Venoarterial Extracorporeal Membrane Oxygenation Research Articles

Influence of timing of impella insertion on the prognosis of acute myocardial infarction complicated with cardiogenic shock requiring ECPELLA

Abstract Background/Introduction In patients with cardiogenic shock (CS), a combination of Impella-a percutaneous ventricular assist device with a catheter-type micro-axial heart pump-and venoarterial extracorporeal membrane oxygenation (ECPELLA) has been reported to have a better prognosis compared to venoarterial extracorporeal membrane oxygenation (VA-ECMO) alone, although it was associated with more complications. In contemporary clinical practice, ECPELLA has often been used in place of VA-ECMO alone. However, in many cases of acute myocardial infarction (AMI) with CS, there is controversy regarding the prioritization of Impella or VA-ECMO installation. Purpose The current study aims to clarify the factors of Impella use before VA-ECMO, the impact of the timing of Impella insertion (before or after VA-ECMO) for 30-day mortality, and major adverse events (MAEs) in the two groups. Methods The Japanese registry for Percutaneous Ventricular Assist Device (J-PVAD) Registry is a nationwide registry enrolling 5,718 consecutive Japanese patients treated with Impella between February 2020 and December 2022. The current study population consisted of 1,082 patients with AMI complicated by CS excluding cardiopulmonary arrest on arrival or using only Impella, who were divided into 2 groups; Impella use before and after VA-ECMO. Results Among the current study population, 323 patients (30%) used Impella before VA-ECMO, and 759 patients (70%) used Impella after VA-ECMO. Patients who used Impella before VA-ECMO were older (72 vs. 68 years old, P<0.0001) and had higher left ventricular ejection fraction (LVEF) (30 vs 20 %, P<0.0001), lower lactate level (5.6 vs 9.1 mmol/L, P<0.0001), and more often ST-elevation myocardial infarction (MI) (82% vs 76%, P<0.0001), whereas those patients had less often out-of-hospital cardiac arrest (OHCA) (13% vs 45%, P<0.0001), in-hospital cardiac arrest (IHCA) (27% vs 63%, P<0.0001), and prior heart failure (9.5% vs 16%, P=0.006). The factors of Impella use before VA-ECMO were 75 years or older, dyslipidemia, the absence of OHCA, the absence of IHCA, the absence of prior MI, and the absence of LVEF less than 30%. The cumulative 30-day incidence of all-cause death was 46.2% in patients with Impella use before VA-ECMO and 53.4% in those with Impella use after VA-ECMO (Log-rank P=0.02). After adjusting confounders, there was no excess risk of Impella use before VA-ECMO relative to Impella use after VA-ECMO (adjusted HR, 0.87; 95%CI, 0.55-1.37; P=0.55). Regarding major adverse events, hemolysis was significantly more frequent in patients with Impella use before VA-ECMO, while stroke was significantly more common in patients with Impella use after VA-ECMO. Conclusions The prognosis with AMI complicated by CS requiring ECPELLA remained poor. The 30-day mortality was lower in patients with Impella use before VA-ECMO compared to after VA-ECMO. However, after adjusting for confounders, there was no difference between the two groups.

A systematic review and meta-analysis of the efficacy and safety of combined mechanical circulatory support in cardiogenic shock complicating acute myocardial infarction

Abstract Background Cardiogenic shock complicating acute myocardial infarction (CSAMI) is a severe complication associated with unacceptably high mortality rates. Since early revascularisation was introduced more than 20 years ago, no subsequent innovation has demonstrated conclusive efficacy in reducing mortality in CSAMI. While mechanical circulatory support (MCS) has emerged as a potential intervention, randomised controlled trials evaluating independent use of veno-arterial extracorporeal membrane oxygenation (VA-ECMO), and intra-aortic balloon pump (IABP) have not shown benefit in CSAMI. In contrast, systematic reviews of observational studies have revealed significant mortality reduction when CSAMI was treated with combined use of MCS, specifically VA-ECMO in conjunction with a left ventricular (LV) unloading device (Impella or IABP). Combination MCS (VA-ECMO + LV unloading) may therefore present a promising approach to CSAMI, but an unresolved dilemma concerning the optimal selection between two LV unloading devices (VA-ECMO + Impella vs VA-ECMO + IABP) warrants further investigation and clarification. Purpose We perform the first systematic review and meta-analysis assessing the short-term efficacy and safety of VA-ECMO + Impella versus VA-ECMO + IABP in treatment of CSAMI. Methods A systematic search was performed on the EMBASE and MEDLINE databases. Studies reporting the short-term (30-day/inpatient) mortality and complications of adult patients with CSAMI treated with VA-ECMO + Impella and VA-ECMO + IABP were included. Fixed effect meta-analyses using Mantel-Haenszel model was used to analyse the pooled odds ratio for short-term mortality and major complications. Subgroup analysis was performed including studies with ACS predominant CS (Cause of CS 100% by AMI). Results Four observational studies with 14,247 patients were included. These studies showed high heterogeneity for the total CSAMI cohort and low heterogeneity for the ACS predominant cohort. There was no significant difference in mortality between VA-ECMO + Impella and VA-ECMO + IABP 56.5% vs 66.5%; OR, 0.90; 95% CI, 0.79–1.02; P=0.09. However, VA-ECMO + Impella was associated with significantly lower mortality in patients with ACS predominant CS 53.2% vs 67.7%; OR, 0.72; 95% CI, 0.62–0.85; P<0.0001. VA-ECMO + Impella was associated with significantly higher risk of major bleeding 15.1% vs 8.6%; OR, 1.87; 95% CI, 1.50–2.32; P<0.00001 and vascular complications 15.0% vs 6.7%; OR, 1.75; 95% CI, 1.41–2.18; P<0.00001. Conclusions When comparing LV unloading devices in patients with CSAMI requiring combination MCS, VA-ECMO + Impella was superior in mortality reduction only in the cohort where 100% of CS was caused by AMI. Concomitantly, VA-ECMO + Impella was associated with greater risk of major bleeding and vascular complications. Additional randomised studies are needed to validate and strengthen the findings presented in these observational data.Forrest plot on short-term mortalityForrest plot on major complications

Incidence and predictors of weaning failure from veno-arterial extracorporeal membrane oxygenation therapy in patients with cardiogenic shock

Abstract Background Mortality in cardiogenic shock (CS) remains high even when mechanical circulatory support (MCS) restores adequate circulation. Despite extensive research efforts in recent years, evidence on MCS in this setting is so far neutral. Especially, weaning from MCS is a challenging aspect of daily MCS management and standardized guidance is not yet available. Purpose This study aims to investigate incidence and predictors of weaning failure from venoarterial extracorporeal membrane oxygenation (VA-ECMO) in patients with CS. Methods Patients with CS treated with VA-ECMO at 23 tertiary-care centres in 7 countries were analysed. Weaning failure was defined as death during VA-ECMO support and death within two days after VA-ECMO explantation. To evaluate whether patient or treatment specific characteristics could serve as predictors for weaning success or failure multivariable logistic regressions models were fitted. Results A total of 685 patients with CS treated with VA-ECMO were included in this study. Median age was 57 (49-66) years and 542 (77.1%) were male. More than half of the patients presented with CS due to acute myocardial infarction (AMI) (n=438, 63.9%) and prior cardiac arrest (n=431, 62.9%). Median lactate upon admission was 7.6 mmol/l (4.1-12.7). Of these, 410 patients (59.9%) were successfully weaned from VA-ECMO, whereas in 275 patients (40.1%) weaning failed. Of the successfully weaned patients 162 (39.5%) died before hospital discharge. The mortality of the overall cohort was 63.8%. AMI was slightly less common in patients with failed weaning. Age (Odds ratio (OR) 1.04, 95% confidence interval (CI): 1.02, 1.06; p<0.001) and cardiac arrest before VA-ECMO implantation (OR 1.68, 95%-CI: 1.09, 2.6; p=0.019) where the only baseline parameters associated with weaning failure. Lactate clearance within 24h after VA-ECMO initiation was associated with successful weaning (OR 0.13, 95%-CI: 0.07, 0.26; p<0.001, Figure 1). Conclusion VA-ECMO weaning is common and fails in 40% of patients in whom it is attempted. 60% of patients are discharged alive after a successful VA-ECMO weaning attempt. Older age, cardiac arrest, and slow clearing of lactate are predictors of failed ECMO weaning. These data illustrate the complex factors contributing to successful mechanical circulatory support.Figure 1

Identifying prognostic factors in patients with cardiogenic shock undergoing VA-ECMO treatment: insights from ECLS-SHOCK using machine learning

Abstract Background/Introduction Venoarterial extracorporeal membrane oxygenation (VA-ECMO) has not been shown to reduce short-term mortality in patients with acute myocardial infarction complicated by cardiogenic shock. However, whether some patients might benefit from VA-ECMO remains to be cleared. Purpose To identify the impact of VA-ECMO therapy on outcomes by leveraging the potential of machine learning. Methods The ECLS-SHOCK trial is a randomized controlled trial where patients with acute myocardial infarction complicated by cardiogenic shock for whom early revascularization was planned were randomly assigned to receive early VA-ECMO plus usual medical treatment or usual medical treatment alone. The primary outcome was death from any cause at 30 days. Extreme gradient boosting (XGBoost) was used to develop a model for the prediction of 30-day all-cause mortality and to assess the influence of VA-ECMO on outcomes. Results Overall, 209 patients were randomized to the VA-ECMO and 208 to control. Baseline characteristics between groups were well balanced (median age 63 years, 81% male, 67% presenting with ST-segment elevation myocardial infarction). At 30-days 100 patients in the VA-ECMO and 102 in the control group were dead. The final XGBoost model contained 27 variables and the 10 most influential variables are shown in Fig. 1. On derivation the model predicted mortality with an AUC of 1.00 and on validation with an AUC of 0.80 (95% CI 0.71 to 0.89), with a sensitivity of 95% (95% CI 88% to 100%) and a specificity of 55% (40% to 69%), resulting in a positive predictive value of 65% and a negative predictive value of 92% at a Youden-derived cut-off. Importantly, neither the VA-ECMO therapy nor its complications were among the most influential factors of the model with a relative importance of 1.1% for VA-ECMO therapy and 0.25% for peripheral vascular complications and bleeding complications even being discarded by the model. Conclusion In patients with acute myocardial infarction complicated by cardiogenic shock the influence of VA-ECMO therapy on 30-day mortality, even when investigated with complex machine learning models, is negligibly low.

Impact of extracorporeal cardiopulmonary resuscitation with ECPELLA on improvement of short-term survival in patients with refractory cardiac arrest

Abstract Background Extracorporeal cardiopulmonary resuscitation (E-CPR) is considered for cardiac arrest (CA) patients when conventional CPR is ineffective. While veno-arterial extracorporeal membrane oxygenation (VA-ECMO) robustly maintains systemic perfusion, it also increases left ventricular (LV) afterload. Recently, the transcatheter LV assist device Impella has been introduced, and the potential benefits of its combined use with VA-ECMO (ECPELLA) are anticipated. However, the utility and effective management of ECPELLA remain unclear. Purpose This single-site cohort study aimed to assess the impact of ECPELLA compared to VA-ECMO with or without intra-aortic balloon pump (IABP) in patients with refractory CA who received E-CPR. Methods We retrospectively reviewed 207 consecutive patients who underwent E-CPR between January 2012 and September 2023 at our institute. The patients were divided into two groups, ECEPLLA (n = 65) and VA-ECMO with or without IABP (n = 141). A propensity score analysis was conducted, utilizing 1:1 score matching based on variables including age, the rate of male gender, acute coronary syndrome, out-of-hospital CA (OHCA), in-hospital CA, shockable rhythm, and the time from collapse to VA-ECMO initiation, known as low flow time (LFT). We evaluated 180-day survival rates, hemodynamic data, and safety profiles. Result After propensity score matching, 57 ECPELLA patients and 57 VA-ECMO patients were included for analysis. No significant differences in the adjusted factors and comorbidities were found between the two groups. In the VA-ECMO group, 42 patients (74%) received concomitant use of IABP. During the first 72 hours following the initiation of VA-ECMO, the ECPELLA group received significantly higher total mechanical circulatory support flow compared to the VA-ECMO group, correspondingly received less catecholamine administration, and had more patients started on vasodilators and cardioprotective medications. There were no statistical differences in safety profiles, except for hemolysis and embolic cerebral infarction, between the two groups. Kaplan-Meier analysis demonstrated that the 180-day survival rates were significantly higher in the ECPELLA group than in the VA-ECMO group. In a multivariate Cox proportional hazard analysis that included age, shockable rhythm, OHCA, initial lactate levels, LFT, and ECPELLA, it was found that age (hazard ratio [HR], 1.28 [for 10-year increase]; 95% confidence interval [CI], 1.09–1.51; p = 0.002), initial lactate level (HR, 1.06; 95% CI, 1.01-1.11; p = 0.04), and ECPELLA (HR, 0.55; 95% CI, 0.36–0.85; p = 0.007) were significantly associated with 180-day mortality. Conclusion ECPELLA was associated with improvement of 180-day mortality in patient who received E-CPR. The results suggest that not only the choice of ECPELLA but also sufficient circulatory support during the acute phase, along with modulating catecholamines and vasodilators, may have influenced the prognosis.

Prognostic influence of the neurological complications in patients supported with venoarterial extracorporeal membrane oxygenation

Abstract Background Neurologic injuries including ischemic or hemorrhagic stroke and hypoxic-ischemic encephalopathy are common in patients supported with venoarterial extracorporeal membrane oxygenation (VA-ECMO). Purpose Our objective was to analyze the prognostic influence of neurological injuries on in-hospital survival. Methods Retrospective analysis of consecutive VA-ECMO cases in a referal center. We studied the neurological diagnoses and the results of complementary tests (brain computed tomography –CT- and electroencephalogram –EEG-) and their influence on in-hospital evolution. Results 238 VA-ECMO were implanted between oct 2013-jan 2024. Baseline, admission and evolution characteristics are collected in the table. 58.4% of patients had suffered cardiac arrest (prior to VA-ECMO implantation, and extracorporeal cardiopulmonary resuscitation was performed in 28.6% of cases. 6 (2.5%) suffered intracranial hemorrhage, 13 (5.5%) ischemic stroke and 40 (16.8%) some degree of hypoxic-ischemic encephalopathy. In-hospital survival was 32.4% (n=77). In 17.2% of the cases neurological damage influenced death (adequacy of therapeutic effort or non-escalation of therapies) and in 14.7% of cases death was directly due to neurological cause (table). Survival was lower in patients with ischemic (stroke survival 23.1% vs no stroke 33.2%, p=0.555) or hemorrhagic stroke (16.7% vs 33%, p=0.667), although without statistically significant differences. The presence of hypoxic brain damage was related to lower hospital survival (survival in patients with encephalopathy 15% vs. without 36.8%, p=0.009). Best EEG pattern registered was related to survival: I survival 33.3% and II 12.5% (good prognosis), III 25% (uncertain prognosis), IV 16.7% and V 0% (poor prognosis), p=0.048. The presence of status epilepticus showed a non-statistically significant trend towards lower survival (survival status 0% vs no estatus 25%, p=0.082). VA-ECMO preimplantation cardiac arrest was associated with the occurrence of encephalopathy (encephalopathy 84% vs. not 40%, p=0.049). The duration of cardiac arrest and lactate before VA-ECMO implantation were significantly higher as the EEG pattern was worse (figure). Conclusions Neurological damage is relevant in patients under VA-ECMO support, being a determining factor in death in up to 17.2% of patients. Hypoxic-ischemic encephalopathy was associated with lower survival, with the EEG pattern associated with previous cardiac arrest, its duration and lactate.Table.Baseline, admission and follow-upFigure.Cardiac arrest, lactate and EEG

Novel risk scoring model to assess the need for venoarterial-extracorporeal membrane oxygenation in patients with acute myocarditis

Abstract Background Some patients with acute myocarditis unpredictably deteriorate into a fulminant form and their prognosis is poor. However, it is uncertain which acute myocarditis patients are likely to exacerbate and even require venoarterial-extracorporeal membrane oxygenation (VA-ECMO). Objectives This study aimed to identify the risk factors associated with the need for VA-ECMO in patients with acute myocarditis and to develop a predictive model. Methods This retrospective study included 841 patients from seven hospitals in Korea with biopsy-proven or clinically suspected acute myocarditis. Logistic regression was performed to identify clinical characteristics of patients who required VA-ECMO and to construct a scoring system that can predict the need for VA-ECMO. Results Among the study population, 217 (25.8%) patients underwent VA-ECMO. The study population was divided into training (N=621) and testing (N=220) cohorts according to participating center. The final predictive model of VA-ECMO insertion derived from the training cohort included the following: initial mean blood pressure <65mmHg, cardiac arrest, Glasgow Coma Scale ≤12, platelet <100×103/mL, pulmonary congestion on chest X-ray, QRS interval ≥120ms, left or right bundle branch block, and left ventricular ejection fraction <40%. Using this predictive model, a β-coefficient-weighted Korean Acute Myocarditis (KAM) score was developed. The VA-ECMO insertion rate increased with increasing KAM score (odds ratio 1.683, 95% confidence interval 1.529-1.853, P<0.001). External validation of the predictive model and KAM score using the testing cohort showed excellent discriminant ability (areas under the curve of 0.945 and 0.921, respectively). Furthermore, at a KAM score of 8 or higher, which was the cut-off KAM score to predict the need for VA-ECMO, patients without VA-ECMO tended to have higher in-hospital mortality than patients who needed VA-ECMO. Conclusions A risk scoring system based on simple clinical and laboratory parameters at initial presentation could predict the need for VA-ECMO and clinical course in patients with acute myocarditis.Graphic Abstract

Impact of inhaled nitric oxide therapy in patients with cardiogenic shock treated with veno-arterial extracorporeal membrane oxygenation combined with Impella

Abstract Background Mortality rates remain high in patients with cardiogenic shock (CS) requiring veno-arterial extracorporeal membrane oxygenation (VA-ECMO) combined with Impella (ECPELLA) support. Early weaning from VA-ECMO may be the first step in reducing mortality in these patients. Inhaled nitric oxide (iNO) therapy improves right ventricular function by decreasing pulmonary arterial resistance, resulting in increased Impella flow rate, which may facilitate early withdrawal of VA-ECMO and improve survival. Purpose The purpose of this study was to investigate the prognostic impact of iNO therapy on ECPELLA patients. Methods We retrospectively studied consecutive patients with CS due to acute myocardial infarction (AMI-CS) or decompensated heart failure (ADHF-CS) supported with ECPELLA from September 2019 to January 2024 at our hospital. The VA-ECMO withdrawal rate, time to withdrawal, and 30-day survival were compared for ECPELLA patients with and without iNO therapy. Results A total of 47 patients were included (AMI-CS, n=26, and ADHF-CS, n=21). Of these, 21 patients (44.7%) were treated with iNO therapy. Patient characteristics were not significantly different between those with and without iNO therapy, including age, gender, percentage of cardiopulmonary arrest or acute coronary syndrome, and lactate levels at mechanical circulatory support induction. Patients receiving iNO therapy had significantly higher VA-ECMO withdrawal rates (90% vs. 50%, P=0.003) and shorter time to VA-ECMO withdrawal (5.0±1.3 vs. 7.8±5.6 days, P=0.04) than those not receiving iNO therapy. Furthermore, Kaplan-Meier analysis demonstrated that the 30-day survival rate was significantly higher in patients receiving iNO therapy than those without (P=0.003, Figure). Conclusion Adjuvant iNO therapy for CS patients supported by ECPELLA facilitates early withdrawal of VA-ECMO and improve survival representing a useful therapeutic option.Figure

VA-ECMO-related complications seem not causally related to mortality in patients with acute myocardial infarction complicated by cardiogenic shock

Abstract Background Recently published randomized controlled trials and an individual patient data meta-analysis showed that the routine use of veno-arterial extracorporeal membrane oxygenation (VA-ECMO) did not reduce mortality compared to medical therapy alone in patients with acute myocardial infarction complicated by cardiogenic shock (AMI-CS). Purpose The aim of this study was to investigate as to whether possible VA-ECMO-related medical complications might be associated with an increased mortality risk, which might explain the observed equipoise among mortality outcomes between VA-ECMO and usual care in patients with AMI-CS. Methods Using data from the randomized ECLS-SHOCK trial (Extracorporeal Life Support in Infarct-Related Cardiogenic Shock), which compared routine VA-ECMO use versus medical therapy alone. Causal mediation analyses (primary analysis; VA-ECMO-related complications used as a mediator), logistic regression and causes of death analyses (secondary analyses) were utilised to test potential effects of possible VA-ECMO-related complications on 30-day mortality. Analyses were adjusted for risk factors of bleeding and vascular complications. Results In total, 417 patients were included in this analysis. Moderate and severe bleeding as well as peripheral vascular complications requiring intervention were identified as possible VA-ECMO-related complications. A total of 88 patients (21.1%) developed possible VA-ECMO-related complications, which mostly occurred within five days after randomisation and more frequently in the VA-ECMO group than in the control group: 49 (23.4%) vs. 20 (9.6%) patients, p<0.001 for bleeding and 23 (11.0%) vs. 8 (3.8%) patients, p=0.01 for peripheral vascular complications, respectively. Causal mediation analyses revealed no significant mediation effect of possible VA-ECMO-related complications on 30-day mortality (p=n.s.; Figure). Logistic regression and causes of death analyses of possible VA-ECMO-related complications confirmed no significant associations between the incidence of VA-ECMO-related complications and mortality (p=n.s.). Conclusion VA-ECMO use in patients with AMI-CS was associated with increased incidences of moderate to severe bleeding as well as vascular complications warranting intervention. In this causal mediation analysis, VA-ECMO-related complications do not appear to mediate an increased mortality risk.

Research Progress on Acute Kidney Injury in Patients with Cardiogenic Shock Undergoing Venoarterial Extracorporeal Membrane Oxygenation

Cardiogenic shock (CS) is a life-threatening syndrome characterized by peripheral hypoperfusion and organ dysfunction caused by primary heart disease. Venoarterial extracorporeal membrane oxygenation (VA-ECMO) is a temporary mechanical circulatory support device for CS, used in cases of profound shock, biventricular failure, respiratory failure, and cardiac arrest that require urgent maximal support. While VA-ECMO provides effective tissue perfusion and ensures oxygen supply to organs, it is also associated with severe complications, among which acute kidney injury (AKI) is one of the most common and serious. To date, no comprehensive review has been conducted on the pathophysiology, influencing factors, and treatment of AKI associated with VA-ECMO. This paper aims to elaborate on the pathophysiological mechanisms, influencing factors, and treatment options for AKI in patients with CS undergoing VA-ECMO, providing clinical and nursing references.

Association between arterial oxygen tension with clinical outcomes in patients undergoing VA-ECMO support: a systematic review and dose-response meta-analysis

Abstract Background Arterial hyperoxia has been associated with a worse prognosis in critically ill patients. However, studies conducted in patients undergoing Veno-Arterial Extracorporeal Membrane Oxygenation (VA-ECMO) used inconsistent and arbitrary thresholds for defining hyperoxia, which impeded the determination of the optimal target for arterial oxygen tension (PaO2) in this population. Purpose To investigate and visualise the dose-response relationship between post-ECMO level of PaO2 with early mortality (in-hospital and 1-month) and poor neurological outcomes in adult patients undergoing VA-ECMO support, including Extracorporeal Cardiopulmonary Resuscitation (ECPR). Methods A systematic search was conducted through Pubmed and Embase to include studies that stratified patients based on PaO2 levels and evaluated relevant outcomes. We utilised either adjusted Odds Ratio (OR) with 95% Confidence Interval (CI) when available, or unadjusted OR against the lowest exposure category. The median, mean, or midpoint value of PaO2 was assigned as the corresponding dose. A random-effects one-stage dose-response meta-analysis was performed to assess linear association for every 10 mmHg increase in PaO2, while potential non-linear relationship was explored with restricted cubic splines at 3 knots (10th, 50th, and 90th percentile). Non-linearity was assessed by using Wald test with p value <0.05 considered significant. Statistical analyses were performed using STATA 17.0. Results Fourteen eligible records were identified (cardiogenic shock/CS = 5 records; ECPR = 8 records; both = 1 record). Only four studies classified a separate category for hypoxemic patients (<60 mmHg). PaO2 levels were measured within 24-72 hours of VA-ECMO initiation, except in one study. PaO2 level was not associated with early mortality (9 studies; OR 1.021 [95% CI 0.988–1.055]; p for non-linearity = 0.893), but found to have a linear association with composite poor neurological outcomes (6 studies; OR 1.016 [1.009–1.024]; p for non-linearity = 0.346). Subgroup analysis of CS patients revealed a linear association between PaO2 >100 mmHg and early mortality (4 studies; OR 1.025 [95%CI 1.018–1.032]; p for non-linearity = 0.255). For ECPR patients, a J-shaped relationship was observed between PaO2 and early mortality (5 studies; p for non-linearity = 0.004), with the lowest odds being at PaO2 level of 110-210 mmHg, while PaO2 level >110 mmHg showed a linear trend towards higher odds of poor neurological function (4 studies; OR 1.091 [95%CI 0.938–1.269]; p for non-linearity = 0.257). Conclusion Pooled data from observational studies suggest that PaO2 >100 mmHg should be avoided in CS patients on VA-ECMO support, given its linear association with mortality, but it cannot be extrapolated to hypoxemic patients. In ECPR patients, PaO2 level around 110-210 mmHg conferred the best clinical outcomes. However, these findings should be confirmed through randomised controlled trials.

Risk factors of 30-day mortality following cardiac surgery in adults with congenital heart disease: analysis from the Japanese registry

Abstract Background With advancements in pediatric therapies, the adult congenital heart disease (ACHD) population has grown consistently. ACHD patients often face complications necessitating cardiac surgery, and understanding surgical risk factors is essential. Purpose This study aims to assess ACHD surgical risk factors using big data, addressing evidence gaps in previous research limited to univariate analysis due to few perioperative adverse events. Methods We analyzed the Japanese Registry of All Cardiac and Vascular Diseases-Diagnosis Procedure Combination (JROAD-DPC) database from April 2013 to March 2020. The JROAD-DPC database covers nearly all teaching hospitals with cardiovascular beds participation in JROAD. Our study included ACHD patients (>15 years) undergoing open-heart surgery. Our primary outcome was 30-day mortality. We assessed clinical backgrounds, admission status, treatment, and length of hospital stay. Results Out of 13,677 ACHD patients (mean age: 53 years, females 47%) undergoing cardiac surgery assessed for 30-day mortality, 13,516 (98.8%) patients were categorized into the survival group and 161 (1.2%) into the death group. Mortality rates varied by complexity of congenital heart disease (CHD): 0.8% for simple, 1.8% for moderate, and 0.9% for great. The figure shows that a significant increase in 30-day mortality rates with age was demonstrated in simple and moderate complexity (p<0.001 for trend analysis in both categories). In contrast, for cases of great complexity, the increase in 30-day mortality rates with aging was not statistically significant (p=0.443). The death group was significantly older and had higher rates of ambulance admissions, renal disease, and peripheral vascular disease. Intra-aortic balloon pumps (IABP), veno-arterial extracorporeal membrane oxygenation (VA-ECMO), and dialysis during hospitalization were significantly higher among deceased patients. Length of ICU stay was significantly longer in the death group (median [IQR]; 3 [2-4] vs. 6 [3-11], p<0.001). Cox proportional-hazards model showed that age, moderate complexity, emergency admission, hospital bed counts, renal disease, and use of IABP and VA-ECMO were independently associated with 30-day mortality (Table). Conclusions The present study, which utilizes the nationwide administrative DPC database, demonstrates that surgical outcomes for patients with ACHD, as measured by 30-day mortality rates, are generally favorable. These outcomes significantly depend on factors such as age, complexity of CHD, emergency admissions, hospital capacity, renal disease, and use of mechanical circulatory support.

Multi-dimensional assessment of long-term outcomes in patients treated with extracorporeal cardiopulmonary resuscitation during refractory cardiac arrest

Abstract Background Recent randomised controlled trials showed short-term survival benefits with extracorporeal cardiopulmonary resuscitation (ECPR) compared to standard cardiac arrest treatment in selected patients with refractory cardiac arrest. Only limited data exist on multi-dimensional long-term outcomes after ECPR. Purpose To investigate multi-dimensional long-term outcomes of ECPR survivors, that is general health status, as well as cardiac, cognitive and psychological functions. Methods This is a multicenter, mixed-method clinical study conducted by cardiologists, neurologists and psychologists between May 2021 and December 2023. Adult patients who survived ECPR with veno-arterial extracorporeal membrane oxygenation (VA-ECMO) or "ECMELLA" (i.e., VA-ECMO plus percutaneous left-ventricular assist device) in two German tertiary care centers were included. A comprehensive set of functional outcomes across multiple dimensions were assessed at approximately 18 months after the index cardiac arrest event (see Figure for stations A to E and explanation of abbreviations). Results Long-term outcomes were assessed in 32 ECPR survivors, out of whom 15 patients (46%) had received VA-ECMO and 18 (54%) ECMELLA treatment. 23 patients (70%) were male and the average age was 55 years (±13). Vital signs and laboratory markers were unremarkable. Most patients denied heart failure symptoms although the average EQ-5D-5L score was 52 (±8). The left-ventricular ejection fraction was 51% (±9), which improved by 14% (±11) in the ECMO group and 31% (±15) in the ECMELLA group since the index cardiac arrest event. Bicycle exercise (on average 6 minutes duration with a power of up to 100 Watts) and 6-minute walk test (average distance of 394 meters ±145) revealed physical impairments. 29 patients (88%) had a good cerebral performance (i.e., Cerebral Performance Category scale of 1) and the average mental status was good (mini–mental state examination score 29 ±1). 22 patients (56%) perceived (partial) impairments in activities of daily living although the average Barthel index was 100 (±5) and modified Rankin scale was 1 (±1). 12 patients (36%) were unable to return to their jobs. Remarkably, 17 (51%) and 4 (12%) patients reported depressive symptoms and suicidal thoughts, respectively. Conclusion Although ECPR remains a highly complex procedure, cardiac and neurologic functions in survivors have almost recovered, while physical and psychological impairments still persisted at 18 months after cardiac arrest. Physical rehabilitation and psychological care appear to be important measures for ECPR survivors.

Optimizing elective high-risk PCI with ECMO support: the value of completely percutaneous use of VA-ECMO

Abstract Background Veno-arterial extracorporeal membrane oxygenation (VA-ECMO) is a suitable manner to prevent hemodynamic deterioration during high-risk percutaneous coronary intervention (PCI). VA-ECMO is mainly surgically deployed under general anaesthesia. New developments now facilitate completely percutaneous insertion of VA-ECMO with only local anaesthesia, reducing operating team size and hospital costs. Purpose The aim of this study is to provide data on the outcomes of completely percutaneous use of VA-ECMO during high-risk PCI with local anaesthesia. Methods A retrospective single-centre registry was performed including all patients undergoing ECMO-assisted high-risk PCI, who were rejected for coronary artery bypass graft (CABG) as primary treatment option. Primary endpoint was the incidence of major adverse cardiac events (MACE), assessed during hospital admission and after discharge up to 90 days. Results Between January 2020 and February 2024, 34 patients undergoing ECMO-assisted high-risk PCI were included. The mean age of the population is 71.9 (± 8.4) and 27 (79.4%) patients are male. The mean left ventricular ejection fraction is 28.5 (± 11.1) percent and complexity indices were high, including STS mortality score: 4.1 (± 2.8), SYNTAX score I: 31.7 (± 9.4), SYNTAX score II: (PCI) 54.8 (± 10.8). Femoral artery was used for cannulation in 30 (88.2%) patients, of which one patient required an additional femoral backflow cannula due to prolonged ECMO support. Local anaesthesia in combination with preprocedural oral benzodiazepine was the preferred choice of anaesthesia (85.3%). Closure was predominantly performed with a percutaneous closure device (97.1%). Successful revascularization and procedural success were achieved in all patients. In-hospital MACE occurred in 2 (6.1%) patients. MACE occurred within 90 days in 5 (20.8%) patients after discharge. Conclusion High-risk PCI with completely percutaneous use of VA-ECMO with local anaesthesia is a novel concept, providing a suitable alternative to the standard surgical use of VA-ECMO with general anaesthesia.

Clinical significance of residual ischemia in acute myocardial infarction complicated by cardiogenic shock undergoing VA-ECMO

Abstract Background Although culprit-only revascularization during the index procedure has been recommended in patients with acute myocardial infarction (AMI) complicated by cardiogenic shock (CS), the reduction of residual ischemia is also emphasized to improve clinical outcomes. However, few data are available about the significance of residual ischemia in patients undergoing mechanical circulatory supports. Objectives This study aimed to evaluate the effects of residual ischemia on clinical outcomes in AMI patients undergoing venoarterial-extracorporeal membrane oxygenation (VA-ECMO). Methods AMI patients with multivessel disease who underwent VA-ECMO due to refractory CS were pooled from the RESCUE and SMC-ECMO registries. The included patients were classified into three groups according to residual ischemia evaluated using the residual SYNTAX score (rSS): rSS=0, 0<rSS≤8, and rSS>8. The primary outcome was 1-year all-cause death. Results A total of 408 patients were classified into the rSS=0 (N=100, 24.5%), 0<rSS≤8 (N=136, 33.3%), and rSS>8 (N=172, 42.2%) groups. The cumulative incidence of the primary outcome differed significantly according to rSS (33.9% vs. 55.4% vs. 66.1% for rSS=0, 0<rSS≤8, and rSS>8, respectively, overall P<0.001). In a multivariable model, rSS was independently associated with the risk of 1-year all-cause death (HRadj 1.03, 95% CI 1.01–1.05, P=0.003). Conversely, the baseline SYNTAX score was not associated with the risk of the primary outcome. Furthermore, when patients were stratified by rSS, the primary outcome did not differ significantly between the high and low delta SYNTAX score groups. Conclusions In AMI patients with refractory CS who underwent VA-ECMO, residual ischemia was associated with an increased risk of 1-year mortality. Therefore, revascularization strategies to minimize residual ischemia should be considered in advanced CS, particularly in cases requiring VA-ECMO.

LA reservoir strain predicts elevated left atrial pressure in patients with Veno-Arterial (VA) extracorporeal membrane oxygenator (ECMO) support for cardiogenic shock

Abstract Background Veno-arterial (VA) extracorporeal membrane oxygenator (ECMO) is not a left ventricular (LV) support system as it increases aortic pressure and LV afterload due to retrograde blood flow in the aorta. This can lead to complications such as increased LV volume (LV distention), increased LV and left atrial (LA) pressures, and pulmonary edema. We sought to investigate the correlation between LA strain and invasive LA pressure (LAP) in patients with ECMO support for cardiogenic shock undergoing atrial septostomy with stenting. Methods and Results A total of 24 consecutive patients (52±20 years; 83% were male) undergoing atrial septostomy with stenting while being on ECMO support for cardiogenic shock for left heart decompression were analyzed. LAP was measured immediately after transeptal puncture and before deployment of interatrial septal stent. A comprehensive echocardiogram was performed in all patients prior to atrial septostomy. Median time difference between echocardiogram and LAP measurement was 3.5 (0.5-20) hours. LA strain analysis was performed using the TomTec Arena 2D-cardiac performance analysis (CPA) software. LA reservoir strain was measured at peak systole during the reservoir phase in a single apical 4-chamber view. Intraclass correlation coefficients between 2 different investigators were excellent (All> 0.95). Median LA reservoir strain and LAP were 3.2 (0.5-1) % and 23 (8-53) mmHg, respectively. LA reservoir strain significantly correlated with LAP (r=0.53, p=0.034). LA reservoir strain of < 1.5% can effectively predict markedly elevated LAP (LA> 30 mmHg) (OR =9.9, p =0.0016). Conclusions LA reservoir strain significantly correlated with invasive LAP. With the advent of strain imaging software, LA reservoir strain is a feasible, reproducible, noninvasive, and straightforward method to predict the need for left heart decompression and/or to guide optimal afterload management in patients with VA-ECMO for cardiogenic shock. Further a prospective simultaneous echocardiographic and invasive LAP study is needed.

The clinical outcome reflects the heart rhythm profile after defibrillation for shockable rhythm in refractory out-of-hospital cardiac arrest

Abstract Background The prognosis of refractory out-of-hospital cardiac arrest (OHCA) is generally poor. A recent Prague OHCA study has demonstrated that an invasive approach (including extracorporeal cardiopulmonary resuscitation, ECPR) is a feasible treatment strategy in refractory OHCA. Post-hoc analysis of Prague OHCA showed that patients with initial ventricular fibrillation (VF) had manifested better clinical outcomes than those with non-shockable rhythms irrespective of cardiopulmonary resuscitation (CPR) strategy. However, initial shockable rhythm could deteriorate to a non-shockable rhythm during CPR, mainly after defibrillation. The study aimed to stratify the prognosis of patients according to rhythm profile after initial VF in refractory OHCA during pre-hospital and early hospital periods. Methods The analysis enrolled patients with a witnessed OHCA of presumed cardiac cause, with initial VF, and without early recovery of spontaneous circulation. The primary outcome was a composite of survival with Cerebral Performance in Category (CPC) 1 or 2 at 180 days. Results 155 (median age 56y, 10 % females) patients with initial VF were enrolled. The median (IQR) duration of resuscitation was 54 (33-69) minutes. Overall survival with CPC 1 or 2 was 40.4 %. 71 patients were randomized to invasive CPR arm and 84 subjects were treated with conventional CPR. Out of all invasively treated patients, ECPR (veno-arterial extracorporeal membrane oxygenation, VA ECMO) was used in 56 cases without stable recovery of spontaneous circulation and 8 patients primary allocated in conventional group. A proportion of survival with CPC 1 or 2 varied by rhythm course: ongoing VF (9 / 28; 32 %), recovery of organized rhythm (43 / 63; 68 %), documentation of pulseless electrical activity (7 / 30; 23%), and progression to asystole (4 / 34; 12 %); P < 0.05. Tables 1 and 2 show differences in primary endpoint according to rhythm profile between invasive and conventional study arms. Conclusion Deterioration of initial shockable rhythm to asystole bears a poor prognosis in refractory OHCA even when ECPR is readily available. An invasive approach (including VA ECMO) seems to be beneficial in patients with ongoing VF and with regular electrical activity regardless of effective pulsation.

Short-term mechanical circulatory support in adults with congenital heart disease: indications and outcomes

Abstract Background An increasing number of adults with congenital heart disease (ACHD) present with heart failure (HF), which may require short- or long-term mechanical circulatory support (MCS), often around cardiac surgery or other interventions. Even though MCS has entered ACHD practice over the last few years, little is known on its indications and outcomes in this population. Purpose To assess the use and outcomes of short-term MCS in ACHD patients in a specialist centre, and assess the predictive power of the Survival After Veno-Arterial Extracorporeal Membrane Oxygenation (SAVE) score in this population. Methods Data on all ACHD patients who received MCS since 2008 in a single tertiary centre were collected. Immediate, short and longer-term outcomes were also collected, including death, complications, and weaning success. Logistic regression and ROC analysis were performed to identify predictors of in-hospital mortality. Result There were 65 episodes of MCS in 63 patients during the study period: age 36.9+-13.6 years, 61.5% male. Most patients had CHD of moderate or severe complexity (49.2% moderate and 10.8% severe according to ESC guidelines). The most common anatomical diagnoses were left outflow tract obstruction in 35.4%, Marfan syndrome in 20.0% and tetralogy of Fallot or pulmonary atresia in 10.8%. The most common indications for ECMO were perioperative support (not endocarditis) in 55.6%, HF in 14.3%, pneumonia in 12.7% and endocarditis-related surgery in 7.9%. A critical preoperative status was present in 26.8%; median PEACH score (a validated ACHD peri-operative risk score) was 1.0[1.0-3.0] and ACHS score was 0.6[0.6-1.0]. Median SAVE score was -4.0[-9.0–2.0], with 21(43.8%) in SAVE class 4 or 5. VA-ECMO was used in 69.2%, VV-ECMO in 21.5%, BiVAD-ECMO in 4.6% and RVAD support in 4.6% of patients. The median duration of ECMO support was 198.6[133.0-354.2] hours. Complications included ischemic stroke (15.4%), intracerebral bleeding (9.2%), and other thromboembolism (23.8%). Successful weaning was achieved in 56.2%, whereas 4.6% were switched to more definitive MCS. In-hospital mortality was 47.7%, and this was higher in patients receiving VA support (OR 4.92, 95%CI:1.32-23.93, p=0.03). For patients on VA-ECMO or BiVAD support, the presence of Marfan syndrome (OR 4.92, 95%CI:1.32-23.93, p=0.03) and a lower (worse) SAVE score (OR 1.3 per point reduction, 95%CI:1.11-1.59, p=0.004) were associated with in-hospital mortality. An adjusted SAVE score that accounted for the presence of heritable thoracic aortic diseases (HTAD, -3 points) performed well at predicting in-hospital mortality (AUC increasing from 0.73 to 0.8, Figure). Conclusions Short-term MCS is a useful temporary rescue intervention in patients with ACHD, as a bridge to recovery or durable support, with 1 in 2 patients surviving to hospital discharge. The SAVE score adjusted for HTAD can reliably predict outcomes in patients with VA-ECMO and requires external validation.Figure

European practices on antithrombotic management during percutaneous mechanical circulatory support in adults: insights from an international survey

Abstract Background Bleeding and thrombotic complications remain a major concern in cardiogenic shock (CS) patients undergoing percutaneous mechanical circulatory support (pMCS) with veno-arterial extracorporeal membrane oxygenation (V-A ECMO) and/or microaxial flow pumps like the Impella. Antithrombotic practices strongly determine the coagulopathic risk, but standardized protocols are lacking in this context. Purpose This survey outlines European practices on antithrombotic management in adults on pMCS for CS, making an initial effort to standardize practices, inform future trials, and enhance outcomes. Methods This online cross-sectional survey was distributed through digital newsletters and social media platforms by the Association of Acute Cardiovascular Care (ACVC) of the ESC and the European branch of the Extracorporeal Life Support Organization (EuroELSO). The survey was accessible from April 17th to May 23rd, 2023. The target population were European clinicians involved in care for adults on pMCS. Results We included 105 responses from 26 European countries. In 72.4% of the European respondents’ institutions, a standardized local anticoagulation protocol is present, with unfractionated heparin (UFH) being the predominantly used anticoagulant (Impella: 97.0%; V-A ECMO: 96.1%). Similarly, the purge solution during Impella support is most frequently UFH-based (84.1%). A bicarbonate-based purge solution (BBPS) as standard purge is reported by only 1.6%. UFH titration based on the activated partial thromboplastin time (APTT) alone is the most common practice either for Impella (43.1%) and for V-A ECMO (32.9%). A minority of 16.9% and 13.2% indicate relying on activated clotting time (ACT) for UFH-titration during Impella and V-A ECMO support, respectively. UFH-titration protocols are anti-Xa based for 12.3% (Impella) and 10.5% (V-A ECMO) of the respondents. An UFH anticoagulant protocol based on APTT and anti-Xa in parallel is the preferred option for 10.8% (Impella) and 14.5% (V-A ECMO) of the respondents. Anticoagulant targets for APTT, ACT and anti-Xa varied across institutions. The majority (83.8%) does not alter their anticoagulation management in case of combined Impella plus V-A ECMO-approach (ECMELLA). Typical thresholds for transfusion or administration of blood products without acute bleeding as indication vary substantially and are frequently not predefined. Following acute coronary syndrome without percutaneous coronary intervention (PCI), 54.0% and 42.7% administered dual antiplatelet therapy during Impella and V-A ECMO support, increasing to 93.7% and 84.0% after PCI. Conclusions Our survey validated the considerable variation in antithrombotic management in adults in CS on pMCS across European centres. There is a pressing demand for a standardized approach to antithrombotic management in this context to mitigate the impact of coagulopathic complications and, consequently, enhance outcomes.Figure 1.Figure 2.

Classification of 90-day mortality risk among patients with cardiogenic shock requiring advanced mechanical circulatory support

Abstract Background The SCAI shock classification aims to provide a simple and practical stratification of the severity of patients with cardiogenic shock (CS) and to immediately offer them crucial treatments such as mechanical circulatory support (MCS). Additionally, the IABP shock II risk score is designed to predict 30-day mortality in patients with CS following acute coronary syndrome (ACS), and the SAVE score can also predict in-hospital mortality for patients after veno-arterial extracorporeal membrane oxygenation (V-A ECMO) insertion due to refractory CS. However, previous studies on SCAI staging in patients with MCS have been inconsistent, and the association with prognosis remains unclear. Purpose The aim of this study is to investigate the correlation between the SCAI shock stage and prognosis in ACS patients requiring advanced MCS, and to compare it with other prognostic scores. Methods From January 2012 to July 2023, 137 ACS patients with advanced MCS (excluding IABP) were evaluated. Upon ICU admission, patients were categorized into SCAI stages B to E. The IABP shock II score and the SAVE score were also calculated to serve as prognostic tools. The type of MCS was categorized as Impella, VA-ECMO with IABP, and ECPELLA (VA-ECMO with Impella). We compared the 90-day survival rates with the SCAI shock stage and other prognostic tools. Result The distribution for SCAI classifications stage B to E was 13 (10%), 38 (28%), 21 (15%), and 65 (47%), respectively. There were no significant differences among the groups regarding age, gender, comorbidities, the ratio of ST-elevation myocardial infarction, door-to-balloon time, and onset-to-reperfusion time. In SCAI Stage E, a significantly higher proportion of patients (86%) underwent extracorporeal cardiopulmonary resuscitation, exhibiting elevated lactate and peak CK-MB levels, along with higher IABP Shock II and lower SAVE scores, compared to other stages. A Kaplan-Meier analysis of 90-day mortality, based on the SCAI, the IABP Shock II, the SAVE categories, and the type of MCS, demonstrated that outcomes deteriorated as the stage advanced across all classifications. In the univariate Cox regression analysis for 90-day mortality, significant differences in outcomes were observed across the four classifications. However, in the multivariate Cox regression analysis that incorporated all four classifications, only the type of MCS (Impella vs. ECMO with IABP; hazard ratio [HR] 0.36; 95% confidence interval [CI], 0.16 - 0.78, p = 0.012) and the SCAI classification (stage E vs. stage C; HR 3.03; 95% CI, 1.51 - 6.08, p = 0.002) demonstrated a significant association with 90-day mortality. Conclusion The SCAI shock stage upon ICU admission suggests the potential for convenient prediction of mid-term outcomes in ACS patients who received advanced MCS.