Addition of eptifibatide and manual thrombus aspiration to ticagrelor does not improve long-term survival after STEMI treated with primary PCI.

Background: Current guidelines recommend that glycoprotein IIb/IIIa inhibitor (GPI) and manual aspiration thrombectomy should not be routinely used in patients with ST-segment elevation myocardial infarction (STEMI) treated by primary percutaneous coronary intervention (pPCI), although there is a lack of dedicated studies. The aim of this study was to examine the impact of combined usage of a potent P2Y12 inhibitor, GPI, and manual aspiration thrombectomy on long-term survival after STEMI. Methods: All STEMI patients treated by pPCI in a tertiary center who have been included prospectively in the local PCI registry between January 2016 and December 2022 were analyzed in this study. Patients were excluded if they required oral anticoagulation or bridging between clopidogrel or ticagrelor during hospitalization. Results: A total of 1,210 patients were included in the present study, with a median follow-up of 2.78 (1.00-4.88) years. Ticagrelor significantly reduced all-cause and cardiovascular-cause mortality [HR = 0.27 (0.21-0.34), p < 0.0001 and HR = 0.23 (0.17-0.30), p < 0.0001, respectively]. Eptifibatide significantly reduced all-cause and cardiovascular-cause mortality [HR = 0.72 (0.57-0.92), p = 0.002, and HR = 0.68 (0.52-0.89), p = 0.001, respectively]. Manual thrombus aspiration had no significant effect on both all-cause and cardiovascular-cause mortality. In multivariate Cox regression, all-cause mortality was reduced by ticagrelor, while eptifibatide or manual thrombus aspiration had no significant effect. However, cardiovascular-cause mortality was reduced by both ticagrelor and eptifibatide, while manual thrombus aspiration had no significant effect. Conclusion: Ticagrelor consistently reduced cardiovascular and all-cause mortality, while eptifibatide reduced only cardiovascular mortality. Manual thrombus aspiration provided no long-term benefit. Our findings support the current guideline recommendation that GPI and manual aspiration thrombectomy should not be routinely used in treatment of STEMI with pPCI.

Emerging Biomarkers for Predicting Clinical Outcomes in Patients with Heart Disease.

Cardiovascular disease is most frequently caused by the development and progression of atherosclerosis. When coronary arteries are afflicted, and the stenoses caused by atherosclerotic plaques are severe enough, the metabolic supply-and-offer balance is disturbed, leading to myocardial ischemia. If atherosclerotic plaques become unstable and local thrombosis develops, a myocardial infarction occurs. Sometimes, myocardial ischemia and infarction may result in significant and irreversible heart failure. To prevent severe complications, such as acute coronary syndromes and ischemia-related heart failure, extensive efforts have been made for developing biomarkers that would help identify patients at increased risk for cardiovascular events. In this two-part study, we attempted to provide a review of existing knowledge of blood biomarkers that may be used in this setting. The first part of this work was dedicated to conventional biomarkers, which are already used in clinical practice. In the second part, here presented, we discuss emerging biomarkers which have not yet become mainstream.

Conventional Biomarkers for Predicting Clinical Outcomes in Patients with Heart Disease.

Atherosclerosis is the main cause of cardiovascular disease worldwide. The progression of coronary atherosclerosis leads to coronary artery disease, with impaired blood flow to the myocardium and subsequent development of myocardial ischemia. Acute coronary syndromes and post-myocardial infarction heart failure are two of the most common complications of coronary artery disease and are associated with worse outcomes. In order to improve the management of patients with coronary artery disease and avoid major cardiovascular events, several risk assessment tools have been developed. Blood and imaging biomarkers, as well as clinical risk scores, are now available and validated for clinical practice, but research continues. The purpose of the current paper is to provide a review of recent findings regarding the use of humoral biomarkers for risk assessment in patients with heart disease.

Inflammatory Biomarkers Associated with In-Hospital Mortality in Critical COVID-19 Patients.

The COVID-19 pandemic poses global healthcare challenges due to its unpredictable clinical course. The aim of this study is to identify inflammatory biomarkers and other routine laboratory parameters associated with in-hospital mortality in critical COVID-19 patients. We performed a retrospective observational study on 117 critical COVID-19 patients. Following descriptive statistical analysis of the survivor and non-survivor groups, optimal cut-off levels for the statistically significant parameters were determined using the ROC method, and the corresponding Kaplan-Meier survival curves were calculated. The inflammatory parameters that present statistically significant differences between survivors and non-survivors are IL-6 (p = 0.0004, cut-off = 27.68 pg/mL), CRP (p = 0.027, cut-off = 68.15 mg/L) and IL-6/Ly ratio (p = 0.0003, cut-off = 50.39). Additionally, other statistically significant markers are creatinine (p = 0.031, cut-off = 0.83 mg/dL), urea (p = 0.0002, cut-off = 55.85 mg/dL), AST (p = 0.0209, cut-off = 44.15 U/L), INR (p = 0.0055, cut-off = 1.075), WBC (p = 0.0223, cut-off = 11.68 × 109/L) and pH (p = 0.0055, cut-off = 7.455). A survival analysis demonstrated significantly higher in-hospital mortality rates of patients with values of IL-6, IL-6/Ly, AST, INR, and pH exceeding previously mentioned thresholds. In our study, IL-6 and IL-6/Ly have a predictive value for the mortality of critically-ill patients diagnosed with COVID-19. The integration of these parameters with AST, INR and pH could contribute to a prognostic score for the risk stratification of critical patients, reducing healthcare costs and facilitating clinical decision-making.

Prediction of 3-year all-cause and cardiovascular cause mortality in a prospective percutaneous coronary intervention registry: Machine learning model outperforms conventional clinical risk scores.

BACKGROUND AND AIMS: Machine learning (ML) models have been proposed as a prognostic clinical tool and superiority over clinical risk scores is yet to be established. Our aim was to analyse the performance of predicting 3-year all-cause- and cardiovascular cause mortality using ML techniques and compare it with clinical scores in a percutaneous coronary intervention (PCI) population. METHODS: An all-comers patient population treated by PCI in a tertiary cardiovascular centre that have been included prospectively in the local registry between January 2016-December 2017 was analysed. The ML model was trained to predict 3-year mortality and prediction performance was compared with that of GRACE, ACEF, SYNTAX II 2020 and TIMI scores. RESULTS: A total number of 2242 patients were included with 12.1% and 14.9% 3-year cardiovascular and -all-cause mortality, respectively. The area under receiver operator characteristic curve for the ML model was higher than that of GRACE, ACEF, SYNTAX II and TIMI scores: 0.886 vs. 0.797, 0.792, 0.757 and 0.696 for 3-year cardiovascular- and 0.854 vs. 0.762, 0.764, 0.730 and 0.691 for 3-year all-cause mortality prediction, respectively (all p ≤ 0.001). Similarly, the area under precision-recall curve for the ML model was higher than that of GRACE, ACEF, SYNTAX II and TIMI scores: 0.729 vs. 0.474, 0.469, 0.365 and 0.389 for 3-year cardiovascular- and 0.718 vs. 0.483, 0.466, 0.388 and 0.395 for 3-year all-cause mortality prediction, respectively (all p ≤ 0.001). CONCLUSION: The ML model was superior in predicting 3-year cardiovascular- and all-cause mortality when compared to clinical scores in a prospective PCI registry.

Absence of Both Right and Left Main Coronary in a COVID Survivor.

The prevalence of isolated right coronary artery (RCA) absence ranges from 0.014% to 0.066% in the general population, but its combination with an absent left main (dual ostium left anterior descending [LAD] and super-dominant left circumflex [LCx]) has not been previously described. We report the case of a rare coronary artery anomaly: an absent RCA with LAD and LCx coronary arteries arising separately from the left coronary sinus. A 53-year-old male with recent COVID-19 infection was referred to our service for coronary computed tomography angiography (CCTA) due to the recent onset of atypical chest pain. The RCA was absent, with no vessel leaving the right or non-coronary sinus. The LAD and LCx emerged from the left coronary sinus, with a "double-barrel" appearance. The LAD was unremarkable, with small, non-stenosed calcified plaque. The LCx had a 3 mm diameter, arching downward in the left atrioventricular groove, passing through the crux cordis, continuing into the right atrioventricular groove, and ending as a left acute artery and sinonodal artery. No significant stenosis was found on any of the vessels, ruling out atherosclerotic coronary disease.

Efficient singlet-state deactivation of cyano-substituted indolines in protic solvents via CN--HO hydrogen bonds.

The photophysical properties of indoline (I) and three of its derivatives, namely, N-methylindoline (MI), 5-cyanoindoline (CI), and 5-cyano-N-methylindoline (CMI), are studied in H-donating solvents of varying polarity. Based on measurements of fluorescence yield and lifetime, and of triplet yield and hydrated-electron formation, two distinct mechanisms of solvent-induced fluorescence quenching are evidenced. The first mechanism involves the cyano substituent and leads to an increase in the rate constant of internal conversion of one order of magnitude in ethanolic solution and of more than two orders of magnitude in water, as compared to solutions in n-hexane or acetonitrile. A similar trend had previously been observed in the case of 4-N,N-dimethylaminobenzonitrile (DMABN). The second mechanism reduces the fluorescence lifetimes of the non-cyanated derivatives in aqueous solution by one order of magnitude and is related to the formation of hydrated electrons. Neither of these mechanisms is influenced by methylation at the ring nitrogen. Quantum chemical calculations are performed on the ground and excited states of the hydrogen-bonded complexes between protic solvents and MI as well as CMI. Stable hydrogen-bonded configurations involving the CN substituent and a solvent OH group are found; these configurations are stable both in the ground and the first excited singlet states, whereas the corresponding complex at the ring amino nitrogen is stable in the ground state only. The CN--HO configuration is therefore a prime candidate for a mechanistic explanation of the observed quenching by the first mechanism. These findings may have useful applications for the design of fluorescence probes for water in biological systems.

Absorption, fluorescence, and cd spectroscopic study of chiral recognition by a binaphthyl-derived chromogenic calixcrown host.

The (R)- and (S)-enantiomers of a binaphthyl-appended calix[4]crown-6 ether with two 2,4-dinitrophenylazo chromophore units ((R)-1 and (S)-1) as chiral hosts were tested in their reactions with the enantiomers of alpha-methylbenzylamine ((R)-MBA, (S)-MBA)) and phenylglycinol ((R)-PGL, (S)-PGL) as chiral guests. The visible absorption spectra indicate a two-step process: the first is a nonenantioselective proton transfer from the host to the guest, which is followed by the enantioselective real complexation. In the visible range of the CD spectra a positive/negative band belongs to the absorption of pure (R)-1/(S)-1, and a negative/positive exciton couplet to the absorption of (R)-1-(S)-MBA/(S)-1-(R)-MBA complexes. The latter phenomenon suggests that the complexation of amines is accompanied by a chiral arrangement of the two chromophore units in the hosts. The UV fluorescence of (R)-1/(S)-1 arising from the binaphthyl moiety is quenched by K+ ions, but not by the amine guests, showing that the interaction between the binaphthyl group and the complexed amines is weak.