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OBJECTIVE Posthemorrhagic hydrocephalus (PHH) is associated with significant morbidity, smaller hippocampal volumes, and impaired neurodevelopment in preterm infants. The timing of temporary CSF (tCSF) diversion has been studied; however, the optimal time for permanent CSF (pCSF) diversion is unknown. The objective of this study was to determine whether cumulative ventricle size or timing of pCSF diversion is associated with neurodevelopmental outcome and hippocampal size in preterm infants with PHH. METHODS Twenty-five very preterm neonates (born at ≤ 32 weeks’ gestational age) with high-grade intraventricular hemorrhage (IVH), subsequent PHH, and pCSF diversion with a ventriculoperitoneal shunt (n = 20) or endoscopic third ventriculostomy (n = 5) were followed until 2 years of age. Infants underwent serial cranial ultrasounds from birth until 1 year after pCSF diversion, brain MRI at term-equivalent age, and assessment based on the Bayley Scales of Infant and Toddler Development, Third Edition, at 2 years of age. Frontooccipital horn ratio (FOHR) measurements were derived from cranial ultrasounds and term-equivalent brain MRI. Hippocampal volumes were segmented and calculated from term-equivalent brain MRI. Cumulative ventricle size until the time of pCSF diversion was estimated using FOHR measurements from each cranial ultrasound performed prior to permanent intervention. RESULTS The average gestational ages at tCSF and pCSF diversion were 28.9 and 39.0 weeks, respectively. An earlier chronological age at the time of pCSF diversion was associated with larger right hippocampal volumes on term-equivalent MRI (Pearson’s r = −0.403, p = 0.046) and improved cognitive (r = −0.554, p = 0.047), motor (r = −0.487, p = 0.048), and language (r = −0.414, p = 0.021) outcomes at 2 years of age. Additionally, a smaller cumulative ventricle size from birth to pCSF diversion was associated with larger right hippocampal volumes (r = −0.483, p = 0.014) and improved cognitive (r = −0.711, p = 0.001), motor (r = −0.675, p = 0.003), and language (r = −0.618, p = 0.011) outcomes. There was no relationship between time to tCSF diversion or cumulative ventricle size prior to tCSF diversion and neurodevelopmental outcome or hippocampal size. Finally, a smaller cumulative ventricular size prior to either tCSF diversion or pCSF diversion was associated with a smaller ventricular size 1 year after pCSF diversion (r = 0.422, p = 0.040, R2 = 0.178 and r = 0.519, p = 0.009, R2 = 0.269, respectively). CONCLUSIONS In infants with PHH, a smaller cumulative ventricular size and shorter time to pCSF diversion were associated with larger right hippocampal volumes, improved neurocognitive outcomes, and reduced long-term ventriculomegaly. Future prospective randomized studies are needed to confirm these findings.

Objective To investigate resting‐state functional connectivity (FC) in pediatric patients with tuberous sclerosis complex and intractable epilepsy requiring surgery. Methods Resting‐state functional MRI was utilized to investigate functional connectivity in 13 pediatric patients with tuberous sclerosis complex (TSC) and intractable epilepsy requiring surgery. Results The majority of patients demonstrated a resting‐state network architecture similar to those reported in healthy individuals. However, preoperative differences were evident between patients with high versus low tuber burden, as well as those with good versus poor neurodevelopmental outcomes, most notably in the cingulo‐opercular and visual resting‐state networks. One patient with high tuber burden and poor preoperative development and seizure control had nearly normal development and seizure resolution after surgery. This was accompanied by significant improvement in resting‐state network architecture just one day postoperatively. Significance Although many patients with tuberous sclerosis complex and medically refractory epilepsy demonstrate functional connectivity patterns similar to healthy children, relationships within and between RSNs demonstrate clear differences in patients with higher tuber burden and worse outcomes. Improvements in resting‐state network organization postoperatively may be related to epilepsy surgery outcomes, providing candidate biomarkers for clinical management in this high‐risk population.

Purpose: Higher risk of bleeding with ticagrelor over clopidogrel in elderly patients with acute coronary syndrome (ACS) who underwent percutaneous coronary intervention (PCI) has been suggested. We assessed the incidence of major bleedings (MB), reinfarction (re-MI), and all-cause death to evaluate safety and efficacy of ticagrelor versus clopidogrel in such population. Methods: Real-world registries RENAMI and BleeMACS were merged. The pooled cohort was divided into two groups, clopidogrel versus ticagrelor. Statistical analysis considered patients

Objectives: This study sought to compare the pharmacodynamic effects of pre-hospitally administered P2Y12 inhibitor prasugrel in crushed versus integral tablet formulation in patients with ST-segment elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention (pPCI). Background: Early dual antiplatelet therapy is recommended in STEMI patients. Yet, onset of oral P2Y12 inhibitor effect is delayed and varies according to formulation administered. Methods: The COMPARE CRUSH (Comparison of Pre-hospital Crushed Versus Uncrushed Prasugrel Tablets in Patients With STEMI Undergoing Primary Percutaneous Coronary Interventions) trial randomized patients with suspected STEMI to crushed or integral prasugrel 60-mg loading dose in the ambulance. Pharmacodynamic measurements were performed at 4 time points: before antiplatelet treatment, at the beginning and end of pPCI, and 4 h after study treatment onset. The primary endpoint was high platelet reactivity at the end of pPCI. The secondary endpoint was impact of platelet reactivity status on markers of coronary reperfusion. Results: A total of 441 patients were included. In patients with crushed prasugrel, the occurrence of high platelet reactivity at the end of pPCI was reduced by almost one-half (crushed 34.7% vs. uncrushed 61.6%; odds ratio [OR] = 0.33; 95% confidence interval [CI] = 0.22 to 0.50; p < 0.01). Platelet reactivity 12 reactivity units at the beginning of coronary angiography correlated with improved Thrombolysis In Myocardial Infarction flow grade 3 in the infarct artery pre-pPCI (OR: 1.78; 95% CI: 1.08 to 2.94; p = 0.02) but not ST-segment resolution (OR: 0.80; 95% CI: 0.48 to 1.34; p = 0.40). Conclusions: Oral administration of crushed compared with integral prasugrel significantly improves platelet inhibition during the acute phase in STEMI patients undergoing pPCI. However, a considerable number of patients still exhibit inadequate platelet inhibition at the end of pPCI, suggesting the need for alternative agents to bridge the gap in platelet inhibition.

We compared the effects of Heat-not-Burn cigarette (HNBC) to those of tobacco cigarette (Tcig), on myocardial, coronary and arterial function as well as on oxidative stress and platelet activation in 75 smokers. In the acute study, 50 smokers were randomised into smoking a single Tcig or a HNBC and after 60 min were crossed-over to the alternate smoking. For chronic phase, 50 smokers were switched to HNBC and were compared with an external group of 25 Tcig smokers before and after 1 month. Exhaled carbon monoxide (CO), pulse wave velocity (PWV), malondialdehyde (MDA) and thromboxane B2 (TxB2) were assessed in the acute and chronic study. Global longitudinal strain (GLS), myocardial work index (GWI), wasted myocardial work (GWW), coronary flow reserve (CFR), total arterial compliance (TAC) and flow-mediated dilation (FMD) were assessed in the chronic study. Acute HNBC smoking caused a smaller increase of PWV than Tcig (change 1.1 vs 0.54 m/s, p Trial registration Registered on https://clinicaltrials.gov/ (NCT03452124, 02/03/2018).

Summary Background The accuracy of current prediction tools for ischaemic and bleeding events after an acute coronary syndrome (ACS) remains insufficient for individualised patient management strategies. We developed a machine learning-based risk stratification model to predict all-cause death, recurrent acute myocardial infarction, and major bleeding after ACS. Methods Different machine learning models for the prediction of 1-year post-discharge all-cause death, myocardial infarction, and major bleeding (defined as Bleeding Academic Research Consortium type 3 or 5) were trained on a cohort of 19 826 adult patients with ACS (split into a training cohort [80%] and internal validation cohort [20%]) from the BleeMACS and RENAMI registries, which included patients across several continents. 25 clinical features routinely assessed at discharge were used to inform the models. The best-performing model for each study outcome (the PRAISE score) was tested in an external validation cohort of 3444 patients with ACS pooled from a randomised controlled trial and three prospective registries. Model performance was assessed according to a range of learning metrics including area under the receiver operating characteristic curve (AUC). Findings The PRAISE score showed an AUC of 0·82 (95% CI 0·78–0·85) in the internal validation cohort and 0·92 (0·90–0·93) in the external validation cohort for 1-year all-cause death; an AUC of 0·74 (0·70–0·78) in the internal validation cohort and 0·81 (0·76–0·85) in the external validation cohort for 1-year myocardial infarction; and an AUC of 0·70 (0·66–0·75) in the internal validation cohort and 0·86 (0·82–0·89) in the external validation cohort for 1-year major bleeding. Interpretation A machine learning-based approach for the identification of predictors of events after an ACS is feasible and effective. The PRAISE score showed accurate discriminative capabilities for the prediction of all-cause death, myocardial infarction, and major bleeding, and might be useful to guide clinical decision making. Funding None.

Background The fear of contagion during the coronavirus disease-2019 (COVID-19) pandemic may have potentially refrained patients with ST-segment elevation myocardial infarction (STEMI) from accessing the emergency system, with subsequent impact on mortality. Objectives The ISACS-STEMI COVID-19 registry aims to estimate the true impact of the COVID-19 pandemic on the treatment and outcome of patients with STEMI treated by primary percutaneous coronary intervention (PPCI), with identification of “at-risk” patient cohorts for failure to present or delays to treatment. Methods This retrospective registry was performed in European high-volume PPCI centers and assessed patients with STEMI treated with PPPCI in March/April 2019 and 2020. Main outcomes are the incidences of PPCI, delayed treatment, and in-hospital mortality. Results A total of 6,609 patients underwent PPCI in 77 centers, located in 18 countries. In 2020, during the pandemic, there was a significant reduction in PPCI as compared with 2019 (incidence rate ratio: 0.811; 95% confidence interval: 0.78 to 0.84; p, Central Illustration

Background: Acute myocardial infarction (AMI) recurrence is still high despite great progress in secondary prevention. Patients with recurrent AMI suffer worse prognosis compared to those with first AMI. The objective was to evaluate the effect of optimal medical therapy (OMT) on these patients with recurrent AMI. Methods and results: Sub-analysis was performed including 13,343 patients with AMI from the international multicenter Bleeding complications in a Multicenter registry of patients discharged with diagnosis of Acute Coronary Syndrome (BleeMACS) registry. OMT was defined as the combination of aspirin, any P2Y12 inhibitor, statin, angiotensin converting enzyme inhibitor/angiotensin receptor blocker, and beta-blocker. Among 1285 patients with prior AMI, 56.8% received OMT prescription. Patients receiving OMT suffered from less congestive heart failure, peripheral artery disease, malignancy, and bleeding history. Kaplan-Meier survival estimates revealed that OMT was strongly related to decreased in all-cause death (4.2% vs. 10.1%, p < .001) and the composite endpoint of death/re-AMI (11.1% vs. 16.9%, p = .005) at 1-year follow-up. OMT was the independent protect factor of primary endpoint even after adjusting for multiple possible confounders (HR, 0.46; 95% CI, 0.27–0.78; p = .004). However, no significant difference was observed regarding re-AMI between OMT and non-OMT groups. OMT also reduced all-cause death in patients with recurrent AMI after propensity score matching. Conclusions: The prescription of OMT was seriously insufficient in patients with recurrent AMI, especially high-risk patients, even though OMT was associated with improved prognosis. Further improvements in pharmacological therapy are needed to reduce subsequent recurrent events.

Patients with atrial fibrillation (AF) undergoing percutaneous coronary intervention (PCI) are a high-risk subset of patients, whose optimal antithrombotic treatment strategy, involving a combination of anticoagulant and antiplatelet agents, has not been well defined. Our study aims to investigate contemporary “real-world” trends of antithrombotic treatment strategies in AF patients undergoing PCI, as well as identify factors affecting decision-making at hospital discharge. “Real-world” data were retrieved from the GReek-AntiPlatElet Atrial Fibrillation (GRAPE-AF) registry, a contemporary, nationwide, multicenter, observational study of AF patients undergoing PCI. Characteristics of patients discharged on triple antithrombotic therapy (TAT) or dual antithrombotic therapy (DAT) were compared in order to identify factors that could influence treatment decisions. A total of 654 patients were enrolled (42% with stable coronary artery disease, 58% with acute coronary syndrome). TAT was adopted in 49.9% and DAT in 49.2% of patients at discharge. Regarding anticoagulants, the vast majority of patients (92.9%) received non-vitamin K antagonist oral anticoagulants (NOACs) and only 7.1% received vitamin K antagonists (VKAs). Dyslipidemia, insulin-dependent diabetes mellitus, prior myocardial infarction, acute coronary syndrome at presentation, and regional variations were predictive of TAT adoption, whereas the use of NOACs or ticagrelor was predictive of DAT adoption. Contemporary “real-world” data concerning antithrombotic treatment in AF patients undergoing PCI indicate a strong shift towards the use of NOACs instead of VKAs, along with a large subset of patients adopting an aspirin-free strategy early after index PCI, with clinical as well as treatment characteristics affecting decision-making. ClinicalTrials.gov Identifier: NCT03362788 (First Posted: December 5, 2017)

Background: The rate of intracranial haemorrhage after an acute coronary syndrome has been studied in detail in the era of thrombolysis; however, in the contemporary era of percutaneous coronary intervention, most of the data have been derived from clinical trials. With this background, we aim to analyse the incidence, timing, predictors and prognostic impact of post-discharge intracranial haemorrhage in patients with acute coronary syndrome undergoing percutaneous coronary intervention. Methods: We analysed data from the BleeMACS registry (patients discharged for acute coronary syndrome and undergoing percutaneous coronary intervention from Europe, Asia and America, 2003–2014). Analyses were conducted using a competing risk framework. Uni and multivariate predictors of intracranial haemorrhage were assessed using the Fine–Gray proportional hazards regression analysis. The endpoint was 1-year post-discharge intracranial haemorrhage. Results: Of 11,136 patients, 30 presented with intracranial haemorrhage during the first year (0.27%). The median time to intracranial haemorrhage was 150 days (interquartile range 55.7–319.5). The fatality rate of intracranial haemorrhage was very high (30%). After multivariate analysis, only age (subhazard ratio 1.05, 95% confidence interval 1.01–1.07) and prior stroke/transient ischaemic attack (hazard ratio 3.29, 95% confidence interval 1.36–8.00) were independently associated with a higher risk of intracranial haemorrhage. Hypertension showed a trend to associate with higher intracranial haemorrhage rate. The combination of older age (⩾75 years), prior stroke/transient ischaemic attack, and/or hypertension allowed us to identify most of the patients with intracranial haemorrhage (86.7%). The annual rate of intracranial haemorrhage was 0.1% in patients with no risk factors, 0.2% in those with one factor, 0.6% in those with two factors and 1.3% in those with three factors. Conclusion: The incidence of intracranial haemorrhage in the first year after an acute coronary syndrome treated with percutaneous coronary intervention is low. Advanced age, previous stroke/transient ischaemic attack, and hypertension are the main predictors of increased intracranial haemorrhage risk.

International audience; Background: Dual antiplatelet therapy constitutes the cornerstone of medical treatment in patients with ST elevation myocardial infarction (STEMI). However, oral antiplatelet agents, such as prasugrel or ticagrelor, are characterized by slow gastrointestinal drug absorption in the acute phase of STEMI, leading to decreased bioavailability and therefore delayed onset of platelet inhibition. Evidence suggests that administration of crushed tablets of the P2Y12 inhibitor prasugrel improves drug absorption and achieves earlier antiplatelet effects in STEMI patients undergoing primary percutaneous coronary intervention (PCI). However, the clinical implications of these pharmacokinetic and pharmacodynamic findings are unknown.Hypothesis: The present study is designed to test the hypothesis that patients presenting with STEMI planned for primary PCI will have improved markers of optimal reperfusion and clinical outcomes by prehospital administration of crushed tablets of prasugrel loading dose.Study design: COMPARE CRUSH (NCT03296540) is a randomized trial in a regionally organized ambulance care setting evaluating the efficacy and safety of pre-hospital loading dose with prasugrel crushed tablets versus integral tablets in approximately 674 patients presenting with STEMI planned for primary PCI. The independent primary endpoints are percentage of patients reaching thrombolysis in myocardial infarction (TIMI) flow grade 3 in the infarct-related artery at initial angiography, or achieving ≥70% ST-segment elevation resolution at 1 hour post-PCI. Secondary clinical endpoints are death, myocardial infarction, revascularization, and stent thrombosis followed up to 1 year. Moreover, the primary safety endpoint is bleeding events assessed at 48 hours.Conclusions: The COMPARE CRUSH trial will assess whether prehospital administration of loading dose prasugrel in form of crushed tablets - which is expected to provide faster platelet inhibition compared to standard treatment with integral tablets - results in improved reperfusion and clinical outcomes.

BACKGROUND The risk of recurrent ischemia and bleeding after percutaneous coronary intervention (PCI) for acute coronary syndrome (ACS) may vary during the first year of follow-up according to clinical presentation, and medical and interventional strategies. METHODS BleeMACS and RENAMI are 2 multicenter registries enrolling patients with ACS treated with PCI and clopidogrel, prasugrel, or ticagrelor. The average daily ischemic and bleeding risks (ADIR and ADBR) in the first year after PCI were the primary end points. The difference between ADBR and ADIR was calculated to estimate the potential excess of bleeding/ischemic events in a given period or specific subgroup. RESULTS A total of 19,826 patients were included. Overall, in the first year after PCI, the ADBR was 0.008085%, whereas ADIR was 0.008017% (P = .886). In the first 2 weeks ADIR was higher than ADBR (P = .013), especially in patients with ST-segment elevation myocardial infarction or incomplete revascularization. ADIR continued to be, albeit non-significantly, greater than ADBR up to the third month, whereas ADBR became higher, although not significantly, afterward. Patients with incomplete revascularization had an excess in ischemic risk (P = .003), whereas non-ST-segment elevation ACS patients and those on ticagrelor had an excess of bleeding (P = .012 and P = .022, respectively). CONCLUSIONS In unselected ACS patients, ADIR and ADBR occurred at similar rates within 1 year after PCI. ADIR was greater than ADBR in the first 2 weeks, especially in ST-segment elevation myocardial infarction patients and those with incomplete revascularization. In the first year, ADIR was higher than ADBR in patients with incomplete revascularization, whereas ADBR was higher in non-ST-segment elevation ACS patients and in those discharged on ticagrelor.

Patients undergoing complex percutaneous coronary intervention (PCI) are at an increased risk of atherothrombotic complications. Although dual antiplatelet therapy is the mainstay of treatment for patients undergoing PCI with stent implantation, deciding its type and duration in complex PCI patients has long been considered a challenge for clinicians. This is because the beneficial effects of prolonged treatment and/or more potent antiplatelet agents’ use in preventing ischemic events are hindered by a concomitant increase in bleeding complications. The aim of this review is to highlight current evidence regarding the optimal antithrombotic therapy regimens used in complex PCI patients, focusing on the evaluation of both safety and efficacy outcomes as well as addressing future perspectives.

Background Platelet reactivity (PR) has been indicated as a pathophysiological key element for ST-Elevation Myocardial Infarction (STEMI) development. In STEMI patients, PR following pharmacological treatment has been extensively studied with focus on patients with on-treatment high platelet reactivity (HPR). Patients with before-treatment not-high platelet reactivity (NHPR) have been poorly studied so far. Purpose Aim of the study is to investigate the prevalence, clinical characteristics, response to therapy and outcomes of baseline prior to treatment NHPR among patients with STEMI undergoing primary PCI. Methods We analysed the data from 358 STEMI patients with assessment of PR by VerifyNowbefore P2Y12 inhibitor loading dose (LD). All patients received a P2Y12 inhibitor (ticagrelor or prasugrel) LDafter baseline PR assessment. Blood samples were obtained at baseline (T0), and after 1 hour (T1), 2 hours (T2), 4–6 hours (T3) and 8–12 hours (T4) after LD. HPR was defined as Platelet Reactivity Unit values ≥208, while patients with values Results Overall, 20% patients had NHPR. Patients with before-treatment NHPR values were more frequently young, of male gender and more frequently smokers (p=0.005), overweight or obese (p=0.009), affected by dyslipidemia (p=0.03) and with a family history of coronary artery disease (p=0.04). Age and male gender resulted both independent predictors of NHPR, even after propensity score adjustment. The percentage of inhibition of PR after ticagrelor or prasugrel LD was similar between HPR and NHPR patients at each time point (figure 1) and residual PR was constantly lower in patients with before-treatment PRU Conclusions A significant proportion of patients presenting with STEMI has a baseline NHPR; they are predominantly young males with a high-risk cardiovascular profile. NHPR is associated with better in-hospital outcomes as compare with patients with HPR. Further studies are needed to better understand the underlying pathophysiology in order to find out potential personalized treatments in this setting. Funding Acknowledgement Type of funding sources: None.

Introduction: Inhibition of P2Y12 platelet receptors consists a crucial target of pharmacologic treatment in acute coronary syndrome patients. Several controversial issues however still remain and ...

Aims Clopidogrel is prescribed for the prevention of atherothrombotic events. While investigations have identified genetic determinants of inter-individual variability in on-treatment platelet inhibition (e.g. CYP2C19*2), evidence that these variants have clinical utility to predict major adverse cardiovascular events (CVEs) remains controversial. Methods and results We assessed the impact of 31 candidate gene polymorphisms on adenosine diphosphate (ADP)-stimulated platelet reactivity in 3391 clopidogrel-treated coronary artery disease patients of the International Clopidogrel Pharmacogenomics Consortium (ICPC). The influence of these polymorphisms on CVEs was tested in 2134 ICPC patients (N = 129 events) in whom clinical event data were available. Several variants were associated with on-treatment ADP-stimulated platelet reactivity (CYP2C19*2, P = 8.8 × 10−54; CES1 G143E, P = 1.3 × 10−16; CYP2C19*17, P = 9.5 × 10−10; CYP2B6 1294 + 53 C > T, P = 3.0 × 10−4; CYP2B6 516 G > T, P = 1.0 × 10−3; CYP2C9*2, P = 1.2 × 10−3; and CYP2C9*3, P = 1.5 × 10−3). While no individual variant was associated with CVEs, generation of a pharmacogenomic polygenic response score (PgxRS) revealed that patients who carried a greater number of alleles that associated with increased on-treatment platelet reactivity were more likely to experience CVEs (β = 0.17, SE 0.06, P = 0.01) and cardiovascular-related death (β = 0.43, SE 0.16, P = 0.007). Patients who carried eight or more risk alleles were significantly more likely to experience CVEs [odds ratio (OR) = 1.78, 95% confidence interval (CI) 1.14–2.76, P = 0.01] and cardiovascular death (OR = 4.39, 95% CI 1.35–14.27, P = 0.01) compared to patients who carried six or fewer of these alleles. Conclusion Several polymorphisms impact clopidogrel response and PgxRS is a predictor of cardiovascular outcomes. Additional investigations that identify novel determinants of clopidogrel response and validating polygenic models may facilitate future precision medicine strategies.

Oral P2Y12 receptor inhibitors represent a mainstay treatment in patients with acute coronary syndrome and those undergoing percutaneous coronary intervention. In the setting of ST-elevation myocardial infarction, when early platelet inhibition is highly desirable, the onset of action of oral P2Y12 receptor inhibitors is, however, delayed, likely due to delayed drug absorption. Crushing the tablets, which are to be used for patient loading with an oral P2Y12 receptor inhibitor, has been shown to provide earlier platelet inhibition than standard, integral tablets administration. Chewed ticagrelor tablets may also result in a similar effect. Such findings should be interpreted with caution, mainly due to the small number of patients enrolled and the nature (pharmacodynamic/pharmacokinetic) of the respective studies. Furthermore, in patients with out-of-hospital cardiac arrest, who remain comatose, crushing tablets is commonly applied in clinical practice for platelet P2Y12 receptor inhibition. In this review, we focus on current evidence regarding the role of crushed P2Y12 receptor inhibitor pills, analyzing clinical scenarios where most of the promise exists along with future expectations from this type of formulation. Large randomized studies are needed to draw firm conclusions regarding the clinical benefit of ‘crushing’ over the usual ‘not-crushing’ practice.

Introduction and objectives There is little evidence on rates of stent thrombosis (ST) in patients receiving dual antiplatelet therapy (DAPT) with ticagrelor or prasugrel . The aim of this study was to analyze the incidence and predictors of ST after an acute coronary syndrome among patients receiving DAPT with ticagrelor vs prasugrel. Methods We used data from the RENAMI registry (REgistry of New Antiplatelet therapy in patients with acute Myocardial Infarction), analyzing a total of 4123 acute coronary syndrome patients discharged with DAPT with ticagrelor or prasugrel in 11 centers in 6 European countries. The endpoint was definite ST within the first year. A competitive risk analysis was carried out using a Fine and Gray regression model, with death being the competitive event. Results A total of 2604 patients received DAPT with ticagrelor and 1519 with prasugrel; ST occurred in 41 patients (1.10%), with a similar cumulative incidence between ticagrelor (1.21%) and prasugrel (0.90%). The independent predictors of ST were age (sHR, 1.03; 95% C I, 1.01-1.06), ST segment elevation (sHR, 2.24; 95%CI, 1.22-4.14), previous myocardial infarction (sHR, 2.56; 95%CI, 1.19-5.49), and serum creatinine (sHR, 1.29; 95%CI, 1.08-1.54). Conclusions Stent thrombosis is infrequent in patients receiving DAPT with ticagrelor or prasugrel. The variables associated with an increased risk of ST were advanced age, ST segment elevation, previous myocardial infarction, and serum creatinine.

Resumen Introduccion y objetivos Hay muy poca evidencia sobre las tasas de trombosis del stent (TS) en pacientes que reciben tratamiento antiagregante plaquetario doble (TAPD) con ticagrelor o prasugrel. El objetivo de este estudio es analizar la incidencia y predictores de la TS tras un sindrome coronario agudo en pacientes que reciben TAPD con ticagrelor frente a prasugrel. Metodos Se utilizaron datos del registro RENAMI (REgistry of New Antiplatelet therapy in patients with acute Myocardial Infarction), y se analizo en total a 4.123 pacientes con sindrome coronario agudo dados de alta con TAPD con ticagrelor o prasugrel en 11 centros de 6 paises europeos. Se considero como evento la TS confirmada en el primer ano. Se realizo un analisis de riesgos competitivos mediante un modelo de regresion de Fine y Gray, siendo la muerte el evento competitivo. Resultados Recibieron TAPD con ticagrelor 2.604 pacientes y con prasugrel, 1.519; 41 pacientes (1,10%) presentaron TS, con incidencias acumuladas similares entre ticagrelor (1,21%) y prasugrel (0,90%). Los predictores independientes de la TS fueron: la edad (sHR = 1,03; IC95%, 1,01-1,06), la elevacion del segmento ST (sHR = 2,24; IC95%, 1,22-4,14), el antecedente de infarto de miocardio (sHR = 2,56; IC95%, 1,19-5,49) y la creatinina serica (sHR = 1,29; IC95%, 1,08-1,54). Conclusiones La TS es infrecuente en pacientes que reciben TAPD con ticagrelor y prasugrel. La edad avanzada, la elevacion del segmento ST, el antecedente de infarto y la creatinina serica son las variables que se asocian con mayor riesgo de TS.

Anakinra, an interleukin-1 receptor antagonist and tocilizumab, an interleukin-6 receptor blocker, are used for the treatment of rheumatoid arthritis. We investigated the differential effects of anakinra and tocilizumab on myocardial and vascular function in an atherosclerosis model of patients with rheumatoid arthritis. 120 patients with rheumatoid arthritis were randomized to anakinra (n = 40), tocilizumab (n = 40) or prednisolone (n = 40) for 3 months. Primary outcome measure was the change of left ventricular longitudinal strain after 3 months of treatment. Additionally, we measured coronary flow reserve, flow-mediated dilatation of the brachial artery, carotid-femoral pulse wave velocity, malondialdehyde and protein carbonyls as oxidative stress markers and C-reactive protein blood levels at baseline and post-treatment. At baseline, patients among the three treatment arms had similar age, sex, disease activity score and atherosclerotic risk factors. Compared with baseline, all patients had improved longitudinal strain (− 16% vs. − 17.8%), coronary flow reserve (2.56 vs. 2.9), malondialdehyde (2.0 vs. 1.5 µM/L), protein carbonyls (0.0132 vs. 0.0115 nmol/mg), and C-reactive protein post-treatment. In all patients, the percent decrease of malondialdehyde was correlated with percent increase of longitudinal strain (p

Resumen Introduccion y objetivos La puntuacion PARIS permite una estratificacion combinada de los riesgos isquemico y hemorragico de los pacientes con cardiopatia isquemica tratados con stent coronario y tratamiento antiagregante plaquetario doble (TAPD). Se desconoce su utilidad en pacientes con sindrome coronario agudo (SCA) tratados con ticagrelor o prasugrel. Se investiga este aspecto en un registro internacional. Metodos Estudio retrospectivo multicentrico con participacion voluntaria de 11 centros de 6 paises europeos. Se estudio a 4.310 pacientes con SCA dados de alta en TAPD con ticagrelor o prasugrel. Se definio evento isquemico como trombosis de stent o infarto de miocardio espontaneo, y evento hemorragico segun BARC (Bleeding Academic Research Consortium) tipo 3 o 5. Se calculo la discriminacion y la calibracion para ambas vertientes de la puntuacion PARIS (PARISisquemico y PARIShemorragico). El beneficio neto isquemico-hemorragico se obtuvo mediante la diferencia entre las probabilidades predichas de eventos isquemicos y hemorragicos. Resultados Durante 17,2 ± 8,3 meses, hubo 80 eventos isquemicos (el 1,9% anual) y 66 eventos hemorragicos (el 1,6% anual). PARISisquemico y PARIShemorragico se asociaron con el riesgo de eventos isquemicos (sHR = 1,27; IC95%, 1,16-1,39) y hemorragicos (sHR = 1,14; IC95%, 1,01-1,30) respectivamente. La discriminacion de eventos isquemicos fue discreta (indice C = 0,64) y la de eventos hemorragicos, pobre (indice C = 0,56), con buena calibracion para ambos. El beneficio neto isquemico-hemorragico resulto negativo (mas eventos hemorragicos) en pacientes con alto riesgo hemorragico y positivo (mas eventos isquemicos) en pacientes con alto riesgo isquemico. Conclusiones En pacientes con SCA tratados con TAPD con ticagrelor o prasugrel, la escala PARIS ayuda a establecer un equilibrio apropiado del riesgo isquemico-hemorragico.

Background The use of potent P2Y12 inhibitors (ticagrelor & prasugrel) in acute coronary syndrome (ACS) patients undergoing percutaneous coronary interventions (PCI) is a class I recommendation. We performed a sex-specific analysis comparing the difference in efficacy and safety outcomes between ticagrelor and prasugrel in a real-world ACS population. Methods Data from the multicenter REgistry of New Antiplatelets in patients with Myocardial Infarction (RENAMI) for 4424 ACS patients who underwent PCI and were treated with ticagrelor or prasugrel between 2012 to 2016 were analyzed. Mean follow-up was 17±9 months. Results After propensity score matching, there was no significant difference in the occurrence of primary endpoint of net adverse cardiac events between ticagrelor and prasugrel in men (HR: 0.94; 95% CI: 0.69-1.29; P=0.71), or women (HR: 1.17; 95% CI: 0.63-2.20; P=0.62; P interaction [sex] = 0.40). Similarly, no differences were found in the occurrence of any of the secondary endpoints (MACE, all cause death, re-infarction, stent thrombosis, BARC major bleeding and BARC any bleeding) between the two P2Y12 groups between men and women. Conclusions In this real-world ACS population, no relative difference in efficacy or safety outcomes were found between ticagrelor and prasugrel between sexes.

Revascularization of both left main and bifurcation lesions is currently considered an important feature of complex percutaneous coronary intervention (PCI), whereas stenting distal left main bifurcation is fairly challenging. Recent evidence shows that such lesions are associated with an increased risk of ischemic events. There is no universal consensus on the optimal PCI strategy or the appropriate type and duration of antithrombotic therapy to mitigate the thrombotic risk. Prolonged dual antiplatelet therapy or use of more potent P2Y12 inhibitors have been investigated in the context of this high-risk subset of the population undergoing PCI. Thus, while complex PCI is a growing field in interventional cardiology, left main and bifurcation PCI constitutes a fair amount of the total complex procedures performed recently, and there is cumulative interest regarding antithrombotic therapy type and duration in this subset of patients, with decision-making mostly based on clinical presentation, baseline bleeding, and ischemic risk, as well as the performed stenting strategy.

The optimal antithrombotic treatment in patients receiving oral anticoagulation undergoing percutaneous coronary intervention (PCI) has been a field of intensive research. Although triple antithrombotic therapy had been, until lately, the strategy of choice, recent evidence points to the superiority of dual antithrombotic therapy regarding bleeding prevention, without significantly compromising efficacy. In the further challenging scenario of complex PCI, associated with a higher ischemic risk, the efficacy of an aspirin-free strategy, adopted shortly after the index event is under question, rendering decision-making a fairly difficult scenario for clinicians. Since patients with an indication for oral anticoagulation undergoing complex PCI are underrepresented in randomized trials, there are scarce data regarding the optimal treatment strategy in such patients. This review aims to analyze and compare different approaches regarding the type and duration of antithrombotic regimens, focusing on both safety and efficacy outcomes, as well as to discuss recent guidelines’ suggestions regarding the therapeutic approach in patients receiving oral anticoagulation undergoing PCI procedures of increased complexity.

Chronic total occlusion (CTO) recanalization is among the most complex subsets of coronary interventions. Hence, optimum peri- and post-procedural anticoagulation and antiplatelet therapy is key for the achievement of successful revascularization and reduction of major adverse cardiovascular outcomes in patients undergoing CTO percutaneous coronary intervention (PCI). Unfractionated heparin is still considered the gold standard anticoagulant because its action can be reversed by protamine administration, with bivalirudin being reserved mainly for patients with heparin-induced thrombocytopenia. However, small studies comparing unfractionated heparin with bivalirudin in CTO interventions have shown similar outcomes. Glycoprotein IIb/IIIa inhibitors should, in general, be avoided. Aspirin in combination with clopidogrel for 6–12 months is the standard post CTO PCI dual antiplatelet regimen. For the most complex cases, clopidogrel can be substituted by a more potent P2Y12 inhibitor, namely ticagrelor or prasugrel.

The optimal management for severely calcified coronary artery disease is multi-adjunctive. Different strategies with dedicated devices should be available in the cardiac catheterization laboratory with their selection depending on the nature of the calcific disease and its anatomical distribution. Shockwave Intravascular Lithotripsy (S-IVL) system offers a novel option for lesion preparation of heavily calcified plaques in coronary and peripheral vessels. S-IVL is based on the fundamental principles of lithotripsy, a technology that has been used to modify renal stones for over 30 years. Pulsatile mechanical energy is used to fragment selectively amorphous calcium, sparing soft tissue. S-IVL has the potential of more widespread adoption because of its proven safety, efficacy and operational simplicity, but cost-effectiveness of such advanced technology will need to be analyzed.

Seizures are underrecognized in preterm infants, and little is known about their impact on brain growth. We aimed to define the association between early seizures and subsequent brain growth.Infants30 weeks gestation underwent 72 h of prospective amplitude-integrated electroencephalography (aEEG) monitoring, term-equivalent age (TEA) magnetic resonance imaging (MRI), and 2-year neurodevelopmental testing. Seizures were defined as trains of sharp waves10 s, evolving in frequency/amplitude/morphology, and identified using automated algorithms with manual review. Using T2-weighted images, cortical surface area (CSA) and gyrification index (GI) were calculated and volumes were segmented into five tissue classes: cerebrospinal fluid, gray matter, white matter (WM), deep nuclear gray matter, and cerebellum. Correlations between total seizure burden and tissue-specific volumes were evaluated, controlling for clinical variables of interest.Ninety-nine infants underwent aEEG/MRI assessments (mean GA = 26.3 weeks, birthweight = 899 g). Seizure incidence was 55% with a median of two events; median length = 66 s and mean burden = 285 s. Greater seizure burden was associated with smaller CSA and volumes across all tissue types, most prominently in WM (RSeizures in preterm infants are common and associated with smaller TEA brain volumes. This relationship was strongest for WM and independent of clinical factors.Seizures in preterm infants are common. Little is known about the association between early seizures and later brain growth. Greater seizure burden is linked with smaller volumes of all brain tissue types, most prominently the WM. This relationship is true even controlling for other factors. Additional study is needed to identify the optimal EEG monitoring and seizure treatment strategy for improved brain growth and neurodevelopmental outcomes.

CA extern - Weitere Nicht-UDE-Autoren sind nicht genannt. Aim: The SAMe-TT2R2 score helps identify patients with atrial fibrillation (AF) likely to have poor anticoagulation control during anticoagulation with vitamin K antagonists (VKA) and those with scores >2 might be better managed with a target-specific oral anticoagulant (NOAC). We hypothesized that in clinical practice, VKAs may be prescribed less frequently to patients with AF and SAMe-TT2R2 scores >2 than to patients with lower scores. Methods and results: We analyzed the Phase III dataset of the Global Registry on Long-Term Oral Antithrombotic Treatment in Patients with Atrial Fibrillation (GLORIA-AF), a large, global, prospective global registry of patients with newly diagnosed AF and ≥1 stroke risk factor. We compared baseline clinical characteristics and antithrombotic prescriptions to determine the probability of the VKA prescription among anticoagulated patients with the baseline SAMe-TT2R2 score >2 and ≤ 2. Among 17,465 anticoagulated patients with AF, 4,828 (27.6%) patients were prescribed VKA and 12,637 (72.4%) patients an NOAC: 11,884 (68.0%) patients had SAMe-TT2R2 scores 0-2 and 5,581 (32.0%) patients had scores >2. The proportion of patients prescribed VKA was 28.0% among patients with SAMe-TT2R2 scores >2 and 27.5% in those with scores ≤2. Conclusions: The lack of a clear association between the SAMe-TT2R2 score and anticoagulant selection may be attributed to the relative efficacy and safety profiles between NOACs and VKAs as well as to the absence of trial evidence that an SAMe-TT2R2-guided strategy for the selection of the type of anticoagulation in NVAF patients has an impact on clinical outcomes of efficacy and safety. The latter hypothesis is currently being tested in a randomized controlled trial. Clinical trial registration: URL: https://www.clinicaltrials.gov//Unique identifier: NCT01937377, NCT01468701, and NCT01671007. © 2020 Hellenic Society of Cardiology

Platelet reactivity (PR) has been indicated as a pathophysiological key element for ST-Elevation Myocardial Infarction (STEMI) development. Patients with not-high before-treatment platelet reactivity (NHPR) have been poorly studied so far. The aim of this study is to investigate the prevalence, clinical characteristics, response to therapy and outcomes of baseline prior to treatment NHPR among patients with STEMI undergoing primary PCI. We analyzed the data from 358 STEMI patients with assessment of PR by VerifyNow before P2Y12 inhibitor loading dose (LD). Blood samples were obtained at baseline, and after 1 hour, 2 hours, 4–6 hours and 8–12 hours after LD. High platelet reactivity (HPR) was defined as Platelet Reactivity Unit values ≥208, while patients with values p = .017) as compared with the NHPR group. In conclusion, a significant proportion of patients presenting with STEMI has a baseline NHPR that is associated with better in-hospital outcomes as compared with patients with HPR. Further studies are needed to better elucidate the potential therapeutic implications of NHPR in terms of secondary prevention.

Funding Acknowledgements Type of funding sources: None. Aim/Introduction: Heat-not-burn cigarette (HNBC) constitutes a non-combustible smoke product. Purpose We compare the effects of heat-not-burn and conventional cigarettes on coronary flow, myocardial and vascular function, platelet activation and oxidative stress. Methods We compared the effects of HNBC to those of tobacco cigarette (TCig), on arterial stiffness, oxidative stress, and platelet activation, acutely and after 1 month of switching to HNBC, as well as on endothelial, myocardial, and coronary function after 1 month of switching to HNBC. In the acute study, 50 smokers were randomized into smoking a single Tcig or an HNBC and after 60 minutes were crossed over to the alternate smoking (HNBC or Tcig). For the chronic phase, 75 smokers were examined. Of those, 50 were switched to HNBC and 25 continued Tcig for 1 month. Pulse wave velocity (PWV) and biomarkers [malondialdehyde (MDA), protein carbonyls (PC), and thromboxane B2 (TXB2)] were assessed in the acute and chronic study. Myocardial deformation [global longitundinal strain (GLS), myocardial work index (GWI) and wasted myocardial work (GWW)], coronary flow reserve (CFR) by Doppler echocardiography, total arterial compliance (TAC), and flow-mediated dilation (FMD) were additionally assessed in the chronic study. Results Compared to baseline, TCig smoking acutely increased exhaled CO, PWV, MDA, and TxB2 (p Conclusions HNBCs exert a less detrimental effect on vascular, cardiac and platelet function than combustible tobacco.

Background It has been suggested the COVID pandemic may have indirectly affected the treatment and outcome of STEMI patients, by avoidance or significant delays in contacting the emergency system. No data have been reported on the impact of diabetes on treatment and outcome of STEMI patients, that was therefore the aim of the current subanalysis conducted in patients included in the International Study on Acute Coronary Syndromes–ST Elevation Myocardial Infarction (ISACS-STEMI) COVID-19. Methods The ISACS-STEMI COVID-19 is a retrospective registry performed in European centers with an annual volume of > 120 primary percutaneous coronary intervention (PCI) and assessed STEMI patients, treated with primary PCI during the same periods of the years 2019 versus 2020 (March and April). Main outcomes are the incidences of primary PCI, delayed treatment, and in-hospital mortality. Results A total of 6609 patients underwent primary PCI in 77 centers, located in 18 countries. Diabetes was observed in a total of 1356 patients (20.5%), with similar proportion between 2019 and 2020. During the pandemic, there was a significant reduction in primary PCI as compared to 2019, similar in both patients with (Incidence rate ratio (IRR) 0.79 (95% CI: 0.73–0.85, p p p Furthermore, the pandemic was independently associated with a significant increase in door-to-balloon and total ischemia times only among patients without diabetes, which may have contributed to the higher mortality, during the pandemic, observed in this group of patients. Conclusions The COVID-19 pandemic had a significant impact on the treatment of patients with STEMI, with a similar reduction in primary PCI procedures in both patients with and without diabetes. Hypertension had a significant impact on PCI reduction only among patients without diabetes. We observed a significant increase in ischemia time and door-to-balloon time mainly in absence of diabetes, that contributed to explain the increased mortality observed in this group of patients during the pandemic. Trial registration number: NCT 04412655.

Background: Early treatment with a potent oral platelet P2Y 12 inhibitor is recommended in patients presenting with ST-segment–elevation myocardial infarction scheduled to undergo primary percutaneous coronary intervention (pPCI). The impact on coronary reperfusion of crushed P2Y 12 inhibitor tablets, which lead to more prompt and potent platelet inhibition, is unknown. Methods: We conducted a randomized controlled, multicenter trial in the Netherlands, enrolling patients with ST-segment–elevation myocardial infarction scheduled to undergo pPCI. Patients were randomly allocated to receive in the ambulance, before transfer, a 60-mg loading dose of prasugrel either as crushed or integral tablets. The independent primary end points were thrombolysis in myocardial infarction (TIMI) 3 flow in the infarct-related artery at initial coronary angiography, and complete (≥70%) ST-segment resolution 1 hour after pPCI. The safety end points were TIMI major and Bleeding Academic Research Consortium ≥3 bleedings. Secondary end points included platelet reactivity and ischemic outcomes. Results: A total of 727 patients were assigned to either crushed or integral tablets of prasugrel loading dose. The median time from study treatment to wire-crossing during pPCI was 57 (47–70) minutes. The primary end point TIMI 3 flow in the infarct-related artery before pPCI occurred in 31.0% in the crushed group versus 32.7% in the integral group (odds ratio, 0.92 [95% CI, 0.65–1.30], P =0.64). Complete ST-segment resolution 1 hour after pPCI was present in 59.9% in the crushed group versus 57.3% in the integral group (odds ratio, 1.11 [95% CI, 0.78–1.58], P =0.55). Platelet reactivity at the beginning of pPCI, measured as P2Y 12 reactivity unit, differed significantly between groups (crushed, 192 [132–245] versus integral, 227 [184–254], P ≤0.01). TIMI major and Bleeding Academic Research Consortium ≥3 bleeding occurred in 0% in the crushed group versus 0.8% in the integral group, and in 0.3% in the crushed group versus 1.1% in the integral group, respectively. There were no differences observed between groups regarding ischemic events at 30 days. Conclusions: Prehospital administration of crushed prasugrel tablets does not improve TIMI 3 flow in the infarct-related artery before pPCI or complete ST-segment resolution 1 h after pPCI in patients presenting with ST-segment–elevation myocardial infarction scheduled for pPCI. Registration: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT03296540.

Complex percutaneous coronary intervention (PCI) patients are a high-risk population for ischemic complications. Antiplatelet therapy in such patients remains controversial, as the beneficial effects of more potent agents use or prolonged dual antiplatelet treatment (DAPT) on atherothrombotic complications are hindered by a concomitant increase in bleeding rates. The aim of this article is to describe ischemic and bleeding outcomes associated with complex PCI procedures and to compare different types and durations of DAPT regimens in terms of safety and efficacy outcomes. Issues concerning special patient groups, such as those with left main, chronic total occlusion, or bifurcation lesions, are discussed.

Heat-not-burn cigarette (HNBC) constitutes a non-combustible smoke product. Methods We compared the effects of HNBC to those of tobacco cigarette (TCig), on arterial stiffness, oxidative stress, and platelet activation, acutely and after 1 month of switching to HNBC, as well as on endothelial, myocardial, and coronary function after 1 month of switching to HNBC. In the acute study, 50 smokers were randomised into smoking a single Tcig or an HNBC and after 60 minutes were crossed over to the alternate smoking (HNBC or Tcig). For the chronic phase, 75 smokers were examined. Of those, 50 were switched to HNBC and 25 continued Tcig for 1 month. Pulse wave velocity (PWV) and biomarkers [malondialdehyde (MDA), protein carbonyls (PC), and thromboxane B2 (TXB2)] were assessed in the acute and chronic study. Myocardial deformation [global longitundinal strain (GLS), myocardial work index (GWI) and wasted myocardial work (GWW)], coronary flow reserve (CFR) by echocardiography, total arterial compliance (TAC), and flow-mediated dilation (FMD) were additionally assessed in the chronic study. Results Compared to baseline, TCig smoking acutely increased exhaled CO, PWV, MDA, and TxB2 (p Conclusions HNBCs exert a less detrimental effect on vascular, cardiac and platelet function than tobacco Funding Acknowledgement Type of funding source: Public Institution(s). Main funding source(s): Hellenic Association of Lipidiology, Atherosclerosis and Vascular disease

Background and aims Increased b-amyloid and decreased Mitochondrial-derived peptide (MOTS-c), are reported in diabetes. We investigated their additive value to high on-clopidogrel platelet reactivity (HPR) for adverse outcome in type 2 diabetics after recent revascularization. Patients and methods In 121 type II diabetics, treated with clopidogrel and aspirin, (93 males, mean age 67.2 years) we measured: a). maximum platelet aggregation to adenosine diphosphate (ADP) by Light Transmission Aggregometry (LTAmax), b) Malondialdehyde (MDA), as oxidative stress marker, c) MOTS-c, d) b-amyloid blood levels. Cardiac death and acute coronary syndromes (MACE) were recorded during 2 years of follow-up. Results Out of 121 patients, 32 showed HPR (LTAmax >48%,). At baseline, HPR was associated with b-amyloid >51 pg/ml (p=0.006) after adjusting clinical variables, HbA1c, MOTS-c, MDA and medication. During follow-up, 22 patients suffered a MACE. HPR, b-amyloid >51 pg/ml and MOTS-c51mg/dl or HPR and MOTS-c concentration Conclusions Increased b-amyloid or low MOTS-c are additive predictors to high on-clopidogrel platelet reactivity for adverse outcome in diabetics with CAD during 2-years follow- up. Funding Acknowledgement Type of funding source: None

Backround and Objective: We sought to assess in adult congenital heart disease (ACHD) patients the prognostic value of plasma galectin-3 (Gal-3) levels and systemic ventricular global longitudinal strain (SV GLS) as well as their association with NTproBNP and arrhythmogenesis. Materials and Methods: We studied 58 patients (26 men, mean age 37 &plusmn, 16.8 years) with various congenital heart diseases. Patients underwent echocardiogram, 24 h ambulatory ECG monitoring, while NTproBNP and Gal-3 were measured. They were followed up (median of 790.5 days -IQR 350.3 days) and major cardiovascular events (MACE) were recorded. Results. Mean Gal-3 levels were 17.07 &plusmn, 6.38 ng/m. Plasma Gal-3 was correlated with LogNTproBNP (r = 0.456, p = 0.001).Gal-3 levels associated with supraventricular tachycardia (SVT) (p &lt, 0.001) and ventricular tachycardia (VT) (p &lt, 0.001), but was not associated with MACE (HR 1.018, 95% CI 0.944&ndash, 1.098, p = 0.641).Mean SVGLS in patients with systemic left ventricle was &minus, 15.91% &plusmn, 4.09%, which was significantly lower compared to patients with systemic right ventricle and patients with single ventricle (&minus, 11.42% &plusmn, 3.37% and &minus, 11.9% &plusmn, 5.06%, respectively, p = 0.021).SV GLS correlated with plasma Gal-3 (r = 0.313, p = 0.027) and logNTproBNP (r = 0.479, p &lt, 0.001). SVGLS correlated with VT arrhythmias (p = 0.004). NTproBNP predicted MACE (AUC 0.750, p = 0.03). SVGLS also predicted MACE (AUC 0.745, p = 0.03. In multivariate analysis, SVGLS and logNTproBNP maintained their predictive value (p = 0.004 and p = 0.009, respectively) Conclusion: In ACHD patients, SV GLS was found to predict MACE independently from NTproBNP and correlated with VT. Gal-3 correlated with NTproBNP and SVGLS as well as SVT and VT, but has not been shown to bear significant prognostic potential.

Dual antiplatelet therapy (DAPT) duration in patients undergoing percutaneous coronary intervention (PCI) has long been considered a matter of controversy. Complex-PCI (C-PCI) is considered to be associated with an increased ischemic risk that tends to be greater with progressively higher procedural complexity. Thus, with a view to balance ischemic versus bleeding risks, high complexity of PCI intuitively represents an advocate of prolonged DAPT duration. However, the optimal DAPT strategy in this high ischemic risk subset of patients remains unclear, a fact that is exacerbated by the absence of a universal definition of C-PCI, resulting in a significant between-study heterogeneity. The aim of this review is to highlight the increased risks associated with C-PCI, compare long- versus short-term DAPT regimens regarding safety and efficacy endpoints as well as investigate outcomes in special C-PCI cohorts, such as patients with bifurcation, left main or chronic total occlusion lesions. Furthermore, controversial issues, such as antithrombotic regimens in C-PCI patients with atrial fibrillation, and future perspectives are addressed.

Aims Currently available data indicate that reduction of ticagrelor maintenance dose (MD) 1-3 years after acute myocardial infarction (AMI) not only provides sufficient platelet inhibition but also can improve ticagrelor's safety profile. The aim of this study was to compare the antiplatelet effect of reduced and standard ticagrelor MD in stable patients beginning 1 month after AMI. Methods and results In a single-centre, randomized, open-label, active-controlled trial, on Day 30 following AMI, 52 patients (26 in each study arm) were assigned in a 1:1 ratio to receive either reduced (60 mg b.i.d) or standard (90 mg b.i.d) ticagrelor MD for the following 2 weeks. On Day 45 after AMI the antiplatelet effect of ticagrelor was evaluated with the VASP assay and Multiplate, and there were no significant differences in platelet inhibition between patients on reduced vs. standard MD [VASP: 10.4 (5.6-22.2) vs. 14.1 (9.4-22.1) platelet reactivity index; P = 0.30; Multiplate: 30.0 (24.0-39.0) vs. 26.5 (22.0-35.0) U; P = 0.26]. Likewise, no differences were found regarding the prevalence of on-ticagrelor high platelet reactivity between patients on ticagrelor 60 mg b.i.d vs. 90 mg b.i.d (VASP: 4% vs. 8%; P = 0.67; Multiplate: 15% vs. 8%; P = 0.54). Administration of reduced MD resulted in proportionally lower plasma concentrations of ticagrelor and its active metabolite on Day 45 after AMI. Conclusion These results suggest that lowering ticagrelor MD 1 month after AMI confers an adequate antiplatelet effect that is comparable to the standard dose. The tested strategy warrants further research to assess its clinical efficacy and safety. Clinicaltrials.gov identifier NCT03251859.

Coronary artery bypass surgery has been the accepted treatment for left main coronary artery disease for over 50 years. Balloon angioplasty was later used then abandoned because of deaths likely due to restenosis or thrombotic occlusion. However, rapid innovations in drug-eluting stent designs leading to more biocompatible thin strut platforms with optimal drug elution profiles and further advances in modern pharmacotherapy involving potent P2Y12 inhibitors combined with utilization of intracoronary imaging and physiologic assessment for procedural planning and optimization have transformed percutaneous interventions into successful alternatives to coronary artery bypass graft surgery (CABG) in selected LM anatomic territories. Herein, we provide an evidence-based practical guide on how to approach and perform LM percutaneous interventions (PCI).

Patients with atrial fibrillation (AF) undergoing percutaneous coronary intervention (PCI) have traditionally received triple antithrombotic therapy (TAT) consisting of aspirin and a P2Y12 inhibitor plus an oral anticoagulant (OAC) to reduce atherothrombotic events, even though this strategy is associated with a high risk of severe bleeding. Recent trials have indicated that dual antithrombotic therapy (DAT), consisting of a P2Y12 inhibitor plus an OAC, may be superior to TAT in terms of bleeding risk; however, the trade-off regarding ischemic complications may be questionable. Patients who have had a myocardial infarction (MI) before undergoing PCI warrant special consideration because of the accompanying high ischemic risk, including stent thrombosis, which might be exacerbated by an aspirin-free strategy such as DAT. In particular, in the acute phase of ST-segment elevation MI (STEMI), the highly prothrombotic milieu may necessitate initial TAT, though durations may vary, making a tailored antithrombotic regimen for this high-risk subset of patients a fairly challenging and difficult scenario for clinicians. Since patients with MI, especially STEMI, are underrepresented in randomized trials, data regarding the optimal antithrombotic treatment in such patients are sparse. This review aims to analyze the outcomes of different antithrombotic regimens in patients with MI and AF undergoing PCI, define the role of DAT versus TAT regarding safety and efficacy outcomes, and address controversial issues and future perspectives.

Increased β-amyloid and decreased mitochondrial-derived peptide (MOTS-c), are reported in diabetes. We investigated their additive value to high on-clopidogrel platelet reactivity (HPR) for adverse outcome in type 2 diabetics after recent revascularization.In 121 type II diabetics, treated with clopidogrel and aspirin, (93 males, mean age 67.2 years) we measured: (a) maximum platelet aggregation to adenosine diphosphate (ADP) by light transmission aggregometry (LTAmax), (b) malondialdehyde (MDA), as oxidative stress marker, (c) MOTS-c, (d) β-amyloid blood levels. Cardiac death and acute coronary syndromes (MACE) were recorded during 2 years of follow-up.Out of 121 patients, 32 showed HPR (LTAmax 48%,). At baseline, HPR was associated with β-amyloid 51 pg/ml (p = 0.006) after adjusting clinical variables, HbA1c, MOTS-c, MDA and medication. During follow-up, 22 patients suffered a MACE. HPR, β-amyloid 51 pg/ml and MOTS-c 167 ng/ml were predictors of MACE (relative risk 3.1, 3.5 and 3.8 respectively, p 0.05) after adjusting for confounders and medication. There was significant interaction between HPR and β-amyloid or MOTS-c for the prediction of MACE (p 0.05). Patients with HPR and β-amyloid 51 mg/dl or HPR and MOTS-c concentration 167 ng/ml had a fourfold higher risk for MACE than patients without these predictors (relative risk 4.694 and 4.447 respectively p 0.01). The above results were confirmed in an external validation cohort of 90 patients with diabetes and CAD.Increased β-amyloid or low MOTS-c are additive predictors to high on-clopidogrel platelet reactivity for adverse outcome in diabetics with CAD during 2-years follow-up. Clinical Trial Registration-URL: https://www.clinicaltrials.gov. Unique identifier: NCT04027712.

Background: Endothelial function may be improved by ticagrelor through adenosine-mediated mechanisms. We aimed to assess the effect of ticagrelor versus prasugrel on endothelial function in patients with stable coronary artery disease (CAD). Methods: In a prospective, randomized, crossover study, 22 stable CAD patients under prasugrel 10 mg once daily maintenance dose (MD) for at least 3 months were randomized to either ticagrelor 90 mg twice daily or prasugrel 10 mg once daily for 15 days with a direct treatment-crossover for another 15 days. Endothelial function was assessed by peripheral arterial tonometry (EndoPAT 2000 system, Itamar Medical, Caesarea, Israel) at Day 0 (randomization), Day 15, and Day 30. Reactive Hyperemia Index (RHI) was calculated by using an automated software, and endothelial dysfunction (ED) was defined as RHI

Ticagrelor is a P2Y12 receptor antagonist with proven clinical benefit in patients with acute coronary syndrome. Apart from its principal antiplatelet action, pleiotropic effects have been implicated in the clinical profile of ticagrelor, including a potentially beneficial impact on endothelial function. In light of the common presence and prognostic value of endothelial dysfunction in patients with coronary artery disease, several clinical studies have investigated the postulated effect of ticagrelor on endothelial function, yielding conflicting results. Limitations of the relevant studies as well as substantial differences in patient population, study design, and methods may account for these controversial findings. Most of these studies, however, support a beneficial impact of ticagrelor on endothelial function, which seems to be significant in the higher risk patients. In order to elucidate this effect, further research efforts should aim to clarify how quickly does endothelial function respond to ticagrelor, how sustained this response is during the dosing intervals and in the long term, which mechanisms are implicated, and whether this pleiotropic action is clinically significant. Future studies should include larger and diverse populations of patients, assess endothelial function at several time points after treatment initiation, and use multiple methods of endothelial function measurement, while implementing strict methodology. Nevertheless, the extent of the clinical benefit of ticagrelor attributable to actions beyond its potent and consistent antiplatelet effect remains uncertain.