Rationale and design of the ULYSS trial: A randomized multicenter evaluation of the efficacy of early Impella CP implantation in acute coronary syndrome complicated by cardiogenic shock.

CONTEXT: Despite 20 years of improvement in acute coronary syndromes care, patients with acute myocardial infarction complicated by cardiogenic shock (AMICS) remains a major clinical challenge with a stable incidence and mortality. While intra-aortic balloon pump (IABP) did not meet its expectations, percutaneous mechanical circulatory supports (pMCS) with higher hemodynamic support, large availability and quick implementation may improve AMICS prognosis by enabling early hemodynamic stabilization and unloading. Both interventional and observational studies suggested a clinical benefit in selected patients of the IMPELLAⓇ CP device within in a well-defined therapeutic strategy. While promising, these preliminary results are challenged by others suggesting a higher rate of complications and possible poorer outcome. Given these conflicting data and its high cost, a randomized clinical trial is warranted to delineate the benefits and risks of this new therapeutic strategy. DESIGN: The ULYSS trial is a prospective randomized open label, 2 parallel multicenter clinical trial that plans to enroll patients with AMICS for whom an emergent percutaneous coronary intervention (PCI) is intended. Patients will be randomized to an experimental therapeutic strategy with pre-PCI implantation of an IMPELLAⓇ CP device on top of standard medical therapy or to a control group undergoing PCI and standard medical therapy. The primary objective of this study is to compare the efficacy of this experimental strategy by a composite end point of death, need to escalate to ECMO, long-term left ventricular assist device or heart transplantation at 1 month. Among secondary objectives 1-year efficacy, safety and cost effectiveness will be assessed. CLINICAL TRIAL REGISTRATION: NCT05366452.

TicagRelor Or Clopidogrel in severe or terminal chronic kidney patients Undergoing PERcutaneous coronary intervention for acute coronary syndrome: The TROUPER trial.

Chronic kidney disease (CKD) is associated with an increased risk of acute coronary syndrome (ACS) and cardiovascular death. CKD patients suffering from ACS are exposed to an increased risk of thrombotic recurrences and a higher bleeding rate than patients with normal renal function. However, CKD patients are excluded or underrepresented in clinical trials. Therefore, determining the optimal antiplatelet strategy in this population is of utmost importance. We designed the TicagRelor Or Clopidogrel in severe or terminal chronic kidney patients Undergoing PERcutaneous coronary intervention for acute coronary syndrome (TROUPER) trial: a prospective, controlled, multicenter, randomized trial to investigate the optimal P2Y12 antagonist in CKD patients with ACS. Patients with stage ≥3b CKD are eligible if the diagnosis of ACS is made and invasive strategy scheduled. Patients are randomized 1:1 between a control group with a 600-mg loading dose of clopidogrel followed by a 75-mg/d maintenance dose for 1 year and an experimental group with a 180-mg loading dose of ticagrelor followed by a 90-mg twice daily maintenance dose for the same duration. The primary end point is defined by the rate of major adverse cardiovascular events, including death, myocardial infarction, urgent revascularization, and stroke at 1 year. Safety will be evaluated by the bleeding rate (Bleeding Academic Research Consortium). To demonstrate the superiority of ticagrelor on major adverse cardiovascular events, we calculated that 508 patients are required. The aim of the TROUPER trial is to compare the efficacy of ticagrelor and clopidogrel in stage >3b CKD patients presenting with ACS and scheduled for an invasive strategy. RCT# NCT03357874.

Antithrombotic efficacy of bivalirudin compared to unfractionated heparin during percutaneous coronary intervention for acute coronary syndrome.

Bivalirudin is associated with an increased risk of acute stent thrombosis (AST) compared to unfractionated heparin (UFH) in acute coronary syndrome patients (ACS) during short-duration percutaneous coronary intervention (PCI). The mechanisms involved are unknown. We aimed to investigate the antithrombotic efficacy of bivalirudin compared to UFH during PCI. In a monocenter study, we prospectively enrolled 30 patients undergoing PCI for a non-ST elevation ACS. They were randomly assigned to a single intravenous (IV) bolus of UFH (70 IU/kg) or an IV bolus of bivalirudin 0.75 mg/kg followed by a 1.75 mg/kg/h infusion during PCI. All patients received a loading dose (LD) of 180 mg of ticagrelor at the time of PCI. The VASP index and activated partial thromboplastin time (aPTT) were used to assess the course of platelet reactivity (PR) and antithrombotic activity. The two groups were similar regarding baseline, angiographic, and interventional characteristics. There was no difference between the two groups in the course of PR following ticagrelor LD. An optimal PR inhibition was obtained 4 h after the LD of ticagrelor. The level of antithrombotic activity was significantly lower in the bivalirudin group compared to the UFH group (p < 0.001) during PCI but similar at 2 and 4 h post-PCI. We observed that, in ACS undergoing PCI, the antithrombotic efficacy of an IV bolus of bivalirudin is significantly lower than that of a 70-IU/kg UFH bolus. This could contribute to the excess in thrombotic acute events observed during short-duration PCI.

Device-Related Thrombus After Left Atrial Appendage Occlusion With the Amulet Device.

BACKGROUND: Left atrial appendage occlusion (LAAO) is increasingly used for stroke prevention in patients with atrial fibrillation who are considered unsuitable for a lifelong oral anticoagulant regimen. Recently, a single-centre study reported device-related thrombus formation in 16.7% of patients treated with the second-generation Amulet device (St. Jude Medical, St. Paul, MN, USA), presenting a potential major safety concern. As "real-world" data on device-related thrombus formation following LAAO with the Amulet occluder are scarce, we aimed to evaluate this outcome in a retrospective registry. METHODS: Clinical and tranosesophageal echocardiography data after LAAO with the Amulet in consecutive patients from three centres were collated. RESULTS: Among 38 patients (mean age 75.8 years), mean (standard deviation) CHA2DS2-VASc and HAS-BLED scores were 4.4 (1.2) and 3.4 (0.9), respectively. All patients underwent successful device placement without procedure-related adverse events. The antithrombotic regimen at discharge consisted of dual antiplatelet therapy (DAPT) in 27 patients (71.1%), single antiplatelet therapy in 10 patients (26.3%), and no antithrombotic therapy in one patient (2.6%). Device-related thrombus was observed in one patient (2.6%) despite DAPT regimen. The outcome of this patient was uncomplicated after adjustment of oral anticoagulant therapy. No patients presented with a thromboembolic event following LAAO during a mean (standard deviation) follow-up of 15 (5) months. CONCLUSIONS: In this retrospective study, device-related thrombus formation with the second-generation Amulet device was rare and occurred at a rate similar to that of the previous device. Importantly, no patient experienced a device-related thromboembolic event during follow-up. Larger real-life studies are required to confirm the safety profile of this increasingly used device.

Adenosine Plasma Level and A2A Receptor Expression in Patients With Cardiogenic Shock.

OBJECTIVES: To investigate whether adenosine A2A receptors lead to vasodilation and positive inotropic function under stimulation and whether they play a role in the control of blood pressure in patients with cardiogenic shock. DESIGN: Prospective observational study. SETTING: Monocentric, Hopital Nord, Marseille, France. SUBJECTS: Patients with cardiogenic shock (n = 16), acute heart failure (n = 16), and acute myocardial infarction (n = 16). INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Arterial adenosine plasma level and A2A receptor expression on peripheral blood mononuclear cells were evaluated by mass spectrometry and Western blot, respectively, at admission and after 24 hours. Hemodynamic parameters, including systemic vascular resistance, were also assessed. Mean adenosine plasma level at admission was significantly higher in patients with cardiogenic shock (2.74 ± 1.03 µM) versus acute heart failure (1.33 ± 0.27) or acute myocardial infarction (1.19 ± 0.27) (normal range, 0.4-0.8 µM) (p < 0.0001). No significant correlation was found between adenosine plasma level and systemic vascular resistance. Mean adenosine plasma level decreased significantly by 24 hours after admission in patients with cardiogenic shock (2.74 ± 1.03 to 1.53 ± 0.68; p < 0.001). Mean A2A receptor expression was significantly lower in patients with cardiogenic shock (1.18 ± 0.11) versus acute heart failure (1.18 ± 0.11 vs 1.39 ± 0.08) (p = 0.005). CONCLUSIONS: We observed high adenosine plasma level and low A2A receptor expression at admission in patients with cardiogenic shock versus acute heart failure or acute myocardial infarction. This may contribute to the physiopathology of cardiogenic shock.

Uric acid levels are associated with endothelial dysfunction and severity of coronary atherosclerosis during a first episode of acute coronary syndrome.

The role of serum uric acid in coronary artery disease has been extensively investigated. It was suggested that serum uric acid level (SUA) is an independent predictor of endothelial dysfunction and related to coronary artery lesions. However, the relationship between SUA and severity of coronary atherosclerosis evaluated via endothelial dysfunction using peripheral arterial tone (PAT) and the reactive hyperhemia index (RHI) has not been investigated during a first episode of acute coronary syndrome (ACS). The aim of our study was to address this point. We prospectively enrolled 80 patients with a first episode of ACS in a single-center observational study. All patients underwent coronary angiography, evaluation of endothelial function via the RHI, and SUA measurement. The severity of the coronary artery lesion was assessed angiographically, and patients were classified in three groups based on the extent of disease and Gensini and SYNTAX scores. Endothelial function was considered abnormal if RHI < 1.67. We identified a linear correlation between SUA and RHI (R2 = 0.66 P < 0.001). In multivariable analyses, SUA remained associated with RHI, even after adjustment for traditional cardiovascular risk factors and renal function. SUA was associated with severity of coronary artery disease. SUA is associated with severity of coronary atherosclerosis in patients with asymptomatic hyperuricemia. This inexpensive, readily measured biological parameter may be useful to monitor ACS patients.

Ventricular Arrhythmia Occurrence and Compliance in Patients Treated With the Wearable Cardioverter Defibrillator Following Percutaneous Coronary Intervention.

BACKGROUND: The wearable cardioverter defibrillator (WCD) is a life-saving therapy in patients with high risk of arrhythmic death. We aimed to evaluate ventricular arrhythmia (VA) occurrence rate and compliance with the WCD during the first 90 days following myocardial revascularisation with percutaneous coronary intervention (PCI) in patients with left ventricular ejection fraction (LVEF) <30%. METHODS: From September 2015 to November 2016, clinical characteristics, WCD recordings and compliance data of the aforementioned subset of patients were prospectively collected. RESULTS: Twenty-four patients (men=20, 80%) were included in this analysis. Mean age was 56±10 years and mean LVEF at enrolment was 26.6±4.3%. During a mean wearing period of 3.0±1.3 months, two episodes of VA occurred in two patients (8.3%): one successfully treated with WCD shock and one with spontaneous termination. The mean and median daily use of the WCD was 21.5hours and 23.5hours a day, respectively. Eighteen patients (75%) wore the WCD more than 22hours a day. CONCLUSIONS: The rate of VA, during the WCD period use after myocardial revascularisation with PCI, was high in our study. Otherwise it underlined that patient compliance is critical during the WCD period use. Remote monitoring and patient education are keys to achieve good compliance.

COMparison of Platelet reactivity following prAsugrel and ticagrelor loading dose in ST-Segment elevation myocardial infarctION patients: The COMPASSION study.

Prasugrel and ticagrelor are potent P2Y12-ADP receptor antagonists which are superior to clopidogrel in acute coronary syndromes. To date no clinical trial directly compared these two drugs. Platelet reactivity correlates with ischemic and bleeding events in patients undergoing percutaneous coronary intervention. Recent pharmacological studies have observed a delayed onset of action of these two drugs in ST-segment elevation myocardial infarction (STEMI). We provide the first adequately powered pharmacological study comparing PR following ticagrelor and prasugrel loading dose (LD) in STEMI patients when the maximal biological effect is reached. In the present study, ticagrelor was associated with a lower rate of high on-treatment PR compared to prasugrel.

Simultaneous pulmonary vein cryoablation and cavotricuspid isthmus radiofrequency ablation in patients with combined atrial fibrillation and typical atrial flutter.

Pulmonary vein isolation (PVI) using cryoballoon (CB) technique and cavotricuspid isthmus (CTI) ablation using radiofrequency (RF) are established interventions for drug-resistant atrial fibrillation (AF) and typical atrial flutter (AFL). Twelve patients with a mean age of 62 ± 12 years underwent simultaneous delivery of RF energy at the CTI during CB applications at the PV ostia. Pulmonary vein isolation was achieved in all PVs and sustained bidirectional CTI conduction block obtained in all patients. The reported ablation protocol of combined paroxysmal AF and typical AFL did not result in prolongation of the procedure duration or in prolonged radiation exposure when compared to CB-PVI alone. No interferences between both ablation energy systems were observed. These preliminary results suggest that combined paroxysmal AF and typical AFL can be successfully and safely ablated using hybrid energy sources with simultaneous CTI ablation using RF during CB applications at the PV ostia.

Impact of targeted pulmonary arterial hypertension therapies in severe pulmonary hypertension in chronic lung diseases.

Research questions: Patients with severe pulmonary hypertension associated with chronic lung disease have a poor prognosis. Targeted pulmonary arterial hypertension therapies might improve exercise capacity and outcome, but there are no guidelines on treatments which are not recommended because of an unproven benefit, with discordant results from few studies in this context. The aim of our study was to evaluate targeted pulmonary arterial hypertension therapies for severe group 3 pulmonary hypertension patients. Study design and methods: We conducted an observational retrospective monocentre study on patients with severe group 3 pulmonary hypertension diagnosed on right heart catheterisation treated with targeted therapies. Primary outcome was an improvement of the distance on 6-min walk test of ≥30 m. Secondary end-points included changes in haemodynamics (pulmonary vascular resistance (PVR) and mean pulmonary arterial pressure (mPAP)) and identification of potential predictive factors of therapeutic response. Results: 139 patients were enrolled. Most patients had monotherapy with phosphodiesterase 5 inhibitors (n=128; 92%). Mean change in 6-min walk distance was +1.5 m after treatment (p=0.59). Forced expiratory volume in 1 s and forced vital capacity were not predictive factors for response. We found a significant improvement of PVR and mPAP of -1.0 Wood Units (p<0.001) and -4 mmHg (p<0.001), respectively, under treatment. 18% of patients had to withdraw treatment for intolerance. Treatment duration <3 months was associated with poor survival (hazard ratio 2.75, p=0.0005). Conclusion: Oral targeted pulmonary arterial hypertension therapies do not improve exercise capacity in patients with severe pulmonary hypertension associated with chronic lung disease, but could improve haemodynamic parameters.

Ventricular allorhythmia during infarct-related ventricular tachycardia.

Ventricular allorhythmia is an electrocardiogram feature leading to a pattern of "regularly irregular" arrhythmia mainly reported during non-life-threatening organized atrial tachycardia. We report the infrequent case of a patient presenting with ventricular allorhythmia during infarct-related ventricular tachycardia. The potential mechanisms of this tachycardia are discussed.

Survival and Factors Associated with Survival with Extracorporeal Life Support During Cardiac Arrest: A Systematic Review and Meta-Analysis.

The survival rate after cardiac arrest (CA) remains low. The utilization of extracorporeal life support is proposed to improve management. However, this resource-intensive tool is associated with complications and must be used in selected patients. We performed a meta-analysis to determine predictive factors of survival. Among the 81 studies included, involving 9256 patients, survival was 26.2% at discharge and 20.4% with a good neurologic outcome. Meta-regressions identified an association between survival at discharge and lower lactate values, intrahospital CA, and lower cardio pulmonary resuscitation (CPR) duration. After adjustment for age, intrahospital CA, and mean CPR duration, an initial shockable rhythm was the only remaining factor associated with survival to discharge (ß = 0.02, 95% CI: 0.007-0.02; p = 0.0004).

FCGR2A-HH Gene Variants Encoding the Fc Gamma Receptor for the C-Reactive Protein Are Associated with Enhanced Monocyte CD32 Expression and Cardiovascular Events' Recurrence after Primary Acute Coronary Syndrome.

Fcγ receptors (FcγRs) interact with the C-reactive protein (CRP) and mediate activation of inflammation-related pathogenic mechanisms affecting cardiovascular health. Our study evaluated whether FcγRIIA and FcγRIIIA profiles are associated with the recurrence of adverse cardiovascular events during the first year after a primary acute coronary syndrome (ACS). The primary endpoint was the recurrence of cardiovascular events (RCE), identified as a composite outcome comprising acute heart failure (AHF) and major adverse cardiovascular events (MACE). We obtained blood samples of 145 ACS patients to measure hsCRP circulating levels, to identify FcγRIIA-131RH rs1801274 and FcγRIIIA-158FV rs396991 polymorphisms, to analyze circulating monocytes and NK cell subsets expressing CD16 and CD32, and to detect serum-mediated FCGR2A-HH activation by luciferase reporter assays. The hsCRP, CD32-expression, and Fc-R mediated activation levels were similar in all patients regardless of their MACE risk. In contrast, the hsCRP levels and the proportion of CD14+ circulating monocytes expressing the CD32 receptor for CRP were significantly higher in the patients who developed AHF. The FCGR2A rs1801274 HH genotype was significantly more common in patients who developed RCE and MACE than in RCE-free patients and associated with an enhanced percentage of circulating CD32+CD14+ monocytes. The FCGR2A-HH genotype was identified as an independent predictor of subsequent RCE (OR, 2.7; p = 0.048; CI, 1.01-7.44) by multivariate analysis. These findings bring preliminary evidence that host FCGR2A genetic variants can influence monocyte CD32 receptor expression and may contribute to the fine-tuning of CD32-driven chronic activating signals that affect the risk of developing RCEs following primary ACS events.

Antithrombotic strategies in elderly patients with acute coronary syndrome.

Elderly patients represent a growing proportion of the acute coronary syndrome population in Western countries. However, their frequent atypical symptoms at presentation often lead to delays in management and to misdiagnosis. Furthermore, their prognosis is poorer than that of younger patients because of physiological changes in platelet function, haemostasis and fibrinolysis, but also a higher proportion of comorbidities and frailty, both of which increase the risk of recurrent thrombotic and bleeding events. This complex situation, with ischaemic and haemorrhagic risk factors often being intertwined, may lead to confusion about the required treatment strategy, sometimes resulting in inadequate management or even to therapeutic nihilism. It is therefore critical to provide a comprehensive overview of our understanding of the pathophysiological processes underlying acute coronary syndrome in elderly patients, and to summarise the results from the latest clinical trials to help decision making for these high-risk patients.

Impella CP Implantation during Cardiopulmonary Resuscitation for Cardiac Arrest: A Multicenter Experience.

BACKGROUND: Impella CP is a left ventricular pump which may serve as a circulatory support during cardiopulmonary resuscitation (CPR) for cardiac arrest (CA). Nevertheless, the survival rate and factors associated with survival in patients undergoing Impella insertion during CPR for CA are unknown. METHODS: We performed a retrospective multicenter international registry of patients undergoing Impella insertion during on-going CPR for in- or out-of-hospital CA. We recorded immediate and 30-day survival with and without neurologic impairment using the cerebral performance category score and evaluated the factors associated with survival. RESULTS: Thirty-five patients had an Impella CP implanted during CPR for CA. Refractory ventricular arrhythmias were the most frequent initial rhythm (65.7%). In total, 65.7% of patients immediately survived. At 30 days, 45.7% of patients were still alive. The 30-day survival rate without neurological impairment was 37.1%. In univariate analysis, survival was associated with both an age < 75 years and a time from arrest to CPR ≤ 5 min (p = 0.035 and p = 0.008, respectively). CONCLUSIONS: In our multicenter registry, Impella CP insertion during ongoing CPR for CA was associated with a 37.1% rate of 30-day survival without neurological impairment. The factors associated with survival were a young age and a time from arrest to CPR ≤ 5 min.