Evaluation of the safety and efficacy of the Cobra PzF NanoCoated coronary stent in routine, consecutive, prospective, and high-risk patients: The e-Cobra study.

BACKGROUND: The Cobra PzF coronary stent is cobalt chromium with flat thin struts, nano-coated with Polyzene-F that enhance rapid reendothelialization and reduce the risk of stent thrombosis and restenosis. It is designed to overcome shortfalls of BMS and DES in patients requiring short DAPT duration. AIMS: To report procedural and 1-year clinical outcomes following Cobra PzF stent implantation in routine practice PCI. METHODS: e-Cobra registry is a multicenter prospective study to evaluate Cobra PzF stent in routine practice in patients deemed appropriate for short DAPT after PCI. The primary endpoint was MACE rate at 12 months (Cardiac death, MI, TLR). The secondary endpoint was definite stent thrombosis at 12 months. RESULTS: Among 940 patients (72% men, 72.8 ± 13.4 years) with multiple co-morbidities, 47% had acute coronary syndromes, and 62% were defined as high bleeding risk. A total of 1,229 lesions were treated with 1,314 stents. 36% of patients had lesion type B2 or C classification. Angiographic success was achieved in all cases. One-year follow-up was available for 97% of patients. The primary endpoint occurred in 9.0% of patients, including cardiac death 3.7%, MI 4.8%, and TLR 4.3%. Definite stent thrombosis occurred in six out of 915 (0.7%). CONCLUSION: The Cobra PzF stent was safe and effective in routine practice patients and seems feasible in situations when short DAPT or Mono Antiplatelet Therapy (MAPT) is needed. One-year follow-up was associated with satisfactory clinical outcomes and validate previously reported data.

Incomplete Recovery From Takotsubo Syndrome Is a Major Determinant of Cardiovascular Mortality.

BACKGROUND: Although there is an apparent rapid and spontaneous recovery of left ventricular ejection fraction (LVEF) in patients with Takotsubo syndrome (TTS), recent studies have demonstrated a long-lasting functional impairment in those patients. The present study sought to evaluate the predictors of incomplete recovery following TTS and its impact on cardiovascular mortality.Methods and Results:Patients with TTS between 2008 and 2018 were retrospectively enrolled at 3 different institutions. After exclusion of in-hospital deaths, 407 patients were split into 2 subgroups according to whether their LVEF was >50% (recovery group; n=341), or ≤50% (incomplete recovery group; n=66) at the chronic phase. Multivariate logistic regression analysis found that LVEF (odds ratio [OR]: 0.94; 95% confidence interval [CI]: 0.91-0.98; P<0.001) and C-reactive protein levels (OR: 1.11; 95% CI: 1.02-1.22; P=0.02) at discharge were independent predictors of incomplete recovery. At a median follow up of 52 days, a higher cardiovascular mortality was evident in the incomplete recovery group (16% vs. 0.6%; P<0.001). CONCLUSIONS: This study demonstrated that incomplete recovery after TTS is characterized by residual systemic inflammation and an increased cardiac mortality at follow up. Altogether, the present study findings determined that patients with persistent inflammation are a high-risk subgroup, and should be targeted in future clinical trials with specific therapies to attenuate inflammation.

Nonculprit Artery Myocardial Infarction and Complex Coronary Lesions in Anterior ST-Elevated Myocardial Infarction Patients: Data from the CIRCUS Study.

AIMS: Periprocedural myocardial infarctions have been reported in the setting of planned percutaneous coronary intervention (PCI). We assessed the prevalence of nonculprit artery acute myocardial infarction (NCAMI) and its relationship with coronary artery characteristics, final infarct size, and 1-year adverse clinical outcomes in a population of anterior ST-elevated myocardial infarction (STEMI) patients. METHODS AND RESULTS: Late gadolinium-enhanced cardiac magnetic resonance (LGE-CMR) studies were performed within 7 days of admission in 129 anterior STEMI patients from the CIRCUS trial treated by primary PCI. Infarct in the noninfarct artery territory (circumflex, right coronary) was assessed on LGE-CMR and T2-weighted images. Eleven (8.5%) patients exhibited NCAMI. The only independent characteristic significantly associated with NCAMI was the presence of multiple complex coronary lesions (odds ratio = 12.9, 95% confidence interval [3.1-53.4]; p < 0.001). There was a significantly increased infarct size in NCAMI patients compared to patients without NCAMI (45.8 ± 20.4% of the left ventricle [LV] vs. 31.0 ± 15.1% of LV, respectively; p = 0.02), with lower LV ejection fraction (46 ± 10% vs. 34 ± 8%, respectively; p < 0.001). CONCLUSION: NCAMIs are present in 8.5% of anterior STEMI patients and are significantly associated with multiple complex coronary lesions without significant relationship to any revascularization procedural technique. NCAMI was associated with a greater infarct size and reduced LVEF but not worse clinical outcomes at 1 year.

Periprocedural Predictors of New-Onset Conduction Abnormalities After Transcatheter Aortic Valve Replacement.

BACKGROUND: New-onset conduction abnormalities (CAs) following transcatheter aortic valve replacement (TAVR) are associated with hospital rehospitalization and long-term mortality, but available predictors are sparse. This study sought to determine clinical predictors of new-onset left bundle branch block (LBBB) and new permanent pacemaker (PPM) implantation in patients undergoing TAVR.Methods and Results:We enrolled 290 patients who received SAPIEN 3 (Edwards Lifesciences, Irvine, CA, USA; n=217) or Evolut R (Medtronic, Minneapolis, MN, USA; n=73) from a prospective registry at Nouvel Hôpital Civil, Strasbourg, France between September 2014 and February 2018. Of 242 patients without pre-existing LBBB, 114 (47%) experienced new-onset LBBB and/or new PPM implantation. A difference between membranous septal length and implantation depth (∆MSID) was the only predictor of CAs for both types of valves. In the multivariate analysis, PR interval and ∆MSID remained as sole predictors of CAs. The risk for adverse clinical events, including all-cause death, myocardial infarction, stroke, and heart failure hospitalization, was higher for patients with CAs as compared with patients without CAs (hazard ratio: 2.10; 95% confidence interval: 1.26 to 3.57; P=0.004). CONCLUSIONS: Computed tomography assessment of membranous septal anatomy and implantation depth predicted CAs after TAVR with new-generation valves. Future studies are required to identify whether adjustment of the implantation depth can reduce the risk of CAs and adverse clinical outcomes.

Cyclosporine before PCI in Patients with Acute Myocardial Infarction.

BACKGROUND: Experimental and clinical evidence suggests that cyclosporine may attenuate reperfusion injury and reduce myocardial infarct size. We aimed to test whether cyclosporine would improve clinical outcomes and prevent adverse left ventricular remodeling. METHODS: In a multicenter, double-blind, randomized trial, we assigned 970 patients with an acute anterior ST-segment elevation myocardial infarction (STEMI) who were undergoing percutaneous coronary intervention (PCI) within 12 hours after symptom onset and who had complete occlusion of the culprit coronary artery to receive a bolus injection of cyclosporine (administered intravenously at a dose of 2.5 mg per kilogram of body weight) or matching placebo before coronary recanalization. The primary outcome was a composite of death from any cause, worsening of heart failure during the initial hospitalization, rehospitalization for heart failure, or adverse left ventricular remodeling at 1 year. Adverse left ventricular remodeling was defined as an increase of 15% or more in the left ventricular end-diastolic volume. RESULTS: A total of 395 patients in the cyclosporine group and 396 in the placebo group received the assigned study drug and had data that could be evaluated for the primary outcome at 1 year. The rate of the primary outcome was 59.0% in the cyclosporine group and 58.1% in the control group (odds ratio, 1.04; 95% confidence interval [CI], 0.78 to 1.39; P=0.77). Cyclosporine did not reduce the incidence of the separate clinical components of the primary outcome or other events, including recurrent infarction, unstable angina, and stroke. No significant difference in the safety profile was observed between the two treatment groups. CONCLUSIONS: In patients with anterior STEMI who had been referred for primary PCI, intravenous cyclosporine did not result in better clinical outcomes than those with placebo and did not prevent adverse left ventricular remodeling at 1 year. (Funded by the French Ministry of Health and NeuroVive Pharmaceutical; CIRCUS ClinicalTrials.gov number, NCT01502774; EudraCT number, 2009-013713-99.).

Safety and efficacy outcomes of 3rd generation DES in an all-comer population of patients undergoing PCI: 12-month and 24-month results of the e-Biomatrix French registry.

OBJECTIVES: The French Ebiomatrix registry aimed to confirm the results of the Leaders trial in an all-comer population in France. BACKGROUND: The Leaders trial showed the Biolimus-eluting-sent (BES) to be equivalent to the Cypher stent in terms of safety and efficacy at 1 year and superior regarding stent thrombosis after 1 year. METHODS: BES recipients were enrolled in 42 French centers with up to 24-month clinical follow up. RESULTS: 2365 patients were included. Mean age: 65.7 ±11.2 years, 76.1% males, 31.8% had diabetes, 36.5% ACS (28.7% non-ST-elevation MI and 7.8% with ST-elevation MI). 1.7 ± 1.0 stents/patient were implanted and procedural success was 99.5%. 12-month follow-up was completed in 94.3% patients and 24 months in 91.4%. MACCE rates at 12 and 24 months were 5.8% and 9% (all cause-death 1.5% and 2.2%; stent thrombosis definite/probable 0.4% and 0.6%), respectively. MACCE were not significantly higher in diabetic patients compared with non-diabetics but cardiac death was higher (1.6% vs. 0.6%, P = 0.01 at 1 year and 1.9% vs. 0.6, P = 0.005 at 2 years) as was stent thrombosis (0.9% vs. 0.2%, P = 0.009 and 1.2 vs. 0.3% P = 0.008). Compared with non-ACS patients, MACCE was significantly higher in the ACS subgroup (7.5% vs. 4.8%, P = 0.001 at 1 year and 10.3% vs.8.1%, P = 0.07 at 2 years). CONCLUSION: In this large real-world registry, the BES with biodegradable polymer showed excellent acute and mid-term outcomes with a 5.8% and 9% rate of MACCE at one and 2 years and a very low rate of stent thrombosis between 1 and 2 years (0.2%), thus demonstrating the replicability of the LEADERS trial in a registry population. © 2017 The Authors Catheterization and Cardiovascular Interventions Published by Wiley Periodicals, Inc.

Effective Orifice Area of Balloon-Expandable and Self-Expandable Transcatheter Aortic Valve Prostheses: An Echo Doppler Comparative Study.

Published data on the size-specific effective orifice area (EOA) of transcatheter heart valves (THVs) remain scarce. Here, we sought to investigate the intra-individual changes in EOA and mean transvalvular aortic gradient (MG) of the Sapien 3 (S3), CoreValve (CV), and Evolut R (EVR) prostheses both at short-term and at 1-year follow-up. The study sample consisted of 260 consecutive patients with severe aortic stenosis who underwent transcatheter aortic valve implantation (TAVI). EOAs and MGs were measured with Doppler echocardiography for the following prostheses: S3 23 mm (n = 74; 28.5%), S3 26 mm (n = 67; 25.8%), S3 29 mm (n = 20; 7.7%), CV 23 mm (n = 2; 0.8%), CV 26 mm (n = 15; 5.8%), CV 29 mm (n = 24; 9.2%), CV 31 mm (n = 9; 3.5%), EVR 26 mm (n = 22; 8.5%), and EVR 29 mm (n = 27; 10.4%). Values were obtained at discharge, 1 month, 6 months, and 1 year from implantation. At discharge, EOAs were larger and MGs lower for larger-size prostheses, regardless of being balloon-expandable or self-expandable. In patients with small aortic annulus size, the hemodynamic performances of CV and EVR prostheses were superior to those of S3. However, we did not observe significant differences in terms of all-cause mortality according to THV type or size. Both balloon-expandable and self-expandable new-generation THVs show excellent hemodynamic performances without evidence of very early valve degeneration.

Impact of residual inflammation on myocardial recovery and cardiovascular outcome in Takotsubo patients.

AIMS: Recent insights have emphasized the importance of myocardial and systemic inflammation in Takotsubo syndrome (TTS). In a large registry of unselected patients, we sought to evaluate whether residual high inflammatory response (RHIR) could impact cardiovascular outcome after TTS. METHODS AND RESULTS: Patients with TTS were retrospectively included between 2008 and 2018 in three general hospitals. Three hundred eighty-five patients with TTS were split into three subgroups, according to tertiles of C-reactive protein (CRP) levels at discharge (CRP <5.2 mg/L, CRP range 5.2 to 19 mg/L, and CRP >19 mg/L). The primary endpoint was the impact of RHIR, defined as CRP >19 mg/L at discharge, on cardiac death or hospitalization for heart failure. Follow up was obtained in 382 patients (99%) after a median of 747 days. RHIR patients were more likely to have a history of cancer or a physical trigger. Left ventricular ejection fraction (LVEF) at admission and at discharge were comparable between groups. By contrast, RHIR was associated with lower LVEF at follow up (61.7% vs. 60.7% vs. 57.9%; P = 0.004) and increased cardiac late mortality (0% vs. 0% vs. 10%; P = 0.001). By multivariate Cox regression analysis, RHIR was an independent predictor of cardiac death or hospitalization for heart failure (hazard ratio: 1.87; 95% confidence interval: 1.08 to 3.25; P = 0.025). CONCLUSIONS: Residual high inflammatory response was associated with impaired LVEF at follow up and was evidenced as an independent factor of cardiovascular events. All together, these findings underline RHIR patients as a high-risk subgroup, to target in future clinical trials with specific therapies to attenuate RHIR.

ST-segment elevation myocardial infarction: Management and association with prognosis during the COVID-19 pandemic in France.

BACKGROUND: Systems of care have been challenged to control progression of the COVID-19 pandemic. Whether this has been associated with delayed reperfusion and worse outcomes in French patients with ST-segment elevation myocardial infarction (STEMI) is unknown. AIM: To compare the rate of STEMI admissions, treatment delays, and outcomes between the first peak of the COVID-19 pandemic in France and the equivalent period in 2019. METHODS: In this nationwide French survey, data from consecutive STEMI patients from 65 centres referred for urgent revascularization between 1 March and 31 May 2020, and between 1 March and 31 May 2019, were analysed. The primary outcome was a composite of in-hospital death or non-fatal mechanical complications of acute myocardial infarction. RESULTS: A total of 6306 patients were included. During the pandemic peak, a 13.9±6.6% (P=0.003) decrease in STEMI admissions per week was observed. Delays between symptom onset and percutaneous coronary intervention were longer in 2020 versus 2019 (270 [interquartile range 150-705] vs 245 [140-646]min; P=0.013), driven by the increase in time from symptom onset to first medical contact (121 [60-360] vs 150 [62-420]min; P=0.002). During 2020, a greater number of mechanical complications was observed (0.9% vs 1.7%; P=0.029) leading to a significant difference in the primary outcome (112 patients [5.6%] in 2019 vs 129 [7.6%] in 2020; P=0.018). No significant difference was observed in rates of orotracheal intubation, in-hospital cardiac arrest, ventricular arrhythmias and cardiogenic shock. CONCLUSIONS: During the first peak of the COVID-19 pandemic in France, there was a decrease in STEMI admissions, associated with longer ischaemic time, exclusively driven by an increase in patient-related delays and an increase in mechanical complications. These findings suggest the need to encourage the population to seek medical help in case of symptoms.

Paradoxical Increase of Stroke in Patients with Defect of High Molecular Weight Multimers of the von Willebrand Factors following Transcatheter Aortic Valve Replacement.

BACKGROUND: Stroke is a major cause of disability after transcatheter aortic valve replacement (TAVR) and stroke prediction models and data are crucially needed. Following TAVR, high molecular weight (HMW) multimers defect of von Willebrand factor (VWF) as assessed by closure time of adenosine diphosphate (CT-ADP) value > 180 seconds is an independent predictor of bleeding events. This study sought to identify predictors of ischemic neurological events in patients who underwent TAVR and the specific impact of HMW multimers defect of VWF. METHODS: Patients were prospectively enrolled between November 2012 and May 2018 at our institution. The CT-ADP, a point-of-care measure of hemostasis, was assessed the day before and 24 hours after the procedures. The rate of ischemic stroke and transient ischemic attack (TIA) was recorded up to 30 days after the procedures. RESULTS: Of 565 TAVR patients, ischemic stroke/TIA was observed in 21 (3.7%) patients within 30 days. Ischemic stroke/TIA was associated with major/life-threatening bleeding complications (MLBCs) (9 [43%] vs. 88 [16%], p = 0.002) and postprocedure CT-ADP > 180 seconds (10 [48%] vs. 116 [21%], p = 0.01). By multivariate analysis, MLBCs (odds ratio [OR]: 3.58; 95% confidence interval [CI]: 1.45-8.84; p = 0.006) and postprocedure CT-ADP > 180 seconds (OR: 3.38; 95% CI: 1.38-8.25; p = 0.008) were evidenced as independent predictors of ischemic stroke/TIA. CONCLUSION: MLBCs and CT-ADP > 180 seconds were identified as predictors for ischemic stroke or TIA. The present study suggests that the defects of HMW multimers of the VWFs may contribute not only to bleeding events but also to thrombotic events.

Predictive value of early cardiac magnetic resonance imaging functional and geometric indexes for adverse left ventricular remodelling in patients with anterior ST-segment elevation myocardial infarction: A report from the CIRCUS study.

BACKGROUND: Postinfarction adverse left ventricular (LV) remodelling is strongly associated with heart failure events. Conicity index, sphericity index and LV global functional index (LVGFI) are new LV remodelling indexes assessed by cardiac magnetic resonance (CMR). AIM: To assess the predictive value of the new indexes for 1-year adverse LV remodelling in patients with anterior ST-segment elevated myocardial infarction (STEMI). METHODS: CMR studies were performed in 129 patients with anterior STEMI (58±12 years; 78% men) from the randomized CIRCUS trial (CMR substudy) treated with primary percutaneous coronary intervention and followed for the occurrence of major adverse cardiovascular events (MACE) (death or hospitalization for heart failure). Conicity index, sphericity index, LVGFI, infarct size and microvascular obstruction (MVO) were assessed by CMR performed 5±4 days after coronary reperfusion. Adverse LV remodelling was defined as an increase in LV end-diastolic volume of ≥15% by transthoracic echocardiography at 1 year. RESULTS: Adverse LV remodelling occurred in 27% of patients at 1 year. Infarct size and MVO were significantly predictive of adverse LV remodelling: odds ratio [OR] 1.03, 95% confidence interval [CI] 1.01-1.05 (P<0.001) and OR 1.12, 95% CI 1.05-1.22 (P<0.001), respectively. Among the newly tested indexes, only LVGFI was significantly predictive of adverse LV remodelling (OR 1.10, 95% CI 1.03-1.16; P=0.001). In multivariable analysis, infarct size remained an independent predictor of adverse LV remodelling at 1 year (OR 1.05, 95% CI 1.02-1.08; P<0.001). LVGFI and infarct size were associated with occurrence of MACE: OR 1.21, 95% CI 1.08-1.37 (P<0.001) and OR 1.02, 95% CI 1.00-1.04 (P=0.018), respectively. Conicity and sphericity indexes were not associated with MACE. CONCLUSIONS: LVGFI was associated with adverse LV remodelling and MACE 1 year after anterior STEMI.

Importance of inflammation and neurohumoral activation in Takotsubo cardiomyopathy.

BACKGROUND: To gain more insight into the involvement of inflammatory response and neurohumoral activation in Takotsubo cardiomyopathy (TTC), we investigated C-reactive protein (CRP), leukocytes, plasma catecholamines levels, iodine 123 meta-iodobenzylguanidine (123I-mIBG) myocardial uptake, myocardial perfusion (thallium 201 [201Tl] or technetium [Tc] 99m-tetrofosmin myocardial single photon emission computed tomography [SPECT]), and metabolism (fluorine 18-fluorodeoxyglucose positron emission tomography). METHODS AND RESULTS: Inflammatory status and brain natriuretic peptide (BNP) levels in 17 patients with TTC were compared with 14 age-matched patients. In TTC, elevated levels of CRP were evidenced on admission, reaching a peak in the following days (P < .01). CRP levels were correlated to baseline left ventricular ejection fraction (LVEF) and BNP levels (P < .05). Leukocytes were correlated to BNP and noradrenaline levels. Myocardial 123I-mIBG SPECT showed a reduced activity in the midventricle and apex corresponding to 35% +/- 23% of the total myocardial mass, partially reversible at follow-up. An identical pattern was retrieved when assessing myocardial glucose metabolism. At rest, no relevant abnormalities of myocardial perfusion could be evidenced at the subacute phase. CONCLUSION: Inflammatory status in TTC was related to LVEF impairment and to the extent of neurohormonal activation. The hypothesis of a catecholamine-induced myocardial "stunning" is emphasized by the evidence of a reduced 123I-mIBG myocardial activity, impairment of myocardial glucose metabolism, and wall motion kinetic after the same temporospatial distribution.

Does Transcatheter Aortic Valve Replacement Modulate the Kinetic of Superoxide Anion Generation?

Reactive oxygen species (ROS) are central bioenergetic markers linked to aortic stenosis (AS) development and severity. We sought to evaluate the time course and impact of ROS assessed by plasmatic superoxide anion (SA) among patients undergoing transcatheter aortic valve replacement (TAVR). Among 106 patients, SA significantly decreased after TAVR. Dropped values were measured 10 min after TAVR (0.590 ± 0.181 vs. 0.648 ± 0.193; p < 0.001) and persistent at 3 days (0.611 ± 0.0.228 vs. 0.646 ± 0.199; p = 0.033) and 30 days follow-up (0.572 ± 0.207 vs. 0.639 ± 0.199; p = 0.005). Increased baseline SA (>75 percentile) was continuously associated with higher postprocedural SA values 10 min after valve expansion (p < 0.001), at 3 days (p < 0.001) and 30 days (p < 0.001). Higher baseline SA was linked to higher inflammatory response assessed by higher C-reactive protein values at day 1 and day 3. The composite endpoint of all-cause mortality and/or stroke and/or pacemaker implantation and/or significant paravalvular aortic regurgitation ≥mild at 30 days did not differ significantly according to SA baseline values (p = 0.055). This is the first report identifying a decrease in oxidative stress level after TAVR. Our observation leads to the hypothesis that oxidative stress biomarkers may survive the journey from bench to bedside in AS and TAVR and become new biomarkers with both diagnostic and prognostic values. Antioxid. Redox Signal. 31, 420-426.

Primary Hemostatic Disorders and Late Major Bleeding After Transcatheter Aortic Valve Replacement.

BACKGROUND: Periprocedural and late (>30 days) bleedings represent major complications after transcatheter aortic valve replacement and have been identified as potential areas for improved patient care. OBJECTIVES: The authors sought to evaluate the impact of ongoing primary hemostasis disorders on late major/life-threatening bleeding complications (MLBCs). METHODS: Bleedings were assessed according to the VARC-2 (Valve Academic Research Consortium-2) criteria. Closure time of adenosine diphosphate (CT-ADP), a surrogate marker of high molecular weight von Willebrand multimers proteolysis was assessed 24 h after the procedure. Ongoing primary hemostasis disorder was defined by a CT-ADP >180 s. RESULTS: Among 372 patients who survived at 30 days, MLBCs occurred in 42 patients (11.3%) at a median follow-up of 383 days (interquartile range: 188 to 574 days). MLBCs were mainly of gastrointestinal origin (42.8%) and were associated with increased overall mortality (hazard ratio [HR]: 5.66; 95% confidence interval [CI]: 3.10 to 10.31; p < 0.001) and cardiac mortality (HR: 11.62; 95% CI: 4.59 to 29.37; p < 0.001). A 2.5-fold elevation of MLBCs could be evidenced in patients with a CT-ADP > 180 s (27.4% vs. 11.5%; p < 0.001). Multivariate regression analysis identified paravalvular leak (PVL) (HR: 6.31; 95% CI: 3.43 to 11.60; p < 0.0001) and CT-ADP > 180 s (HR: 3.08; 95% CI: 1.62 to 5.81; p = 0.0005) as predictor of MLBCs. CONCLUSIONS: MLBCs after transcatheter aortic valve replacement are frequent and associated with an increased morbidity and mortality. PVL and CT-ADP >180 s were identified as strong predictors for MLBCs. These findings strongly suggest that persistent HMW defects contribute to enhanced bleeding risk in patients with residual PVL.

CT-ADP Point-of-Care Assay Predicts 30-Day Paravalvular Aortic Regurgitation and Bleeding Events following Transcatheter Aortic Valve Replacement.

BACKGROUND: Paravalvular aortic regurgitation (PVAR) remains a frequent postprocedural concern following transcatheter aortic valve replacement (TAVR). Persistence of flow turbulence results in the cleavage of high-molecular-weight von Willebrand multimers, primary haemostasis dysfunction and may favour bleedings. Recent data have emphasized the value of a point-of-care measure of von Willebrand factor-dependent platelet function (closure time [CT] adenosine diphosphate [ADP]) in the monitoring of immediate PVAR. This study examined whether CT-ADP could detect PVAR at 30 days and bleeding complications following TAVR. METHODS: CT-ADP was assessed at baseline and the day after the procedure. At 30 days, significant PVAR was defined as a circumferential extent of regurgitation more than 10% by transthoracic echocardiography. Events at follow-up were assessed according to the Valve Academic Research Consortium-2 consensus classification. RESULTS: Significant PVAR was diagnosed in 44 out of 219 patients (20.1%). Important reduction of CT-ADP could be found in patients without PVAR, contrasting with the lack of CT-ADP improvement in significant PVAR patients. By multivariate analysis, CT-ADP > 180 seconds (hazard ratio [HR]: 5.1, 95% confidence interval [CI]: 2.5-10.6; p < 0.001) and a self-expandable valve were the sole independent predictors of 30-day PVAR. At follow-up, postprocedural CT-ADP >180 seconds was identified as an independent predictor of major/life-threatening bleeding (HR: 1.7, 95% CI [1.0-3.1]; p = 0.049). Major/life-threatening bleedings were at their highest levels in patients with postprocedural CT-ADP > 180 seconds (35.2 vs. 18.8%; p = 0.013). CONCLUSION: Postprocedural CT-ADP > 180 seconds is an independent predictor of significant PVAR 30 days after TAVR and may independently contribute to major/life-threatening bleedings.

Thrombotic and bleeding events after coronary stenting according to clopidogrel and aspirin platelet reactivity: VerifyNow French Registry (VERIFRENCHY).

BACKGROUND: Dual antiplatelet therapy, comprising aspirin and clopidogrel, is recommended in patients undergoing coronary stenting to avoid the occurrence of stent thrombosis and others ischaemic events. Interindividual response to clopidogrel varies, however, with poor response associated with an increased risk of ischaemic events. New assays are available for testing aspirin and clopidogrel response routinely at the bedside. AIM: To evaluate the prognostic value of testing antiplatelet response in an intermediate-risk population undergoing stent implantation. METHODS: We prospectively assessed clopidogrel and aspirin response using the VerifyNow assay at the time of coronary stenting in 1001 patients who presented with stable coronary disease or non-ST-segment elevation acute coronary syndrome. The main ischaemic endpoint was the composite of definite and probable stent thrombosis, cardiovascular death or spontaneous myocardial infarction at one year. The safety endpoint was major bleeding. RESULTS: Overall, 36.0% of patients had high on-clopidogrel platelet reactivity (OCR) and 8.6% had high on-aspirin platelet reactivity (OAR). The main ischaemic composite endpoint occurred in 3.9% of patients with high vs. 2.3% of patients with normal OCR (hazard ratio 1.66, 95% confidence interval 0.78-3.54; P=0.18). Definite or probable stent thrombosis occurred in 1.1% of patients with high vs. 0.3% of patients with normal OCR (P=0.86). There was no significant difference in ischaemic endpoints according to OAR and there was no difference in rates of major bleeding between patients with high versus normal on-treatment platelet reactivity. CONCLUSIONS: On-treatment platelet reactivity was not associated with 1-year ischaemic or bleeding events in an intermediate-risk population undergoing stent implantation.

Clopidogrel 150 mg/day to overcome low responsiveness in patients undergoing elective percutaneous coronary intervention: results from the VASP-02 (Vasodilator-Stimulated Phosphoprotein-02) randomized study.

OBJECTIVES: We investigated whether maintenance therapy with clopidogrel 150 mg/day produces greater platelet inhibition than the standard 75-mg/day dose and whether the higher maintenance dose increases platelet inhibition in low responders to clopidogrel 75 mg/day. BACKGROUND: Patients show interindividual variability in their platelet response to clopidogrel. Low responders could potentially obtain greater clinical benefit from greater doses of clopidogrel. METHODS: One hundred fifty-three elective percutaneous coronary intervention patients were randomized to clopidogrel 150 mg/day (n = 58) or 75 mg/day (n = 95) for 4 weeks, with vasodilator-stimulated phosphoprotein assay-guided switching to clopidogrel 150 mg/day after 2 weeks in low responders (platelet reactivity index >or=69%). All patients received aspirin 75 mg/day. RESULTS: After 2 weeks, clopidogrel 150 mg/day produced a significantly lower platelet reactivity index than clopidogrel 75 mg/day (43.9 +/- 17.3% vs. 58.6 +/- 17.7%; p < 0.0001). The proportion of low responders was significantly lower in patients randomized to clopidogrel 150 mg/day than in those randomized to clopidogrel 75 mg/day (8.6% vs. 33.7%; p = 0.0004). In the clopidogrel 75 mg/day group, 64.5% (20 of 31) of low responders became responders after switching to clopidogrel 150 mg/day for 2 weeks. No major bleeds occurred during the study; the incidence of minor bleeds was similar in each treatment group. CONCLUSIONS: In elective percutaneous coronary intervention patients, a 150-mg/day clopidogrel maintenance dose produces greater inhibition of platelet function than clopidogrel 75 mg/day. In low responders to clopidogrel 75 mg/day, switching to clopidogrel 150 mg/day overcomes low responsiveness in a majority of patients. These findings warrant further clinical evaluation. (VASP-02; EudraCT number: 2004-005230-40).