Clinical Research Directory

Prognosis of Patients With Mixed Cardiogenic-Vasoplegic Shock

Mixed cardiogenic-vasoplegic shock (M-CS) represents a distinct and severe phenotype of cardiogenic shock characterized by concomitant myocardial dysfunction and inappropriate systemic vasodilation. Despite its clinical relevance, the epidemiology, management, and outcomes of M-CS remain poorly defined. This retrospective, multicenter, observational registry aims to evaluate the clinical outcomes and prognostic factors associated with mixed cardiogenic-vasoplegic shock. The study will analyze clinical, biological, and invasive hemodynamic data routinely collected during patient management for M-CS. All included patients will have been admitted for cardiogenic shock, with or without vasoplegia, defined by low cardiac output and, when present, decreased systemic vascular resistance despite adequate filling pressures requiring vasopressor support. The primary objective is to describe mortality and organ failure rates, while secondary analyses will identify determinants of adverse outcomes and potential phenotypic subgroups. The PROMIX registry will be conducted across three French university hospitals (CHU Amiens-Picardie, CHU Dijon-Bourgogne, and CHU Rouen-Normandie). This study is non-interventional, involving only data obtained as part of routine critical care, and will provide the first multicenter overview of this complex and underrecognized form of cardiogenic shock.

Hong Kong Cardiogenic Shock Initiative

Acute myocardial infarction complicated by cardiogenic shock (AMI-CS) is a severe condition with high mortality. Early revascularization and Impella device (Abiomed) support improve outcomes. Observational studies like the National Cardiogenic Shock Initiative (NCSI), Inova-Shock registry, and J-PVAD (Japan registry for percutaneous ventricular assist device) registry emphasize the importance of structured care systems when using mechanical circulatory support (MCS). Following the release of the Danger Shock trial, MCS use is expected to rise. Hospitals will need to monitor practices and work with payers to ensure coverage. Using regional real-world data can assist this process, making the collection and analysis of MCS outcomes essential. The NCSI (NCT03677180) aimed to evaluate outcomes with a protocolized approach prioritizing rapid diagnosis, timely MCS delivery, and invasive hemodynamic monitoring via pulmonary artery (PA) catheters. The study involved 406 patients from 2016 to 2020, with an average age of 64 years. Most (67%) had shock, with 85% on vasoactive drugs. Witnessed outof-hospital cardiac arrest occurred in 17%, and in-hospital arrest in 30%. During MCS implantation, 9% were actively resuscitating. Patients mostly in SCAI stage C/D (73%) and stage E (27%) presented with low blood pressure, high lactate, and reduced cardiac power output. About 70% received MCS before PCI, with 90% using PA catheters. Most had STEMI, with median door-to-support and door-to-balloon times of about 78 and 81 minutes. Survival rates were high: 99% procedural, 79% to discharge, 77% at 30 days, and 62% at one year for stage C/D shock. Patients with stage E shock had lower survival. Early use of MCS improved hemodynamics and survival. Further research, like the CERAMICS (Can Escalation Reduce Acute Myocardial Infarction in Cardiogenic Shock) study, aims to refine escalation strategies. The Danger Shock trial highlighted the importance of minimizing complications such as bleeding, limb ischemia, haemolysis, and kidney injury. Currently in Hong Kong, prevalence of CS among AMI patients is 5-10%, in-line with global statistics. Among which, 30-day and 1-year mortality of AMI-CS patients in Hong Kong was reported at 29% and 39.5% respectively. Although the use of MCS has been shown in the above overseas studies to improved survival rates of AMI-CS patients, the utilisation rate of MCS among AMI-CS patients in Hong Kong was reported at 36.5% in a previous single-centre study, limited by an array of factors including limited device availability, allocations of resources and patient selection strategy, lack of region-specific evidence and device affordability. Global Cardiogenic Shock Initiative (GCSI) is an ongoing international multicenter registry involving centers from USA, Germany, and Hong Kong, and focus on the outcomes of AMI-CS patients received Impella support. The GCSI is expanding to many other regions. In the Hong Kong Cardiogenic Shock Initiative (HK-CGSI) study we aim to include sites with experience in MCS, all of whom have the capability of MCS escalation and evaluate outcomes across these centers. The goal is not only to capture the effects of previously established best practices but gain insights into regional best practices, and together with data from the global cardiogenic shock initiative (GCSI), to better establish the adoption of novel best practices and their effect on complication rates. In parallel to GCSI-eligible cohort, i.e. Impella used as the first supporting device for patients with AMI-CS, given the significant portion of patients who could not receive MCS under current limitations in Hong Kong, in the HK-CSI, we will include also the GCSI-ineligible cohort, i.e. AMI-CSI without using Impella or not as the first MCS used, to understand the full picture of clinical outcomes of AMI-CS patients of Hong Kong. The HK-CSI study is an observational registry solely and not a treatment study. This single-arm registry captures data generated during procedures which are considered standard of care. Participation in this registry will be performed with waiver of consent of the patient and will have no influence on the type and extent of treatment.

Prospective Validation of the STOPSHOCK Score - Artificial Intelligence Based Predictive Scoring System to Identify the Risk of Developing Cardiogenic Shock (CS) in Patients Suffering From Acute Coronary Syndrome (ACS)

Cardiogenic shock (CS) is a severe complication of acute coronary syndrome (ACS) with mortality approaching 50% despite the use of percutaneous mechanical circulatory support devices (pMCS). Identifying high-risk patients prior to the development of CS could allow pre-emptive use of pMCS possibly preventing CS. For this purpose, we derived and externally validated a machine learning score to predict in-hospital CS in patients with ACS with c-statistics: 0.844 (95% confidence interval, 0.841-0.847). STOPSCHOCK score is available as a web or smartphone application. The aim of this study is to prospectively validate the STOPSHOCK score on a large cohort of ACS patients in a real- world clinical environment.

Early Preventive Left Ventricle Unloading After VA-ECMO for Refractory Cardiogenic Shock

Venoarterial extracorporeal membrane oxygenation (VA-ECMO) is increasingly being used worldwide to treat severe cardiogenic shock. The survival rate of these patients has increased in the last decade, reaching 45-50% for patients with acute myocardial infarction (AMI), the most frequent indication of the technique, 50-60% for patients with end-stage dilated cardiomyopathy bridged to heart transplantation or long-term left ventricle assist device (LVAD) surgery, 60-70% for fulminant myocarditis, while it remains lower for post-cardiotomy cardiogenic shock (25-35%) and after cardiac arrest (20-40%). However, peripherally inserted VA-ECMO increases left ventricular (LV) afterload, that may lead to poorer clinical outcomes by fostering left ventricular distension, blood stagnation, aortic valve closure, all of which increasing pulmonary congestion and the need for mechanical ventilation and compromising myocardial recovery whenever it is possible, or delaying a bridge to a heart transplantation or long-term left ventricle assist device (LVAD) surgery for patients with end-stage cardiac dysfunction. Several methods have been proposed to reduce afterload after VA-ECMO, including the use of an intra-aortic balloon pump (IABP), balloon atrial septostomy, transseptal left atrial cannula insertion, and use of the left-sided Impella device (Abiomed, Danvers, MA, USA). The clinical benefits of left ventricular unloading have been suggested by many retrospective case-control studies, including a study by our group that showed that associating an IABP with peripheral VA-ECMO was independently associated with a lower frequency of hydrostatic pulmonary edema under ECMO and more days off mechanical ventilation. More recently, unloading the left ventricle with an IABP was associated with the best survival rate and security profile as compared to no unloading or unloading with a microaxial pump in 12,734 VA-ECMO patients included in the Extracorporeal Life Support Organization registry. It should also be mentioned that another large registry study showed that the greatest benefit of LV unloading under ECMO was observed with early versus delayed insertion of the unloading device. Lastly, the EARLY-UNLOAD randomized trial in which a transseptal left atrial cannula was used for LV unloading yielded negative results. However, it is important to note that 50% of control patients were rapidly transitioned to LV unloading, thereby compromising the opportunity to demonstrate a mortality benefit. It was also underpowered for the primary outcome of D30 mortality since it included only 116 patients As a result, the recourse to systematic early LV unloading remains highly heterogeneous in clinical practice. For example, , while IABP was EULODIA - Protocol, version 1.0 dated 24/01/2025 Page 6 sur 54 This document is the property of DRCI/AP-HP. All reproduction is strictly prohibited. Version no. 4.0 of 31/05/2019 associated to ECMO in \>70% of the cases in our series of AMI CS patients, only 5.8% of the patients included in the ECMO arm of the recent ECLS-Shock trial received an unloading device, which may have contributed to the neutral result of the study and the only randomized trial to date was underpowered and flawed by a very high rate of early cross-over. Indeed, there is large heterogeneity in current clinical practice, where decisions on whether to add an additional mechanical unloading device during VA-ECMO support vary widely. Therefore, a new and adequately powered trial comparing systematic early left ventricular unloading to a conventional approach, with rescue left ventricular unloading only in case of clear and urgent indication, i.e. if overt hydrostatic cardiogenic pulmonary edema occurs, is urgently needed. The EULODIA trial is designed to test the hypothesis that early preventive left ventricle unloading with an IABP improves clinical outcomes as compared to conventional care with delayed curative unloading in patients under VA-ECMO for refractory cardiogenic shock.

Protective Effect of EECP Against Negative Inflammatory Response and Organ Dysfunction After Cardiovascular Surgery

Enhanced external counterpulsation (EECP) is a noninvasive, non-pharmacologic intervention proven to increase nitric oxide bioavailability in patients with coronary artery disease. Although EECP showed short-term effects in improving coronary flow in patients with coronary slow flow, whether such improvement is durable remains uncertain, and the relationships between such improvement and changes in multiple organ functions as well as inflammatory markers have not been elucidated. The purpose of this study will be to evaluate the potential clinical benefits of EECP on organ function and proinflammatory cytokine concentrations during post-acute sequela of cardiovascular surgery.