Background There are limited data on the association of diabetes mellitus (DM) and levels of glycated hemoglobin (HbA1c) with outcomes in patients with atrial fibrillation (AF). Methods This retrospective cohort study included patients who were recently hospitalized with a primary or secondary diagnosis of AF from December 2015 through June 2018. Kaplan–Meier curves and Cox-regression adjusted hazard ratios (aHR) were calculated for the primary outcome of all-cause mortality and for the secondary outcomes of cardiovascular (CV) mortality and the composite outcome of CV death or hospitalization. Competing-risk regression analyses were performed to calculate the cumulative risk of stroke, major bleeding, AF- or HF-hospitalizations adjusted for the competing risk of all-cause death. Spline curve models were fitted to investigate associations of HbA1c values and mortality among patients with AF and DM. Results In total 1109 AF patients were included, of whom 373 (33.6%) had DM. During a median follow-up of 2.6 years, 414 (37.3%) patients died. The presence of DM was associated with a higher risk of all-cause mortality (aHR = 1.40 95% confidence intervals [CI] 1.11–1.75), CV mortality (aHR = 1.39, 95% CI 1.07–1.81), sudden cardiac death (aHR = 1.73, 95% CI 1.19–2.52), stroke (aHR = 1.87, 95% CI 1.01–3.45) and the composite outcome of hospitalization or CV death (aHR = 1.27, 95% CI 1.06–1.53). In AF patients with comorbid DM, the spline curves showed a positive linear association between HbA1c levels and outcomes, with values 7.6–8.2% being independent predictors of increased all-cause mortality, and values < 6.2% predicting significantly decreased all-cause and CV mortality. Conclusions The presence of DM on top of AF was associated with substantially increased risk for all-cause or CV mortality, sudden cardiac death and excess morbidity. HbA1c levels lower than 6.2% were independently related to better survival rates suggesting that optimal DM control could be associated with better clinical outcomes in AF patients with DM.

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Background Coronary artery disease (CAD) remains one of the leading causes of mortality and morbidity worldwide. As oxygen and nutrient supply to the myocardium significantly decrease during ischemic periods, important changes occur regarding myocardial intermediary energy metabolism. Metabolomics is an emerging field in systems biology, which quantifies metabolic changes in response to disease progression. This study aims to evaluate the diagnostic utility of plasma metabolomics-based biomarkers for determining the complexity and severity of CAD, as it is assessed via the SYNTAX score. Methods Corlipid is a prospective, non-interventional cohort trial empowered to enroll 1065 patients with no previous coronary intervention history, who undergo coronary angiography in University Hospital AHEPA, Thessaloniki. Venous blood samples are collected before coronary angiography. State-of the-art analytical methods are performed to calculate the serum levels of novel biomarkers: ceramides, acyl-carnitines, fatty acids, and proteins such as galectin-3, adiponectin, and the ratio of apolipoprotein B/apolipoprotein A1. Furthermore, all patients will be categorized based on the indication for coronary angiography (acute coronary syndrome, chronic coronary syndrome, preoperative coronary angiography) and on the severity of CAD using the SYNTAX score. Follow-up of 12 months after enrollment will be performed to record the occurrence of major adverse cardiovascular events. A risk prediction algorithm will be developed by combining clinical characteristics with established and novel biomarkers to identify patients at high risk for complex CAD based on their metabolite signatures. The first patient was enrolled in July 2019 and completion of enrollment is expected until May 2021. Discussion CorLipid is an ongoing trial aiming to investigate the correlation between metabolic profile and complexity of coronary artery disease in a cohort of patients undergoing coronary angiography with the potential to suggest a decision-making tool with high discriminative power for patients with CAD. To our knowledge, Corlipid is the first study aspiring to create an integrative metabolomic biomarkers-based algorithm by combining metabolites from multiple classes, involved in a wide range of pathways with well-established biochemical markers. Trial registration CorLipid trial registration: ClinicalTrials.gov number: NCT04580173. Registered 8 October 2020—Retrospectively registered, https://clinicaltrials.gov/ct2/show/NCT04580173.

Background: Angiographic detection of thrombus in STEMI is associated with adverse outcomes. However, routine thrombus aspiration failed to demonstrate the anticipated benefit. Hence, management of high coronary thrombus burden remains challenging. We sought to assess for the first time extracted thrombotic material characteristics utilizing micro-computed tomography (micro-CT).Methods: One hundred thirteen STEMI patients undergoing thrombus aspiration were enrolled. Micro-CT was undertaken to quantify retrieved thrombus volume, surface, and density. Correlation of these indices with angiographic and electrocardiographic outcomes was performed.Results: Mean aspirated thrombus volume, surface, and density (±standard deviation) were 15.71 ± 20.10 mm3, 302.89 ± 692.54 mm2, and 3139.04 ± 901.88 Hounsfield units, respectively. Aspirated volume and surface were significantly higher (p &lt; 0.001) in patients with higher angiographic thrombus burden. After multivariable analysis, independent predictors for thrombus volume were reference vessel diameter (RVD) (p = 0.011), right coronary artery (RCA) (p = 0.039), and smoking (p = 0.027), whereas RVD (p = 0.018) and RCA (p = 0.019) were predictive for thrombus surface. Thrombus volume and surface were independently associated with distal embolization (p = 0.007 and p = 0.028, respectively), no-reflow phenomenon (p = 0.002 and p = 0.006, respectively), and angiographically evident residual thrombus (p = 0.007 and p = 0.002, respectively). Higher thrombus density was correlated with worse pre-procedural TIMI flow (p &lt; 0.001). Patients with higher aspirated volume and surface developed less ST resolution (p = 0.042 and p = 0.023, respectively).Conclusions: Angiographic outcomes linked with worse prognosis were more frequent among patients with larger extracted thrombus. Despite retrieving larger thrombus load in these patients, current thrombectomy devices fail to deal with thrombotic material adequately. Further studies of novel thrombus aspiration technologies are warranted to improve patient outcomes.Clinical Trial Registration: QUEST-STEMI trial ClinicalTrials.gov number: NCT03429608 Date of registration: February 12, 2018. The study was prospectively registered.

Background Diabetes mellitus (DM) and coronary artery disease (CAD) constitute inter-related clinical entities. Biomarker profiling emerges as a promising tool for the early diagnosis and risk stratification of either DM or CAD. However, studies assessing the predictive capacity of novel metabolomics biomarkers in coexistent CAD and DM are scarce. Methods This post-hoc analysis of the CorLipid trial (NCT04580173) included 316 patients with CAD and comorbid DM who underwent emergency or elective coronary angiography due to acute or chronic coronary syndrome. Cox regression analyses were performed to identify metabolomic predictors of the primary outcome, which was defined as the composite of major adverse cardiovascular or cerebrovascular events (MACCE: cardiovascular death, myocardial infarction, stroke, major bleeding), repeat unplanned revascularizations and cardiovascular hospitalizations. Linear regression analyses were also performed to detect significant predictors of CAD complexity, as assessed by the SYNTAX score. Results After a median 2-year follow up period (IQR = 0.7 years), the primary outcome occurred in 69 (21.8%) of patients. Acylcarnitine ratio C4/C18:2, apolipoprotein (apo) B, history of heart failure (HF), age > 65 years and presence of acute coronary syndrome were independent predictors of the primary outcome in diabetic patients with CAD (aHR = 1.89 [1.09, 3.29]; 1.02 [1.01, 1.04]; 1.28 [1.01, 1.41]; 1.04 [1.01, 1.05]; and 1.12 [1.05–1.21], respectively). Higher levels of ceramide ratio C24:1/C24:0, acylcarnitine ratio C4/C18:2, age > 65 and peripheral artery disease were independent predictors of higher CAD complexity (adjusted β = 7.36 [5.74, 20.47]; 3.02 [0.09 to 6.06]; 3.02 [0.09, 6.06], respectively), while higher levels of apoA1 were independent predictors of lower complexity (adjusted β= − 0.65 [− 1.31, − 0.02]). Conclusions In patients with comorbid DM and CAD, novel metabolomic biomarkers and metabolomics-based prediction models could be recruited to predict clinical outcomes and assess the complexity of CAD, thereby enabling the integration of personalized medicine into routine clinical practice. These associations should be interpreted taking into account the observational nature of this study, and thus, larger trials are needed to confirm its results and validate them in different and larger diabetic populations.

Adults with congenital heart disease (ACHD) experience more thromboembolic complications than the general population. We systematically searched and critically appraised all studies on the safety and efficacy of non-vitamin-K oral anticoagulants (NOACs) in adult patients with various forms of congenital heart disease. PubMed and the Cochrane Central Register of Controlled Trials (CENTRAL) were used, with duplicate extraction of data and risk of bias assessment. The Newcastle-Ottawa quality assessment scale was used to assess study quality. Three studies fulfilled the inclusion criteria and were analyzed. The total number of participants was 766, with a total follow-up of 923 patient-years. The majority of patients (77%) received a NOAC for atrial arrhythmias, while the remainder were prescribed NOACs for secondary (19%) or primary (4%) thromboprophylaxis. The annual rate of thromboembolic and major bleeding events was low: 0.98% (95% CI: 0.51–1.86) and 1.74% (95% CI: 0.86–3.49) respectively. In Fontan patients, the annual rate of thromboembolic and major bleeding events was 3.13% (95% CI: 1.18–8.03) and 3.17% (95% CI: 0.15–41.39) respectively. NOACs appear safe and effective in ACHD without mechanical prostheses. Additional studies are, however, needed to confirm their efficacy in complex ACHD, especially those with a Fontan-type circulation.

ST-elevation myocardial infarction (STEMI) remains one of the leading causes of mortality worldwide. The identification of novel metabolic and imaging biomarkers could unveil key pathophysiological mechanisms at the molecular level and promote personalized care in patients with acute coronary syndromes. We studied 38 patients with STEMI who underwent primary percutaneous coronary intervention and thrombus aspiration. We sought to correlate serum ceramide levels with micro-CT quantified aspirated thrombus volume and relevant angiographic outcomes, including modified TIMI thrombus grade and pre- or post-procedural TIMI flow. Higher ceramide C16:0 levels were significantly but weakly correlated with larger aspirated thrombus volume (Spearman r = 0.326, p = 0.046), larger intracoronary thrombus burden (TB; p = 0.030) and worse pre- and post-procedural TIMI flow (p = 0.049 and p = 0.039, respectively). Ceramides C24:0 and C24:1 were also significantly associated with larger intracoronary TB (p = 0.008 and p = 0.001, respectively). Receiver operating characteristic analysis demonstrated that ceramides C24:0 and C24:1 could significantly predict higher intracoronary TB (area under the curve: 0.788, 95% CI: 0.629–0.946 and 0.846, 95% CI: 0.706–0.985, respectively). In conclusion, serum ceramide levels were higher among patients with larger intracoronary and aspirated TB. This suggests that quantification of serum ceramides might improve risk-stratification of patients with STEMI and facilitate an individualized approach in clinical practice.

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