Clinical Outcomes Among Cardiogenic Shock Patients Supported with High-Capacity Impella Axial Flow Pumps: A Report from the Cardiogenic Shock Working Group.

BACKGROUND: The Impella 5.0 and 5.5 pumps (Abiomed, Danvers, MA) are large-bore transvalvular micro-axial assist devices used in cardiogenic shock (CS) for patients requiring high-capacity flow. Despite their increasing use, real-world data regarding indications, rates of utilization and clinical outcomes with this therapy are limited. OBJECTIVES: To examine clinical profiles and outcomes of patients in a contemporary, real-world CS registry of patients who received an Impella 5.0/5.5 alone or in combination with other temporary mechanical circulatory support (tMCS) devices. METHODS: The CS Working Group (CSWG) Registry includes patients from 34 US hospitals. For this analysis, data from patients who received an Impella 5.0/5.5 between 2020-2023 were analyzed. Use of Impella 5.0/5.5 with or without additional tMCS therapies, duration of support, adverse events and outcomes at hospital discharge were studied. Adverse events including stroke, limb ischemia, bleeding and hemolysis were not standardized by the registry but reported per individual CSWG Primary Investigator discretion. For those who survived, rates of native heart recovery (NHR) or heart replacement therapy (HRT) including heart transplant (HT), or durable ventricular assist device (VAD) were recorded. We also assessed outcomes based on based on shock etiology (acute myocardial infarction or MI-CS vs. heart failure-related CS or HF-CS). RESULTS: Among 6,205 patients, 754 received an Impella 5.0/5.5 (12.1%), including 210 MI-CS (27.8%) and 484 HF-CS (64.1%) patients. Impella 5.0/5.5 was used as the sole tMCS device in 32% of patients, while 68% of pts received a combination of tMCS devices. Impella cannulation sites were available for 524/754 (69.4%) of patients, with 93.5% axillary configuration. Survival to hospital discharge for those supported with an Impella 5.0/5.5 was 67%, with 20.4% NHR and 45.5% HRT. Compared to HF-CS, patients with MI-CS supported on Impella 5.0/5.5 had higher in-hospital mortality (45.2% vs 26.2%, p<0.001) and were less likely to receive HRT (22.4% vs 56.6%, p<0.001. For patients receiving a combination of tMCS during hospitalization, this was associated with higher rates of limb ischemia (9% vs. 3%, p<0.01), bleeding (52% vs. 33%, p<0.01), and mortality (38% vs 25%; p<0.001) compared to Impella 5.0/5.5 alone. Among Impella 5.5 recipients, the median duration of pump support was 12.9 days (IQR: 6.8-22.9) and longer in patients bridged to HRT (14 days; IQR: 7.7-28.4). CONCLUSIONS: In this multi-center cohort of patients with CS, use of Impella 5.0/5.5 was associated with an overall survival of 67.1% and high rates of HRT. Lower adverse event rates were observed when Impella 5.0/5.5 was the sole support device used. Further study is required to determine whether a strategy of early Impella 5.0/5.5 use for CS improves survival. CONDENSED ABSTRACT: High capacity Impella heart pumps provide up to 5.5 L/min of flow, while axillary surgical cannulation allows for ambulation. Patients with advanced cardiogenic shock from acute myocardial infarction or heart failure requiring temporary mechanical circulatory support may benefit from upfront use of Impella 5.5 to improve overall survival, including native heart recovery or successful bridge to durable left ventricular assist device surgery or heart transplantation, and to reduce adverse event rates.

Atrial fibrillation increases thrombogenicity of LVAD therapy.

BACKGROUND: This study investigates the hypothesis that presence of atrial fibrillation (AF) in LVAD patients increases thrombogenicity in the left ventricle (LV) and exacerbates stroke risk. METHODS: Using an anatomical LV model implanted with an LVAD inflow cannula, we analyze thrombogenic risk and blood flow patterns in either AF or sinus rhythm (SR) using unsteady computational fluid dynamics (CFD). To analyze platelet activation and thrombogenesis in the LV, hundreds of thousands of platelets are individually tracked to quantify platelet residence time (RT) and shear stress accumulation history (SH). RESULTS: The irregular and chaotic mitral inflow associated with AF results in markedly different intraventricular flow patterns, with profoundly negative impact on blood flow-induced stimuli experienced by platelets as they traverse the LV. Twice as many platelets accumulated very high SH in the LVAD + AF case, resulting in a 36% increase in thrombogenic potential score, relative to the LVAD + SR case. CONCLUSIONS: This supports the hypothesis that AF results in unfavorable blood flow patterns in the LV adding to an increased stroke risk for LVAD + AF patients. Quantification of thrombogenic risk associated with AF for LVAD patients may help guide clinical decision-making on interventions to mitigate the increased risk of thromboembolic events.

Discordance between aPTT and anti-Xa in monitoring heparin anticoagulation in mechanical circulatory support.

AIMS: It is unclear whether activated partial thromboplastin time (aPTT) or anti-Xa is more accurate for monitoring heparin anticoagulation in mechanical circulatory support (MCS) patients. This study investigates the relationship between aPTT and anti-Xa in MCS patients and identifies predictors of discordance. METHODS AND RESULTS: aPTT and anti-Xa were simultaneously measured in a prospective cohort of MCS patients receiving unfractionated heparin at a tertiary academic medical centre. Therapeutic aPTT and anti-Xa levels were 60-100 s and 0.3-0.7 IU/mL, respectively, and concordance was defined as both levels being subtherapeutic, therapeutic, or supratherapeutic. To identify predictors of discordance, both a machine learning random forest model and a multivariate regression model were applied to patient demographics, device type, and 14 laboratory variables; 23 001 pairs of simultaneously measured aPTT/anti-Xa were collected from 699 MCS patients. aPTT and anti-Xa were concordant in 35.5% of paired observations and discordant in 64.5% (aPTT > antiXa 61.5%; aPTT < antiXa 3.0%). Discordance with a high aPTT relative to anti-Xa (aPTT > antiXa) was associated with high INR, eGFR, and total bilirubin, as well as low platelets, haemoglobin, pre-albumin, white blood cell count, and haptoglobin. Total artificial heart and durable ventricular assist devices were more likely to be associated with aPTT > anti-Xa than temporary MCS devices. CONCLUSIONS: aPTT and anti-Xa were frequently discordant in MCS patients receiving heparin anticoagulation. Clinical conditions common in MCS patients such as concurrent warfarin use, malnutrition, haemolysis, and thrombocytopenia, as well as durable type of MCS devices were associated with a high aPTT relative to anti-Xa.

A Computational Investigation of the Effects of Temporal Synchronization of Left Ventricular Assist Device Speed Modulation with the Cardiac Cycle on Intraventricular Hemodynamics.

Patients with advanced heart failure are implanted with a left ventricular assist device (LVAD) as a bridge-to-transplantation or destination therapy. Despite advances in pump design, the risk of stroke remains high. LVAD implantation significantly alters intraventricular hemodynamics, where regions of stagnation or elevated shear stresses promote thrombus formation. Third generation pumps incorporate a pulsatility mode that modulates rotational speed of the pump to enhance in-pump washout. We investigated how the timing of the pulsatility mode with the cardiac cycle affects intraventricular hemodynamic factors linked to thrombus formation. Computational fluid dynamics simulations with Lagrangian particle tracking to model platelet behavior in a patient-specific left ventricle captured altered intraventricular hemodynamics due to LVAD implantation. HeartMate 3 incorporates a pulsatility mode that modulates the speed of the pump every two seconds. Four different timings of this pulsatility mode with respect to the cardiac cycle were investigated. A strong jet formed between the mitral valve and inflow cannula. Blood stagnated in the left ventricular outflow tract beneath a closed aortic valve, in the near-wall regions off-axis of the jet, and in a large counterrotating vortex near the anterior wall. Computational results showed good agreement with particle image velocimetry results. Synchronization of the pulsatility mode with peak systole decreased stasis, reflected in the intraventricular washout of virtual contrast and Lagrangian particles over time. Temporal synchronization of HeartMate 3 pulsatility with the cardiac cycle reduces intraventricular stasis and could be beneficial for decreasing thrombogenicity.

Outcomes of Patients Transferred to Tertiary Care Centers for Treatment of Cardiogenic Shock: A Cardiogenic Shock Working Group Analysis.

BACKGROUND: Consensus recommendations for cardiogenic shock (CS) advise transfer of patients in need of advanced options beyond the capability of "spoke" centers to tertiary/"hub" centers with higher capabilities. However, outcomes associated with such transfers are largely unknown beyond those reported in individual health networks. OBJECTIVES: To analyze a contemporary, multicenter CS cohort with the aim of comparing characteristics and outcomes of patients between transfer (between spoke and hub centers) and nontransfer cohorts (those primarily admitted to a hub center) for both acute myocardial infarction (AMI-CS) and heart failure-related HF-CS. We also aim to identify clinical characteristics of the transfer cohort that are associated with in-hospital mortality. METHODS: The Cardiogenic Shock Working Group (CSWG) registry is a national, multicenter, prospective registry including high-volume (mostly hub) CS centers. Fifteen U.S. sites contributed data for this analysis from 2016-2020. RESULTS: Of 1890 consecutive CS patients enrolled into the CSWG registry, 1028 (54.4%) patients were transferred. Of these patients, 528 (58.1%) had heart failure-related CS (HF-CS), and 381 (41.9%) had CS related to acute myocardial infarction (AMI-CS). Upon arrival to the CSWG site, transfer patients were more likely to be in SCAI stages C and D, when compared to nontransfer patients. Transfer patients had higher mortality rates (37% vs 29%, < 0.001) than nontransfer patients; the differences were driven primarily by the HF-CS cohort. Logistic regression identified increasing age, mechanical ventilation, renal replacement therapy, and higher number of vasoactive drugs prior to or within 24 hours after CSWG site transfer as independent predictors of mortality among HF-CS patients. Conversely, pulmonary artery catheter use prior to transfer or within 24 hours of arrival was associated with decreased mortality rates. Among transfer AMI-CS patients, BMI > 28 kg/m2, worsening renal failure, lactate > 3 mg/dL, and increasing numbers of vasoactive drugs were associated with increased mortality rates. CONCLUSION: More than half of patients with CS managed at high-volume CS centers were transferred from another hospital. Although transfer patients had higher mortality rates than those who were admitted primarily to hub centers, the outcomes and their predictors varied significantly when classified by HF-CS vs AMI-CS.

Impact of Female Sex on Cardiogenic Shock Outcomes: A Cardiogenic Shock Working Group Report.

BACKGROUND: Studies reporting cardiogenic shock (CS) outcomes in women are scarce. OBJECTIVES: The authors compared survival at discharge among women vs men with CS complicating acute myocardial infarction (AMI-CS) and heart failure (HF-CS). METHODS: The authors analyzed 5,083 CS patients in the Cardiogenic Shock Working Group. Propensity score matching (PSM) was performed with the use of baseline characteristics. Logistic regression was performed for log odds of survival. RESULTS: Among 5,083 patients, 1,522 were women (30%), whose mean age was 61.8 ± 15.8 years. There were 30% women and 29.1% men with AMI-CS (P = 0.03). More women presented with de novo HF-CS compared with men (26.2% vs 19.3%; P < 0.001). Before PSM, differences in baseline characteristics and sex-specific outcomes were seen in the HF-CS cohort, with worse survival at discharge (69.9% vs 74.4%; P = 0.009) and a higher rate of maximum Society for Cardiac Angiography and Interventions stage E (26% vs 21%; P = 0.04) in women than in men. Women were less likely to receive pulmonary artery catheterization (52.9% vs 54.6%; P < 0.001), heart transplantation (6.5% vs 10.3%; P < 0.001), or left ventricular assist device implantation (7.8% vs 10%; P = 0.01). Regardless of CS etiology, women had more vascular complications (8.8% vs 5.7%; P < 0.001), bleeding (7.1% vs 5.2%; P = 0.01), and limb ischemia (6.8% vs 4.5%; P = 0.001). More vascular complications persisted in women after PSM (10.4% women vs 7.4% men; P = 0.06). CONCLUSIONS: Women with HF-CS had worse outcomes and more vascular complications than men with HF-CS. More studies are needed to identify barriers to advanced therapies, decrease complications, and improve outcomes of women with CS.

Intermacs quarterly report analysis to monitor longitudinal outcomes in a centrifugal flow assist device.

In June 2021, HVAD System distribution ceased due to observational data demonstrating increased mortality and neurological events compared to another commercial device, and a device malfunction with delay or failure to restart, especially in certain subpopulations. To assess ongoing risk for patients on support following subsequent device recalls, the manufacturer's Intermacs HVAD System 2022 Quarterly Reports were queried to identify mortality and adverse events trends in a contemporary cohort of 3110 primary HVAD implantations since October 2017, stratified by year-of-implant. Mean duration of support was 21 ± 16 months, with 33% alive on original device, 25% transplanted, 6% undergoing device exchange, 4% recovered, and 32% expired. Kaplan-Meier and event-per-patient-year estimates for survival, freedom from device explant, stroke, and pump thrombus were similar across year-of-implant. Following market withdrawal and recent device recalls, there appears to be no increase in mortality, stroke, pump thrombus, or explant for HVAD-supported patients. Quarterly report monitoring is ongoing.

Clinical Course of Patients in Cardiogenic Shock Stratified by Phenotype.

BACKGROUND: Cardiogenic shock (CS) patients remain at 30% to 60% in-hospital mortality despite therapeutic innovations. Heterogeneity of CS has complicated clinical trial design. Recently, 3 distinct CS phenotypes were identified in the CSWG (Cardiogenic Shock Working Group) registry version 1 (V1) and external cohorts: I, "noncongested;" II, "cardiorenal;" and III, "cardiometabolic" shock. OBJECTIVES: The aim was to confirm the external reproducibility of machine learning-based CS phenotypes and to define their clinical course. METHODS: The authors included 1,890 all-cause CS patients from the CSWG registry version 2. CS phenotypes were identified using the nearest centroids of the initially reported clusters. RESULTS: Phenotypes were retrospectively identified in 796 patients in version 2. In-hospital mortality rates in phenotypes I, II, III were 23%, 41%, 52%, respectively, comparable to the initially reported 21%, 45%, and 55% in V1. Phenotype-related demographic, hemodynamic, and metabolic features resembled those in V1. In addition, 58.8%, 45.7%, and 51.9% of patients in phenotypes I, II, and III received mechanical circulatory support, respectively (P = 0.013). Receiving mechanical circulatory support was associated with increased mortality in cardiorenal (OR: 1.82 [95% CI: 1.16-2.84]; P = 0.008) but not in noncongested or cardiometabolic CS (OR: 1.26 [95% CI: 0.64-2.47]; P = 0.51 and OR: 1.39 [95% CI: 0.86-2.25]; P = 0.18, respectively). Admission phenotypes II and III and admission Society for Cardiovascular Angiography and Interventions stage E were independently associated with increased mortality in multivariable logistic regression compared to noncongested "stage C" CS (P < 0.001). CONCLUSIONS: The findings support the universal applicability of these phenotypes using supervised machine learning. CS phenotypes may inform the design of future clinical trials and enable management algorithms tailored to a specific CS phenotype.

Pulmonary Artery Catheter Use and Risk of In-hospital Death in Heart Failure Cardiogenic Shock.

BACKGROUND: Pulmonary artery catheters (PACs) are increasingly used to guide management decisions in cardiogenic shock (CS). The goal of this study was to determine if PAC use was associated with a lower risk of in-hospital mortality in CS owing to acute heart failure (HF-CS). METHODS AND RESULTS: This multicenter, retrospective, observational study included patients with CS hospitalized between 2019 and 2021 at 15 US hospitals participating in the Cardiogenic Shock Working Group registry. The primary end point was in-hospital mortality. Inverse probability of treatment-weighted logistic regression models were used to estimate odds ratios (ORs) and corresponding 95% confidence intervals (CI), accounting for multiple variables at admission. The association between the timing of PAC placement and in-hospital death was also analyzed. A total of 1055 patients with HF-CS were included, of whom 834 (79%) received a PAC during their hospitalization. In-hospital mortality risk for the cohort was 24.7% (n = 261). PAC use was associated with lower adjusted in-hospital mortality risk (22.2% vs 29.8%, OR 0.68, 95% CI 0.50-0.94). Similar associations were found across SCAI stages of shock, both at admission and at maximum SCAI stage during hospitalization. Early PAC use (≤6 hours of admission) was observed in 220 PAC recipients (26%) and associated with a lower adjusted risk of in-hospital mortality compared with delayed (≥48 hours) or no PAC use (17.3% vs 27.7%, OR 0.54, 95% CI 0.37-0.81). CONCLUSIONS: This observational study supports PAC use, because it was associated with decreased in-hospital mortality in HF-CS, especially if performed within 6 hours of hospital admission. CONDENSED ABSTRACT: An observational study from the Cardiogenic Shock Working Group registry of 1055 patients with HF-CS showed that pulmonary artery catheter (PAC) use was associated with a lower adjusted in-hospital mortality risk (22.2% vs 29.8%, odds ratio 0.68, 95% confidence interval 0.50-0.94) compared with outcomes in patients managed without PAC. Early PAC use (≤6 hours of admission) was associated with a lower adjusted risk of in-hospital mortality compared with delayed (≥48 hours) or no PAC use (17.3% vs 27.7%, odds ratio 0.54, 95% confidence interval 0.37-0.81).

First-in-Man Use of a Modified Controller to Resolve HVAD Failure-to-Restart.

We report a case of Medtronic HeartWare ventricular assist device (HVAD) pump failure-to-restart. Despite HVAD withdrawal from the market in June 2021, up to 4,000 patients remain on HVAD support worldwide, and many are at high risk for this serious complication. This report describes the first-in-man use of a new HVAD controller that restarted a defective HVAD pump and avoided a fatal outcome. This new controller has the potential of preventing unnecessary VAD exchanges and saving lives.

In Vitro Investigation of the Effect of the Timing of Left Ventricular Assist Device Speed Modulation on Intraventricular Flow Patterns.

Thromboembolic events remain a common complication for left ventricular assist device (LVAD) patients. To prevent in-pump thrombosis, third-generation LVADs use speed modulation, which is not synchronized with the native left ventricle (LV) contractility. This study aims to investigate the effect of speed modulation on intraventricular flow patterns, and specifically, the impact of timing relative to pressure variations in the LV. Stereo-particle image velocimetry measurements were performed in a patient-derived LV implanted with an LVAD, for different timings of the speed modulation and speed. Speed modulation has a strong effect on instantaneous afterload and flowrate (-16% and +20%). The different timings of the speed modulation resulted in different flowrate waveforms, exhibiting different maxima (5.3-5.9 L/min, at constant average flowrate). Moreover, the timing of the speed modulation was found to strongly influence intraventricular flow patterns, specifically, stagnation areas within the LV. These experiments highlight, once more, the complex relationship between LVAD speed, hemodynamic resistance, and intraventricular pressure. Overall, this study demonstrates the importance of considering native LV contractility in future LVAD controls, to improve hemocompatibility and reduce the risk of thromboembolic complications.

Surfaceome mapping of primary human heart cells with CellSurfer uncovers cardiomyocyte surface protein LSMEM2 and proteome dynamics in failing hearts.

Cardiac cell surface proteins are drug targets and useful biomarkers for discriminating among cellular phenotypes and disease states. Here we developed an analytical platform, CellSurfer, that enables quantitative cell surface proteome (surfaceome) profiling of cells present in limited quantities, and we apply it to isolated primary human heart cells. We report experimental evidence of surface localization and extracellular domains for 1,144 N-glycoproteins, including cell-type-restricted and region-restricted glycoproteins. We identified a surface protein specific for healthy cardiomyocytes, LSMEM2, and validated an anti-LSMEM2 monoclonal antibody for flow cytometry and imaging. Surfaceome comparisons among pluripotent stem cell derivatives and their primary counterparts highlighted important differences with direct implications for drug screening and disease modeling. Finally, 20% of cell surface proteins, including LSMEM2, were differentially abundant between failing and non-failing cardiomyocytes. These results represent a rich resource to advance development of cell type and organ-specific targets for drug delivery, disease modeling, immunophenotyping and in vivo imaging.

Explainable Machine Learning Analysis of Right Heart Failure After Left Ventricular Assist Device Implantation.

Right heart failure (RHF) remains a common and serious complication after durable left ventricular assist device (LVAD) implantation. We used explainable machine learning (ML) methods to derive novel insights into preimplant patient factors associated with RHF. Continuous-flow LVAD implantations from 2008 to 2017 in the Interagency Registry for Mechanically Assisted Circulatory Support (INTERMACS) were included. A total of 186 preimplant patient factors were analyzed and the primary outcome was 30 days of severe RHF. A boosted decision tree ML algorithm and an explainable ML method were applied to identify the most important factors associated with RHF, nonlinear relationships and interactions, and risk inflection points. Out of 19,595 patients, 19.1% developed severe RHF at 30 days. Thirty top predictors of RHF were identified with the top five being INTERMACS profile, Model for End-stage Liver Disease score, the number of inotropic infusions, hemoglobin, and race. Many top factors exhibited nonlinear relationships with key risk inflection points such as INTERMACS profile between 2 and 3, right atrial pressure of 15 mmHg, pulmonary artery pressure index of 3, and prealbumin of 23 mg/dl. Finally, the most important variable interactions involved INTERMACS profile and the number of inotropes. These insights could help formulate patient optimization strategies prior to LVAD implantation.

A bridge-to-bridge approach to heart transplantation using extracorporeal membrane oxygenation and total artificial heart.

BACKGROUND: This study aims to describe the outcomes after heart transplantation using a bridge-to-bridge strategy with a sequence of extracorporeal membrane oxygenation (ECMO) support followed by temporary total artificial heart implantation (TAH-t). METHODS: A retrospective, multicenter analysis of 54 patients who underwent TAH-t implantation following an ECMO for cardiogenic shock was performed (ECMO-TAH-t group). A control group of 163 patients who underwent TAH-t implantation as a direct bridge to transplantation (TAH-t group) was used to assess this strategy's impact on outcomes. RESULTS: Fifty-four patients, averaging 47 ± 13 year old, underwent implantation of a TAH-t after 5.3 ± 3.4 days of ECMO perfusion for cardiogenic shock. In the ECMO-TAH-t group, 20 patients (20/54%; 37%) died after TAH-t implantation and 57 patients (57/163%; 35%) died in the TAH-t group (Gray test; P = .49). The top 3 causes of death of patients on TAH-t support were multisystem organ failure (40%), sepsis (20%), and neurologic events (20%). Overall, 32 patients (32/54%; 59%) underwent heart transplantation in the ECMO-TAH-t group compared with 106 patients (106/163%, 65%) in the TAH-t group (P = .44). No significant difference in survival was observed at 6 months, 1 year, and 3 years after heart transplant (ECMO-TAH-t group: 94%, 87%, and 80% vs 87%, 83%, and 76% in the TAH-t group, respectively). Deterioration of liver function (bilirubin, aspartate transaminase, and alanine aminotransferase levels on TAH-t) was associated with increased mortality before heart transplant in both groups. CONCLUSIONS: Sequential bridging from ECMO to TAH-t followed by heart transplantation is a viable option for a group of highly selected patients.

Clinical Presentation and In-Hospital Trajectory of Heart Failure and Cardiogenic Shock.

BACKGROUND: Heart failure-related cardiogenic shock (HF-CS) remains an understudied distinct clinical entity. OBJECTIVES: The authors sought to profile a large cohort of patients with HF-CS focused on practical application of the SCAI (Society for Cardiovascular Angiography and Interventions) staging system to define baseline and maximal shock severity, in-hospital management with acute mechanical circulatory support (AMCS), and clinical outcomes. METHODS: The Cardiogenic Shock Working Group registry includes patients with CS, regardless of etiology, from 17 clinical sites enrolled between 2016 and 2020. Patients with HF-CS (non-acute myocardial infarction) were analyzed and classified based on clinical presentation, outcomes at discharge, and shock severity defined by SCAI stages. RESULTS: A total of 1,767 patients with HF-CS were included, of whom 349 (19.8%) had de novo HF-CS (DNHF-CS). Patients were more likely to present in SCAI stage C or D and achieve maximum SCAI stage D. Patients with DNHF-CS were more likely to experience in-hospital death and in- and out-of-hospital cardiac arrest, and they escalated more rapidly to a maximum achieved SCAI stage, compared to patients with acute-on-chronic HF-CS. In-hospital cardiac arrest was associated with greater in-hospital death regardless of clinical presentation (de novo: 63% vs 21%; acute-on-chronic HF-CS: 65% vs 17%; both P < 0.001). Forty-five percent of HF-CS patients were exposed to at least 1 AMCS device throughout hospitalization. CONCLUSIONS: In a large contemporary HF-CS cohort, we identified a greater incidence of in-hospital death and cardiac arrest as well as a more rapid escalation to maximum SCAI stage severity among DNHF-CS. AMCS use in HF-CS was common, with significant heterogeneity among device types. (Cardiogenic Shock Working Group Registry [CSWG]; NCT04682483).

COMPETENCE Trial: The EVAHEART 2 continuous flow left ventricular assist device.

BACKGROUND: Continuous flow left ventricular assist devices have improved outcomes in patients with end-stage heart failure that require mechanical circulatory support. Current devices have an adverse event profile that has hindered widespread application. The EVAHEART®2 left ventricular assist device (EVA2) has design features such as large blood gaps, lower pump speeds and an inflow cannula that does not protrude into the left ventricle that may mitigate the adverse events currently seen with other continuous flow devices. METHODS: A prospective, multi-center randomized non-inferiority study, COMPETENCE Trial, is underway to assess non-inferiority of the EVA2 to the HeartMate 3 LVAS when used for the treatment of refractory advanced heart failure. The primary end-point is a composite of the individual primary outcomes: Survival to cardiac transplant or device explant for recovery; Free from disabling stroke; Free from severe Right Heart Failure after implantation of original device. Randomization is in a 2:1 (EVA2:HM3) ratio. RESULTS: The first patient was enrolled into the COMPETENCE Trial in December of 2020, and 25 subjects (16 EVA2 and 9 HM3) are currently enrolled. Enrollment of a safety cohort is projected to be completed by third quarter of 2022 at which time an interim analysis will be performed. Short-term cohort (92 EVA2 subjects) and long-term cohort is expected to be completed by the end of 2023 and 2024, respectively. CONCLUSIONS: The design features of the EVA2 such as a novel inflow cannula and large blood gaps may improve clinical outcomes but require further study. The ongoing COMPETENCE trial is designed to determine if the EVA2 is non-inferior to the HM3.

Rationale and Design of the Proactive-HF Trial for Managing Patients With NYHA Class III Heart Failure by Using the Combined Cordella Pulmonary Artery Sensor and the Cordella Heart Failure System.

BACKGROUND: Optimizing guideline-directed medical therapy (GDMT) and monitoring congestion in patients with heart failure (HF) are key to disease management and preventing hospitalizations. A pulmonary artery pressure (PAP)-guided HF management system providing access to body weight, blood pressure, heart rate, blood oxygen saturation, PAP, and symptoms, may provide new insights into the effects of patient engagement and comprehensive care for remote GDMT titration and congestion management. METHODS: The PROACTIVE-HF study was originally approved in 2018 as a prospective, randomized, controlled, single-blind, multicenter trial to evaluate the safety and effectiveness of the Cordella PAP Sensor in patients with HF and with New York Heart Association (NYHA) functional class III symptoms. Since then, robust clinical evidence supporting PAP-guided HF management has emerged, making clinical equipoise and enrolling patients into a standard-of-care control arm challenging. Therefore, PROACTIVE-HF was changed to a single-arm trial in 2021 with prespecified safety and effectiveness endpoints to provide evidence for a similar risk/benefit profile as the CardioMEMS HF System. CONCLUSION: The single-arm PROACTIVE-HF trial is expected to further demonstrate the benefits of PAP-guided HF management of patients with NYHA class III HF. The addition of vital signs, patient engagement and self-reported symptoms may provide new insights into remote GDMT titration and congestion management.

Feasibility of Very Early Identification of Cardiogenic Shock by Semi-automated Ultrasound Exam in the Emergency Department.

Background Cardiogenic shock (CS) is critical end-organ hypoperfusion due to reduced cardiac output. Early therapy, such as vasoactive agents or the initiation of mechanical circulatory support (MCS), requires early diagnosis and is associated with better outcomes. A novel ultrasound platform (GE Healthcare, Milwaukee, WI) has semi-automated imaging software (SAIS), which could simplify the point-of-care ultrasound (POCUS) diagnosis of CS. We assessed the feasibility of using POCUS with SAIS in patients in shock, determined the ability of SAIS to identify the subset of patients with CS, and described the process and outcome of care of patients with vs. without CS after presenting to Emergency Department (ED) with hypotension. Methods This prospective case-control study was conducted at an urban ED. Physicians with prior POCUS education received one hour of training with the study device. The qualitative ejection fraction was determined by visual assessment. SAIS measurements of hemodynamics were made with the study device and included left ventricle outflow tract velocity time integral (LVOT VTI), inferior vena cava collapsibility or distensibility indices, and pulmonary B-line assessment. ED patients with a systolic blood pressure ≤ 90 mmHg or need for a vasopressor initiation in the ED were enrolled. The diagnosis of CS was determined by a medical record review. All data were summarized descriptively. Results Twenty-nine cases underwent POCUS, and 87 controls did not. Baseline characteristics, process, and outcome of care were similar between groups. Seventy-nine percent (79%) of cases had a complete POCUS with SAIS. Of these, 55% had reduced LVOT VTI, 38% had IVC collapsibility <50%, and 48% of cases had a B-line pattern consistent with pulmonary edema. The mean LVOT VTI for cases with CS was 9.4± 5.4 cm; the mean LVOT VTI for cases without CS was 15.2 ± 6.0 cm. Among patients who did not undergo POCUS, 31 (36%) had a formal echocardiogram, and eight (9%) had a final diagnosis of cardiogenic shock during hospitalization. Conclusion Physicians with one hour of platform-specific training were able to implement POCUS with SAIS among patients who present with shock. POCUS with SAIS may aid in the early recognition of CS.