Plasma Soluble Glycoprotein VI, Platelet Function, Bleeding, and Ischemic Events in Patients Undergoing Elective Percutaneous Coronary Intervention.

BACKGROUND AND AIMS: Glycoprotein VI (GPVI) is the major platelet-specific collagen receptor. GPVI shedding with generation of soluble GPVI (sGPVI) is an endogenous feedback mechanism preventing platelet overstimulation. sGPVI has not been investigated in patients with chronic coronary syndrome (CCS) undergoing percutaneous coronary intervention (PCI), especially regarding its potential value as a predictor of ischemic and bleeding risk. METHODS: Baseline plasma sGPVI levels were available in 318 patients with CCS undergoing PCI. Platelet function was assessed by measuring both adenosine diphosphate (ADP) and collagen-induced platelet aggregation. Co-primary endpoints were a composite of death or myocardial injury at 48 hours after PCI, and Bleeding Academic Research Consortium (BARC) type 1 to 5 bleeding at 30 days. RESULTS: There was no significant correlation between sGPVI and platelet function at baseline or at 48 hours after PCI and loading with antiplatelet drugs. Baseline plasma sGPVI levels were not associated with the ischemic risk: the incidence of the ischemic endpoint was 25.0% in the lower, 22.9% in the middle, and 26.7% in the upper sGPVI tertile (p = 0.82). There was a significant nonlinear relationship between sGPVI and the risk of bleeding: the incidence of the bleeding endpoint was 11.8% in the lower, 12.6% in the middle, and 26.4% in the upper sGPVI tertile (p = 0.006). CONCLUSION: In patients with CCS undergoing PCI, plasma levels of sGPVI did not correlate with ADP- or collagen-induced platelet aggregation. Patients with higher baseline levels of sGPVI may carry an increased risk of bleeding at 30 days after PCI but no excess risk of ischemic events.

Survival with Good Neurological Outcome despite Prolonged Cardiopulmonary Resuscitation and Extreme Acidosis after Out-of-Hospital Cardiac Arrest Due to Acute Myocardial Infarction: A Case Report and Review of the Literature.

We report the case of a 49-year-old male who suffered from a myocardial infarction with subsequent cardiac arrest. The emergency medical team began cardiopulmonary resuscitation, including defibrillation of ventricular fibrillation. Although a return of spontaneous circulation was achieved after approximately 30 min of continued efforts, the patient went back into cardiac arrest on the way to the hospital and resuscitation had to be resumed. On admission, the patient was severely acidotic with a pH of 6.67, lactatemia of 19 mmol/L, and pronounced hypercapnia (pCO2 127 mmHg). Despite the poor prognosis, all possible efforts including coronary intervention and therapeutic hypothermia were carried out and the patient made a quick recovery with discharge from the intensive care unit on day 5. Survival of extreme acidosis, such as in this case, is rare. This is the first report of survival with good neurologic outcome in a patient with myocardial infarction, cardiac arrest, and pH of under 6.7 on admission at the clinic.

Impact of body mass on P2Y12-inhibitor de-escalation in acute coronary syndromes-a substudy of the TROPICAL-ACS trial.

AIMS: Clinical guidelines recommend de-escalation antiplatelet strategies to reduce bleeding risk in acute coronary syndrome (ACS) patients, albeit with a weak recommendation. This substudy of the TROPICAL-ACS trial aimed to determine the impact of body mass on the efficacy of a platelet function testing-guided de-escalation regimen in ACS patients after percutaneous coronary intervention. METHODS AND RESULTS: Patients were randomized to prasugrel (control group) or a platelet function testing-guided regimen with clopidogrel or prasugrel defined after 1-week clopidogrel. The primary endpoint was the net clinical benefit [cardiovascular death, myocardial infarction, stroke, or Bleeding Academic Research Consortium (BARC) 2-5 bleeding] for 12 months. Overweight was defined as a body mass index >25 kg/m2.Patients without overweight showed a significant net clinical benefit from the de-escalation strategy, while in overweight cases de-escalation was comparable to prasugrel treatment [hazard ratio (HR): 0.52; 95% confidence interval (CI): 0.31-0.88; P = 0.013 and HR: 0.95; 95% CI: 0.69-1.31, P = 0.717, P-non-inferiority = 0.03, respectively, P-interaction = 0.053]. The benefit of de-escalation in terms of the risk of bleeding or of the ischaemic events did not reach statistical significance. Bleeding events with de-escalation were less frequent in non-overweight patients but comparable in overweight patients (HR: 0.55; 95% CI: 0.30-1.03; P = 0.057 and HR: 0.95; 95% CI: 0.64-1.41, respectively, P-interaction = 0.147). Non-overweight patients had lower ischaemic event rates with de-escalation, while overweight cases had slightly less (HR: 0.47; 95% CI: 0.18-1.25; P = 0.128 and HR: 0.89; 95% CI: 0.53-1.50, respectively, P-interaction = 0.261). CONCLUSION: The strategy of guided dual antiplatelet therapy de-escalation was associated with a significant net clinical benefit in non-overweight patients, while the two strategies were equivalent in overweight patients.

Efficacy and Safety of Revacept, a Novel Lesion-Directed Competitive Antagonist to Platelet Glycoprotein VI, in Patients Undergoing Elective Percutaneous Coronary Intervention for Stable Ischemic Heart Disease: The Randomized, Double-blind, Placebo-Controlled ISAR-PLASTER Phase 2 Trial.

Importance: The assessment of new antithrombotic agents with a favorable safety profile is clinically relevant. Objective: To test the efficacy and safety of revacept, a novel, lesion-directed antithrombotic drug, acting as a competitive antagonist to platelet glycoprotein VI. Design, Setting, and Participants: A phase 2 randomized clinical trial; patients were enrolled from 9 centers in Germany from November 20, 2017, to February 27, 2020; follow-up ended on March 27, 2020. The study included patients with stable ischemic heart disease (SIHD) undergoing elective percutaneous coronary intervention (PCI). Interventions: Single intravenous infusion of revacept, 160 mg, revacept, 80 mg, or placebo prior to the start of PCI on top of standard antithrombotic therapy. Main Outcomes and Measures: The primary end point was the composite of death or myocardial injury, defined as an increase in high-sensitivity cardiac troponin to at least 5 times the upper limit of normal within 48 hours from randomization. The safety end point was bleeding type 2 to 5 according to the Bleeding Academic Research Consortium criteria at 30 days. Results: Of 334 participants (median age, 67.4 years; interquartile range, 60-75.1 years; 253 men [75.7%]; and 330 White participants [98.8%]), 120 were allocated to receive the 160-mg dose of revacept, 121 were allocated to receive the 80-mg dose, and 93 received placebo. The primary end point showed no significant differences between the revacept and placebo groups: 24.4%, 25.0%, and 23.3% in the revacept, 160 mg, revacept, 80 mg, and placebo groups, respectively (P = .98). The high dose of revacept was associated with a small but significant reduction of high-concentration collagen-induced platelet aggregation, with a median 26.5 AU × min (interquartile range, 0.5-62.2 AU × min) in the revacept, 160 mg, group; 43.5 AU × min (interquartile range, 22.8-99.5 AU × min) in the revacept, 80 mg, group; and 41.0 AU × min (interquartile range, 31.2-101.0 AU × min) in the placebo group (P = .02), while adenosine 5'-diphosphate-induced aggregation was not affected. Revacept did not increase Bleeding Academic Research Consortium type 2 or higher bleeding at 30 days compared with placebo: 5.0%, 5.9%, and 8.6% in the revacept, 160 mg, revacept, 80 mg, and placebo groups, respectively (P = .36). Conclusions and Relevance: Revacept did not reduce myocardial injury in patients with stable ischemic heart disease undergoing percutaneous coronary intervention. There were few bleeding events and no significant differences between treatment arms. Trial Registration: ClinicalTrials.gov Identifier: NCT03312855.

Cardiac allograft vasculopathy: Differences of absolute and relative intimal hyperplasia in children versus adults in optical coherence tomography.

BACKGROUND: Intracoronary imaging enables an early detection of intimal changes. To what extend the development of absolute and relative intimal hyperplasia in intracoronary imaging differs depending on age and post-transplant time is not known. METHODS: Aim of our retrospective study was to compare findings between 24 pediatric (cohort P) and 21 adult HTx patients (cohort A) using optical coherence tomography (OCT) at corresponding post-transplant intervals (≤5 years: P1 (n = 11) and A1 (n = 10); >5 and ≤ 10 years: P2 (n = 13) and A2 (n = 11),. Coronary intima thickness (IT), media thickness (MT) and intima to media ratio (I/M) were assessed per quadrant. Maximal IT >0.3 mm was considered absolute, I/M > 1 relative intimal hyperplasia. RESULTS: Compared to A1, I/M was significantly higher in P1 (maximal I/M: P1: 5.41 [2.81-13.39] vs. A1: 2.30 [1.55-3.62], p = 0.005), whereas absolute IT values were comparable. In contrast, I/M was comparable between P2 and A2, but absolute IT were significantly higher in A2 (maximal IT: P2: 0.16 mm [0.11-0.25] vs. A2: 0.40 mm [0.30-0.71], p < 0.001). A2 presented with higher absolute IT (maximal: A1: 0.16 mm [0.12-0.44] vs. A2: 0.40 mm [0.30-0.71], p = 0.02) and I/M (maximal I/M A1: 2.30 [1.55-3.62] vs. A2: 3.79 [3.01-5.62], p = 0.04). CONCLUSION: Our results suggest an age- and time-dependent difference in the prevalence of absolute and relative intimal hyperplasia in OCT, with an early peak in children and a progressive increase in adults.

Gender and Outcomes following Guided De-Escalation of Antiplatelet Treatment in Acute Coronary Syndrome Patients: The TROPICAL-ACS Gender Substudy.

OBJECTIVES: This prespecified analysis of the TROPICAL-ACS trial aimed to assess the impact of gender on clinical outcomes and platelet reactivity (PR) following guided de-escalation of dual antiplatelet treatment (DAPT) in acute coronary syndrome (ACS) patients. BACKGROUND: Guided de-escalation of DAPT was recently identified as an effective alternative treatment strategy in ACS. METHODS: We used Cox proportional hazards models and linear regression analysis to assess the interaction of gender with clinical endpoints and PR. RESULTS: In both male (n = 2,052) and female (n = 558) patients, the 1-year incidence of the primary endpoint did not differ in guided de-escalation versus control group patients (male: 7.0% vs. 9.0%; hazard ratio [HR], 0.78, 95% confidence interval [CI], 0.57-1.06, p = 0.11; female: 8.4% vs. 9.2%; HR, 0.92, 95% CI, 0.53-1.62, p = 0.76, p int = 0.60). The 1-year incidence of combined ischemic events (male: 2.5% vs. 3.3%; HR, 0.76, 95% CI, 0.46-1.26, p = 0.29; female: 2.2% vs. 2.8%; HR, 0.78,95% CI, 0.27-2.25, p = 0.65, p int = 0.96) as well as Bleeding Academic Research Consortium ≥ 2 bleeding (male: 4.6% vs. 6.0%; HR, 0.77, 95% CI, 0.52-1.12, p = 0.17; female: 6.2% vs. 6.4%; HR, 0.99, 95% CI, 0.51-1.92, p = 0.97, p int = 0.51) was similar in the guided de-escalation versus control group for both male and female patients. Interaction testing revealed no significant impact of gender on PR levels (prasugrel or clopidogrel) across treatment groups (p int = 0.72). CONCLUSION: Guided de-escalation of DAPT appears to be equally safe and effective in women and men. Especially in patients with increased bleeding risk and independent from gender, a guided DAPT de-escalation strategy may be used as an alternative treatment strategy. CLINICAL TRIAL REGISTRATION: URL: https//www.clinicaltrials.gov. Unique Identifier: NCT: 01959451.

Revacept, a Novel Inhibitor of Platelet Adhesion, in Patients Undergoing Elective PCI-Design and Rationale of the Randomized ISAR-PLASTER Trial.

Despite dual antiplatelet therapy patients undergoing percutaneous coronary intervention (PCI) continue to experience periprocedural ischemic events. In addition, all currently used antithrombotic drugs increase the bleeding risk. Thus, there is an unmet clinical need for antithrombotic strategies with improved efficacy and no increase in bleeding. Revacept is a novel, lesion-directed antithrombotic drug that does not interfere with the function of circulating platelets. This dimeric fusion protein of the extracellular domain of glycoprotein VI (the major platelet collagen receptor) and the human Fc-fragment inhibits collagen-mediated platelet adhesion and subsequent aggregation at the site of vascular injury. The randomized, double-blinded, phase II ISAR-PLASTER trial is based on extensive preclinical evaluation of Revacept and a favorable first-in-man trial. A total of 332 patients with stable coronary artery disease undergoing elective PCI will be randomized to either Revacept 160 mg, Revacept 80 mg, or placebo administered as single intravenous infusion directly before the intervention, on top of standard dual antiplatelet therapy and either heparin or bivalirudin, based on local practice and current guidelines. The primary endpoint is the composite of death or myocardial injury (defined as increase in high sensitivity troponin T ≥ 5 times the upper limit of normal) at 48 hours. The safety endpoint is bleeding of class 2 or higher according to the Bleeding Academic Research Consortium at 30 days. This phase II randomized, double blind trial will assess for the first time the efficacy and safety of Revacept-a lesion-directed inhibitor of platelet adhesion-in patients undergoing elective PCI.

Diurnal Variability of On-Treatment Platelet Reactivity in Clopidogrel versus Prasugrel Treated Acute Coronary Syndrome Patients: A Pre-Specified TROPICAL-ACS Sub-Study.

Long-term evidence supports a clustering of cardiovascular events in the early morning and smaller mechanistic studies in aspirin-treated patients have shown increased platelet reactivity at the end of the dosing interval. Comparative pharmacodynamic analyses for different adenosine diphosphate (ADP) receptor inhibitors in percutaneous coronary intervention-treated acute coronary syndrome (ACS) patients are lacking and this pre-specified analysis from the randomized Testing Responsiveness To Platelet Inhibition On Chronic Antiplatelet Treatment For Acute Coronary Syndromes (TROPICAL-ACS) trial aimed for the first time at investigating diurnal variability of on-treatment platelet reactivity in clopidogrel versus prasugrel treated patients. TROPICAL-ACS randomized 2,610 ACS patients to either treatment with prasugrel (control group) or to a platelet function testing-guided de-escalation of anti-platelet treatment with a switch to clopidogrel (guided de-escalation group). This study design enabled a diurnal comparison of on-prasugrel versus on-clopidogrel treatment platelet reactivity under steady-state conditions. For 2,526 patients (97%), both the exact time of blood sampling and the ADP-induced platelet aggregation value (in units, Multiplate analyser) were available. Platelet reactivity in patients on clopidogrel (n = 1,265) was higher and subject to significant diurnal variability (p = 0.019) with a peaking of platelet reactivity in the early morning (5-10 a.m.). In prasugrel-treated patients (n = 1,261), there was no sign for diurnal variability (p = 0.174) or a peaking of platelet reactivity in the morning. The potent ADP receptor inhibitor prasugrel is not subject to diurnal variability while we observed a significant diurnal variability of on-clopidogrel platelet reactivity. The clinical impact of this observation may differ for patients with and without an adequate response to clopidogrel treatment and the issue of diurnal variability of platelet reactivity in ACS patients warrants further investigation.

Percutaneous Decannulation Instead of Surgical Removal for Weaning After Venoarterial Extracorporeal Membrane Oxygenation-A Crossed Perclose ProGlide Closure Device Technique Using a Hemostasis Valve Y Connector.

Improvements in cannula removal techniques, and in particular a standardized decannulation technique with a suitable closure device, are needed to further improve patients' outcomes after percutaneous cannulation. The decannulation techniques described so far are neither sufficiently standardized nor proven enough to be used in the large group of venoarterial extracorporeal membrane oxygenation patients. To meet this challenge, we have established a highly standardized and safe decannulation technique based on the Perclose ProGlide closure system (Abbott Vascular, Lake Bluff, IL). DESIGN: Establishment of a highly standardized and safe decannulation technique based on the Perclose ProGlide closure system, which is described in detail with comprehensive instructions for the executive clinician and first application in the context of a pilot study. MEASUREMENTS AND MAIN RESULTS: So far our technique has already been used successfully in seven patients since January 2019 as a standard procedure on our ICU with only one minor complication occurred after the first procedure, that is, a small pseudoaneurysm likely originating from antegrade perfusion puncture site which was sealed by thrombin injection. CONCLUSIONS: Our crossed ProGlide technique using a hemostasis valve Y connector ensuring no blood loss seems to be a very promising decannulation technique.

Aortic annulus to left coronary distance as a predictor for persistent left bundle branch block after TAVI.

OBJECTIVES: To identify potential predictors for ventricular conduction delay and to evaluate the impact of interventricular dyssynchrony on mortality after implantation of a balloon-expandable aortic valve (BEV). METHODS AND RESULTS: Clinical, computertomographical (CT), and electrocardiographical (ECG) data from 225 transcatheter aortic valve implantation (TAVI) patients were analyzed. Procedures were performed between May 2010 and September 2013 via transfemoral access using a BEV. Incidence of new-onset left bundle branch block (NOP-LBBB) at discharge was 23.1% (n = 52). Predictive factors for NOP-LBBB were first degree atrioventricular (AV) block (odds ratio (OR): 3.91, 95% confidence interval (CI): 1.58 to 9.64), area cover index (OR: 1.83, 95% CI: 1.26 to 2.67), annulus calcification > first degree (OR: 3.01, 95% CI: 1.36 to 6.66), and annulus to left coronary distance (OR: 0.65, 95% CI: 0.44 to 0.96). At 1-year follow-up, no significant difference was observed concerning all-cause mortality (15.6% among non NOP-LBBB and 9.6% among NOP-LBBB patients, P = 0.278) and cardiovascular mortality (4.6% among non NOP-LBBB and 5.8% among NOP-LBBB patients, P = 0.737). CONCLUSION: In addition to previous predictors, annulus to left coronary distance and area cover index have been identified as new predictors for NOP-LBBB. NOP-LBBB showed no relevant impact on mortality after one year. Further investigation including larger populations and longer follow-up is required to confirm these findings and develop an algorithm for identification of patients at risk for NOP-LBBB associated adverse events. © 2016 Wiley Periodicals, Inc.

Long-Term Outcomes of Carotid Artery Stenting in Clinical Practice.

BACKGROUND: There is a lack of long-term data and data outside of controlled clinical trials in carotid artery stenting. Thus, we sought to evaluate the long-term effectiveness in stroke prevention by carotid artery stenting in a large number of patients in a real-world setting. METHODS AND RESULTS: The present work represents an all-comer registry with a strict, prospectively designed, follow-up protocol, including an independent pre- and postprocedural neurological assessment. Between November 1999 and March 2015, 1000 procedures in 901 patients were consecutively performed in a single center. Mean age was 71±9 years, and symptomatic stenosis was present in 262 patients (29.1%). The population was also characterized by a high comorbidity: 289 patients (32.1%) would have been excluded according to the CREST protocol (Carotid Revascularization Endarterectomy Versus Stent Trial). The median length of follow-up was 5.5 (interquartile range, 2.6-7.9) years and complete in 93% of the patients. The rate of the primary end point (composite of stroke, death, and myocardial infarction [major adverse cardiac or cerebrovascular event] by day 30 plus ipsilateral stroke beyond 30 days) was 6.9% (9.9% in symptomatic versus 5.7% in asymptomatic patients; P=0.03). The rate was higher in CREST ineligible than in CREST eligible patients (11.4% versus 4.9%; P=0.001). CONCLUSIONS: Long-term stroke prevention by carotid artery stenting is effective in experienced centers. A high percentage of patients who would have been excluded from controlled clinical trials undergoes carotid artery stenting in daily clinical practice. However, these patients have a substantially higher risk for an acute major adverse cardiac or cerebrovascular event.

Predictors of minor versus major stroke during carotid artery stenting: results from the carotid artery stenting (CAS) registry of the Arbeitsgemeinschaft Leitende Kardiologische Krankenhausärzte (ALKK).

BACKGROUND: Patient outcome, quality of life as well as health care costs differ between patients with minor versus major stroke during carotid artery stenting. Evaluation of predictors for both subtypes of strokes is of paramount importance. METHODS AND RESULTS: We analyzed data from the prospective, web-based German carotid artery stenting (CAS) registry. All patients entered in this registry were included as of January 2011. During the periprocedural period (until patient discharge or transfer) 1.5 % of the patients (85/5,794) sustained a major and 1.3 % (75/5,784) a minor stroke (total periprocedural stroke rate 2.8 %). Mean age of all patients was 71 years, 72 % were male and 50 % had a symptomatic carotid stenosis. Regression analysis identified age (OR 1.44; 95 % CI 1.05-1.98), symptomatic stenosis (OR 3.17; 95 % CI 1.74-5.76) and procedural duration per 10 min (OR 1.22; 95 % CI 1.13-1.31) as independent predictors for major strokes. Age (OR 1.43; 95 % CI 1.03-1.98), diabetes (OR 1.75; 95 % CI 1.04-2.94), and procedural duration (OR 1.17; 95 % CI 1.08-1.27) predicted for minor strokes. The use of an embolic protection device significantly prevented both type of strokes (OR 0.31; 95 % CI 0.15-0.62 for major strokes; OR 0.40; 95 % CI 0.18-0.91 for minor strokes), female patients suffered less major strokes (OR 0.47; 95 % CI 0.24-0.92). Moreover, minor and major strokes were associated with death, contralateral embolism and a longer hospital stay more frequently. CONCLUSION: Patients with one or more risk factors for periprocedural stroke seem to require special attention in terms of optimal preprocedural assessment of the carotid stenosis and vascular anatomy, as well as adequate patient preparation. Identifying these risk factors may help in patient selection, encourage further refinement in carotid artery stenting technique and avoid procedural complications. The use of an embolic protection device system was associated with less periprocedural minor and major strokes.

The role of endovascular expertise in carotid artery stenting: results from the ALKK-CAS-Registry in 5,535 patients.

PURPOSE: Several scientific committees have proposed an accentuation of operator minimal requirements before accreditation for carotid artery stenting is granted. The current study aims to identify potential effects from increasing site experience on periprocedural safety and outcome of carotid artery stenting (CAS). METHODS: Between 1996 and December 2009, 5,535 procedures have been entered into the prospective, controlled ALKK-CAS-Registry. The total cohort was divided in four subgroups according to the consecutive patient order at each participating center: patients 1-49 (n = 1,485), 50-99 (n = 1,118), 100-199 (n = 1,521) and ≥200 (n = 1,411). RESULTS: The median age of all patients was 71 years; 52.8 % had a symptomatic carotid stenosis. A decline in the rates of in-hospital major stroke (2.1, 1.9, 1.6, 0.9, p for trend 0.014) and of ipsilateral strokes (3.1, 2.4, 2.5, 1.6 %, p for trend 0.019) was substantiated with increasing site experience. This significant trend was preserved in the combined rate of major stroke and death (4.0, 3.2, 3.4, 2.4 %, p for trend 0.034). Apart from CAS experience, improvements in CAS technique, a decreasing number of symptomatic patients and an increasing number of procedures under embolic protection (each p for trend <0.05) might have contributed to these results. CONCLUSIONS: The results show a gradual reduction of in-hospital stroke rates with increasing center experience. Extensive supervision of CAS learners and further promotion of proctorship programs seem to be essential.