Mechanical Left Ventricular Unloading Research Articles

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.

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

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

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

(489) - Association of ECMO Flow Index and Survival in Adults with Cardiogenic Shock Receiving Venoarterial Extracorporeal Membrane Oxygenation with Concomitant Left Ventricular Mechanical Unloading Device: An ELSO Registry Analysis

(489) - Association of ECMO Flow Index and Survival in Adults with Cardiogenic Shock Receiving Venoarterial Extracorporeal Membrane Oxygenation with Concomitant Left Ventricular Mechanical Unloading Device: An ELSO Registry Analysis

Abstract 17212: Arterial Cannula Size and 30-Day Mortality in Adults With Cardiogenic Shock Supported With Venoarterial Extracorporeal Membrane Oxygenation and Concomitant Left Ventricular Mechanical Unloading: An ELSO Registry Analysis

Introduction: VA-ECMO with left ventricular mechanical unloading (LVMU), including intra-aortic balloon pump (IABP) or percutaneous left ventricular assist device (pVAD), is commonly used to support patients with cardiogenic shock (CS). The impact of arterial return cannula size on short-term mortality in the presence of LVMU is unknown. Hypothesis: The 30-day inpatient survival in patients with VA-ECMO and LVMU will be the same with a small vs large arterial cannula. Methods: We queried the ELSO Registry from 2017-2022 for adults with CS receiving VA-ECMO and concomitant LVMU, with either IABP or pVAD placed within -24h to +2h of ECMO initiation. We restricted to patients with body surface area (BSA) 1.8-2.2 m2 and excluded those with central cannulation, multiple ECMO runs, and ECPR. The primary outcome of 30-day inpatient mortality was compared using time-to-event analysis. Secondary outcomes included 24h lactate clearance and rates of acute renal and hepatic injury. Results: Among 2055 patients supported with VA-ECMO and LVMU (54.3% IABP; 45.7% pVAD), 292 (14.2%) patients received a small cannula and 1763 (86.8%) patients a large arterial cannula. Patients with a small cannula were less likely to be male, had smaller BSA, less often had a distal perfusion cannula, and had a lower incidence of pre-ECMO concomitant organ failures (Figure, A). There was no difference in 30-day inpatient mortality between the cannula size groups (Figure, B), which persisted in multivariable modeling with adjusted hazard ratio 0.94 (95% CI: 0.72-1.23), p=0.65. Patients with a small arterial cannula had no significant difference in 24h lactate clearance (Figure, C) or in the rates of acute renal injury (37.3% vs 39.8%, p = 0.42) or hyperbilirubinemia (5.5% vs 6.5%, p=0.52). Conclusions: In adults with CS receiving VA-ECMO with LVMU, the use of a smaller arterial return cannula was associated with no difference in 30-day inpatient mortality or metrics of end-organ perfusion.

Abstract 18693: Effect of Mechanical Unloading on Cardiogenic Shock Severity in Venoarterial Extracorporeal Membrane Oxygenation Patients

Introduction: Mechanical unloading (MU) with Intra-aortic balloon pump (IABP) or Impella is commonly used to prevent left ventricular (LV) distension in VA-ECMO patients, but its impact on shock severity is not well described. Methods: Patients treated with VA-ECMO in our hospital between 2016-2022 for cardiogenic shock (CS) due to LV failure not related to cardiac surgery were included if no MU was used or it was instituted within 24h of ECMO cannulation. Patients were grouped according to MU: ECMO alone, ECMO + IABP or ECMO + Impella. Linear mixed effects models adjusting for age, sex, hypertension, acute myocardial infarction (AMI) etiology of shock and pre-ECMO cardiac arrest (CA) were used to assess the impact of MU on hemodynamic and perfusion markers. R version 4 was used for analysis. Results: Among 68 patients included, 18 received ECMO alone, 17 ECMO + IABP, and 33 ECMO + Impella. Age and CA were similar across groups. The Impella group had a higher proportion of men and patients with AMI. Pulmonary artery diastolic pressure was unchanged in all groups. Compared to ECMO alone, MU did not enhance lactate clearance (interaction: IABP p=0.7, Impella p=0.22), but it did improve the vasopressor-inotropic score (IABP p=0.03, Impella p=0.01), serum creatinine (IABP p=0.03, Impella p=0.04), and alanine transaminase (IABP only p=0.02). Survival to decannulation was similar in patients with ECMO alone (50%), Impella (64%) and IABP (65%) (p=0.68). Conclusions: In adults treated with VA-ECMO for CS unrelated to cardiac surgery, LV MU can lead to improvements in CS severity.

Abstract 13045: Myofibroblasts Revert to an Inactive Phenotype During Regression of Heart Failure

Introduction: The therapy of left ventricular mechanical unloading, such as transcatheter aortic valve replacement(TAVR)and left ventricular assist devices(LVAD)has significantly improved prognosis for patients with heart failure. However, the detailed cellular and/or molecular mechanisms of recovery of cardiac function remain unknown. Objective: We aimed to build a cellular atlas of the heart that experienced stress and de-stress process, with a focus on myofibroblasts, specifically its cell fate of differentiation and function. Methods: We conducted single-cell and ATAC sequencing on non-myocardial cells from mouse heart samples of pressure overload-induced heart failure and recovery, using TAC (transverse aortic arch constriction)/deTAC (with suture for the constriction removed 2 weeks after TAC) model to identify the dynamic changes. Lineage tracing technique was also used to gain further insight into cell fate and reciprocal interactions. Macrophage subgroup was cleared using various approaches to investigate the cross-talk between myofibroblast and macrophage. Results: We generated a TAC/deTAC mouse model which can faithfully simulate a reversal process of functioning for the heart that underwent a pressure overload stress. Multi-omics sequencing reveals the genetic changes and transcriptional regulation of cell populations at different stages. Among the different cell types, significant changes in the gene expression pattern were observed in fibroblasts. Aided by myofibroblast lineage tracing, flow cytometry examinations suggested that remaining in a quiescent state rather than showing a decrease in its number appeared as the main fate of myofibroblasts. Surprisingly, however, simultaneous pressure unloading and macrophage clearance resulted in a significant reduction in the number of myofibroblasts. Conclusions: With a reliable TAC/deTAC mouse model, our multi-omics data revealed dynamic changes in cell populations of the heart that underwent pressure overload followed by unloading, our data demonstrated a quiescent state rather than a reduction in number was the major fate for the activated myofibroblasts for which macrophages were involved. These findings provide a theoretical basis for further treatment.

216: Arterial Cannula Size and the Need for Delayed Left Ventricular Mechanical Unloading in Adults Supported with VA-ECMO: An ELSO Registry Analysis

216: Arterial Cannula Size and the Need for Delayed Left Ventricular Mechanical Unloading in Adults Supported with VA-ECMO: An ELSO Registry Analysis

Perspectives and Considerations of IABP in the Era of ECMO for Cardiogenic Shock.

The development of mechanical circulatory support (MCS) has been rapid, and its use worldwide in patients with cardiogenic shock is increasingly widespread. However, current statistical data and clinical research do not demonstrate its significant improvement in the patient prognosis. This review focuses on the widely used intra-aortic balloon pumps (IABP) and veno-arterial extracorporeal membrane oxygenation (VA-ECMO), analyzing and comparing their characteristics, efficacy, risk of complications, and the current exploration status of left ventricular mechanical unloading. Subsequently, we propose a rational approach to viewing the negative outcomes of current MCS, and look ahead to the future development trends of IABP.

Negative Impact of Acute Reloading after Mechanical Left Ventricular Unloading.

Mechanical LV unloading for acute myocardial infarction (MI) is a promising supportive therapy to reperfusion. However, no data is available on exit strategy. We evaluated hemodynamic and cellular effects of reloading after Impella-mediated LV unloading in Yorkshire pigs. First, we conducted an acute study in normal heart to observe effects of unloading and reloading independent of MI-induced ischemic effects. We then completed an MI study to investigate optimal exit strategy on one-week infarct size, no-reflow area, and LV function with different reloading speeds. Initial studies showed that acute reloading causes an immediate rise in end-diastolic wall stress followed by a significant increase in cardiomyocyte apoptosis. The MI study did not result in any statistically significant findings; however, numerically smaller average infarct size and no-reflow area in the gradual reloading group prompt further examination of reloading approach as an important clinically relevant consideration.

Rationale and Design of JenaMACS-Acute Hemodynamic Impact of Ventricular Unloading Using the Impella CP Assist Device in Patients with Cardiogenic Shock.

Introduction: Cardiogenic shock due to myocardial infarction or heart failure entails a reduction in end organ perfusion. Patients who cannot be stabilized with inotropes and who experience increasing circulatory failure are in need of an extracorporeal mechanical support system. Today, small, percutaneously implantable cardiac assist devices are available and might be a solution to reduce mortality and complications. A temporary, ventricular, continuous flow propeller pump using magnetic levitation (Impella®) has been approved for that purpose. Methods and Study Design: JenaMACS (Jena Mechanical Assist Circulatory Support) is a monocenter, proof-of-concept study to determine whether treatment with an Impella CP® leads to improvement of hemodynamic parameters in patients with cardiogenic shock requiring extracorporeal, hemodynamic support. The primary outcomes of JenaMACS are changes in hemodynamic parameters measured by pulmonary artery catheterization and changes in echocardiographic parameters of left and right heart function before and after Impella® implantation at different support levels after 24 h of support. Secondary outcome measures are hemodynamic and echocardiographic changes over time as well as clinical endpoints such as mortality or time to hemodynamic stabilization. Further, laboratory and clinical safety endpoints including severe bleeding, stroke, neurological outcome, peripheral ischemic complications and occurrence of sepsis will be assessed. JenaMACS addresses essential questions of extracorporeal, mechanical, cardiac support with an Impella CP® device in patients with cardiogenic shock. Knowledge of the acute and subacute hemodynamic and echocardiographic effects may help to optimize therapy and improve the outcome in those patients. Conclusion: The JenaMACS study will address essential questions of extracorporeal, mechanical, cardiac support with an Impella CP® assist device in patients with cardiogenic shock. Knowledge of the acute and subacute hemodynamic and echocardiographic effects may help to optimize therapy and may improve outcome in those patients. Ethics and Dissemination: The protocol was approved by the institutional review board and ethics committee of the University Hospital of Jena. Written informed consent will be obtained from all participants of the study. The results of this study will be published in a renowned international medical journal, irrespective of the outcomes of the study. Strengths and Limitations: JenaMACS is an innovative approach to characterize the effect of additional left ventricular mechanical unloading during cardiogenic shock via a minimally invasive cardiac assist system (Impella CP®) 24 h after onset and will provide valuable data for acute interventional strategies or future prospective trials. However, JenaMACS, due to its proof-of-concept design, is limited by its single center protocol, with a small sample size and without a comparison group.

Left Ventricular Remodeling After Anterior-STEMI PCI: Imaging Observations in the Door-to-Unload (DTU) Pilot Trial.

To determine the predictive value of cardiac magnetic resonance (CMR) and echocardiographic parameters on left ventricular (LV) remodeling in ST-segment elevation myocardial infarction (STEMI) patients without cardiogenic shock and treated with mechanical LV unloading followed by immediate or delayed percutaneous coronary intervention (PCI)-mediated reperfusion. In STEMI, infarct size (IS) directly correlates with major cardiovascular outcomes. Preclinical models demonstrate mechanical LV unloading before reperfusion reduces IS. The door-to-unload (DTU)-STEMI pilot trial evaluated the safety and feasibility of LV unloading and delayed reperfusion in patients with STEMI. This multicenter, prospective, randomized, safety and feasibility trial evaluated patients with anterior STEMI randomized 1:1 to LV unloading with the Impella CP (Abiomed) followed by immediate reperfusion vs delayed reperfusion after 30 minutes of unloading. Patients were assessed by CMR at 3-5 days and 30 days post PCI. Echocardiographic evaluations were performed at 3-5 and 90 days post PCI. At 3-5 days post PCI, patients were compared based on IS as percentage of LV mass (group 1 ≤25%, group 2 >25%). Selection of IS threshold was performed post hoc. Fifty patients were enrolled from April 2017 to May 2018. At 90 days, group 1 (IS ≤25%) exhibited improved LV ejection fraction (from 53.1% to 58.9%; P=.001) and group 2 (IS >25%) demonstrated no improvement (from 37.6% to 39.1%; P=.55). LV end-diastolic volume and end-systolic volume were unchanged in group 1 and worsened in group 2. There was correlation between 3-5 day and 30-day CMR measurements of IS and 90-day echocardiography-derived LV ejection fraction. Immediate 3-5 day post-therapy IS by CMR correlates with 90-day echocardiographic LVEF and indices of remodeling. Patients with post-therapy IS >25% demonstrated evidence of adverse remodeling. Larger studies are needed to corroborate these findings with implications on patient management and prognosis.

Mechanical Left Ventricular Unloading in Patients Undergoing Venoarterial Extracorporeal Membrane Oxygenation

BackgroundVenoarterial extracorporeal membrane oxygenation (VA-ECMO) increases left ventricular (LV) afterload, potentially provoking LV distention and impairing recovery. LV mechanical unloading (MU) with intra-aortic balloon pump (IABP) or percutaneous ventricular assist device (pVAD) can prevent LV distension, potentially at the risk of more complications, and net clinical benefit remains uncertain. ObjectivesThis study aims to determine the association between MU and outcomes for patients undergoing VA-ECMO. MethodsThe authors queried the Extracorporeal Life Support Organization registry for adults receiving peripheral VA-ECMO from 2010 to 2019 and stratified them by MU with IABP or pVAD. The primary outcome was in-hospital mortality; secondary outcomes included on-support mortality and complications during VA-ECMO. ResultsAmong 12,734 VA-ECMO patients, 3,399 (26.7%) received MU: 2,782 (82.9%) IABP and 580 (17.1%) pVAD. MU patients were older (age 56.3 vs 52.7 years) and, before extracorporeal membrane oxygenation, more often required >2 vasopressors (41.7% vs 27.2%) and had respiratory (21.1% vs 15.9%), renal (24.6% vs 15.8%), and liver failure (4.4% vs 3.1%) (all P < 0.001). MU patients had lower in-hospital mortality (56.6% vs 59.3%, P = 0.006), which persisted in multivariable modeling (adjusted OR [aOR]: 0.84; 95% CI: 0.77-0.92; P < 0.001). MU was associated with more cannula site bleeding (aOR: 1.25; 95% CI: 1.11-1.40; P < 0.001) and hemolysis (aOR: 1.27; 95% CI: 1.03-1.57; P = 0.02). Compared to pVAD, MU patients with IABP had similar mortality (aOR: 0.80; 95% CI: 0.64-1.01; P = 0.06) and less medical bleeding (aOR: 0.45; 95% CI: 0.31-0.64; P < 0.001), cannula site bleeding (aOR: 0.72; 95% CI: 0.54-0.96; P = 0.03), and renal injury (aOR: 0.78; 95% CI: 0.62-0.98; P = 0.03). ConclusionsAmong adults receiving VA-ECMO, MU was associated with lower in-hospital mortality despite increased complications including hemolysis and cannulation site bleeding. Compared to pVAD, MU with IABP was associated with similar mortality and lower complication rates.

Impaired Diastolic Function Predicts Improved Ischemic Myocardial Flow by Mechanical Left Ventricular Unloading in a Swine Model of Ischemic Heart Failure.

Background: Impact of mechanical left ventricular (LV) unloading on myocardial tissue perfusion and its regulating factors remain unclear. This study was conducted to elucidate the predictors of regional blood flow (RBF) improvement by mechanical LV unloading.Materials and Methods: One to four weeks after percutaneous induction of myocardial infarction (MI), Yorkshire pigs (n = 15) underwent mechanical LV unloading using Impella CP. Hemodynamic parameters were collected prior to LV unloading. RBF in infarct, border and remote myocardium were measured by fluorescent microsphere injections before and 120 min after LV unloading.Results: RBF showed variable responses to mechanical LV unloading. While infarct RBF improved in general (0.33 ± 0.13 to 0.42 ± 0.19 mL/min/g, p = 0.06), there were a few pigs that showed little improvement. Meanwhile, there were no clear trends in the border (1.07 ± 0.47 to 1.02 ± 0.65 mL/min/g, p = 0.73) and remote myocardial RBF (1.25 ± 0.52 to 1.23 ± 0.68 mL/min/g, p = 0.85). In the simple linear regression analysis, cardiac output, mean pulmonary arterial wedge pressure, mean left atrial pressure, minimum LV pressure, end-diastolic LV pressure, maximum dP/dt, slope of end-diastolic pressure-volume relationship (EDPVR) and end-diastolic wall stress were significantly associated with % change of infarct RBF. In the multiple regression model, slope of EDPVR and maximum dP/dt remained as independent predictors of infarct RBF change.Conclusion: Steeper EDPVR and lower maximum dP/dt were associated with increased blood perfusion in the infarct area after LV unloading. Our data suggests mechanical LV unloading is more beneficial in post-MI patients with high diastolic pressure associated with increased LV stiffness and in those with worse cardiac contractility.

"Clipping the Leak" - A Case Series of Transcatheter Mitral Valve Repair after Left Ventricular Assist Device

Introduction Mitral regurgitation (MR) often co-exists with severe left ventricular (LV) systolic dysfunction and there is controversy regarding the need for corrective surgery at the time of left ventricular assist device (LVAD) implantation as it often improves with mechanical LV unloading. We describe three patients with significant MR after LVAD implant in which transcatheter mitral valve repair (TMVR) [MitraClip] was utilized. To our knowledge, this is the largest case series of TMVR post-LVAD implant reported. Case Report Patient #1 is a 40-year-old male with severe LV dysfunction due to a non-ischemic cardiomyopathy (CM) who presented in cardiogenic shock (CS) and underwent centrifugal-flow LVAD [Heartmate 3]. MR was severe due to bileaflet tethering at time of implant and improved to mild to moderate immediately after. With medical and device optimization, EF improved to 35-40% however he had right ventricular (RV) dysfunction with recurrence of severe MR secondary to bileaflet prolapse. Given NYHA III symptoms, he underwent TMVR with improvement in MR to mild to moderate and improvement in his symptoms to NYHA class II. Patient #2 is a 27-year-old female who presented with acute severe LV dysfunction with moderate to severe functional MR due to viral myocarditis. She required extracorporeal membrane oxygenation and initially improved but decompensated after removal of support and subsequently underwent implantation of Heartmate 3. Her LV function recovered and she was scheduled for LVAD explantation but pre-operative tranesophageal echocardiogram revealed moderate to severe MR secondary to bileaflet prolapse so the procedure was deferred. She successfully underwent TMVR with improvement to mild to moderate MR and is planned for LVAD explant in the future. She had unchanged NYHA I symptoms before and after TMVR. Patient #3 is a 76-year-old male who underwent an axial-flow LVAD [Heartmate 2] seven years prior for ischemic CM. He reported worsening dyspnea despite device and medication optimization and was found to have moderate to severe MR (secondary to leaflet tethering). He underwent a successful TMVR with reduction in MR to mild to moderate, as well as improvement of NYHA class III to II. Summary Persistence of MR after LVAD implantation can be associated with worse outcomes. We describe three patients who underwent successful TMVR to reduce morbidity.

Acute Hemodynamic Effects of Cardiac Resynchronization Therapy Versus Alternative Pacing Strategies in Patients With Left Ventricular Assist Devices

BackgroundThe hemodynamic effects of cardiac resynchronization therapy in patients with left ventricular assist devices (LVADs) are uncharacterized. We aimed to quantify the hemodynamic effects of different ventricular pacing configurations in patients with LVADs, focusing on short‐term changes in load‐independent right ventricular (RV) contractility.Methods and ResultsPatients with LVADs underwent right heart catheterization during spontaneous respiration without sedation and with pressures recorded at end expiration. Right heart catheterization was performed at different pacemaker configurations (biventricular pacing, left ventricular pacing, RV pacing, and unpaced conduction) in a randomly generated sequence with >3 minutes between configuration change and hemodynamic assessment. The right heart catheterization operator was blinded to the sequence. RV maximal change in pressure over time normalized to instantaneous pressure was calculated from digitized hemodynamic waveforms, consistent with a previously validated protocol. Fifteen patients with LVADs who were in sinus rhythm were included. Load‐independent RV contractility, as assessed by RV maximal change in pressure over time normalized to instantaneous pressure, was higher in biventricular pacing compared with unpaced conduction (15.7±7.6 versus 11.0±4.0 s−1; P=0.003). Thermodilution cardiac output was higher in biventricular pacing compared with unpaced conduction (4.48±0.7 versus 4.38±0.8 L/min; P=0.05). There were no significant differences in heart rate, ventricular filling pressures, or atrioventricular valvular regurgitation across all pacing configurations.ConclusionsBiventricular pacing acutely improves load‐independent RV contractility in patients with LVADs. Even in these patients with mechanical left ventricular unloading via LVAD who were relative pacing nonresponders (required LVAD support despite cardiac resynchronization therapy), biventricular pacing was acutely beneficial to RV contractility.

Impact of Concomitant Vasoactive Treatment in Mechanical Left Ventricular Unloading in Profound Cardiogenic Shock

To compare the effect of equipotent dosages of epinephrine, dopamine, norepinephrine, and phenylephrine on left ventricular (LV) work and end-organ perfusion in a porcine model of profound ischemic cardiogenic shock (CS) supported by Impella CP. CS was induced in 10 pigs by stepwise intracoronary injection of microspheres. After CS was induced and Impella CP support initiated, animals were treated in a blinded crossover design with norepinephrine (0.10 µg/kg/min), epinephrine (0.10 µg/kg/min) or dopamine (10 µg/kg/min) for 30 minutes each. Phenylephrine (10 µg/kg/min) was given at the end of the study for 20 minutes. LV work was estimated using a conductance catheter. Main outcome measure was LV work estimated by pressure volume area (PVA) x heart rate. End-organ perfusion was evaluated by mixed venous oxygen saturation (SVO2) from the pulmonary artery and arterial lactate levels. Multilevel mixed-effects linear regression was used to evaluate treatment effect. All vasoactive drugs induced a significant increase in LV work, borderline for norepinephrine by 92.4 (mmHg*mL)*103/min ⦋95%CI(-1.1, 186), p=0.053)⦌. For all catecholamines, stroke work was significantly increased, but unchanged with phenylephrine, which on the other hand caused a significant increase in potential energy by 483 mmHg*mL ⦋95%CI(195, 772), p=0.001)⦌. SVO2 increased significantly with catecholamines and decreased borderline with phenylephrine by -9 %point ⦋95%CI(-19, 0.49), p=0.063)⦌ which also increased arterial lactate levels by 2.4 mmol/L ⦋95%CI(0.89, 3.92), p=0.002)⦌. There was a trend toward lower arterial lactate levels with norepinephrine by -1.53 mmol/L ⦋95%CI(-3.15, 0.09), p=0.064)⦌ CONCLUSION: Catecholamines increased SVO2 but at the expense of increased LV work, least for norepinephrine and highest for dopamine (figure). Isolated vasoconstriction (phenylephrine) caused an increase in LV work, a decrease in SVO2 and increase in arterial lactate levels.

Impact of concomitant vasoactive treatment and mechanical left ventricular unloading in a porcine model of profound cardiogenic shock

BackgroundConcomitant vasoactive drugs are often required to maintain adequate perfusion pressure in patients with acute myocardial infarction (AMI) and cardiogenic shock (CS) receiving hemodynamic support with an axial flow pump (Impella CP).ObjectiveTo compare the effect of equipotent dosages of epinephrine, dopamine, norepinephrine, and phenylephrine on cardiac work and end-organ perfusion in a porcine model of profound ischemic CS supported with an Impella CP.MethodsCS was induced in 10 pigs by stepwise intracoronary injection of polyvinyl microspheres. Hemodynamic support with Impella CP was initiated followed by blinded crossover to vasoactive treatment with norepinephrine (0.10 μg/kg/min), epinephrine (0.10 μg/kg/min), or dopamine (10 μg/kg/min) for 30 min each. At the end of the study, phenylephrine (10 μg/kg/min) was administered for 20 min. The primary outcome was cardiac workload, a product of pressure-volume area (PVA) and heart rate (HR), measured using the conductance catheter technique. End-organ perfusion was assessed by measuring venous oxygen saturation from the pulmonary artery (SvO2), jugular bulb, and renal vein. Treatment effects were evaluated using multilevel mixed-effects linear regression.ResultsAll catecholamines significantly increased LV stroke work and cardiac work, dopamine to the greatest extend by 341.8 × 103 (mmHg × mL)/min [95% CI (174.1, 509.5), p < 0.0001], and SvO2 significantly improved during all catecholamines. Phenylephrine, a vasoconstrictor, caused a significant increase in cardiac work by 437.8 × 103 (mmHg × mL)/min [95% CI (297.9, 577.6), p < 0.0001] due to increase in potential energy (p = 0.001), but no significant change in LV stroke work. Also, phenylephrine tended to decrease SvO2 (p = 0.063) and increased arterial lactate levels (p = 0.002).ConclusionCatecholamines increased end-organ perfusion at the expense of increased cardiac work, most by dopamine. However, phenylephrine increased cardiac work with no increase in end-organ perfusion.

Primary mechanical unloading in high-risk myocardial infarction: Perspectives in view of a paradigm shift

The improvement achieved in recent years in early myocardial infarction (MI) mortality poses several new clinical challenges, owing to late consequences of myocardial loss and the significant incidence of heart failure (HF) observed thereafter. A still unaddressed residual reperfusion injury (RI) contributes to final infarct size, acute MI mortality and longer-term HF development. Despite many cardioprotective lines of research in the setting of MI, no treatment has significantly altered clinical practice or convincingly improved outcomes either. Left ventricular mechanical unloading before culprit vessel reopening may reduce RI and prime (biologically and mechanically) the myocardium for reperfusion, thus limiting infarct size and preventing subsequent adverse remodeling. Aim of this review is to summarize key pre-clinical and clinical experiences furnishing a rationale to the approach of mechanical unloading before myocardial reperfusion with a translational outlook on its implications for the management of MI patients.

Mechanical Left Ventricular Unloading to Reduce Infarct Size During Acute Myocardial Infarction: Insight from Preclinical and Clinical Studies.

Acute myocardial infarction (AMI) remains a leading cause of morbidity and mortality. Pioneering preclinical work reported by Peter Maroko and Eugene Braunwald in 1971 identified oxygen supply and demand are primary determinants of myocardial infarct size in the setting of a heart attack. Since the 1950s, advances in mechanical engineering led to the development of short-term circulatory support devices that range from pulsatile to continuous flow pumps. The primary objective of these pumps is to reduce native heart work, enhance coronary blood flow, and sustain systemic perfusion. Whether these pumps could reduce myocardial infarct size in the setting of AMI became an intense focus for preclinical investigation with variable animal models, experimental algorithms, and pump platforms being tested. In this review, we discuss the design of these preclinical studies and the evolution of mechanical support platforms and attempt to translate these experimental methods into clinical trials.