Scrutinizing the Role of Venoarterial Extracorporeal Membrane Oxygenation: Has Clinical Practice Outpaced the Evidence?

The use of venoarterial extracorporeal membrane oxygenation (VA-ECMO) for temporary mechanical circulatory support in various clinical scenarios has been increasing consistently, despite the lack of sufficient evidence regarding its benefit and safety from adequately powered randomized controlled trials. Although the ARREST trial (Advanced Reperfusion Strategies for Patients with Out-of-Hospital Cardiac Arrest and Refractory Ventricular Fibrillation) and a secondary analysis of the PRAGUE OHCA trial (Prague Out-of-Hospital Cardiac Arrest) provided some evidence in favor of VA-ECMO in the setting of out-of-hospital cardiac arrest, the INCEPTION trial (Early Initiation of Extracorporeal Life Support in Refractory Out-of-Hospital Cardiac Arrest) has not found a relevant improvement of short-term mortality with extracorporeal cardiopulmonary resuscitation. In addition, the results of the recently published ECLS-SHOCK trial (Extracorporeal Life Support in Cardiogenic Shock) and ECMO-CS trial (Extracorporeal Membrane Oxygenation in the Therapy of Cardiogenic Shock) discourage the routine use of VA-ECMO in patients with infarct-related cardiogenic shock. Ongoing clinical trials (ANCHOR [Assessment of ECMO in Acute Myocardial Infarction Cardiogenic Shock, NCT04184635], REVERSE [Impella CP With VA ECMO for Cardiogenic Shock, NCT03431467], UNLOAD ECMO [Left Ventricular Unloading to Improve Outcome in Cardiogenic Shock Patients on VA-ECMO, NCT05577195], PIONEER [Hemodynamic Support With ECMO and IABP in Elective Complex High-risk PCI, NCT04045873]) may clarify the usefulness of VA-ECMO in specific patient subpopulations and the efficacy of combined mechanical circulatory support strategies. Pending further data to refine patient selection and management recommendations for VA-ECMO, it remains uncertain whether the present usage of this device improves outcomes.

Unloading the Left Ventricle in Venoarterial ECMO: In Whom, When, and How?

Venoarterial extracorporeal membrane oxygenation provides cardiorespiratory support to patients in cardiogenic shock. This comes at the cost of increased left ventricle (LV) afterload that can be partly ascribed to retrograde aortic flow, causing LV distension, and leads to complications including cardiac thrombi, arrhythmias, and pulmonary edema. LV unloading can be achieved by using an additional circulatory support device to mitigate the adverse effects of mechanical overload that may increase the likelihood of myocardial recovery. Observational data suggest that these strategies may improve outcomes, but in whom, when, and how LV unloading should be employed is unclear; all techniques require balancing presumed benefits against known risks of device-related complications. This review summarizes the current evidence related to LV unloading with venoarterial extracorporeal membrane oxygenation.

Bilateral Femoral Cannulation Is Associated With Reduced Severe Limb Ischemia-Related Complications Compared With Unilateral Femoral Cannulation in Adult Peripheral Venoarterial Extracorporeal Membrane Oxygenation: Results From the Extracorporeal Life Support Registry.

OBJECTIVES: Peripheral venoarterial extracorporeal membrane oxygenation (ECMO) with femoral access is obtained through unilateral or bilateral groin cannulation. Whether one cannulation strategy is associated with a lower risk for limb ischemia remains unknown. We aim to assess if one strategy is preferable. DESIGN: A retrospective cohort study based on the Extracorporeal Life Support Organization registry. SETTING: ECMO centers worldwide included in the Extracorporeal Life Support Organization registry. PATIENTS: All adult patients (≥ 18 yr) who received peripheral venoarterial ECMO with femoral access and were included from 2014 to 2020. INTERVENTIONS: Unilateral or bilateral femoral cannulation. MEASUREMENTS AND MAIN RESULTS: The primary outcome was the occurrence of limb ischemia defined as a composite endpoint including the need for a distal perfusion cannula (DPC) after 6 hours from implantation, compartment syndrome/fasciotomy, amputation, revascularization, and thrombectomy. Secondary endpoints included bleeding at the peripheral cannulation site, need for vessel repair, vessel repair after decannulation, and in-hospital death. Propensity score matching was performed to account for confounders. Overall, 19,093 patients underwent peripheral venoarterial ECMO through unilateral ( n = 11,965) or bilateral ( n = 7,128) femoral cannulation. Limb ischemia requiring any intervention was not different between both groups (bilateral vs unilateral: odds ratio [OR], 0.92; 95% CI, 0.82-1.02). However, there was a lower rate of compartment syndrome/fasciotomy in the bilateral group (bilateral vs unilateral: OR, 0.80; 95% CI, 0.66-0.97). Bilateral cannulation was also associated with lower odds of cannulation site bleeding (bilateral vs unilateral: OR, 0.87; 95% CI, 0.76-0.99), vessel repair (bilateral vs unilateral: OR, 0.55; 95% CI, 0.38-0.79), and in-hospital mortality (bilateral vs unilateral: OR, 0.85; 95% CI, 0.81-0.91) compared with unilateral cannulation. These findings were unchanged after propensity matching. CONCLUSIONS: This study showed no risk reduction for overall limb ischemia-related events requiring DPC after 6 hours when comparing bilateral to unilateral femoral cannulation in peripheral venoarterial ECMO. However, bilateral cannulation was associated with a reduced risk for compartment syndrome/fasciotomy, lower rates of bleeding and vessel repair during ECMO, and lower in-hospital mortality.

The management of heart failure cardiogenic shock: an international RAND appropriateness panel.

BACKGROUND: Observational data suggest that the subset of patients with heart failure related CS (HF-CS) now predominate critical care admissions for CS. There are no dedicated HF-CS randomised control trials completed to date which reliably inform clinical practice or clinical guidelines. We sought to identify aspects of HF-CS care where both consensus and uncertainty may exist to guide clinical practice and future clinical trial design, with a specific focus on HF-CS due to acute decompensated chronic HF. METHODS: A 16-person multi-disciplinary panel comprising of international experts was assembled. A modified RAND/University of California, Los Angeles, appropriateness methodology was used. A survey comprising of 34 statements was completed. Participants anonymously rated the appropriateness of each statement on a scale of 1 to 9 (1-3 as inappropriate, 4-6 as uncertain and as 7-9 appropriate). RESULTS: Of the 34 statements, 20 were rated as appropriate and 14 were rated as inappropriate. Uncertainty existed across all three domains: the initial assessment and management of HF-CS; escalation to temporary Mechanical Circulatory Support (tMCS); and weaning from tMCS in HF-CS. Significant disagreement between experts (deemed present when the disagreement index exceeded 1) was only identified when deliberating the utility of thoracic ultrasound in the immediate management of HF-CS. CONCLUSION: This study has highlighted several areas of practice where large-scale prospective registries and clinical trials in the HF-CS population are urgently needed to reliably inform clinical practice and the synthesis of future societal HF-CS guidelines.

Left ventricular unloading in patients supported with veno-arterial extra corporeal membrane oxygenation; an international EuroELSO survey.

INTRODUCTION: Veno-arterial extracorporeal membrane oxygenation (V-A ECMO) improves end-organ perfusion in cardiogenic shock but may increase afterload, which can limit cardiac recovery. Left ventricular (LV) unloading strategies may aid cardiac recovery and prevent complications of increased afterload. However, there is no consensus on when and which unloading strategy should be used. METHODS: An online survey was distributed worldwide via the EuroELSO newsletter mailing list to describe contemporary international practice and evaluate heterogeneity in strategies for LV unloading. RESULTS: Of 192 respondents from 43 countries, 53% routinely use mechanical LV unloading, to promote ventricular recovery and/or to prevent complications. Of those that do not routinely unload, 65% cited risk of complications as the reason. The most common indications for unplanned unloading were reduced arterial line pulsatility (68%), pulmonary edema (64%) and LV dilatation (50%). An intra-aortic balloon pump was the most frequently used device for unloading followed by percutaneous left ventricular assist devices. Echocardiography was the most frequently used method to monitor the response to unloading. CONCLUSIONS: Significant variation exists with respect to international practice of ventricular unloading. Further research is required that compares the efficacy of different unloading strategies and a randomized comparison of routine mechanical unloading versus unplanned unloading.

Electrocardiogram alterations in non-traumatic brain injury: a systematic review.

The presence of abnormal electrocardiograms in individuals without known organic heart disease is one of the most common manifestations of cardiac dysfunction occurring during acute non traumatic brain injury. The primary goal of the present review is to provide an overview of the available data and literature regarding the presence of new-onset electrocardiographic (ECG) alterations in acute non traumatic brain injury. The secondary aim is to identify the incidence of ECG alterations and consider the prognostic significance of new-onset ECG changes in this setting. To do so, English language articles from January 2000 to January 2022 were included from PubMed using the following keywords: "electrocardiogram and subarachnoid hemorrhage", "electrocardiogram and intracranial hemorrhage", "Q-T interval and subarachnoid hemorrhage ", "Q-T interval and intracranial bleeding ", "Q-T interval and intracranial hemorrhage", and "brain and heart- interaction in stroke". Of 3162 papers, 27 original trials looking at electrocardiogram alterations in acute brain injury were included following the PRISMA guideline. ECG abnormalities associated with acute brain injury could potentially predict poor patient outcomes. They could even herald the future development of neurogenic pulmonary edema (NPE), delayed cerebral ischemia (DCI), and even in-hospital death. In particular, patients with SAH are at increased risk of having severe ventricular dysrhythmias. These may contribute to a high mortality rate and to poor functional outcome at 3 months. The current data on ECG QT dispersion and mortality appear less clearly associated. While some patients demonstrated poor outcomes, others showed no relationship with poor outcomes or increased in-hospital mortality. Observing ECG alterations carefully after cerebral damage is important in the critical care of these patients as it can expose preexisting myocardial disease and change prognosis.

Transfusion of red blood cells in venoarterial extracorporeal membrane oxygenation: A multicenter retrospective observational cohort study.

BACKGROUND: Evidence-based recommendations for transfusion in patients with venoarterial extracorporeal membrane oxygenation (VA ECMO) are scarce. The current literature is limited to single-center studies with small sample sizes, therefore complicating generalizability. This study aims to create an overview of red blood cell (RBC) transfusion in VA ECMO patients. METHODS: This international mixed-method study combined a survey with a retrospective observational study in 16 centers. The survey inventoried local transfusion guidelines. Additionally, retrospective data of all adult patients with a VA ECMO run >24 h (January 2018 until July 2019) was collected of patient, ECMO, outcome, and daily transfusion parameters. All patients that received VA ECMO for primary cardiac support were included, including surgical (i.e., post-cardiotomy) and non-surgical (i.e., myocardial infarction) indications. The primary outcome was the number of RBC transfusions per day and in total. Univariable logistic regressions and a generalized linear mixed model (GLMM) were performed to assess factors associated with RBC transfusion. RESULTS: Out of 419 patients, 374 (89%) received one or more RBC transfusions. During a median ECMO run of 5 days (1st-3rd quartile 3-8), patients received a median total of eight RBC units (1st-3rd quartile 3-17). A lower hemoglobin (Hb) prior to ECMO, longer ECMO-run duration, and hemorrhage were associated with RBC transfusion. After correcting for duration and hemorrhage using a GLMM, a different transfusion trend was found among the regimens. No unadjusted differences were found in overall survival between either transfusion status or the different regimens, which remained after adjustment for potential confounders. CONCLUSION: RBC transfusion in patients on VA ECMO is very common. The sum of RBC transfusions increases rapidly after ECMO initiation, and is dependent on the Hb threshold applied. This study supports the rationale for prospective studies focusing on indications and thresholds for RBC transfusion.

SCAI stage reclassification at 24 h predicts outcome of cardiogenic shock: Insights from the Altshock-2 registry.

BACKGROUND: Cardiogenic shock (CS) includes several phenotypes with heterogenous hemodynamic features. Timely prognostication is warranted to identify patients requiring treatment escalation. We explored the association of the updated Society for Cardiovascular Angiography and Interventions (SCAI) stages classification with in-hospital mortality using a prospective national registry. METHODS: Between March 2020 and February 2022 the Altshock-2 Registry has included 237 patients with CS of all etiologies at 11 Italian Centers. Patients were classified according to their admission SCAI stage (assigned prospectively and independently updated according to the recently released version). In-hospital mortality was evaluated for association with both admission and 24-h SCAI stages. RESULTS: The overall in-hospital mortality was 38%. Of the 237 patients included and staged according to the updated SCAI classification, 20 (8%) had SCAI shock stage B, 131 (55%) SCAI stage C, 61 (26%) SCAI stage D and 25 (11%) SCAI stage E. In-hospital mortality stratified according to the SCAI classification at 24 h was 18% for patients in SCAI stage B, 27% for SCAI stage C, 63% for SCAI stage D and 100% for SCAI stage E. Both the revised SCAI stages on admission and at 24 h were associated with in-hospital mortality, but the classification potential slightly increased at 24-h. After adjusting for age, sex, lactate level, eGFR, CVP, inotropic score and mechanical circulatory support [MCS], SCAI classification at 24 h was an independent predictor of in-hospital mortality. CONCLUSIONS: In the Altshock-2 registry the utility of SCAI shock stages to identify risk of in-hospital mortality increased at 24 h after admission. Escalation of treatment (either pharmacological or with MCS) should be tailored to achieve prompt clinical improvement within the first 24 h after admission. Registration: http://www. CLINICALTRIALS: gov; Unique identifier: NCT04295252.

The interaction of thrombocytopenia, hemorrhage, and platelet transfusion in venoarterial extracorporeal membrane oxygenation: a multicenter observational study.

BACKGROUND: Thrombocytopenia, hemorrhage and platelet transfusion are common in patients supported with venoarterial extracorporeal membrane oxygenation (VA ECMO). However, current literature is limited to small single-center experiences with high degrees of heterogeneity. Therefore, we aimed to ascertain in a multicenter study the course and occurrence rate of thrombocytopenia, and to assess the association between thrombocytopenia, hemorrhage and platelet transfusion during VA ECMO. METHODS: This was a sub-study of a multicenter (N = 16) study on transfusion practices in patients on VA ECMO, in which a retrospective cohort (Jan-2018-Jul-2019) focusing on platelets was selected. The primary outcome was thrombocytopenia during VA ECMO, defined as mild (100-150·109/L), moderate (50-100·109/L) and severe (< 50·109/L). Secondary outcomes included the occurrence rate of platelet transfusion, and the association between thrombocytopenia, hemorrhage and platelet transfusion, assessed through mixed-effect models. RESULTS: Of the 419 patients included, median platelet count at admission was 179·109/L. During VA ECMO, almost all (N = 398, 95%) patients developed a thrombocytopenia, of which a significant part severe (N = 179, 45%). One or more platelet transfusions were administered in 226 patients (54%), whereas 207 patients (49%) suffered a hemorrhagic event during VA ECMO. In non-bleeding patients, still one in three patients received a platelet transfusion. The strongest association to receive a platelet transfusion was found in the presence of severe thrombocytopenia (adjusted OR 31.8, 95% CI 17.9-56.5). After including an interaction term of hemorrhage and thrombocytopenia, this even increased up to an OR of 110 (95% CI 34-360). CONCLUSIONS: Thrombocytopenia has a higher occurrence than is currently recognized. Severe thrombocytopenia is strongly associated with platelet transfusion. Future studies should focus on the etiology of severe thrombocytopenia during ECMO, as well as identifying indications and platelet thresholds for transfusion in the absence of bleeding. TRIAL REGISTRATION: This study was registered at the Netherlands Trial Registry at February 26th, 2020 with number NL8413 and can currently be found at https://trialsearch.who.int/Trial2.aspx?TrialID=NL8413.

Glimpse into the future.

Randomized studies attempting to prove benefit of mechanical circulatory support in cardiogenic shock have failed to reduce the risk of death. Further, both registry and randomized data suggest increased rates of serious complications associated with these devices. This last review in the supplement discusses current evidence and provides a perspective on how the scientific community could advance cardiogenic shock research focused on mechanical circulatory support.

Differential utilization of Impella devices, extracorporeal membrane oxygenation, and combined therapies as escalation and de-escalation strategies.

Cardiogenic shock (CS) is a life-threatening condition characterized by a state of inadequate systemic tissue perfusion caused by cardiac dysfunction. When to implement, change, or remove the use of a temporary mechanical circulatory support (tMCS) in patients with CS is dependent on the aetiology and severity. Here, patient scenarios underlying the need to escalate, de-escalate, wean, or bridge from tMCS devices are taken into consideration by interdisciplinary heart failure and CS teams. This includes a comprehensive review of and focus on the rationale for specific device escalation and de-escalation strategies, device selection, and general management.

Recognizing patients as candidates for temporary mechanical circulatory support along the spectrum of cardiogenic shock.

A growing body of evidence indicates that the benefits of temporary mechanical circulatory support (tMCS) in patients with cardiogenic shock (CS) is dependent on its aetiology and timing of implantation. As such, appropriate diagnosis, screening, selection, and treatment is crucial to achieving good outcomes with tMCS. Here, the latest guidance on CS phenotypes and diagnostics for correctly identifying tMCS candidates is discussed. This includes comprehensive overviews of patient screening with attention given to differences in CS presentation between the sexes, and contraindications for mechanical circulatory support.

Cardiogenic Shock Integrated PHenotyping for Event Reduction: A Pilot Metabolomics Analysis.

Cardiogenic shock (CS) portends a dismal prognosis if hypoperfusion triggers uncontrolled inflammatory and metabolic derangements. We sought to investigate metabolomic profiles and temporal changes in IL6, Ang-2, and markers of glycocalyx perturbation from admission to discharge in eighteen patients with heart failure complicated by CS (HF-CS). Biological samples were collected from 18 consecutive HF-CS patients at admission (T0), 48 h after admission (T1), and at discharge (T2). ELISA analytical techniques and targeted metabolomics were performed Seven patients (44%) died at in-hospital follow-up. Among the survivors, IL-6 and kynurenine were significantly reduced at discharge compared to baseline. Conversely, the amino acids arginine, threonine, glycine, lysine, and asparagine; the biogenic amine putrescine; multiple sphingolipids; and glycerophospholipids were significantly increased. Patients with HF-CS have a metabolomic fingerprint that might allow for tailored treatment strategies for the patients' recovery or stabilization.

RBC Transfusion in Venovenous Extracorporeal Membrane Oxygenation: A Multicenter Cohort Study.

OBJECTIVES: In the general critical care patient population, restrictive transfusion regimen of RBCs has been shown to be safe and is yet implemented worldwide. However, in patients on venovenous extracorporeal membrane oxygenation, guidelines suggest liberal thresholds, and a clear overview of RBC transfusion practice is lacking. This study aims to create an overview of RBC transfusion in venovenous extracorporeal membrane oxygenation. DESIGN: Mixed method approach combining multicenter retrospective study and survey. SETTING: Sixteen ICUs worldwide. PATIENTS: Patients receiving venovenous extracorporeal membrane oxygenation between January 2018 and July 2019. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: The primary outcome was the proportion receiving RBC, the amount of RBC units given daily and in total. Furthermore, the course of hemoglobin over time during extracorporeal membrane oxygenation was assessed. Demographics, extracorporeal membrane oxygenation characteristics, and patient outcome were collected. Two-hundred eight patients received venovenous extracorporeal membrane oxygenation, 63% male, with an age of 55 years (45-62 yr), mainly for acute respiratory distress syndrome. Extracorporeal membrane oxygenation duration was 9 days (5-14 d). Prior to extracorporeal membrane oxygenation, hemoglobin was 10.8 g/dL (8.9-13.0 g/dL), decreasing to 8.7 g/dL (7.7-9.8 g/dL) during extracorporeal membrane oxygenation. Nadir hemoglobin was lower on days when a transfusion was administered (8.1 g/dL [7.4-9.3 g/dL]). A vast majority of 88% patients received greater than or equal to 1 RBC transfusion, consisting of 1.6 U (1.3-2.3 U) on transfusion days. This high transfusion occurrence rate was also found in nonbleeding patients (81%). Patients with a liberal transfusion threshold (hemoglobin > 9 g/dL) received more RBC in total per transfusion day and extracorporeal membrane oxygenation day. No differences in survival, hemorrhagic and thrombotic complication rates were found between different transfusion thresholds. Also, 28-day mortality was equal in transfused and nontransfused patients. CONCLUSIONS: Transfusion of RBC has a high occurrence rate in patients on venovenous extracorporeal membrane oxygenation, even in nonbleeding patients. There is a need for future studies to find optimal transfusion thresholds and triggers in patients on extracorporeal membrane oxygenation.

Intra-aortic Balloon Pump for Acute-on-Chronic Heart Failure Complicated by Cardiogenic Shock.

The intra-aortic balloon pump (IABP) is widely implanted as temporary mechanical circulatory support for cardiogenic shock (CS). However, its use is declining following the results of the IABP-SHOCK II trial, which failed to show a clinical benefit of the IABP in acute coronary syndrome (ACS)-related CS. Acute-on-chronic heart failure has become an increasingly recognized, distinct cause of CS (HF-CS). The pathophysiology of HF-CS differs from that of ACS-CS because it typically represents the progression from a state of congestion (with relatively preserved cardiac output) to a low-output state with hypoperfusion. The IABP is a volume-displacement pump that promotes forward flow from a high-capacitance reservoir to low-capacitance vessels, improving peripheral perfusion and decreasing left ventricular afterload in the setting of high filling pressures. The IABP can improve ventricular-vascular coupling and, therefore, myocardial energetics. Additionally, many patients with HF-CS are candidates for cardiac replacement therapies (left ventricular assist device or heart transplantation) and, therefore, may benefit from a bridge strategy that stabilizes the hemodynamics and end-organ function in preparation for more durable therapies. Notably, the new United Network for Organ Sharing donor heart allocation system has recently prioritized patients on IABP support. This review describes the role of IABP in the treatment of HF-CS. It also briefly discusses new strategies for vascular access as well as fully implantable versions for longer duration of support.

Use of nafamostat mesilate for anticoagulation during extracorporeal membrane oxygenation: A systematic review.

BACKGROUND: Extracorporeal membrane oxygenation (ECMO) represents an advanced option for supporting refractory respiratory and/or cardiac failure. Systemic anticoagulation with unfractionated heparin (UFH) is routinely used. However, patients with bleeding risk and/or heparin-related side effects may necessitate alternative strategies: among these, nafamostat mesilate (NM) has been reported. METHODS: We conducted a systematic literature search (PubMed and EMBASE, updated 12/08/2021), including all studies reporting NM anticoagulation for ECMO. We focused on reasons for starting NM, its dose and the anticoagulation monitoring approach, the incidence of bleeding/thrombosis complications, the NM-related side effects, ECMO weaning, and mortality. RESULTS: The search revealed 11 relevant findings, all with retrospective design. Of these, three large studies reported a control group receiving UFH, the other were case series (n = 3) or case reports (n = 5). The main reason reported for NM use was an ongoing or high risk of bleeding. The NM dose varied largely as did the anticoagulation monitoring approach. The average NM dose ranged from 0.46 to 0.67 mg/kg/h, but two groups of authors reported larger doses when monitoring anticoagulation with ACT. Conflicting findings were found on bleeding and thrombosis. The only NM-related side effect was hyperkalemia (n = 2 studies) with an incidence of 15%-18% in patients anticoagulated with NM. Weaning and survival varied across studies. CONCLUSION: Anticoagulation with NM in ECMO has not been prospectively studied. While several centers have experience with this approach in high-risk patients, prospective studies are warranted to establish the optimal space of this approach in ECMO.

Eleven Years of Venovenous Extracorporeal Membrane Oxygenation for Acute Respiratory Distress Syndrome: From H1N1 to SARS-CoV-2. Experience and Perspectives of a National Referral Center.

OBJECTIVE: Despite growing expertise and wide application of venovenous extracorporeal membrane oxygenation (VV ECMO) treatment for acute respiratory distress syndrome (ARDS) of different origin and during pandemics (H1N1 Influenza A virus and SARS-CoV-2), large reports are few and pertain mostly to multicenter registries, and randomized trials are difficult to perform. The aim of this study was to report outcomes, trends, and innovations of VV ECMO treatment over the last 11 years. DESIGN, SETTING, AND PARTICIPANTS: Observational study on 142 patients treated at the IRCCS San Raffaele Hospital in Milan from June 2009 (year of the H1N1 pandemic) to May 2020 (SARS-CoV-2 pandemic). INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: The main causes of ARDS were H1N1 pneumonia in 36% of patients, bacterial pneumonia in 17%, and SARS-CoV-2 in 9%. Seventy-two percent of patients were centralized from remote hospitals, of whom 33% had implanted VV ECMO before transport. The most common cannulation strategy was the dual-lumen catheter cannulation system (55%), and anticoagulation was performed with bivalirudin in most patients (79%). Refractory hypoxia was treated with intravenous beta-blockers (64%), nitric oxide (20%), and pronation (8%). Almost one-third of patients (32%) were extubated while on ECMO. Forty-nine percent of patients were discharged from the intensive care unit, and hospital discharge was 46%; survival was lower in patients requiring VV ECMO for more than three weeks compared with shorter support duration (23% v 56%, p = 0.007). Anticoagulation with bivalirudin was associated with higher survival, compared with heparin (55% v 31%, p = 0.03), and lower thrombocytopenia incidence (69% v 35%, p = 0.003). CONCLUSION: VV ECMO is the pivotal rescue treatment for refractory ARDS-timely treatment and optimal care are needed to optimize therapy, as duration of support is associated with outcome. Anticoagulation with bivalirudin may improve outcome.

Right Ventricular Function After Minimally Invasive Mitral Valve Surgery.

OBJECTIVES: Right ventricular (RV) dysfunction is a significant cause of morbidity and mortality after cardiac surgery. Minimally invasive mitral valve surgery (MIMVS) increasingly is being performed. The authors aim was to evaluate postoperative RV function in patients who underwent MIMVS versus traditional mitral valve surgery. DESIGN: Six hundred seventy-five patients who underwent elective isolated mitral valve surgery at Centro Cardiologico Monzino from January 2016 to December 2019 were analyzed. After 1:1 propensity score matching, 60 patients were identified in the MIMVS (study group A) and 58 patients in the median sternotomy (control group B) and compared. SETTING: A university-affiliated scientific institute, monocentric. PARTICIPANTS: Patients. INTERVENTIONS: Mitral valve surgery. MEASUREMENTS AND MAIN RESULTS: No in-hospital deaths occurred. Aortic cross-clamp time (102 [87.5-119] v 83 [61-109] minutes, p = 0.0001), cardiopulmonary bypass duration (161.5 [142.5-181] v 105.5 [74-134] minutes, p < 0.0001) and intensive care unit stay (47 [44-72] v 45 [40-47] hours, p = 0.0015) were significantly longer in group A. The tricuspid annular plane systolic excursion was not different between group A and group B neither postoperatively (15 ± 3 v 14 ± 4 mm, p = 0.1) nor at three-month follow-up (18 ± 4 v 15 ± 3 mm, p = 0.3). No differences in peak postoperative lactates, inotropic score, central venous pressure, and pulmonary artery pulsatility index were observed. The length of hospital stay was significantly shorter in the minimally invasive group (ten [eight-13] v 12 [ten-17], p = 0.006). CONCLUSION: The authors study showed that the surgical strategy had no significant impact on postoperative RV function after mitral valve surgery.

Left Ventricular Unloading Is Associated With Lower Mortality in Patients With Cardiogenic Shock Treated With Venoarterial Extracorporeal Membrane Oxygenation: Results From an International, Multicenter Cohort Study.

BACKGROUND: Venoarterial extracorporeal membrane oxygenation (VA-ECMO) is increasingly used to treat cardiogenic shock. However, VA-ECMO might hamper myocardial recovery. The Impella unloads the left ventricle. This study aimed to evaluate whether left ventricular unloading in patients with cardiogenic shock treated with VA-ECMO was associated with lower mortality. METHODS: Data from 686 consecutive patients with cardiogenic shock treated with VA-ECMO with or without left ventricular unloading using an Impella at 16 tertiary care centers in 4 countries were collected. The association between left ventricular unloading and 30-day mortality was assessed by Cox regression models in a 1:1 propensity score-matched cohort. RESULTS: Left ventricular unloading was used in 337 of the 686 patients (49%). After matching, 255 patients with left ventricular unloading were compared with 255 patients without left ventricular unloading. In the matched cohort, left ventricular unloading was associated with lower 30-day mortality (hazard ratio, 0.79 [95% CI, 0.63-0.98]; P=0.03) without differences in various subgroups. Complications occurred more frequently in patients with left ventricular unloading: severe bleeding in 98 (38.4%) versus 45 (17.9%), access site-related ischemia in 55 (21.6%) versus 31 (12.3%), abdominal compartment in 23 (9.4%) versus 9 (3.7%), and renal replacement therapy in 148 (58.5%) versus 99 (39.1%). CONCLUSIONS: In this international, multicenter cohort study, left ventricular unloading was associated with lower mortality in patients with cardiogenic shock treated with VA-ECMO, despite higher complication rates. These findings support use of left ventricular unloading in patients with cardiogenic shock treated with VA-ECMO and call for further validation, ideally in a randomized, controlled trial.

Early intra-aortic balloon pump in acute decompensated heart failure complicated by cardiogenic shock: Rationale and design of the randomized Altshock-2 trial.

BACKGROUND: Cardiogenic shock (CS) is a systemic disorder associated with dismal short-term prognosis. Given its time-dependent nature, mechanical circulatory support may improve survival. Intra-aortic balloon pump (IABP) had gained widespread use because of the easiness to implant and the low rate of complications; however, a randomized trial failed to demonstrate benefit on mortality in the setting of acute myocardial infarction. Acute decompensated heart failure with cardiogenic shock (ADHF-CS) represents a growing resource-intensive scenario with scant data and indications on the best management. However, a few data suggest a potential benefit of IABP in this setting. We present the design of a study aimed at addressing this research gap. METHODS AND DESIGN: The Altshock-2 trial is a prospective, randomized, multicenter, open-label study with blinded adjudicated evaluation of outcomes. Patients with ADHF-CS will be randomized to early IABP implantation or to vasoactive treatments. The primary end point will be 60 days patients' survival or successful bridge to heart replacement therapy. The key secondary end point will be 60-day overall survival; 60-day need for renal replacement therapy; in-hospital maximum inotropic score, maximum duration of inotropic/vasopressor therapy, and maximum sequential organ failure assessment score. Safety end points will be in-hospital occurrence of bleeding events (Bleeding Academic Research Consortium >3), vascular access complications and systemic (noncerebral) embolism. The sample size for the study is 200 patients. IMPLICATIONS: The Altshock-2 trial will provide evidence on whether IABP should be implanted early in ADHF-CS patients to improve their clinical outcomes.