regimen (p = 0.48), testing method (p = 0.51), sampling time (p = 0.70), follow-up time (p = 0.45), and PCI protocol (p = 0.27) were not sources of heterogeneity in the study. Conclusion The meta-analysis outcomes indicate that in ACS patients receiving PCI and using dual antiplatelet therapy for 1-2 years, HPR was independently positively correlated with major adverse cardiovascular events, all-cause (or cardiac) mortality, recurrent myocardial infarction, in-stent restenosis, and stroke. This suggests that platelet reactivity testing has clinical and translational significance in predicting patients' risk of adverse cardiovascular events.