Independent Predictor Of Major Adverse Cardiovascular Events Research Articles

Prognostic impact of fibrinogen in patients with resistant hypertension.

In this study, we investigated the long-term prognostic effects of fibrinogen levels in patients with resistant hypertension. A total of 266 patients with resistant hypertension who had serum fibrinogen measurements and 5 years of follow-up information were retrospectively included in the study. The patients were stratified according to their fibrinogen levels, which were then divided into tertiles. Clinical outcomes for major adverse cardiovascular events (MACE) were assessed at 5 years. MACE was defined as all-cause mortality, cardiovascular mortality, non-fatal myocardial infarction (MI), non-fatal stroke, a new diagnosis of heart failure, or hospitalization for heart failure and peripheral arterial disease. The incidence of MACE at 5 years in patients with resistant hypertension was higher in the highest tertile of fibrinogen. Multivariate analysis identified fibrinogen as an independent predictor of MACE in patients with resistant hypertension (odds ratio = 1.002; 95% CI: 1.001-1.004; p = 0.009). Compared to the lowest tertile, MACE was approximately 2.5 times higher in tertile 2 and approximately 6.9 times higher in the highest tertile. Fibrinogen was able to predict MACE in patients with resistant hypertension (AUC for MACE 0.662 (95% CI 0.596-0.727; p < 0.001) based on receiver operating characteristic curve analysis. In the Kaplan-Meier curve showing follow-up without MACE (MACE-free) according to the fibrinogen cut-off value, the 5-year incidence of MACE was significantly higher in the high fibrinogen group (p < 0.001). Fibrinogen is a risk marker for MACE in patients with resistant hypertension. Antihypertensive therapy aimed at lowering fibrinogen levels may improve prognosis.

High plasma levels of fortilin are associated with cardiovascular events in patients undergoing coronary angiography.

Excessive apoptosis and its insufficient clearance is characteristic of atherosclerotic plaques. Fortilin has potent antiapoptotic property and is abundantly expressed in atherosclerotic plaques. Fortilin-deficient mice had less atherosclerosis with more macrophage apoptosis. Recently, we reported that plasma fortilin levels were high in patients with coronary artery disease (CAD). However, its prognostic value has not been elucidated. We investigated plasma fortilin levels and major adverse cardiovascular events (MACE) in 404 patients (mean age 68 ± 12 years; 276 males) undergoing coronary angiography for suspected CAD. MACE was defined as cardiovascular death, myocardial infarction, unstable angina, heart failure, stroke, or coronary revascularization. Of the 404 patients, 218 (54%) had CAD. Plasma fortilin levels were higher in patients with CAD than without CAD (median 74.9 vs. 70.9 pg/mL, p < 0.05). During a mean follow-up of 5.7 ± 4.2 years, MACE was observed in 59 (15%) patients. Notably, patients with MACE had higher fortilin levels (median 83.0 vs. 71.4 pg/mL) and more often had fortilin level > 80.0 pg/mL (54% vs. 36%) than those without MACE (p < 0.025). A Kaplan-Meier analysis showed lower event-free survival in patients with fortilin > 80.0 pg/mL than in those with ≤ 80.0 pg/mL (p < 0.001). In multivariate Cox proportional hazards analysis, fortilin level (> 80.0 pg/mL) was an independent predictor of MACE (hazard ratio: 2.29, 95%CI: 1.36-3.85, p < 0.002). Among the 218 patients with CAD, fortilin level was also a significant predictor of MACE (hazard ratio: 2.48; 95%CI: 1.34-4.61, p < 0.005). Thus, high plasma fortilin levels were found to be associated with cardiovascular events in patients with CAD as well as those undergoing coronary angiography.

Cardiovascular outcomes in Parkinson’s disease patients from a retrospective cohort study

Parkinson’s disease (PD) reports high rates of morbidity and mortality, but the risk of adverse cardiovascular outcomes in patients with PD has not been fully elucidated. This bi-center retrospective cohort study using the electronic health records (EHR) database of two tertiary hospitals screened a total of 327,292 subjects who visited the outpatient clinic, and 1194 patients with PD were propensity score-matched with a control population. The primary outcome was the occurrence of major adverse cardiovascular events (MACE). Key secondary outcomes included all-cause death, cardiovascular (CV) death, stroke, myocardial infarction (MI), heart failure hospitalization and 30-day CV death. After PS matching, MACE occurrence was not significantly different between PD and non-PD groups (18.2% vs. 17.5%, log-rank p = 0.98). Key secondary outcomes were also similar between the two groups. In patients with PD, MACE rate, and also CV risk score, were higher in patients with more severe PD (according to Hoehn and Yahr scale and unified Parkinson’s disease rating scale), and after multivariable analysis, PD severity was not an independent predictor of MACE. Patients with PD are at an increased risk of adverse cardiovascular outcomes, but the contribution from other common CV risk factors cannot be ignored. The management of prevalent CV risk factors is therefore important in mitigating adverse outcomes among patients with PD.

Prognosis impact of multiple novel lymphocyte-based inflammatory indices in patients with initially diagnosed coronary artery disease.

This study aimed to evaluate six novel lymphocyte-based inflammatory markers (neutrophil-lymphocyte ratio, monocyte-lymphocyte ratio, platelet-lymphocyte ratio [PLR], systemic immune inflammation index [SII], systemic inflammatory response index, and systemic immune inflammation response index [SIIRI]) in patients with newly diagnosed coronary artery disease [CAD]. A total of 959 patients newly diagnosed with CAD and underwent diagnostic coronary angiography were enrolled in this study and followed for major adverse cardiovascular events (MACEs), including cardiovascular death, nonfatal myocardial infarction, and nonfatal stroke. The best cutoff value was used to compare the six indicators. Cox risk regression analysis evaluated the relationship between novel lymphocyte-based inflammatory markers and MACEs in newly diagnosed CAD patients. During a mean follow-up period of 33.3 ± 9.9 months, 229 (23.9%) MACEs were identified. Multivariate Cox regression analysis showed that only SIIRI (hazard ratio [HR]: 5.853; 95% confidence interval [CI]: 4.092-8.371; p < .001) and PLR (HR: 1.725; 95% CI: 1.214-2.452; p = .002) were independent predictors of MACEs. Nevertheless, following the adjustment for covariates, only the SIIRI was found to be a significant predictor MACEs and its corresponding specific endpoint occurrences. The predictive ability of the model was improved when six different inflammatory markers were added to the basic model established by traditional risk factors, namely, the C-index increased, and the SIIRI increased most significantly (AUC: 0.778; 95% CI: 0.743-0.812; p < .001). However, among the six novel inflammatory markers, only SIIRI had improved net reclassification improvement (NRI) and integrated discrimination improvement (IDI) (NRI: 0.187; 95% CI: 0.115-0.259, p < .001. IDI: 0.135; 95% CI: 0.111-0.159, p < .001), which was superior to the basic model established by traditional risk factors. SIIRI isindependent predictor of MACEs in newly diagnosed CAD patients. SIIRI was superior to other measures in predicting MACEs. The combination of SIIRI and traditional risk factors can more accurately predict MACEs.

Joint Association of Lipoprotein(a) and a Family History of Coronary Artery Disease with the Cardiovascular Outcomes in Patients with Chronic Coronary Syndrome.

No data are currently available regarding the association between Lp(a) and the cardiovascular outcomes in patients with coronary artery disease (CAD) according to their family history (FHx) of CAD. This study aimed to evaluate the significance of Lp(a) in predicting major adverse cardiovascular events (MACEs) in patients with chronic coronary syndrome (CCS) with or without FHx. A total of 6056 patients with CCS were enrolled. Information on FHx was collected, and the plasma Lp(a) levels were measured. All patients were followed up regularly. The independent and joint associations of Lp(a) and FHx with the risk of MACEs, including cardiovascular death, nonfatal myocardial infarction, and stroke, were analyzed. With over an average of 50.35±18.58 months follow-up, 378 MACEs were recorded. A Cox regression analysis showed an elevated Lp(a) level to be an independent predictor for MACEs in patients with [hazard ratio (HR): 2.77, 95% confidence interval (CI): 1.38-5.54] or without FHx (HR: 1.35, 95% CI: 1.02-1.77). In comparison to subjects with non-elevated Lp(a) and negative FHx, patients with elevated Lp(a) alone were at a nominally higher risk of MACEs (HR: 1.26, 95% CI: 0.96-1.67), while those with both had the highest risk (HR: 1.93, 95% CI: 1.14-3.28). Moreover, adding Lp(a) to the original model increased the C-statistic by 0.048 in subjects with FHx (p=0.004) and by 0.004 in those without FHx (p=0.391). The present study is the first to suggest that Lp(a) could be used to predict MACEs in CCS patients with or without FHx; however, its prognostic significance was more noteworthy in patients with FHx.

Relationship Between CHA₂DS₂-VASc Score on Admission and In-Hospital Major Adverse Cardiovascular Events in Patients Diagnosed With ST-Elevation Myocardial Infarction.

The CHA₂DS₂-VASc (congestive heart failure, hypertension, age, diabetes mellitus, stroke, vascular disease, sex) scoring system, which includes conventional risk factors of coronary artery disease, was originally created to quantify the risk of thromboembolism in patients with atrial fibrillation. This study evaluated the usefulness of this score to predict adverse outcomes in STEMI (ST-elevation myocardial infarction) patients without atrial fibrillation. Primary end points were identified as MACE (major adverse cardiovascular events) which included in-hospital death or cerebrovascular accident. MACE rate was 10% (193 patients). The CHA₂DS₂-VASc score was an independent predictor of MACE (95% CI, 2.31 [1.37-3.9]; P = .0016). Other independent predictors of MACE included heart rate (95% CI, 1.56 [0.97-2.50]; P = .0242), admission Killip class (95% CI, 24.19 [10.74-54.46]; P < .0001), admission creatinine level (95% CI, 1.54 [1.10-2.16]; P = .0024), peak CK-MB level (95% CI, 1.63 [0.98-2.70]; P = .0001), and no-reflow (95% CI, 2.45 [1.25-4.80]; P = .0085). A nomogram was developed to estimate the risk of in-hospital adverse outcomes for STEMI patients. The CHA₂DS₂-VASc score was an independent predictor of MACE in STEMI patients. Linear analysis of CHA₂DS₂-VASc score without dichotomization was the main difference of this study from others.

Evaluating the Association between Anomalous Aortic Origin of the Right Coronary Artery from the Left Sinus with Interarterial Course at Coronary CT Angiography and Sudden Cardiac Death.

Purpose To investigate the association between the anomalous aortic origin of the right coronary artery (R-AAOCA) from the left coronary sinus with interarterial course (IAC) found at coronary CT angiography and sudden cardiac death using a large data set from five university hospitals. Materials and Methods From a total of 89 314 CCTA scans (January 2009 to December 2016) that were retrospectively collected, 316 patients with R-AAOCA from the left sinus with IAC were retrospectively collected. After excluding patients with less than 2 years of follow-up, patients who had already undergone cardiovascular surgery or intervention, and patients with arrhythmia or heart failure before undergoing coronary CT angiography, 224 patients were analyzed. Follow-up was terminated upon the occurrence of major adverse cardiovascular events (MACE). Logistic regression was used to identify clinical and radiologic information as independent predictors of MACE. Results The period prevalence of R-AAOCA from the left sinus with IAC was 0.354%. The mean age was 62.03 years, with a male-to-female ratio of 182:134. During follow-up, 19 of 224 patients (8.5%) experienced MACE, but none had sudden cardiac death. Of these cases, only seven (3.13%) were suspected of being due to R-AAOCA from the left sinus with IAC and all of them had unstable angina. Coronary artery disease was significantly associated with MACE (P < .001), while no significant correlation was observed with radiologic features. Conclusion Sudden cardiac death was not associated with R-AAOCA from the left sinus with IAC found at coronary CT angiography. The occurrence of MACE was low, with coronary artery disease being the sole significant predictor of a patient's prognosis. Keywords: Anomalous Aortic Origin of the Right Coronary Artery, Left Coronary Sinus with Interarterial Course, Coronary CT Angiography, Sudden Cardiac Death Supplemental material is available for this article. © RSNA, 2024.

Proposal of a novel cardiovascular risk prediction score in lupus nephritis.

Patients with systemic lupus erythematosus are prone to develop cardiovascular disease (CVD), and have increased morbidity and mortality. We conducted a retrospective analysis on lupus nephritis patients to assess the occurrence and predictors of major adverse cardiovascular events (MACE). Data were collected from patients who underwent kidney biopsy between 2005 and 2020. Statistical analysis was performed to unveil correlations. 91 patients were analyzed in this period, with a mean age of 37.3 ± 12.3 years and 86% being female. The mean follow-up time was 62 ± 48 months. 15.38% of the patients underwent at least one MACE. Two patients deceased of CVD. Increased age (35.81 ± 11.14 vs 45.5 ± 15.11 years, p=0.012) entailed a higher occurrence of MACEs. Neutrophil count (5.15 ± 2.83 vs 7.3 ± 2.99 Giga/L, p=0.001) was higher, whereas diastolic blood pressure (DBP) was lower (89.51 ± 10.96 vs 78.43 ± 6.9 mmHg, p<0.001) at the time of the biopsy in patients with MACE. Age, neutrophil count, and DBP proved to be independent predictors of MACEs. We propose a new model (CANDE - Cardiovascular risk based on Age, Neutrophil count, and Diastolic blood pressure Estimation score) calculated from these variables, which predicts the probability of MACE occurrence. This study underscores the importance of actively screening for cardiovascular risks in this vulnerable patient population. Age, neutrophil count, and diastolic blood pressure have been established as independent risk factors for MACE in lupus nephritis. The CANDE score derived from these parameters may serve as a prompt, cost-effective, and easily accessible estimation tool for assessing the likelihood of major adverse cardiovascular risk. These findings emphasize the necessity for comprehensive management strategies addressing both immune dysregulation and cardiovascular risk factors in systemic lupus erythematosus to mitigate adverse outcomes.

Prevalence, clinical characteristics, and long-term outcomes of new diabetes diagnosis in elderly patients undergoing percutaneous coronary intervention

Previous studies have reported associations between newly diagnosed diabetes and poor outcomes after percutaneous coronary intervention (PCI), but there is limited data focusing on elderly patients (age ≥ 65). This study aimed to analyze the prevalence and clinical implications of newly diagnosed diabetes in elderly patients who underwent PCI. From 2004 to 2021, a total of 2456 elderly patients who underwent invasive PCI at Korea University Guro Hospital were prospectively enrolled and followed up for a median of five years. The primary endpoint was five-year major adverse cardiovascular events (MACE). Cox regression was used to evaluate whether newly diagnosed diabetes impacted on long-term clinical outcomes. Newly diagnosed diabetes was presented in approximately 8.1% to 10.9% of elderly patients who underwent PCI. Those who had a new diagnosis of diabetes had a higher risk of MACE than previously known diabetes (25.28% vs. 19.15%, p = 0.039). After adjusting for significant factors, newly diagnosed diabetes remained an independent predictor of MACE (HR [hazard ratio] 1.64, 95% confidence interval [CI] 1.24–2.17, p < 0.001), cardiac death (HR 2.15, 95% CI 1.29–3.59, p = 0.003) and repeat revascularization (HR 1.52, 95% CI 1.09–2.11, p = 0.013), but not for non-fatal myocardial infarction (HR 1.66, 95% CI 0.94–2.12, p = 0.081). Newly diagnosed diabetes was associated with an increased risk of 5-year MACE compared with non-diabetes and previously diagnosed diabetes in elderly patients underwent PCI. More attention should be given to those elderly newly diagnosed diabetes population.

Serum Apolipoprotein-A2 Levels Are a Strong Predictor of Future Cardiovascular Events in Patients Undergoing Percutaneous Coronary Intervention.

Because apolipoprotein-A2 (ApoA2), a key component of high-density lipoprotein cholesterol (HDL-C), lacks clear clinical significance, we investigated its impact on cardiovascular events in patients undergoing percutaneous coronary intervention (PCI).Methods and Results: We examined 638 patients who underwent PCI with a new-generation drug-eluting stent for acute or chronic coronary syndrome and had their apolipoprotein levels measured between 2016 and 2021. The patients were divided into 2 groups based on the median serum ApoA2 values, and the incidence of major adverse cardiovascular events (MACE) was assessed. Of the 638 patients, 563 (88%) received statin treatment, with a median serum LDL-C level of 93 mg/dL. Furthermore, 137 patients (21.5%) experienced MACE, and Kaplan-Meier analysis revealed that the higher ApoA2 group had a significantly lower incidence of MACE than the lower ApoA2 group (30.9% vs. 41.6%). However, the other apolipoproteins, including ApoA1, ApoB, ApoC2, ApoC3, and ApoE, showed no significant differences in MACE. Multivariable Cox hazard analysis indicated that ApoA2 was an independent predictor of MACEs (hazard ratio, 0.666; 95% confidence interval, 0.465-0.954). Furthermore, ApoA2 levels exhibited the strongest inverse association with high-sensitivity C-reactive protein levels (rs=-0.479). Among all the apolipoproteins, the serum ApoA2 level may be the strongest predictor of future cardiovascular events and prognosis in patients undergoing PCI.

Peri-coronary fat attenuation index combined with high-risk plaque characteristics quantified from coronary computed tomography angiography for risk stratification in new-onset chest pain individuals without acute myocardial infarction.

This study aims to evaluate the role of the peri-coronary Fat Attenuation Index (FAI) and High-Risk Plaque Characteristics (HRPC) in the assessment of coronary heart disease risk. By conducting coronary CT angiography and coronary angiography on 217 patients with newly developed chest pain (excluding acute myocardial infarction), their degree of vascular stenosis, FAI, and the presence and quantity of HRPC were assessed. The study results demonstrate a correlation between FAI and HRPC, and the combined use of FAI and HRPC can more accurately predict the risk of major adverse cardiovascular events (MACE). Additionally, the study found that patients with high FAI were more prone to exhibit high-risk plaque characteristics, severe stenosis, and multiple vessel disease. After adjustment, the combination of FAI and HRPC improved the ability to identify and reclassify MACE. Furthermore, the study identified high FAI as an independent predictor of MACE in patients undergoing revascularization, while HRPC served as an independent predictor of MACE in patients not undergoing revascularization. These findings suggest the potential clinical value of FAI and HRPC in the assessment of coronary heart disease risk, particularly in patients with newly developed chest pain excluding acute myocardial infarction.

Coronary computed tomography angiography-derived total coronary plaque burden associated with subsequent cardiovascular outcomes following percutaneous coronary intervention.

To investigate the association of coronary plaque burden variables derived from coronary computed tomography angiography (CCTA) before patients underwent their first percutaneous coronary intervention (PCI) procedure and major adverse cardiovascular events (MACEs) after PCI. Patients who underwent CCTA before their first PCI were included retrospectively. A radiologist and a cardiologist analyzed CCTA images on a dedicated workstation. The coronary plaque burden variables included total plaque volume, total percent atheroma volume, volumes and fractions of total low-attenuation plaque, total fibrous plaque, and total calcified plaque. The primary outcomes were MACEs, a composite of all-cause death, nonfatal myocardial infarction, nonfatal stroke, and unscheduled coronary revascularization. A total of 230 patients were included in the final analysis. During a median follow-up of 4.8 years, 67 MACEs occurred. Total plaque volume, total percent atheroma volume, volumes of total low-attenuation plaque and total fibrous plaque but not their fractions were independent predictors for MACEs. Compared with the first tertiles, the hazard ratio of the third tertile of total plaque volume, total percent atheroma volume, total low-attenuation plaque volume, and total fibrous plaque volume were 2.06 (95% CI: 1.03-4.15), 2.15 (95% CI: 1.02-4.51), 3.04 (95% CI: 1.45-6.36), and 2.23 (95% CI: 1.11-4.46), respectively. Neither total calcified plaque volume nor fraction was associated with MACEs independently. Selected pre-PCI CCTA-derived variables, including total percent atheroma volume, volumes of total plaque, total low-attenuation plaque and total fibrous plaque, were significantly associated with MACEs after PCI, suggesting that CCTA before PCI reveals the residual risk after revascularization. The coronary plaque burden variables derived from coronary computed tomography angiography before percutaneous coronary intervention are independently associated with major adverse cardiovascular events, which could be instrumental in optimizing patient management. Coronary plaque burden is associated with cardiovascular events in patients with coronary artery disease. Selected total plaque burden variables derived from coronary computed tomography angiography before percutaneous coronary intervention were associated with poor prognosis. Routine coronary computed tomography angiography before percutaneous coronary intervention might be helpful in reducing future risks.

Coronary artery disease severity and risk stratification of patients with non ST-elevation acute coronary syndrome using CHA2DS2-VASc-HSF score

BackgroundRisk stratification assessment of patients with non-ST elevation acute coronary syndrome (NSTE ACS) plays an important role in optimal management and defines the patient’s prognosis. This study aimed to evaluate the ability of CHA2DS2-VASc-HSF score (comprising of the components of the CHA2DS2-VASc score with a male instead of female sex category, hyperlipidemia, smoking, and family history of coronary artery disease respectively) to predict the severity and complexity of CAD and its efficacy in stratification for major adverse cardiovascular events (MACE) in patients with NSTE ACS without known atrial fibrillation.MethodsThis study included 200 patients (males 72.5%, mean age 55.8 ± 10.1 years) who were admitted with NSTE ACS. CHA2DS2-VASC-HSF score was calculated on admission. Patients were classified into three groups according to their CHA2DS2-VASC-HSF score: low score group (< 2; 29 patients), intermediate score group (2–4; 83 patients), and high score group (≥ 5; 88 patients). Coronary angiography was conducted and the Syntax score (SS) was calculated. Clinical follow-up at 6 months of admission for the development of MACE was recorded.ResultsSS was significantly high in the high CHA2DS2-VASc-HSF score group compared with low and intermediate score groups. CHA2DS2-VASc-HSF score had a significant positive strong correlation with syntax score (r = 0.64, P < 0.001). Smoking, vascular disease, hyperlipidemia, and CHA2DS2-VASc-HSF score were independent predictors of high SS. For the prediction of severe and complex CAD, CHA2DS2-VASc-HSF score had a good predictive power at a cut-off value ≥ 5 with a sensitivity of 86% and specificity of 65%. Hypertension, vascular disease, high SS, and CHA2DS2-VASc-HSF score were independent predictors of MACE. CHA2DS2-VASC-HSF score ≥ 4 was identified as an effective cut-off point for the development of MACE with 94% sensitivity and 70% specificity.ConclusionsCHA2DS2-VASC-HSF score is proposed to be a simple bedside score that could be used for the prediction of the severity and complexity of CAD as well as a risk stratification tool for the development of MACE in NSTE ACS patients.

Independent predictors of MACE in patients with cancer

Abstract Funding Acknowledgements None. Background/Introduction Cardiovascular disease and cancer are the leading causes of death worldwide. Both disease entities share common risk factors. More importantly, the main cause of death after disease progression is cardiovascular disease in patients with cancer. Despite the recent advancements in the field of cardio-oncology, the main prognostic factors of major adverse cardiovascular events (MACE) remain elusive. Purpose To investigate prognostic factors of MACE in a single center cardio-oncology registry. Methods Consecutive patients referred to the cardio-oncology outpatient clinic of a tertiary center for cardiologic consultation were included. All patients were followed up clinically or by telephone. Data from national records were also used. Results In total, 115 patients were included in the analysis. Of them, 60 (52.2%) were female and the majority of study population suffered from breast cancer (27%). Thirteen patients (11.3%) had hematologic malignancies and the rest solid tumors. Chemotherapy was received by a total of 94 patients (81,7%). The mean follow -up duration was 446 days. During follow up, 32 MACEs (27.8%) occurred. Death from any cause occurred in 21 patients (including 2 cardiac deaths), hospitalization due to heart failure in 6, myocardial infarction in 2, pulmonary embolism in 3 and stroke in 1 patient. In multivariate logistic regression analysis, diabetes mellitus was an independent predictor of MACE, after adjustment for cardiovascular risk factors and body mass index (OR=3.37, 95% CI 1.14-9.99). In Kaplan Meier plots patients with diabetes mellitus showed higher incidence of MACE (log rank p=0.03). Conclusions In the present single center study, diabetes mellitus emerged as an independent predictor of MACE. This finding confirms the important and primary role of cardio-oncology units in the strict management of cardiovascular risk factors, leading to improved prognosis of this patient-population.Kaplan Meier Curve

In-hospital trimethylamine N-oxide (TMAO) variation predicts major adverse cardiovascular events in myocardial infarction survivors

Abstract Funding Acknowledgements None. Background Trimethylamine N-oxide (TMAO), a gut microbiota result of the fermentation of animal foods rich in choline, L-carnitine and phosphatidylcholine (red meat, egg yolk, dairy food), is associated with alterations in lipid metabolism, increased foam cell formation, promotion of inflammation, oxidative stress, platelet aggregation and thrombosis. To date the data evaluating TMAO as a predictor of mortality and ischemic events in patients with acute myocardial infarction (AMI) based on one-time measurement of TMAO levels lead to conflicting results. TMAO levels are fluctuating and in addition to diet, genetic factors, general condition and some co-morbidities affect its circulating levels. Purpose Since, there is a need for better risk stratification of AMI patients before the hospital discharge for more personalised treatment, we evaluated in-hospital variation in TMAO levels and its impact on outcome. Methods Blood samples from 149 consecutive AMI patients were collected on admission and on discharge. The endpoint was a three-point major adverse cardiovascular events (MACE) composed as all-cause mortality, reinfarction and development of heart failure. Results The majority of AMI patients were male (77%), hospitalized for first coronary event, with mean age 64(11) years. Median circulating TMAO level was significantly higher on admission than on discharge, (7.81 [3.47 –19.98] vs 3.45 [2.3 – 4.78] μM, respectively, p&amp;lt;0.001). In order to evaluate the impact of TMAO variation during the hospital stay on outcome, we estimated TMAO cut-off value by continuous hazard ratio analysis; values above the 3.45 μM were associated with incident of MACE in a linear fashion (Fig. 1a). Subsequently, we stratified AMI patients in 2 groups: 1) LL/HL (low-low/high-low) that included 75 (50.3%) patients whose TMAO levels remained low or were high and decreased during hospitalization and 2) HH/LH (high-high/low-high) including 74 patients (49.7%) patients whose TMAO levels remained elevated or were initially low, but rose above the estimated threshold during hospitalisation (Fig. 1b). Thirty-two (21.5%) patients reached the combined endpoint during the median follow-up of 30 months. The Kaplan-Meier analysis demonstrated that patients from the HH/LH group had a higher likelihood of experiencing MACE (p=0.05) (Fig. 2a). The multivariate Cox analysis revealed that patients in the HH/LH group had over twice the risk of MACE compared to those in the LL/HL group. Furthermore, older age and worse left ventricular systolic function were identified as independent predictors of MACE during long-term follow-up (Fig. 2b). Conclusions AMI patients with permanently elevated or increasing levels of TMAO have a worse outcome. The novelty and the strength of our study is the fact that the direction of variation of TMAO during the index hospitalisation identifies patients at higher risk of MACE during 30 months follow-up.

Prognostic Implications of Left Ventricular Hypertrophy and Mechanical Function in Fabry Disease: A Longitudinal Cohort Study

The prognostic value of different grades of left ventricular hypertrophy (LVH) and left ventricular (LV) mechanical function in Fabry disease is unclear. We aimed to evaluate the association between the severity of LVH, LV mechanical function, and clinical outcomes in Fabry disease. We conducted a retrospective cohort study from a single-center registry of adult patients with Fabry disease. Left ventricular mass index (LVMI) was measured by echocardiography. The severity of LVH was categorized by LVMI using the sex-specific cutoff values. Left ventricular mechanical function was measured as LV global longitudinal strain (GLS) by speckle-tracking analysis. The primary outcome was a composite of major adverse cardiovascular events (MACE) at 5years, including heart failure hospitalization, sustained ventricular tachycardia, acute ischemic stroke, and all-cause mortality. The study included 268 patients (age 50.4±15.4years, men 46.6%) with Fabry disease (83.2% IVS4+919G>A mutation), and 106 patients (39.6%) had LVH. Patients with mild, moderate, or severe LVH had 5-year MACE rates of 7.4%, 10%, and 30.5%, respectively (P<.001). Moreover, patients with impaired LV GLS (<14.1%) had a higher 5-year MACE rate than those with preserved LV GLS (32.1% vs 2.4%, P<.001). Severe LVH was an independent predictor of MACE compared with absence of LVH (adjusted hazard ratio, 12.73; 95% CI, 1.3-124.71; P=.03), after adjusting for age, sex, hypertension, hyperlipidemia, atrial fibrillation, renal function, average E/e', enzyme replacement therapy, and LV GLS. Patients with severe LVH and impaired LV GLS had the highest incidence for MACE (log-rank P<.05), irrespective of sex, genotypes, and whether receiving enzyme replacement therapy or not. Sex-specific grading of LVH by LVMI is practical for risk stratification in patients with Fabry disease, and impaired LV GLS further refines the prognostication.

Intra-hospital variation of gut microbiota product, trimethylamine N-oxide (TMAO), predicts future major adverse cardiovascular events after myocardial infarction

ObjectiveTrimethylamine N-oxide (TMAO) has been associated with atherosclerosis and poor outcome. We evaluated the prognostic impact of intra-hospital TMAO variation on patient outcome. Methods and ResultsBlood samples from 149 patients with acute myocardial infarction (AMI) were taken on admission and discharge. Plasma TMAO was determined by HPLC-MS. The endpoint was a composite three-point MACE (major adverse cardiovascular events), including all-cause mortality, re-infarction, or heart failure (HF) development. Median TMAO concentration on admission was significantly higher than on discharge (respectively, 7.81 [3.47–19.98] vs 3.45 [2.3–4.78] μM, p < 0.001). After estimating the 3.45 μM TMAO cut-off with the analysis of the continuous hazard ratio, we divided our cohort into two groups. The first group included 75 (50.3%) patients whose TMAO levels remained below or decreased under cut-off (low-low/high-low; LL/HL), while the second group included 74 (49.7%) patients whose TMAO levels remained high or increased above the cut-off during hospitalisation (high-high/low-high; HH/LH). During the median 30-month follow-up, 21.5% of patients experienced the composite endpoint. At Kaplan-Meier analysis, a trend of increasing MACE risk was observed in patients in the HH/LH group (p = 0.05). At multivariable Cox analysis, patients from the HH/LH group had more than two times higher risk of MACE during the follow-up than the LL/HL group (HR = 2.15 [95% CI, 1.03–4.5], p = 0.04). Other independent predictors of MACE were older age and worse left ventricular systolic function. ConclusionIn patients with AMI, permanently high or increasing TMAO levels during hospitalisation are associated with a higher risk of MACE during long-term follow-up.

DEep LearnIng-based QuaNtification of epicardial adipose tissue predicts MACE in patients undergoing stress CMR

Background and aimsThis study investigated the additional prognostic value of epicardial adipose tissue (EAT) volume for major adverse cardiovascular events (MACE) in patients undergoing stress cardiac magnetic resonance (CMR) imaging. Methods730 consecutive patients [mean age: 63 ± 10 years; 616 men] who underwent stress CMR for known or suspected coronary artery disease were randomly divided into derivation (n = 365) and validation (n = 365) cohorts. MACE was defined as non-fatal myocardial infarction and cardiac deaths. A deep learning algorithm was developed and trained to quantify EAT volume from CMR. EAT volume was adjusted for height (EAT volume index). A composite CMR-based risk score by Cox analysis of the risk of MACE was created. ResultsIn the derivation cohort, 32 patients (8.7 %) developed MACE during a follow-up of 2103 days. Left ventricular ejection fraction (LVEF) < 35 % (HR 4.407 [95 % CI 1.903–10.202]; p<0.001), stress perfusion defect (HR 3.550 [95 % CI 1.765–7.138]; p<0.001), late gadolinium enhancement (LGE) (HR 4.428 [95%CI 1.822–10.759]; p = 0.001) and EAT volume index (HR 1.082 [95 % CI 1.045–1.120]; p<0.001) were independent predictors of MACE. In a multivariate Cox regression analysis, adding EAT volume index to a composite risk score including LVEF, stress perfusion defect and LGE provided additional value in MACE prediction, with a net reclassification improvement of 0.683 (95%CI, 0.336–1.03; p<0.001). The combined evaluation of risk score and EAT volume index showed a higher Harrel C statistic as compared to risk score (0.85 vs. 0.76; p<0.001) and EAT volume index alone (0.85 vs.0.74; p<0.001). These findings were confirmed in the validation cohort. ConclusionsIn patients with clinically indicated stress CMR, fully automated EAT volume measured by deep learning can provide additional prognostic information on top of standard clinical and imaging parameters.

Cardiovascular outcomes between dapagliflozin versus empagliflozin in patients with diabetes mellitus.

Sodium-glucose co-transporter 2 (SGLT2) inhibitors have been demonstrated to decrease cardiovascular adverse events. However, there is little real-world clinical evidence regarding a direct comparison between dapagliflozin and empagliflozin in patients with diabetes mellitus (DM). A difference in the cardiovascular efficancy of dapagliflozin versus empagliflozin in DM patients was anticipated, aiming to guide the optimal choice of SGLT2 inhibitors based on cardiovascular outcomes. From 2014 to 2020, a total of 1549 patients with DM who were prescribed SGLT2 inhibitors such as dapagliflozin or empagliflozin were retrospectively enrolled. We categorized the study population into two groups: dapagliflozin (n = 981) and empagliflozin group (n = 568). The primary endpoint was major adverse cardiovascular events (MACE), defined as a composite of all-cause death, myocardial infarction (MI), stroke, or hospitalization for heart failure (HF) over a 3-year period. Propensity-score matching was performed (537 patients in each group). The mean age and hemoglobin A1c were 58.2 ± 13.0 years and 8.4 ± 1.7%, respectively. There was no significant difference between the dapagliflozin and empagliflozin groups in the risk of MACE (3.7% vs. 4.8%, hazard ratio [HR], 1.31; 95% confidence interval [CI], 0.73-2.35; p = 0.349). Furthermore, there were no differences between the two groups in secondary endpoints including all-cause death, MI, stroke, and hospitalization for HF. Prior MI and history of HF were independent predictors of MACE. Dapagliflozin and empagliflozin showed no significant difference of real-world clinical cardiovascular outcomes in patients with DM over a 3-year period. Further large randomized clinical trials will be warranted for better evaluation.

Clinical risk factors and features on computed tomography angiography in high-risk carotid artery plaque in patients with type 2 diabetes.

High-risk carotid artery plaque (HPR) is associated with a markedly increased risk of ischemic stroke. The aims of this study were: 1) to examine the prevalence of HRP in a cohort of asymptomatic adults with type 2 diabetes (T2D); 2) to investigate the relationship between HRP, established cardiovascular risk factors and computed tomography angiography (CTA) profile; and 3) to assess whether the presence of HRP is associated with an increased risk of major adverse cardiovascular events (MACE). This was a retrospective cohort study of T2D asymptomatic patients who underwent carotid endarterectomy (CEA) from January 2018 to July 2021. The carotid atherosclerotic plaque (CAP) was assessed for the presence of ulceration, the presence of lipids, fibrosis, thrombotic deposits, hemorrhage, neovascularization, and inflammation. A CAP presenting at least five of these histological features was defined as a HRP (Group A); in all other cases it was defined as a mild to moderate heterogeneous plaque and no-HRP (Group B). CTA features included the presence of rim sign consisting of thin peripheral adventitial calcification (<2 mm) and internal soft plaque (≥2 mm), NASCET percent diameter stenosis, maximum plaque thickness, ulceration, calcification, and intraluminal thrombus were recorded. Binary logistic regression with Uni- and Multivariate was used to evaluate possible predictors for HRP while multivariable Cox Proportional Hazards was used to assess independent predictors for MACE. One hundred eighty-five asymptomatic patients (mean age 73±8 years, 131 men), undergoing carotid endarterectomy, were included. Of these, 124 (67%) had HRP, and the 61 (33%) did not. Diabetic complications (OR 2.4, 95% CI: 1.1-5.1, P=0.01), NASCET stenosis ≥75% (OR 2.4, 95% CI: 1.2-3.7, P=0.02) and carotid RIM sign (OR 4.3, 95% CI: 3.9-7.3, P<0.001) were independently associated with HRP. However, HRP was not associated with a higher risk of MACE (freedom from MACE at 5 years: HRP 83.4% vs. non HRP 87.8%, P=0.72) or a reduction of survival (5-year survival estimates: HRP 96.4% vs. non HRP: 94.6%, P=0.76). A high prevalence of HRP (67%) was observed in asymptomatic and elderly T2D patients. Independent predictors of HRP were diabetic complications, NASCET stenosis ≥75% and carotid RIM sign (OR 4.3, 95% CI: 3.9-7.3, P<0.001). HRP was not associated with an increased risk of MACE during a mean follow-up of 39±24 years.