Global longitudinal strain assessment of cardiac function and extravascular lung water formation after diving using semi-closed circuit rebreather.

PURPOSE: The aim of the present investigation is to study the relationship of ventricular global longitudinal strain (GLS) and ultrasound lung comets (ULC) formation to establish a link between extravascular pulmonary water formation and cardiac contractile dysfunction. METHODS: This is a prospective observational study including 14 active military divers. The subjects performed two sea dives of 120 min each with a semi-closed SCUBA circuit at 10 m depth. Divers were examined at baseline, 15 min (D1) and 60 min (D2) after diving. The evaluation included pulmonary and cardiac echography (including speckle tracking techniques). Blood samples were drawn at baseline and after diving, assessing hs-TnT and Endothelin-1. RESULTS: ULC were detected in 9 (64.2%) and 8 (57.1%) of the subjects after D1 and D2 respectively. No differences were found in right and left ventricular GLS after both immersions (RV: Baseline: - 17.9 4.9 vs. D1: - 17.2 6.5 and D2: - 16.7 5.8 s-1; p = 0.757 and p = 0.529; LV: Baseline: - 17.0 2.3 vs. D1: - 17.4 2.1 and D2: - 16.9 2.2 s-1; p = 0.546 and p = 0.783). However, a decrease in atrial longitudinal strain parameters have been detected after diving (RA: Baseline: 35.5 9.2 vs. D1: 30.3 12.8 and D2: 30.7 13.0 s-1; p = 0.088 and p = 0.063; LA: Baseline: 39.0 10.0 vs. D1: 31.6 6.1 and D2: 32.4 10.6 s-1; p = 0.019 and p = 0.054). CONCLUSION: In the present study, no ventricular contractile dysfunction was observed. However, increase pulmonary vasoconstriction markers were present after diving.

Impact of Comorbidities and Antiplatelet Regimen on Platelet Reactivity Levels in Patients Undergoing Transcatheter Aortic Valve Implantation.

ABSTRACT: The aim of our study is to assess the impact of anemia, chronic kidney disease, and diabetes mellitus on platelet reactivity (PR) in patients with severe aortic stenosis, both at baseline and after transcatheter aortic valve implantation (TAVI). This study is a prespecified subanalysis of the REAC-TAVI prospective, multicenter trial that included patients pretreated with aspirin + clopidogrel before TAVI. PR was measured at baseline and at 5 different time points after TAVI with the VerifyNow assay (Accriva Diagnostics, San Diego, CA), over a 3-month follow-up period. Patients with high PR (HPR) at baseline, before TAVI (n = 48) were randomized to aspirin + clopidogrel or aspirin + ticagrelor for 3 months, whereas those with normal PR (NPR) (n = 20) were continued on aspirin + clopidogrel. A "raiser response" in PR was defined as an increase in PR units >20% of baseline after TAVI. Patients with HPR before TAVI presented concomitant anemia and chronic kidney disease more frequently than their counterparts with NPR. Anemia and higher body mass index were independently associated with HPR to clopidogrel at baseline. Moreover, anemic patients with baseline HPR who were continued on clopidogrel presented higher PR after TAVI than patients with HPR switched to ticagrelor. All patients with baseline NPR presented a "raiser response" after TAVI, which was nonexistent among patients with HPR managed with ticagrelor. In summary, anemia seems as a relevant factor associated with baseline HPR and higher PR after TAVI in patients with baseline HPR randomized to clopidogrel, whereas ticagrelor proved more effective than clopidogrel at attaining sustained reductions in PR during follow-up, regardless of baseline comorbidities.

Antithrombotic Therapy in Patients with Peripheral Artery Disease: A Focused Review on Oral Anticoagulation.

Peripheral artery disease (PAD) is a major cause of morbidity and mortality but it is usually underdiagnosed and undertreated. Patients with PAD present dysregulated procoagulant, anticoagulant, and fibrinolytic pathways leading to arterial and venous thrombosis. The risk of several ischemic-related complications could be mitigated with appropriate antithrombotic therapy, which plays a central role in all types of PAD. For years, antiplatelets have been indicated in patients with symptomatic PAD or those who have undergone revascularization. Unfortunately, a non-negligible proportion of patients with PAD will suffer from adverse events during the follow-up, even despite proper medical therapies for the prevention of PAD complications. Thus, there is room for improving clinical outcomes in these patients. Given the implication of both, primary and secondary hemostasis in arterial thrombosis and the pathophysiology of PAD, the combination of antiplatelets and anticoagulants has emerged as a potential antithrombotic alternative to antiplatelets alone. In this narrative review article, we have highlighted the most recent evidence about antithrombotic therapy in PAD patients, with a special focus on oral anticoagulation. Certainly, COMPASS and VOYAGER PAD trials have shown promising results. Thus, rivaroxaban in combination with aspirin seem to reduce cardiovascular outcomes with a similar bleeding risk compared to aspirin alone. Nevertheless, results from real-world studies are needed to confirm these observations, and other trials will provide novel evidence about the safety and efficacy of emerging anticoagulant agents.

One-year efficacy and safety of prasugrel and ticagrelor in patients with acute coronary syndromes: Results from a prospective and multicentre ACHILLES registry.

BACKGROUND: Prasugrel and ticagrelor have demonstrated higher efficacy than clopidogrel in their main clinical trials for patients with acute coronary syndrome (ACS). However, the long-term prognosis and different clinical characteristics related to the type of antiplatelet prescription in current clinical practice ACS patients have not been analysed in depth. The objective of this study was to analyse the clinical profile of ACS and the efficacy and safety of novel oral P2Y12 inhibitors in current clinical practice patients discharged afterACS. METHODS: We collected data from the ACHILLES registry, and an observational, prospective and multicentre registry of patients discharged after ACS. We analysed baseline characteristics, clinical profile and therapy during ACS admission and compared with the different treatments at discharge. After 1 year of follow-up, ischaemic and major bleeding events were analysed. Multivariate Cox regression analysis and Kaplan Meier curves were also plotted. RESULTS: Of 1717 consecutive patients, 1294 (75.4%) were discharged with a P2Y12 inhibitor without oral anticoagulation. Novel oral P2Y12 inhibitors were indicated in 47%. Patients treated with clopidogrel were elderly (69.1 ± 13.4 vs 60.4 ± 11.5 years; P < .001) and had a higher prevalence of cardiovascular risk factors. GRACE and CRUSADE scores were higher in the clopidogrel than in novel oral P2Y12 inhibitors group (P < .001). After 1 year of follow-up, 64(5.0%/year) patients had a new myocardial infarction, 127(10.0%/year) had a major adverse cardiovascular event (MACE) and 78(6.1%/year) died. Patients treated with clopidogrel had a significantly higher annual rate of cardiovascular mortality, MACE and all-cause mortality (allP < .001) without differences in major bleeding (P = .587) compared with novel oral P2Y12 inhibitors. After multivariate adjustment for the main clinical variables related to adverse prognosis in ACS patients, the discharge with novel oral P2Y12 inhibitors therapy was independently associated with lower risk of all-cause mortality (HR0.49, 95% CI [0.24-0.98], P = .044) and lower risk of MACE (HR0.64, 95% CI [0.41-0.98], P = .044). CONCLUSIONS: In this prospective, observational and current clinical practice ACS registry, the use of novel oral P2Y12 inhibitors was associated with a reduction in adverse events compared with clopidogrel in patients with ACS. Novel oral P2Y12 inhibitors prescription at discharge was independently associated with lower all-cause mortality and MACE without differences in bleeding events. However, clopidogrel remained the most common P2Y12 inhibitor employed for ACS, especially in older and high-risk patients.

Temporal Changes in Platelet Response in Acute Coronary Syndrome Patients With Prasugrel and Clopidogrel After Stent Implantation.

BACKGROUND: Prasugrel has been shown to provide more potency and less variability than clopidogrel, but its potential temporal variability has not been described.Methods and Results:We conducted a prospective open-label study, evaluating platelet reactivity overtime in acute coronary syndrome (ACS) patients on aspirin and clopidogrel (n=60) or prasugrel (n=61), after a percutaneous coronary intervention (PCI). Blood samples were taken at discharge and at 3 and 6 months. Platelet function tests included VerifyNow (VN-P2Y12), and Multiplate Aggregometry (MEA). By means of VN-P2Y12, prasugrel patients displayed significantly (P<0.001) higher platelet inhibition than clopidogrel patients over time, although there were not significant differences using MEA. Prasugrel patients showed higher platelet inhibition at baseline than at 3 months (59.3±8.1 vs. 105.0±49.2; P<0.001), without significant change at 6 months (107.9±72.0; P=0.919 vs. 3 months). Clopidogrel patients showed a similar trend (160.1±65.1, 184.8±62.7 and 185.0±53.3; baseline vs. 3 months P=0.060; 3 months vs. 6 months P=0.974). High platelet reactivity (HPR) was shown in 16.3% prasugrel patients, with no patient consistently remaining in HPR over time. HPR was detected in 36.6% of the clopidogrel patients, being consistently observed in 15.0% of them. Low platelet reactivity (LPR) was detected in 60.5% prasugrel and 9.8% clopidogrel patients. CONCLUSIONS: Prasugrel patients showed less temporal variation than patients on clopidogrel in terms of HPR. In contrast, higher variability in LPR was detected in prasugrel patients for up to 6 months' follow-up.

Acute Myocarditis with Infarct-like Presentation in a Pediatric Population: Role of Cardiovascular Magnetic Resonance.

Chest pain is a typical symptom of acute myocarditis in adolescents. It may be indistinguishable from myocardial ischemia so it is called "infarct-like pattern." Cardiovascular magnetic resonance has an important role as a non-invasive diagnostic tool. The aim of our study is to provide a description of an acute myocarditis series with infarct-like pattern and to evaluate the cardiovascular magnetic resonance role in a pediatric population. We included all pediatric patients (0-16 years) admitted to our hospital (May 2007-May 2016) with clinical diagnosis of acute myocarditis and infarct-like presentation (chest pain, EKG alterations, and released cardiac biomarkers). Diagnosis was confirmed with cardiovascular magnetic resonance using Lake Louise criteria. Seven patients (five males, two females) with a median age of 14 years (12.5-15.2) were included. All patients showed ST-segment changes and released cardiac biomarkers. Three patients had left ventricular hypertrophy and two presented mild systolic left ventricular dysfunction. All patients had at least two positive Lake Louise criteria. Late gadolinium enhancement was positive in all of them. With a median follow-up of 23 months (8-47), all of them are alive, with no cardiac symptoms and normal ventricular function. Infarct-like pattern is a typical presentation of acute myocarditis in adolescents. CMR should be performed in this population and may be considered as a first-line diagnostic tool. Its high sensitivity in infarct-like acute myocarditis may allow us to avoid endomyocardial biopsy. Unlike what was described in adults, late gadolinium enhancement does not imply worse outcome in our series.

Platelet reactivity over time in coronary artery disease patients treated with a bioabsorbable everolimus-eluting scaffold.

Everolimus-eluting bioabsorbable scaffolds (BVSs) have exhibited similar long-term clinical outcomes compared to its everolimus-eluting metallic counterparts. However, reports from earlier studies have shown a signal for an increased rate of stent thrombosis. The aim of the current investigation is to describe the platelet reactivity profiles over time in patients treated with everolimus-eluting BVS in comparison to everolimus-eluting metallic stents. This is a pilot study in which patients on aspirin and clopidogrel with at least 1 everolimus-eluting BVS were included (n = 24). Patients with at least 1 everolimus-eluting metallic stent implanted were included as control group (n = 25). Blood samples were taken at time of discharge and at 3- and 6-month follow-up. Platelet function tests included VerifyNow (VN-P2Y12), multiplate aggregometry (MEA), and light transmission aggregometry (LTA). There was no difference in platelet reactivity at discharge, 3- and 6-month visits (unadjusted p = 0.733 and p = 0.582; p = 0.432 and p = 0.899 after adjusting for discharge value platelet reactivity0, respectively) using VN-P2Y12. Similar findings were observed with LTA. However, patients with BVS showed significantly higher platelet reactivity than patients with metallic stents at 3 and 6 months in the crude analysis (p = 0.003) and after adjusting for discharge value (p = 0.013) measured with ADP-MEA. There were no differences in platelet reactivity mediated by the T × A2 pathway between both groups. Finally, there is no statistical difference in high on-clopidogrel platelet reactivity (HPR) rate between both groups. The results of this pilot study suggest that BVS might have different platelet reactivity profiles, and warrants further investigation in dedicated clinical studies.

Role of thromboelastography and rapid thromboelastography to assess the pharmacodynamic effects of vitamin K antagonists.

Thromboelastography (TEG) measures the effects of antithrombotic agents by assessing global functional clotting status by evaluating the viscoelastic properties of in vitro clot formation. Recently, rapid TEG (r-TEG), which uses tissue factor in addition to standard kaolin to accelerate activation of the clotting cascade, has been proposed to obtain more immediate results. The correlation between results of TEG or r-TEG with international normalized ratio (INR) in patients on vitamin K antagonist (VKA) therapy has not been explored and represents the aim of this study. Patients on chronic therapy with VKAs (n = 100) were included in an observational prospective pharmacodynamic study. The correlation between TEG parameters, in particular markers of thrombus generation [Reaction time (R), maximum rate of thrombus generation (MRTG), and time to maximum rate of thrombus generation (TMRTG)], and INR values as well as the concordance between these parameters and therapeutic INR ranges were evaluated. In addition, in a subgroup of subjects (n = 17), the correlation of r-TEG parameters with TEG parameters and INR values was also assessed. No correlation was found between INR and TEG parameters of thrombus generation, in particular between INR and R (r = 0.189, p = 0.06), MRTG (r = -0.027, p = 0.79), and TMRTG (r = 0.188, p = 0.06). Further, no concordance was found between these parameters and recommended INR ranges. Significant Spearman correlations were found between INR and activated clotting time (rS = 0.546, p < 0.001), r-R (rS = 0.572, p = 0.017), and r-TMRTG (rS = 0.510, p = 0.037), but not r-MRTG (rS = 0.131, p = 0.617). Results were obtained in 24 ± 6 versus 12 ± 4 min with TEG and r-TEG, respectively (p < 0.001). In patients on chronic VKA therapy, TEG is not a useful tool to evaluate VKA anticoagulant effect, compared with standard INR measurements. However, r-TEG parameters of thrombus generation correlate with INR levels, suggesting a possible role of this assay for measuring more expeditiously anticoagulant treatment effects.

Pharmacodynamic effects of EV-077 in patients with diabetes mellitus and coronary artery disease on aspirin or clopidogrel monotherapy: results of an in vitro pilot investigation.

Patients with diabetes mellitus (DM) have increased propensity to generate thromboxane A2 (TXA2) and other eicosanoids which can contribute to their heightened platelet reactivity. EV-077 is a potent thromboxane receptor antagonist and thromboxane synthase inhibitor and thus represents an attractive therapy in patients with DM. However, the effects of EV-077 on pharmacodynamic (PD) profiles in patients with DM and coronary artery disease (CAD) while on antiplatelet therapy is poorly explored and represented the aim of this in vitro pilot investigation. Patients with DM and stable CAD (n = 10) on low-dose aspirin (81 mg/day) were enrolled and then switched to clopidogrel (75 mg/day) monotherapy for 7-10 days. PD assessments were conducted while on aspirin and on clopidogrel using light transmittance aggregometry following stimuli with U-46619 [TXA2 stable analogue (7 µM)], arachidonic acid [AA (1 mM)], collagen (3 µg/mL) and adenosine diphosphate [ADP (5 µM and 20 µM)] with and without in vitro EV-077. EV-077 completely inhibited U-46619-stimulated platelet aggregation (p = 0.005 for both aspirin and clopidogrel) and also showed a significant reduction of collagen-induced aggregation (aspirin p = 0.008; clopidogrel p = 0.005). EV-077 significantly reduced AA-induced platelet aggregation in clopidogrel (p = 0.009), but not aspirin (p = 0.667) treated patients. Ultimately, EV-077 significantly reduced ADP-mediated platelet aggregation in both aspirin (ADP 5 µM p = 0.012; ADP 20 µM p = 0.032) and clopidogrel (ADP 5 µM p = 0.007; ADP 20 µM p = 0.008) treated patients. In conclusion, in DM patients with CAD on aspirin or clopidogrel monotherapy, in vitro EV-077 exerts potent platelet inhibitory effects on multiple platelet signaling pathways. These data support that EV-077 has only additive platelet inhibiting effects on top of standard antiplatelet therapies. These findings warrant further investigation in ex vivo settings.

Cardiovascular considerations on recreational scuba diving. SEC-Clinical Cardiology Association/SEC-Working Group on Sports Cardiology consensus document.

The practice of recreational scuba diving has increased worldwide, with millions of people taking part each year. The aquatic environment is a hostile setting that requires human physiology to adapt by undergoing a series of changes that stress the body. Therefore, physical fitness and control of cardiovascular risk factors are essential for practicing this sport. Medical assessment is not mandatory before participating in this sport and is only required when recommended by a health questionnaire designed for this purpose. However, due to the significance of cardiovascular disease, cardiology consultations are becoming more frequent. The aim of the present consensus document is to describe the cardiovascular physiological changes that occur during diving, focusing on related cardiovascular diseases, their management, and follow-up recommendations. The assessment and follow-up of individuals who practice diving with previous cardiovascular disease are also discussed. This document, endorsed by the Clinical Cardiology Association of the Spanish Society of Cardiology (SEC) and the SEC Working Group on Sports Cardiology of the Association of Preventive Cardiology, aims to assist both cardiologists in evaluating patients, as well as other specialists responsible for assessing individuals' fitness for diving practice.

Pharmacodynamic effects of adjunctive cilostazol therapy in patients with coronary artery disease on dual antiplatelet therapy: impact of high on-treatment platelet reactivity and diabetes mellitus status.

BACKGROUND: In patients on dual antiplatelet therapy with aspirin and clopidogrel, the adjunctive use of cilostazol is associated with enhanced platelet inhibition. However, if cilostazol exerts different pharmacodynamic (PD) effects according to levels of on-treatment platelet reactivity remains unknown. This study aimed to determine the PD effects of cilostazol in patients with and without high on-clopidogrel platelet reactivity (HPR) according to diabetes mellitus (DM) status. METHODS: This is a post-hoc analysis derived from patients (n = 79) enrolled in a prospective, randomized, double-blind, double-dummy, crossover study comparing cilostazol with placebo in stable coronary artery disease patients on aspirin and clopidogrel therapy. In the present analysis, patients were divided according to the presence or absence of HPR (HPR and non-HPR). HPR was defined as a P2Y12 units (PRU) > 240 as assessed by the VerifyNow P2Y12 assay. The PD effects of cilostazol were evaluated in patients with and without HPR according to DM status. RESULTS: Significant absolute changes in PRU values were observed after adjunctive cilostazol in both HPR [53.4 (95% CI 24.7-82.1), P = 0.001] and non-HPR [40.8 (95% CI 28.7-52.8), P < 0.0001] patients. This difference was statistically significant in HPR patients with DM (P = 0.001), but not without DM (P = 0.24), and in non-HPR patients with and without DM (P = 0.0001 for both). The greatest mean reduction in PRU was observed in HPR patients with DM (72.9; 95% CI 33.7-112.0). Thrombin generation was not affected by cilostazol, irrespective of HPR status. CONCLUSION: Cilostazol reduces platelet reactivity both in HPR and non-HPR patients, although these PD effects are enhanced in HPR patients with DM. Nevertheless, larger studies are needed to better evaluate possible differential effects of cilostazol on platelet reactivity by diabetes status.

Successful pregnancy and delivery on prasugrel treatment: considerations for the use of dual antiplatelet therapy during pregnancy in clinical practice.

Ischemic heart disease is uncommon during pregnancy, occurring in approximately 1/10,000 pregnancies resulting in live births. However, the increased age and fertility of mothers has suggested that the coexistence of pregnancy and coronary artery disease is likely to increase. A subject of debate is the management of dual antiplatelet therapy among pregnant women. The potential teratogeneous effects, particularly with regards to thienopyridines, on the fetus are not fully established. In addition, the use of dual antiplatelet therapy is associated with an increased risk for bleeding events, raising concerns in the peripartum period with regards to the route of delivery and choice of anesthestic techniques. Limited data and experience is available with clopidogrel, the most commonly used thienopyridine. Prasugrel is third generation thienopyridine recently introduced into clinical practice with ever growing use in the setting of acute coronary syndrome patients undergoing percutaneous coronary interventions. The present manuscript describes the first case report of a pregnancy while on prasugrel therapy.

Impact of renal function on clopidogrel-induced antiplatelet effects in coronary artery disease patients without diabetes mellitus.

Diabetes mellitus (DM) is the most important predictor of chronic kidney disease (CKD), and pharmacodynamic (PD) studies have shown that DM patients with impaired renal function are characterized by reduced clopidogrel response. However, post-hoc PD studies conducted in unselected cohorts, composed of both DM and non-DM patients, have reached controversial findings on the effects of CKD on clopidogrel response, likely attributed to patient heterogeneity. The impact of renal function on clopidogrel response in non-DM patients remains unexplored and represented the aim of this prospective investigation. We conducted a prospective PD investigation in non-DM patients with and without CKD defined as an estimated glomerular filtration rate (eGFR) below or above 60 mL/min, respectively. All patients had known coronary artery disease and were on maintenance aspirin therapy. PD assessments were assessed at baseline and 2 and 24 h after a 600 mg loading dose of clopidogrel. PD assays included light transmission aggregometry (LTA) using 5 and 20 µmol ADP with and without PGE1 and flow cytometric assessment of the phosphorylation status of the vasodilator-stimulated phosphoprotein (VASP) to determine the platelet reactivity index. A total of 60 patients were studied (n = 30 eGFR ≥60 mL/min; n = 30 eGFR <60 mL/min). At baseline there were no differences between groups. Following clopidogrel loading dose administration, levels of on-treatment platelet reactivity were similar between groups at 2 and 24 h as measured with LTA and VASP. Accordingly, there were no differences in rates of high on-treatment platelet reactivity between groups. In non-DM patients with CAD, the presence of impaired renal function is not associated with differences in clopidogrel-induced antiplatelet effects compared with patients with preserved renal function.

Effects of cangrelor in coronary artery disease patients with and without diabetes mellitus: an in vitro pharmacodynamic investigation.

Platelets from patients with diabetes mellitus (DM) are hyper-reactive and whether cangrelor, a potent intravenous P2Y(12) receptor blocker, has differential pharmacodynamic (PD) effects according DM status is unknown. The aim of this investigation was to evaluate the in vitro PD effects of cangrelor in coronary artery disease (CAD) patients with and without DM. This prospective study enrolled 120 clopidogrel-naïve patients with CAD on aspirin therapy. PD assessments using cangrelor (500 nmol/l) in vitro included vasodilator-stimulated phosphoprotein assay to obtain the P2Y(12) reactivity index (PRI), and multiple electrode aggregometry (MEA). In a 20 patients subgroup, dose-dependent response was assessed following exposure to escalating concentrations (baseline, 5, 50, 500 and 5,000 nmol/l); thrombin generation processes were evaluated by thromboelastography (TEG). PD data were evaluable in 103 patients. No differences in baseline PD parameters were observed in DM (n = 48) and non-DM (n = 45) subjects. Cangrelor reduced PRI values irrespective of DM status (p < 0.0001), yielding no difference in patients with and without DM (16.1 ± 12.3 vs. 16.8 ± 11.3; p = 0.346). All MEA values were significantly reduced, although this was of greater magnitude with purinergic compared to non-purinergic agonists. A trend analysis showed a dose-dependent effect on platelet inhibition, with no interaction due to DM status, whereas no significant dose-dependent effect was observed for TEG-derived parameters. Therefore, in vitro cangrelor provides potent and dose-dependent blockade of the platelet P2Y(12) receptor, with no differential effect in DM and non-DM patients. In addition, in vitro cangrelor exerts moderate inhibitory effects on non-purinergic platelet signaling pathways, without modulating platelet-derived thrombin generation processes.

Simplified Geleijnse score for identifying chest pain features associated with coronary ischemia.

BACKGROUND: The Geleijnse score, which was proposed to assess for coronary ischemia, has practical limitations. OBJECTIVES: Our aim was to design and evaluate a simplified version of the Geleijnse score. METHODS: We enrolled patients with suspected coronary heart disease but negative troponin T or absence of enzymatic curve, and a non-diagnostic 12-lead ECG. The initial study was performed in a retrospective derivation cohort and the results were subsequently validated in a prospective cohort. RESULTS: From 109 patients included in the derivation cohort, 33 (30.3%) received a diagnosis of coronary heart disease. Chest pain with both arms radiation (OR 3.54), severe intensity (OR 2.41), improvement by nitroglycerin (OR 1.61), associated dyspnea (OR 1.97) and prior exertional angina history (OR 2.91) were independently associated with an ischemic origin on multivariate logistic regression analysis. ROC curves comparison demonstrated both the original and simplified scores presented modest predictive ability with significant difference when analyzed using dichotomous cut-offs (0.647 [simplified] vs. 0.544 [original], p = 0.042) but not as a continuous variable (0.670 [simplified] vs. 0.621 [original], p = 0.396). In 305 patients from the validation cohort, the simplified score presented extensively increased predictive accuracy than the Geleijnse, in the continuous (c-indexes = 0.735 vs. 0.685, p = 0.040) and the dichotomic (c-indexes = 0.682 vs. 0.514, p<0.001) forms. CONCLUSIONS: A simplified version of the Geleijnse score, including some routine clinical manifestations associated with coronary heart disease, presented significantly better predictive ability compared to the original score.

Impact of renal function on Ticagrelor-induced antiplatelet effects in coronary artery disease patients.

Background: Chronic renal failure (CKD) is associated with the presence of increased platelet reactivity and lower clinical benefit of clopidogrel. Ticagrelor has a more favorable pharmacodynamic and pharmacokinetic profile compared to clopidogrel, which has translated into better clinical outcomes in patients with acute coronary syndrome (ACS). We conducted a prospective mechanistic cohort study in order to investigate the impact of renal failure on the pharmacokinetics and pharmacodynamics of ticagrelor in patients with acute ACS. Methods: Patients were divided into two groups based on their estimated renal clearances (eGFR ≥ 60 mL/min and eGFR < 60 mL/min). Platelet function was determined using the VerifyNow system at baseline, after the ticagrelor loading dose and at discharge. In addition, levels of ticagrelor and its active metabolite (AR-C124910XX) were determined in the first hour after loading dose. Results: 48 patients were recruited (eGFR ≥ 60 mL/min: 35 and eGFR < 60 mL/min: 13). There were no significant differences between the groups in terms of platelet inhibition after the loading or after 7 days of treatment (p = 0.219). However, the levels of ticagrelor and its active metabolite were lower in subjects with normal renal function than in CKD, especially at 4 (p = 0.02 and 0.04 respectively) and 6 h of loading (p = 0.042 and 0.08 respectively). Conclusion: No differences in platelet inhibition were observed after treatment with ticagrelor in patients with different renal function, although patients with renal impairment showed higher levels of ticagrelor and AR-C124910XX after 4 h of the loading dose.

Mini-STAR as bail-out strategy for percutaneous coronary intervention of chronic total occlusion.

BACKGROUND: Although the advancement of the equipment and the presence of innovative techniques, percutaneous coronary intervention (PCI) for chronic total occlusion (CTO) continues to be affected by lower procedural success in comparison with non occluded vessel PCI. OBJECTIVE: We describe a new technique for the treatment of coronary CTO which utilizes a new generation of polymeric wires. METHODS AND RESULT: From March 2009 to June 2010 different strategies were adopted as "bail out" after an initial attempt failed in 117 consecutive CTO lesions. Among these, conventional strategies (CS) such as parallel wire, sub-intimal tracking and re-entry (STAR), microchannel technique, intracoronary ultrasound guided revascularization and anchor balloon, were used in 75 cases (64.1%), while in the remaining a new technique, the "mini-STAR," was used (39.9%). Although no substantial differences were observed regarding the distribution of clinical features and angiographic lesions characteristics between the populations, mini-STAR was able to achieve a higher rate of procedural success in comparison with other CS (97.6% vs. 52%, P < 0.001) with lower contrast agent use (442 ± 259 cm(3) vs. 561 ± 243 cm(3), P = 0.01) and shorter procedural and fluoroscopy times (122 ± 61 vs. 157 ± 74 min, P = 0.009 and 60 ± 31 min vs. 75 ± 38 min, P = 0.03, respectively). No differences were observed in term of peri-procedural complications such as procedural myocardial infarction, coronary perforations, and contrast-induced nephropathy between mini-STAR and CS. CONCLUSION: The mini-STAR technique is a promising strategy for the treatment of CTO lesions, achieving a high procedural success rate and low occurrence of procedural adverse events.

Advances in platelet function testing assessing bleeding complications in patients with coronary artery disease.

Antiplatelet therapy is the cornerstone of treatment in preventing ischemic events in patients with coronary artery disease (CAD), particularly in the setting of acute coronary syndromes and percutaneous coronary interventions. However, antiplatelet therapy is also associated with an increased risk of bleeding complications, which are more frequent with the use of more potent antiplatelet treatment regimens. Therefore, defining the balance between the risk of thrombotic events and the risk of bleeding is essential to improve overall clinical outcomes. The pharmcodynamic effects of antiplatelet agents vary broadly and may be associated with differences in outcomes. In particular, patients are at an increased risk of ischemic or bleeding complications if the pharmacodynamic effects are reduced or enhanced, respectively. Multiple platelet function assays are currently available to assess the pharmacodynamic effects of commonly used antiplatelet agents. The present manuscript will review the prognostic value of platelet function testing to identify patients with CAD at risk of bleeding complications and the potential applications of these tests in the modern era of antiplatelet pharmacotherapy.

Prasugrel.

Prasugrel is a third-generation thienopyridine which selectively inhibits the platelet P2Y(12) receptor more rapidly, more potently, and with less interindividual response variability compared with the second-generation thienopyridine clopidogrel. Large-scale phase III clinical testing showed that in high-to moderate-risk acute coronary syndrome patients undergoing percutaneous coronary intervention, prasugrel translates into a greater reduction in ischemic events, including stent thrombosis, in the short and long term compared to clopidogrel. Prasugrel, however, is associated with an increased risk of major bleeding, which is more pronounced in certain patient subgroups. The ideal patient population for prasugrel use are those patients without prior transient ischemic attack/stroke, <75 years of age and >60 kg in whom the greatest ischemic benefit is achieved without a significant increase in major bleeding risk. Dose modifications in specific populations or at given time-points may represent an avenue to minimize bleeding risk and therefore maximize the clinical benefit of prasugrel. Ongoing clinical studies with prasugrel will better define the safety and efficacy profiles of this agent and potentially set the basis for new indications for use.

Effect of cocoa (Theobroma cacao L.) on platelet function testing profiles in patients with coronary artery disease: ECLAIR pilot study.

INTRODUCTION: This prospective pharmacodynamic nutraceutical study assessed the effect of a 1-week trial of 30 g/day of 65% cocoa (dark chocolate) (Theobroma cacao L.) consumption intervention on platelet reactivity. METHODS: Patients with stable coronary artery disease (CAD) (n=20) who were on maintenance dual antiplatelet therapy of aspirin (ASA) 81 mg/day and clopidogrel 75 mg/day were recruited. Platelet function was evaluated with the VerifyNow P2Y12 reaction unit (PRU) and aspirin reaction unit (ARU) assays (Werfen, Bedford, Massachusetts, USA) and assessed prior to initiation of and after a 1-week trial of 30 g/day of 65% cocoa consumption intervention. Results were compared with a paired t-test. RESULTS: Cocoa augmented the inhibitory effect of clopidogrel, demonstrated by a reduction of 11.9% (95% CI 5.7% to 18.0%, p value 0.001), significantly decreasing the PRU by 26.85 (95% CI 12.22 to 41.48, p value 0.001). The inhibitory effect of ASA was not impacted by cocoa, reflected by a non-significant reduction in ARU of 17.65 (95% CI 21.00 to 56.3, p value 0.351). No patients experienced any serious adverse events. CONCLUSIONS: Cocoa augmented the inhibitory effect of clopidogrel but not ASA. This nutraceutical study could be potentially informative and applicable for patients with stable CAD. Further long-term studies are required to confirm these exploratory findings. TRIAL REGISTRATION NUMBER: NCT04554901.