Left Ventricular Unloading Research Articles

Early left ventricular unloading during extracorporeal membrane oxygenation in cardiogenic shock: A systematic review and meta-analysis.

Left ventricular (LV) unloading is a crucial intervention to decrease the harmful consequences of extracorporeal membrane oxygenation (ECMO) on hemodynamic status in cardiogenic shock (CS) patients. However, a lingering question preoccupies experts: Should we intervene early or wait until clinical deterioration caused by increasing afterload is detected? A systematic review and meta-analysis synthesizing studies, which were retrieved by systematically searching PubMed, Web of Science, SCOPUS, and Cochrane through December 2023. We used R V. 4.3 to pool dichotomous data using risk ratio (RR) and continuous data using mean difference (MD) with a 95% confidence interval (CI). CRD42024501643. Eight studies with 2.117 patients were included. Early/prophylactic LV unloading was associated with a lower incidence of all-cause mortality [RR: 0.87 with 95% CI (0.79, 0.95), p < 0.01]. However, there was no significant difference between the two groups regarding cardiac mortality [RR: 1.01 with 95% CI (0.68, 1.48), p = 0.98], non-cardiac mortality [RR: 0.86 with 95% CI (0.46, 1.62), p = 0.64], and in-hospital mortality [RR: 0.95 with 95% CI (0.86, 1.05), p = 0.30]. There was no significant difference between the two groups regarding ECMO weaning, myocardial recovery, ECMO duration, and length of hospitalization. Early/prophylactic LV unloading during ECMO for CS patients was associated with a decreased incidence of all-cause mortality and sepsis or infection, with no effect on ECMO weaning, myocardial recovery, ECMO duration, and hospital length of stay.

Right ventricular free wall longitudinal strain as a predictor of myocardial recovery in patients with advanced cardiogenic shock supported with the Impella device

Abstract Background Right ventricular (RV) dysfunction is a known independent factor influencing the outcome of patients in cardiogenic shock (CS). The aim of this monocentric retrospective study was to investigate the impact of left ventricular (LV) unloading on the right heart function and its predictive role regarding weaning following Impella device implantation in patients with profound CS due to LV failure. Methods We performed a retrospective analysis of 41 patients admitted to intensive care unit over a period of 3 years with CS due to LV dysfunction requiring support with Impella. Clinical and echocardiographic data were collected and correlated with weaning success. Finally, a multivariate analysis to identify independent predictors of weaning success was performed. Results After Impella implantation, the following was observed: right ventricular fractional area change (RVFAC) increased from a mean value of 28% to 38% (p=0.01), the tricuspid annular systolic velocity (TASV) increased from 9 cm/s to 10 cm/s (p=0.01), the velocity time integral right ventricular outflow tract (VTI RVOT) increased from 10 to 13 cm3/stroke (p=0.01), the right ventricular free wall longitudinal strain (RVFWLS) increased from -12% to -21% (p&amp;lt; 0.001). However, following LV unloading, a decrease in both RVFAC from 38% to 30% (p 0.01) and in VTI RVOT from 13 to 11 cm3/stroke (p&amp;lt;0.01) was observed. Moreover, there was a significant decrease in RVFWLS from -21% to -14% (p &amp;lt; 0.001). Notably, the percentage of change in RVFWLS between maximum and minimum (Δ%RVFWLSPmax-Pmin) support with Impella during the weaning process was significantly lower in weanable patients (34.5% in weaned vs 86% in non-weaned; p=0.038). Investigating the predicting ability of these parameters, Δ%RVFWLSPmax-Pmin emerged showing an AUC of 0.826 (0.690-0.962) in identifying non-weaned patients with a cut-off value of 38%. According to the multivariate analysis, Δ%RVFWLSPmax-Pmin in non-weaned patients remained the only significant parameter even considering possible confounders. Conclusions LV unloading with Impella in advanced CS patients improved RV function echocardiographic parameters. RVFWLS increased significantly after Impella implantation and its percentage of change between maximum and minimum support was significantly lower in weanable compared to non-weanable patients. Our findings suggest that RVFWLS could be used as a predictor of myocardial recovery allowing to identify weanable patients with adequate accuracy.

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&amp;lt;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&amp;lt;0.00001 and vascular complications 15.0% vs 6.7%; OR, 1.75; 95% CI, 1.41–2.18; P&amp;lt;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

The hemodynamic classification system for hemodynamic-related adverse events in left ventricular assist device patients

Abstract Background Durable left ventricular assist device (LVAD) physiology predisposes to right heart failure (RHF) and aortic insufficiency (AI), recently labelled hemodynamic-related adverse events (HDREs). However, the pathophysiology, incidence, and associated morbidity of HDREs remains largely unsettled due to heterogeneity in data reporting. Purpose We sought to validate the recently proposed LVAD Hemodynamic Classification System (HCS) for HDREs. Methods RHF and AI HDREs were retrospectively adjudicated, staged (mild to severe) and phenotyped (isolated or combined RHF/AI-HDREs) based on the HCS assessed at 6-month post-LVAD implant among 183 consecutive patients undergoing LVAD implant at a quaternary heart failure center, and either alive at 6-month on support (n=175) or deceased due to late HDREs 1 to 6 months post-LVAD implant (n=8). The primary outcome was a composite of first HF hospitalization or cardiovascular death between 6 and 24 months after LVAD-implant. Results At 6-month assessment, RHF-HDRE was adjudicated in all patients, while AI-HDRE could not be adjudicated in 22 (12.0%) patients. Overall, 53 (29.0%) patients developed an RHF-HDRE, and 26 (16.0%) an AI-HDRE (phenotypes: 39 isolated RHF, 15 isolated AI, 11 combined RHF-AI, 3 not-adjudicated). During pre-LVAD assessment, age and pulmonary artery pulsatility index were independently associated with RHF-HDRE; and pre-LVAD AI and systolic pulmonary artery pressure with AI-HDRE. Patients developing the combined RHF-AI phenotype required the most intensive bundle of critical care pre-LVAD implantation, had more frequent pre-LVAD RV dysfunction, the highest rate of early post-LVAD RHF, and the most prominent features of suboptimal left ventricular unloading, RV dysfunction, peripheral congestion, renal damage and impaired functional capacity at 6-month assessment. RHF-HDRE (adj-HR 2.69, 95%CI 1.14-6.34, p=0.024), AI-HDRE (adj-HR 4.21, 95%CI 1.70-10.40, p=0.002) and HDRE phenotype (isolated RHF or AI HDRE vs. no HDRE: adj-HR 2.80, 95%CI 1.03-7.62, p=0.044; combined RHF and AI HDRE vs. no HDRE: adj-HR 4.53, 95%CI 1.33-15.35, p=0.015) were associated with the primary outcome. A graded increase in primary outcome was observed with rising RHF and AI stages. Conclusions The LVAD Hemodynamic Classification System for HDREs identifies pathophysiological and clinical clusters of patients with significant prognostic implications. It may help the development of targeted strategies to mitigate HDREs and improve the success of long-term LVAD support.

Impact of left ventricular unloading on postheart transplantation outcomes in patients bridged with VA-ECMO

Introduction and objectives: The impact of preoperative left ventricular (LV) unloading on postoperative outcomes in patients bridged with venoarterial extracorporeal membrane oxygenation (VA-ECMO) to heart transplantation (HT) is unknown. Our aim was to compare posttransplant outcomes in patients bridged to HT with VA-ECMO, with or without the use of different mechanical strategies for LV decompression.Methods: We conducted a retrospective analysis of the postoperative outcomes of consecutive HT candidates bridged with VA-ECMO, with or without concomitant LV unloading. Patients were included from 16 Spanish centers from 2010 to 2020. The primary endpoint was 1-year post-HT survival, which was assessed using Cox regression.Results: Overall, 245 patients underwent high-emergency HT while supported with VA-ECMO. A mechanical strategy for LV unloading was used in 133 (54.3%) patients, with the intra-aortic balloon pump being the most commonly used method (n = 112; 84.2%). One-year posttransplant survival was 74.4% in the LV unloading group and 59.8% in the control group (P = .025). In multivariate analyses, preoperative LV unloading was independently associated with lower 1-year mortality (adjusted HR, 0.50; 95%CI, 0.32–0.78; P = .003). This association was observed both in patients managed with an intra-aortic balloon pump alone (adjusted HR, 0.52; 95%CI, 0.32–0.84; P = .007) and with other strategies for mechanical LV unloading (adjusted HR, 0.43; 95%CI, 0.19–0.97; P = .042). No significant differences were found between groups regarding other postoperative complications.Conclusions: Preoperative LV unloading was independently associated with increased 1-year posttransplant survival in candidates bridged with VA-ECMO.

A Randomized Embedded Multifactorial Adaptive Platform for Extra Corporeal Membrane Oxygenation (REMAP ECMO) – Design and Rationale of the Left Ventricular Unloading trial domain

BackgroundThe use of Extracorporeal Membrane Oxygenation (ECMO) remains associated with high rates of complications, weaning failure and mortality which can be partly explained by a knowledge gap on how to properly manage patients on ECMO support. To address relevant patient management issues, we designed a “Randomized Embedded Multifactorial Adaptive Platform (REMAP)” in the setting of ECMO (REMAP ECMO) and a first embedded randomized controlled trial (RCT) investigating the effects of routine early left ventricular (LV) unloading through intra-aortic balloon pumping (IABP). MethodsREMAP ECMO describes a registry-based platform allowing for the embedding of multiple response adaptive RCTs (trial domains) which can perpetually address the effect of relevant patient management issues on ECMO weaning success. A first trial domain studies the effects of LV unloading by means of an IABP as an adjunct to veno-arterial (V-A) ECMO versus V-A ECMO alone on ECMO weaning success at 30 days in adult cardiogenic shock patients admitted to the Intensive Care Unit (ICU). The primary outcome of this trial is “successful weaning from ECMO” being defined as a composite of survival without the need for mechanical circulatory support, heart transplantation, or left ventricular assist device (LVAD) at 30 days after initiation of ECMO. Secondary outcomes include the need for interventional escalation of LV unloading strategy, mechanistic endpoints, survival characteristics until one year after ECMO initiation, and quality of life. Trial data will be analysed using a Bayesian statistical framework. The adaptive design allows for a high degree of flexibility, such as response adaptive randomization and early stopping of the trial for efficacy or futility. The REMAP ECMO LV unloading study is approved by the Medical Ethical Committee of the Erasmus Medical Center and is publicly registered. ConclusionThis REMAP ECMO trial platform enables the efficient roll-out of multiple RCTs on relevant patient management issues. A first embedded trial domain will compare routine LV unloading by means of an IABP as an adjunct to V-A ECMO versus V-A ECMO alone. Trial registrationClinicalTrials.gov, NCT05913622

118: Mechanical left ventricular unloading during extracorporeal cardiopulmonary resuscitation: a propensity score-matched analysis of the ELSO registry

118: Mechanical left ventricular unloading during extracorporeal cardiopulmonary resuscitation: a propensity score-matched analysis of the ELSO registry

Management of Myocardial Infarction: Emerging Paradigms for the Future.

Despite significant advancements in managing acute ST-segment elevation myocardial infarctions, the prevalence of heart failure has not decreased. Emerging paradigms with a focus on reducing infarct size show promising evidence in the improvement of the incidence of heart failure after experiencing acute coronary syndromes. Limiting infarct size has been the focus of multiple clinical trials over the past decades and has led to left ventricular (LV) unloading as a potential mechanism. Contemporary use of microaxial flow devices for LV unloading has suggested improvement in mortality in acute myocardial infarction complicated by cardiogenic shock. This review focuses on clinical data demonstrating evidence of infarct size reduction and highlights ongoing clinical trials that provide a new therapeutic approach to the management of acute myocardial infarction.

An analytic method to investigate hemodynamics of the cardiovascular system: Biventricular system.

Previously, we found analytic solutions for single ventricular system based on the lumped parameter model (LPM). In this study, we generalized the method to biventricular system and derived its analytic solutions. LPM is just a set of differential equations, but it is difficult to solve due to time-varying ventricular elastance and high order. Mathematically, there exist no elementary solutions for time-varying equations. It turns out that instead of differential equations, according to volume conservation, a set of algebraic equations can be carried out. The solutions of the set of equations are just physiological states at end of systolic and diastolic phases such as end systolic/diastolic pressure/volume of left ventricle. As a preliminary application, the method is utilized to deduce the hemodynamic effects of VA ECMO. Left ventricular (LV) distension, a serious complication of VA ECMO, is usually attributed to factors such as increased afterload, inadequate LV unloading, reduced myocardial contractility or aortic valve regurgitation (AR), bronchial and Thebesian return in the absence of aortic valve (AoV) opening. Among these, reduced contractility and AR are strongly associated with LV distension. However, in the absence of reduced contractility or AR, it is less clear whether increased afterload or inadequate LV unloading alone can cause LV distension. This leads to the critical question: under what conditions does LV distension occur in the absence of reduced contractility or AR? The analytic formulas derived in this study give conditions for LV distension. Furthermore, the results show that the analytic hemodynamics are coincident with simulated results.

Abstract Tu136: HIF-1α a novel therapeutic target to reduce Cardiac Ischemia Reperfusion Injury during AMI

Acute myocardial infarction (AMI) is a major cause of mortality worldwide. In preclinical models of AMI, using a trans-valvular pump (TVP) to reduce left ventricular (LV) workload for 30 minutes before reperfusion reduces infarct size by 50%. The mechanisms underlying the cardioprotective effect of LV unloading remain poorly understood. Hypoxia inducible factor 1-alpha (HIF-1α) is an oxygen-sensitive transcription factor that activates cardioprotective signaling pathways, improves cell survival and mitochondrial function during myocardial ischemia. We hypothesized that LV unloading limits myocardial injury by activating hypoxia inducible factor 1-a (HIF-1α). To explore the effect of LV unloading on HIF-1α stabilization during ischemia, we performed left anterior descending artery (LAD) occlusion for a total of 120 minutes in adult swine in the presence and absence of LV unloading and further 180 minutes of reperfusion was performed following 120 minutes of LAD occlusion. Trans-valvular unloading activation significantly decreased infarct size both during ischemia (IS/AAR: 4.78±4 % vs 1.5±3%) and post reperfusion when compared ischemia alone and IR alone groups (36.04±8.39 % vs 16.02±3.52 %, p&lt;0.0001) respectively. Interestingly, HIF-1α stabilization is significantly reduced with LV unloading during ischemia and significantly increased post reperfusion in the infarct zone of the swine model of AMI. To test whether HIF1a is necessary for cardioprotection with LV unloading, adult swine were treated with intracoronary delivery of the HIF-1α inhibitor (2-methoxyestradiol; 2ME) before reperfusion. Compared to TVP activation for 30 minutes before reperfusion, addition of 2ME abolished the cardioprotective effect of TVP resulting in increased infarct size (16.03% vs 35.86% p&lt;0.03) and decreased HIF-1a stabilization. Stabilizing HIF-1α post-reperfusion by using a well know HIF-1a stabilizing agent Roxadustat, immediately before reperfusion significantly decreased infarct size in both with and without TVP groups compared to IRI alone. Treatment with Roxadustat also preserved mitochondrial function and increased RISK signaling. We report the novel finding that stabilizing HIF-1a activity before reperfusion plays a critical role in reducing Infarct size in preclinical model of AMI.

Science of left ventricular unloading.

The concept of left ventricular unloading has its foundation in heart physiology. In fact, the left ventricular mechanics and energetics represent the cornerstone of this approach. The novel sophisticated therapies for acute heart failure, particularly mechanical circulatory supports, strongly impact on the mechanical functioning and energy consuption of the heart, ultimately affecting left ventricle loading. Notably, extracorporeal circulatory life support which is implemented for life-threatening conditions, may even overload the left heart, requiring additional unloading strategies. As a consequence, the understanding of ventricular overload, and the associated potential unloading strategies, founds its utility in several aspects of day-by-day clinical practice. Emerging clinical and pre-clinical research on left ventricular unloading and its benefits in heart failure and recovery has been conducted, providing meaningful insights for therapeutical interventions. Here, we review the current knowledge on left ventricular unloading, from physiology and molecular biology to its application in heart failure and recovery.

Hemodynamics with mechanical circulatory support devices using a cardiogenic shock model

Mechanical circulatory support (MCS) devices, including veno-arterial extracorporeal membrane oxygenation (VA-ECMO) and Impella, have been widely used for patients with cardiogenic shock (CS). However, hemodynamics with each device and combination therapy is not thoroughly understood. We aimed to elucidate the hemodynamics with MCS using a pulsatile flow model. Hemodynamics with Impella CP, VA-ECMO, and a combination of Impella CP and VA-ECMO were assessed based on the pressure and flow under support with each device and the pressure–volume loop of the ventricle model. The Impella CP device with CS status resulted in an increase in aortic pressure and a decrease in end-diastolic volume and end-diastolic pressure (EDP). VA-ECMO support resulted in increased afterload, leading to a significant increase in aortic pressure with an increase in end-systolic volume and EDP and decreasing venous reservoir pressure. The combination of Impella CP and VA-ECMO led to left ventricular unloading, regardless of increase in afterload. Hemodynamic support with Impella and VA-ECMO should be a promising combination for patients with severe CS.

Left ventricular unloading via percutaneous assist device during extracorporeal membrane oxygenation in acute myocardial infarction and cardiac arrest.

A feared complication of an acute myocardial infarction (AMI) is cardiac arrest (CA). Even if return of spontaneous circulation is achieved, cardiogenic shock (CS) is common. Venoarterial extracorporeal membrane oxygenation (VA-ECMO) supports patients with CS and is often used in conjunction with an Impella device (2.5 and CP) to off-load the left ventricle, although limited evidence supports this approach. The goal of this study was to determine whether a mortality difference was observed in VA-ECMO alone versus VA-ECMO with Impella (ECPELLA) in patients with CS from AMI and CA. A retrospective chart review of 50 patients with AMI-CS and CA and were supported with VA-ECMO (n = 34) or ECPELLA (n = 16) was performed. The primary outcome was all-cause mortality at 6-months from VA-ECMO or Impella implantation. Secondary outcomes included in-hospital mortality and complication rates between both cohorts and intensive care unit data. Baseline characteristics were similar, except patients with ST-elevation myocardial infarction were more likely to be in the VA-ECMO group (p = 0.044). The ECPELLA cohort had significantly worse survival after VA-ECMO (SAVE) score (p = 0.032). Six-month all-cause mortality was not significantly different between the cohorts, even when adjusting for SAVE score. Secondary outcomes were notable for an increased rate of minor complications without an increased rate of major complications in the ECPELLA group. Randomized trials are needed to determine if a mortality difference exists between VA-ECMO and ECPELLA platforms in patients with AMI complicated by CA and CS.

Automated control of Impella maintains optimal left ventricular unloading during periods of unstable hemodynamics and prevents myocardial damage in acute myocardial infarction

BackgroundLeft ventricular (LV) unloading by Impella, an intravascular microaxial pump, has been shown to exert dramatic cardioprotective effects in acute clinical settings of cardiovascular diseases. Total Impella support (no native LV ejection) is far more efficient in reducing LV energetic demand than partial Impella support, but the manual control of pump speed to maintain stable LV unloading is difficult and impractical. We aimed to develop an Automatic IMpella Optimal Unloading System (AIMOUS), which controls Impella pump speed to maintain LV unloading degree using closed-feedback control. We validated the AIMOUS performance in an animal model. MethodsIn dogs, we identified the transfer function from pump speed to LV systolic pressure (LVSP) under total support conditions (n = 5). Using the transfer function, we designed the feedback controller of AIMOUS to keep LVSP at 40 mmHg and examined its performance by volume perturbations (n = 9). Lastly, AIMOUS was applied in the acute phase of ischemia-reperfusion in dogs. Four weeks after ischemia-reperfusion, we assessed LV function and infarct size (n = 10). ResultsAIMOUS maintained constant LVSP, thereby ensuring a stable LV unloading condition regardless of volume withdrawal or infusion (±8 ml/kg from baseline). AIMOUS in the acute phase of ischemia-reperfusion markedly improved LV function and reduced infarct size (No Impella support: 13.9 ± 1.3 vs. AIMOUS: 5.7 ± 1.9%, P < 0.05). ConclusionsAIMOUS is capable of maintaining optimal LV unloading during periods of unstable hemodynamics. Automated control of Impella pump speed in the acute phase of ischemia-reperfusion significantly reduced infarct size and prevented subsequent worsening of LV function.

Unloading in cardiogenic shock: the rationale and current evidence.

Discussing the rationale and current evidence for left ventricular unloading in cardiogenic shock. Microaxial flow pumps (MFP) and intra-aortic balloon pumps (IABP) augment cardiac output while simultaneously unloading the left ventricle (e.g. reducing left ventricular pressure), thereby targeting a key mechanism of cardiogenic shock. A recent randomized trial has shown a mortality reduction with MFP in selected patients with cardiogenic shock, strengthening the rationale for this strategy, although the evidence for the IABP is so far neutral. MFP/IABP can also be used concomitantly with veno-arterial extracorporeal membrane oxygenation (va-ECMO) to alleviate the va-ECMO-related increase in left ventricular afterload, to facilitate weaning and ultimately to improve myocardial recovery and prognosis of affected patients. However, the use of MFP/IABP in this indication solely relies on retrospective data, which need to be interpreted with caution, especially as these strategies are associated with more complications. Currently ongoing randomized trials will help to further clarify the role of left ventricular unloading in patients on va-ECMO. Left ventricular unloading addresses a key mechanism of cardiogenic shock, with strong evidence to support MFP use in selected patients, but further randomized controlled trials are required to clarify the role of different devices/strategies for the overall shock population.

Impact of Left Ventricular Unloading on Outcome of Heart Transplant Bridging With Extracorporeal Membrane Oxygenation Support in New Allocation Policy.

The new heart allocation policy places veno-arterial extracorporeal membrane oxygenation (VA-ECMO)-supported heart transplant (HT) candidates at the highest priority status. Despite increasing evidence supporting left ventricular (LV) unloading during VA-ECMO, the effect of LV unloading on transplant outcomes following bridging to HT with VA-ECMO remains unknown. From October 18, 2018 to March 21, 2023, 624 patients on VA-ECMO at the time of HT were identified in the United Network for Organ Sharing database and were divided into 2 groups: VA-ECMO alone (N=384) versus VA-ECMO with LV unloading (N=240). Subanalysis was performed in the LV unloading group: Impella (N=106) versus intra-aortic balloon pump (N=134). Recipient age was younger in the VA-ECMO alone group (48 versus 53 years, P=0.018), as was donor age (VA-ECMO alone, 29 years versus LV unloading, 32 years, P=0.041). One-year survival was comparable between groups (VA-ECMO alone, 88.0±1.8% versus LV unloading, 90.4±2.1%; P=0.92). Multivariable Cox hazard model showed LV unloading was not associated with posttransplant mortality after HT (hazard ratio, 0.92; P=0.70). Different LV unloading methods had similar 1-year survival (intra-aortic balloon pump, 89.2±3.0% versus Impella, 92.4±2.8%; P=0.65). Posttransplant survival was comparable between different Impella versions (Impella 2.5, versus Impella CP, versus Impella 5.0, versus Impella 5.5). Under the current allocation policy, LV unloading did not impact waitlist outcome and posttransplant survival in patients bridged to HT with VA-ECMO, nor did mode of LV unloading. This highlights the importance of a tailored approach in HT candidates on VA-ECMO, where routine LV unloading may not be universally necessary.

Left ventricular unloading during venoarterial extracorporeal membrane oxygenation implantation: benefits or complications?

Abstract Funding Acknowledgements None. Introduction Peripheral venoarterial extracorporeal membrane oxygenation (VA ECMO) is a therapeutic option for refractory cardiogenic shock (CS). However, the retrograde flow increases afterload, leading to pulmonary edema, blood stasis in the left ventricle (LV) and formation of thrombi. Several strategies try to reduce LV pressure, including the percutaneous transvalvular microaxial pump (p-MCS) and intra-aortic balloon pump (IABP). However, these interventions are associated to complications, such as limb ischemia, embolism, bleeding and hemolysis. Purpose This study aims to investigate whether simultaneous LV unloading at ECMO implant yields clinical benefits or complications compared to ECMO implantat alone. Methods Consecutive patients (pts) with CS requiring peripheral VA ECMO from January 2020 to August 2023 were prospectively included, comparing the group that received LV unloading through IABP or p-MCS to the group that received ECMO only. Standard statistical methods were used. Results A total of 38 pts required VA ECMO. 18 of them received LV unloading since cannulation (8 with IABP and 10 with p-MCS). In the group without initial LV-unloading (20), 3 pts required IABP and 1 p-MCS during support and 1 was changed to VAV ECMO. Change to axillar configuration was perfomed in 1 pts in the unloaded group and in 2 in the only-ECMO group. A higher prevalence of SCAI E (72.2%) was observed in the unloaded-ECMO, compared to the only-ECMO, where SCAI D was more prevalent (60%) (p=0.024). In the LV unloaded group, acute myocardial infarction (AMI) was the leading cause of CS, while myocarditis was the predominant one in the other group (p=0.01). The simultaneous support had a higher rate of intubation (94.4% vs 50% p=0.004) and more acute pulmonary edema (44.4% vs 10% p=0.027). In the ECMO-only 2 pts required intubation during support and LV stasis was observed in 1, whereas no cases were reported in the LV-unloaded group (p=0.036). The mean PaO2/FiO2 during support were higher in the not unloaded group (284.54 vs 200.50 mmHg p=0.036), necessitating lower FiO2 levels (40.89 vs 61.47% p=0.003). In terms of complications, we included the 4 patients from the ECMO-only group who eventually required LV unloading in the unloaded-ECMO. There were no significant differences in the duration of support, in-hospital mortality, stroke, embolism, systemic and local bleeding, or hemolysis. Conclusions Pts with ECMO and LV unloading since cannulation debuted with more severe CS, more AMI as the underlying cause, higher rates of acute pulmonary edema, and intubation. Despite these challenges, they did not experience worse outcomes in terms of in-hospital mortality or ischemic and hemorrhagic events. Notably, 4 patients initially managed with ECMO eventually required subsequent LV unloading. Consequently, the simultaneous implantation of ECMO and a LV unloading device appears to be a reasonable alternative for select patients with a higher risk profile.

Intravenous angiotensin II as an add-on to standard of care vasopressors in patients with refractory shock on mechanical circulatory support: a single centre retrospective case series

Abstract Funding Acknowledgements None. Background Refractory shock is life-threatening condition characterized by hypotension with mean arterial pressure (MAP) less than 65 mmHg and end-organ dysfunction, despite volume resuscitation and high doses of vasopressors. Mortality rates in refractory shock exceeds 90%. Angiotensin II (Ang II) is a non-catecholamine vasopressor that targets the renin-angiotensin-aldosterone system by agonism of the angiotensin type 1 receptors. Ang II has been studied in settings of vasodilatory shock, however there is paucity of data regarding the usage of Ang II in patients with preexisting heart failure or in patients requiring mechanical circulatory support (MCS), either short term such as venoarterial extracorporeal membrane oxygenation (VA-ECMO) or long term such as left ventricular assist device (LVAD) (1,2). Purpose This report is aimed to analyse baseline characteristics of patients who have received Ang II from the moment it became available in our institution (January 2023). Methods Five patients were included in this retrospective analyses. Demographic, clinical and laboratory parameters as well as hourly changes of vasopressors doses, MAP, lactates, and diuresis were collected and analysed. Results Median age of 5 included patients, 4 of whom were male, was 53 years old (range 18-57). The most common comorbidities were chronic kidney disease (n=3), diabetes mellitus (n=3) and arterial hypertension (n=3), treated with valsartan as chronic therapy. All patients presented with severe shock. 4 patients were on VA-ECMO support, 1 had additionally implanted Impella for left ventricular unloading and 2 had implanted LVAD. All patients had severely reduced left ventricular ejection fraction (median 15%, range 10-25%). In 4 cases vasopressors were initiated due to sepsis and in 1 case during cardiopulmonary resuscitation. Median values prior to administration of Ang II were as following: MAP 51 mmHg (range 41-56 mmHg), lactates 6.7 mmol/L (range 2.4-10.7 mmol/L) and Sequential Organ Failure Assessment (SOFA) score 9 (range 5-11). Four hours following administration of Ang II median MAP was 61 mmHg (range 54-77 mmHg). Patient who ultimately survived had better response to Ang II, with median rise of MAP of 22 mmHg (range 12-22 mmHg). In contrast, patients who ultimately died didn’t respond to Ang II, with rise of MAP of only 2.5 mmHg. Median duration of Ang II administration was 52 h (range 20-96 h). 60% of patients are alive up to the present day. Complete patient data are shown in Table 1. Hourly changes of vasopressor doses and MAP are shown in Figure 1. Conclusion Ang II is an effective vasopressor with rapid effect. This case series suggests that it may be considered as salvage treatment option in patients on MCS with refractory shock. Patients who responded to Ang II had better survival, similar to previous findings. Therefore, Ang II should be considered in earlier phases of shock when maximum doses of vasopressors have not yet been reached.

Venoarterial ECMO in cardiogenic shock: a decade-long single-center analysis

Abstract Funding Acknowledgements None. Introduction Venoarterial Extracorporeal Membrane Oxygenation (VA-ECMO) has emerged as a salvage intervention in refractory cardiogenic shock, offering both circulatory and respiratory support as a bridge to recovery, a bridge to transplant, or a bridge to decision. Purpose This study aimed to assess the demographics, clinical characteristics, and outcomes of VA-ECMO patients with cardiogenic shock in a tertiary center. Methods We conducted a retrospective observational study, encompassing patients admitted with cardiogenic shock and treated with VA-ECMO up to October 2023, marking the milestone of the 100th VA-ECMO patient in our unit. Key patient data, including demographics, clinical presentation, ECMO-related complications, and outcomes, were extracted from medical records. Summary statistics were employed for data analysis. Results From 2012 to October 2023, our hospital treated 100 patients in VA-ECMO. The mean age was 58.4 ± 11.9 years, with a male predominance (60%). Approximately 50% of patients were admitted from the emergency room after sudden cardiac arrest. Acute coronary syndrome (ACS) accounted for 39% of cardiogenic shock cases, followed by complicated post-valvular replacement surgery (13%), myocarditis (10%), and acute decompensated heart failure (9%). The median hospital stay was 12.5 days (range: 0 to 114), with a median of 4.0 days on ECMO (range: 0 to 52). All VA-ECMO reported in this cohort were percutaneous, with 39% requiring left ventricular unloading. In 11% cases VA-ECMO served as a bridge to transplant. When it comes to VA-ECMO-related complications, hematological complications, including anemia and thrombocytopenia necessitating transfusion, were observed in 53% of patients, and thromboembolic complications, such as acute limb ischemia, affected 28% of patients. Bleeding complications were notable, with 12% experiencing significant access bleeding, 16% gastrointestinal bleeding, 9% airway bleeding, and 2% intracerebral hemorrhage. Additionally, 39% necessitated renal replacement therapy due to acute kidney failure. The 5-day survival rate stood at 69% (95% CI, 0.61-0.79), declining to 36% at 30 days (95% CI, 0.27-0.48) (see Figure 1). Of the 100 patients, 41 died while on VA-ECMO, with 36 either discharged or undergoing transplantation. Conclusions Our single-center experience illustrates VA-ECMO's predominant use in younger patients following ACS or cardiothoracic surgery. Despite associated complications, particularly thromboembolic events and severe bleeding, our observed mortality rate is slightly lower than reported for refractory cardiogenic shock. New research has emerged from global VA-ECMO registries, as well as clinical trials, however real-world data is lacking. This analysis provides a foundational understanding of cohort characteristics and sets the stage for future comparative studies.Table 1.Patient CharacteristicsFigure 1.Surviving Curve

Real-time regurgitation estimation in percutaneous left ventricular assist device fully supported condition using an unscented Kalman filter

Objective. Significant aortic regurgitation is a common complication following left ventricular assist device (LVAD) intervention, and existing studies have not attempted to monitor regurgitation signals and undertake preventive measures during full support. Regurgitation is an adverse event that can lead to inadequate left ventricular unloading, insufficient peripheral perfusion, and repeated episodes of heart failure. Moreover, regurgitation occurring during full support due to pump position offset cannot be directly controlled through control algorithms. Therefore, accurate estimation of regurgitation during percutaneous left ventricular assist device (PLVAD) full support is critical for clinical management and patient safety. Approach. An estimation system based on the regurgitation model is built in this paper, and the unscented Kalman filter estimator (UKF) is introduced as an estimation approach. Three offset degrees and three heart failure states are considered in the investigation. Using the mock circulatory loop experimental platform, compare the regurgitation estimated by the UKF algorithm with the actual measured regurgitation; the errors are analyzed using standard confidence intervals of ±2 SDs, and the effectiveness of the mentioned algorithms is thus assessed. The generalization ability of the proposed algorithm is verified by setting different heart failure conditions and different rotational speeds. The root mean square error and correlation coefficient between the estimated and actual values are quantified and the statistical significance of accuracy differences in estimation is illustrated using one-way analysis of variance (One-Way ANOVA), which in turn assessed the accuracy and stability of the UKF algorithm. Main results. The research findings demonstrate that the regurgitation estimation system based on the regurgitation model and UKF can relatively accurately estimate the regurgitation status of patients during PLVAD full support, but the effect of myocardial contractility on the estimation accuracy still needs to be taken into account. Significance. The proposed estimation method in this study provides essential reference information for clinical practitioners, enabling them to promptly manage potential complications arising from regurgitation. By sensitively detecting LVAD adverse events, valuable insights into the performance and reliability of the LVAD device can be obtained, offering crucial feedback and data support for device improvement and optimization.