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Background: Clopidogrel associated with aspirin is the recommended treatment for patients undergoing elective percutaneous coronary intervention (PCI). Although severe PCI-related events are rare, evidence suggests that PCI-related myocardial infarction and myocardial injury are frequent complications that can impact the clinical prognosis of the patients. Antiplatelet therapy with a potent P2Y 12 receptor inhibitor such as ticagrelor may reduce periprocedural ischemic complications while maintaining a similar safety profile as compared with conventional dual antiplatelet therapy by aspirin and clopidogrel in this setting., Methods: Assessment of Loading with the P2Y 12 inhibitor ticagrelor or clopidogrel to Halt ischemic Events in patients Undergoing elective coronary Stenting (ALPHEUS) (NCT02617290) is an international, multicenter, randomized, parallel-group, open-label study in patients with stable coronary artery disease who are planned for an elective PCI. In total, 1,900 patients will be randomized before a planned PCI to a loading dose of ticagrelor 180 mg or a loading dose of clopidogrel (300 or 600 mg) in addition to aspirin. Patients will then receive a dual antiplatelet therapy with aspirin and ticagrelor 90 mg twice daily or clopidogrel 75 mg once daily for 30 days. The primary ischemic end point is PCI-related myocardial infarction (myocardial infarction type 4a or 4b) or major myocardial injury within 48 hours (or at hospital discharge if earlier) after elective PCI/stent. Safety will be evaluated by major bleeding events (Bleeding Academic Research Consortium type 3 or 5) at 48 hours (or discharge if it occurs earlier)., Conclusion: ALPHEUS is the first properly sized trial comparing ticagrelor to clopidogrel in the setting of elective PCI and is especially designed to show a reduction in periprocedural events, a surrogate end point for mortality., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Background: Patients' responses to oral antiplatelet therapy are subject to variation. Bedside monitoring offers the opportunity to improve outcomes after coronary stenting by individualizing therapy., Methods: We randomly assigned 2440 patients scheduled for coronary stenting at 38 centers to a strategy of platelet-function monitoring, with drug adjustment in patients who had a poor response to antiplatelet therapy, or to a conventional strategy without monitoring and drug adjustment. The primary end point was the composite of death, myocardial infarction, stent thrombosis, stroke, or urgent revascularization 1 year after stent implantation. For patients in the monitoring group, the VerifyNow P2Y12 and aspirin point-of-care assays were used in the catheterization laboratory before stent implantation and in the outpatient clinic 2 to 4 weeks later., Results: In the monitoring group, high platelet reactivity in patients taking clopidogrel (34.5% of patients) or aspirin (7.6%) led to the administration of an additional bolus of clopidogrel, prasugrel, or aspirin along with glycoprotein IIb/IIIa inhibitors during the procedure. The primary end point occurred in 34.6% of the patients in the monitoring group, as compared with 31.1% of those in the conventional-treatment group (hazard ratio, 1.13; 95% confidence interval [CI], 0.98 to 1.29; P=0.10). The main secondary end point, stent thrombosis or any urgent revascularization, occurred in 4.9% of the patients in the monitoring group and 4.6% of those in the conventional-treatment group (hazard ratio, 1.06; 95% CI, 0.74 to 1.52; P=0.77). The rate of major bleeding events did not differ significantly between groups., Conclusions: This study showed no significant improvements in clinical outcomes with platelet-function monitoring and treatment adjustment for coronary stenting, as compared with standard antiplatelet therapy without monitoring. (Funded by Allies in Cardiovascular Trials Initiatives and Organized Networks and others; ARCTIC ClinicalTrials.gov number, NCT00827411.).

In order to determine how renal transplantation modifies in hospital and long-term outcome after coronary angioplasty, we compared dialysis and renal transplant patients with control patients without renal failure. Seventy-five consecutive dialysis patients (group D) and 37 renal transplant patients (group T) undergoing coronary angioplasty, were compared with two control groups (groups control D and control T, respectively) matched 1:1 with groups D and T for clinical and angiographic characteristics. The mean follow-up was 50 months. The rate of angiographic success was high and comparable in the four groups (P=0.7). Renal transplant patients were younger than dialysis non-transplant patients (P=0.004). The risk of 4-year cardiac death and nonfatal myocardial infarction was higher in dialysis compared to control dialysis patients (OR 2.6, 95% CI 1.35--5.01, P=0.004), in transplant patients compared to control transplant patients (OR 9.93, 95% CI 1.17--84.04, P=0.03), and there was a trend toward a higher risk in dialysis than in renal transplant patients (OR 1.6, 95% CI 0.8--3.19, P=0.08). The risk of 4-year mortality was higher in dialysis patients than in the other three groups (31% in group D versus 19% in group T, 13% in group control D, and 0% in group control T, P<0.001). After adjusting for age, diabetes, and multivessel disease, long-term mortality risk was similar in dialysis and renal transplant patients. On multivariate analysis, renal function (P=0.002), age (P=0.005), and tobacco consumption (P=0.005) were independently associated with 4-year cardiac death. In patients with end-stage renal disease who undergo coronary angioplasty, renal transplantation was not independently associated with a lower long-term mortality compared to dialysis treatment. Both dialysis and renal transplant patients show lower survival rates compared to matched control patients., ((J Interven Cardiol 2005;18:331-337).)

Aim: The safety and efficacy of ad hoc PTCA has been previously reported and this approach is performed in many angioplasty centers as a routine procedure. The aim of this study is to examine whether this approach reduces the length, and cost of hospital stay., Methods and Results: To determine the hospital costs we studied 2,440 PTCAs over 11 years in our institution (1990-2000). Urgent PTCA for acute coronary syndromes refractory to medical treatment were excluded. In 1809 patients (74%) angioplasty was performed immediately after coronary angiography, while separate procedures were performed in 631 patients. Indication for PTCA was unstable angina in 1342 patients (55%). In the ad hoc PTCA group, 92% of the culprit lesions were successfully treated; complications included myocardial infarction (2%), urgent bypass surgery (0.6%) and death (0.9%). The rate of combined procedure progressively increased from 54% in 1990 to 88% in 2000, with a significant decrease in the rate of complications. After adjusting for clinical and angiographic differences between combined and separate procedures, angiographic success and complication rates were not statistically different in the two groups. Mean length of hospital stay decreased all along the years, and was 45% less in the ad hoc PTCA group (11.4 +/- 6.9 vs 18.2 +/- 7.7 in 1990, 5.4 +/- 4.3 vs 10.8 +/- 5.7 in 2000, P < 0.0001). The cost was 40% lower in the ad hoc PTCA group. For patients with stable angina, the savings were 49%, and for those with unstable angina, they were 29%., Conclusion: In the era of coronary stenting, ad hoc PTCA can be performed in most of the patients as safely and successfully as a separate procedure. It reduces the length, and the cost of hospital stay in patients with stable or unstable angina.

Purpose: We assessed the feasibility of myocardial blood flow (MBF) and flow reserve (MFR) estimation using dynamic SPECT with a novel CZT camera in patients with stable CAD, in comparison with 15O-water PET and fractional flow reserve (FFR).Methods: Thirty patients were prospectively included and underwent FFR measurements in the main coronary arteries (LAD, LCx, RCA). A stenosis ≥50% was considered obstructive and a FFR abnormal if ≤0.8. All patients underwent a dynamic rest/stress 99mTc-sestamibi CZT-SPECT and 15O-water PET for MBF and MFR calculation. Net retention kinetic modeling was applied to SPECT data to estimate global uptake values, and MBF was derived using Leppo correction. Ischemia by PET and CZT-SPECT was considered present if MFR was lower than 2 and 2.1, respectively.Results: CZT-SPECT yielded higher stress and rest MBF compared to PET for global and LAD and LCx territories, but not in RCA territory. MFR was similar in global and each vessel territory for both modalities. The sensitivity, specificity, accuracy, positive and negative predictive value of CZT-SPECT were, respectively, 83.3, 95.8, 93.3, 100 and 85.7% for the detection of ischemia and 58.3, 84.6, 81.1, 36.8 and 93% for the detection of hemodynamically significant stenosis (FFR ≤ 0.8).Conclusions: Dynamic 99mTc-sestamibi CZT-SPECT was technically feasible and provided similar MFR compared to 15O-water PET and high diagnostic value for detecting impaired MFR and abnormal FFR in patients with stable CAD. [ABSTRACT FROM AUTHOR]

The article focuses on a study which examines the electrophysiological impact and the exact antiarrhyhmic properties of potassium canrenoate (PC) during an acute myocardial ischemia-perfusion. Topics discussed include the electrophysiological effects of PC on the border zone, the cycle length dependence of PC and the class I antiarrhythmic effects of PC. Also mentioned are the limitations of the study.

We sought to assess whether multiple biomarkers would correlate with the outcome and could improve event prediction in non–ST-segment elevation acute coronary syndrome populations with low event rates. Nine inflammatory, ischemic, or neurohormonal biomarkers were measured within 48 hours after symptom onset in 440 patients with non–ST-segment elevation acute coronary syndrome from the ARCHIPELAGO (Irbesartan in Patients With Acute Coronary Syndrome Without ST Segment Elevation) trial. We assessed the relation between biomarkers and ischemic or heart failure composite end points at 2 months of follow-up. We also evaluated whether biomarkers could improve the predictive performance of the validated and well-performing Global Registry of Acute Coronary Events risk score. Among all biomarkers measured at baseline, only interleukin-6 correlated with the ischemic end point (adjusted odds ratio 1.69, 95% confidence interval [CI] 1.23 to 2.31). The independent correlates of the heart failure end point were B-type natriuretic peptide (adjusted odds ratio 3.16, 95% CI 1.99 to 5.03), aldosterone (adjusted odds ratio 1.57, 95% CI 1.14 to 2.16) and matrix metalloproteinase-9 (adjusted odds ratio 0.64, 95% CI 0.46 to 0.88). The Global Registry of Acute Coronary Events score predicted poorly the ischemic end point (area under the curve [AUC] 0.591) and fairly (AUC 0.775) the heart failure end point. The performance of the models was significantly improved by the introduction of interleukin-6 (AUC 0.685) for the ischemic end point and of the 3 biomarkers (AUC 0.874) for the heart failure end point. In conclusion, the interleukin-6 level only, and B-type natriuretic peptide, aldosterone, and matrix metalloproteinase-9 together, independently correlated with the ischemic and heart failure end points, respectively. The Global Registry of Acute Coronary Events risk score''s performance was significantly improved with a biomarker strategy. In low-risk populations, a strategy using these biomarkers might help in identifying patients at greater risk of additional events. [Copyright &y& Elsevier]

The article focuses on a study which investigated if immediate intervention on admission can cause a reduction in myocardial infarction. The study included 352 patients from 13 centers in France, who were diagnosed with acute coronary syndromes without ST-segment elevation. The peak troponin value during hospitalization and the composite of death were measured on each patient. Study authors compared the clinical outcome of immediate and delayed intervention. They concluded that immediate and delayed intervention showed no difference in reducing myocardial infarction in patients with acute coronary syndromes without ST-segment elevation.

Right ventricular (RV) dysfunction is a predictor of poor outcome in patients with heart disease. Conventional imaging modalities fail to assess RV volumes accurately. We sought to assess the accuracy and reproducibility of routine breath-hold gradient echo magnetic resonance imaging (MRI)-derived RV mass, volumes and function. We assessed: (1) The accuracy of in vivo MRI-derived RV mass in comparison to the RV weight in 9 minipigs. (2) Intra- and inter-observer reproducibility of RV mass, end-diastolic (EDV) and end-systolic (ESV) volumes and ejection fraction (EF) in 15 normal volunteers and 10 patients with heart disease. (3) Inter-study reproducibility of the former parameters in 25 coronary artery disease patients. (4) The correlation between right and left ventricular stroke volumes in the total population. Strong statistically significant correlations were found between: (1) MRI-derived RV mass and RV weight (r = 0.98, bias = 2.5 g), (2) Intra-observer measurements of RV mass (r = 0.96, bias = 0.5 g), EDV (r = 0.99, bias = -1.5 ml), ESV (r = 0.98, bias = 0.1 ml) and EF (r = 0.92, bias = -1.4%), (3) Inter-observer measurements of RV mass (r = 0.95, bias = 1.1 g), EDV (r = 0.98, bias = -1.1 ml), ESV (r = 0.98, bias = 1.2 ml) and EF (r = 0.87, bias = -1.9%), (4) Inter-study measurements of RV mass (r = 0.91, bias = -0.1 g), EDV (r = 0.96, bias = 3.8 ml), ESV (r = 0.98, bias = 0.3 ml) and EF (r = 0.90, bias = 0.9%), (5) MRI-derived right and left ventricular stroke volumes (r = 0.87). The assessment of the RV mass, volumes and function by routine breath-hold gradient echo MRI is accurate and highly reproducible. The correlation between left and RV MRI-derived stroke volumes indicates excellent coherence of simultaneous bi-ventricular volume measurements. [ABSTRACT FROM AUTHOR]

Inferior acute myocardial infarction (AMI) is associated with a better outcome compared with anterior AMI, even in the presence of comparable infarct size. Whether left ventricular remodeling, a major predictor of poor outcome, and right ventricular (RV) remodeling depend on the site of an AMI remains unknown. Biventricular volumes were assessed by magnetic resonance imaging 7 ± 2 days and 3.4 ± 0.3 months after successful primary stenting in 51 consecutive patients with inferior or anterior AMI. This study documents RV involvement and biventricular reverse remodeling in patients with inferior AMI in the absence of RV infarction, as opposed to those with anterior AMI who show progressive biventricular remodeling. [Copyright &y& Elsevier]

Background The prevalence and associated-risk of asymptomatic multisite artery disease (MSAD) in high risk coronary patients are unknown. Whether systematic identification and aggressive management of asymptomatic MSAD is clinically relevant in high risk coronary patients has not been evaluated. Methods We randomly assigned 521 high risk coronary patients defined by the presence of three-vessel coronary disease ( n = 304) or recent acute coronary syndrome beyond the age of 75 years ( n = 215) to either a strategy of systematic detection of asymptomatic MSAD combined with an aggressive secondary prevention ( n = 263) or to a more conventional strategy based on treatment of coronary artery disease only with standard of care ( n = 258). The primary end point was the time to first occurrence of death, any organ failure or ischemic event leading to re-hospitalization through two years of follow-up. Results The pro-active strategy identified asymptomatic MSAD in 21.7% of patients with few revascularizations (3.6%); the pro-active pharmacological secondary prevention was obtained in > 85% of patients and life-style changes in < 60% of patients. At 2-year follow-up, the primary end point occurred in 44.9% of patients in the pro-active group and 43.0% of patients in the conventional group (HR 1.03; 95% confidence interval [CI], 0.80 to 1.34]. The rate of major bleeding did not differ significantly between groups (4.6% vs 5.0%; HR, 0.97; 95% CI, 0.40 to 1.91). Conclusion In high risk coronary patients, there is no apparent benefit of a systematic detection of asymptomatic extra-coronary atherothrombotic disease and intensified treatment over a 2-year follow-up period. (Funded by the Academic Allies in Cardiovascular Trials Initiatives and Organized Networks and Institut de l'Athérothrombose; AMERICA ClinicalTrials.gov number, NCT00445835 ). [ABSTRACT FROM AUTHOR]

Abstract: Background and aims: Plasma aldosterone has been associated with all-cause and cardiovascular mortality in high-risk cardiovascular populations, including patients with heart failure, myocardial infarction and high-risk coronary artery disease (CAD) patients. In the present study, we evaluated the association of plasma aldosterone levels with vascular events in a large prospective cohort of stable CAD patients recruited in an outpatient setting. Moreover, we investigated the relationship between aldosterone and atherosclerotic burden. Methods and results: Baseline plasma aldosterone levels were measured in 2699 subjects with CAD (mean age 60±10years, 82% male). During a median follow-up of 4.7years, 308 (11%) patients died, of which 203 were from a vascular cause. Vascular endpoints of myocardial infarction, ischemic stroke or vascular death occurred in 355 (13%) patients. Multivariable Cox regression analysis was performed, adjusting for multiple confounders. Aldosterone (median 96pg/mL, interquartile range 70–138pg/mL, normal range 58–362pg/mL) was independently associated with major vascular events (hazard ratio (HR) 1.56, 95% confidence interval (CI) 1.13–2.15) and vascular mortality (HR 1.95, 95% CI 1.27–3.00). By multivariable regression analysis, aldosterone was also associated with the presence of atherosclerosis in additional vascular territories (cerebrovascular disease and/or peripheral artery disease) (p =0.026). Conclusions: In patients with stable coronary artery disease, plasma aldosterone is independently associated with the risk of major vascular events and vascular mortality and with atherosclerotic burden. [Copyright &y& Elsevier]

Objectives: The aim of this study was to assess the association between the loss-of-function cytochrome P450 2C19 (CYP2C19)*2 variant (10 studies, 11,959 patients) or the use of proton pump inhibitors (PPIs) (13 studies, 48,674 patients) and ischemic outcomes (major adverse cardiovascular events [MACE]) in patients treated with clopidogrel. Background: In clopidogrel-treated patients, increased cardiovascular risk has been identified with the loss-of-function CYP2C19*2 allele or the use of PPIs, some of them CYP2C19 inhibitors. To further estimate the effect of a reduction in activity of this enzyme, the authors performed a meta-analysis of the studies available. Methods: The meta-analysis was performed on 23 studies using the odds ratio (OR) as the parameter of efficacy, with a fixed-effect model. The end points were MACE, mortality, or stent thrombosis. Results: Of the 11,959 patients, carriers of the loss-of-function CYP2C19*2 allele (28% [n = 3,418]) displayed a 30% increase in the risk for MACE compared with noncarriers (9.7% vs. 7.8%; OR: 1.29; 95% confidence interval [CI]: 1.12 to 1.49; p < 0.001). This single gene variant (CYP2C19*2) was also associated with an excess of mortality (1.8% vs. 1.0%; OR: 1.79; 95% CI: 1.10 to 2.91; p = 0.019; n = 6,225) and of stent thrombosis (2.9% vs. 0.9%; OR: 3.45; 95% CI: 2.14 to 5.57; p < 0.001; n = 4,905). This increased risk was apparent in both heterozygotes and homozygotes and was independent of the baseline cardiovascular risk. PPI users (42% [n = 19,614]) displayed increased risk for MACE (21.8% vs. 16.7%; OR: 1.41; 95% CI: 1.34 to 1.48; p < 0.001) and mortality (12.7% vs. 7.4%; OR: 1.18; 95% CI: 1.07 to 1.30; p < 0.001; n = 23,977) compared with nonusers. The impact of PPI use was, however, significantly influenced by baseline cardiovascular risk, being significant only in high-risk patients. Conclusions: In this global meta-analysis, reduced CYP2C19 function appears to expose clopidogrel-treated patients to excess cardiovascular risk and mortality. Conflicting results among studies may be explained by differences in types and/or levels of risk of patients. [Copyright &y& Elsevier]

Objectives: The purpose of this study was to determine whether the speed of response to clopidogrel loading predicts the final degree of response. Background: Fast inhibition of platelet aggregation is important in the setting of acute coronary syndromes and percutaneous coronary intervention, but its association with the final degree of inhibition is not well established. Methods: We performed a post hoc analysis of the ALBION study; early kinetic profiles of adenosine diphosphate 20 μmol/l maximal platelet aggregation (MPA) and ΔMPA (with baseline sample as reference) were studied at 8 time points within the 24 h after clopidogrel loading (300, 600, or 900 mg) in non–ST-segment elevation acute coronary syndrome patients. Low response was defined as ΔMPA <10% over the first 24 h, fast response as ΔMPA ≥10% at 1 h or before loading (the others being slow responders), and high post-treatment platelet reactivity as MPA ≥56.56% (fourth quartile). Inflammatory markers (PAC-1 and P-selectin) and vasodilator-stimulated phosphoprotein (VASP) were also evaluated according to onset of action. Results: Fifty-five percent of patients were slow responders. Noncurrent smoking and body mass index ≥25 kg/m2 were associated with slower and lower responses. High post-treatment platelet reactivity was more frequent in slow responders (28% vs. 14%, p < 0.0001). There was a clopidogrel dose-effect relationship on ΔMPA, with a trend toward faster onset of platelet inhibition in the 900-mg loading dose group. Slow responders had a slower and lower decrease in PAC-1 and P-selectin and higher VASP index at 6 h (76.5% vs. 66.4%, p = 0.019) and 24 h (70.3% vs. 61.5%, p = 0.049). Conclusions: Slow response to clopidogrel, within the first hour of administration, is a reliable marker of low response at 24 h and high post-treatment platelet reactivity. [Copyright &y& Elsevier]