BackgroundThe aim of this study was to assess the relationship between extracorporeal blood flow (EBF) and left ventricular (LV) performance during venoarterial extracorporeal membrane oxygenation (VA ECMO) therapy.MethodsFive swine (body weight 45 kg) underwent VA ECMO implantation under general anesthesia and artificial ventilation. Subsequently, acute cardiogenic shock with signs of tissue hypoxia was induced. Hemodynamic and cardiac performance parameters were then measured at different levels of EBF (ranging from 1 to 5 L/min) using arterial and venous catheters, a pulmonary artery catheter and a pressure–volume loop catheter introduced into the left ventricle.ResultsMyocardial hypoxia resulted in a decline in mean (±SEM) cardiac output to 2.8 ± 0.3 L/min and systolic blood pressure (SBP) to 60 ± 7 mmHg. With an increase in EBF from 1 to 5 L/min, SBP increased to 97 ± 8 mmHg (P < 0.001); however, increasing EBF from 1 to 5 L/min significantly negatively influences several cardiac performance parameters: cardiac output decreased form 2.8 ± 0.3 L/min to 1.86 ± 0.53 L/min (P < 0.001), LV end-systolic volume increased from 64 ± 11 mL to 83 ± 14 mL (P < 0.001), LV stroke volume decreased from 48 ± 9 mL to 40 ± 8 mL (P = 0.045), LV ejection fraction decreased from 43 ± 3 % to 32 ± 3 % (P < 0.001) and stroke work increased from 2096 ± 342 mmHg mL to 3031 ± 404 mmHg mL (P < 0.001). LV end-diastolic pressure and volume were not significantly affected.ConclusionsThe results of the present study indicate that higher levels of VA ECMO blood flow in cardiogenic shock may negatively affect LV function. Therefore, it appears that to mitigate negative effects on LV function, optimal VA ECMO blood flow should be set as low as possible to allow adequate tissue perfusion.

Background: Veno-arterial extracorporeal membrane oxygenation (VA-ECMO) is increasingly being used for circulatory support in cardiogenic shock patients, although the evidence supporting its use in this context remains insufficient. The aim of the Extracorporeal Membrane Oxygenation in the Therapy of Cardiogenic Shock (ECMO-CS) trial was to compare immediate implementation of VA-ECMO vs. an initially conservative therapy (allowing downstream use of VA-ECMO) in patients with rapidly deteriorating or severe cardiogenic shock. Methods: This multicenter, randomized, investigator-initiated, academic clinical trial included patients with either rapidly deteriorating or severe cardiogenic shock. Patients were randomly assigned to immediate VA-ECMO or no immediate VA-ECMO. Other diagnostic and therapeutic procedures were performed as per current standard(s) of care. In the early conservative group, VA-ECMO could be used downstream in case of worsening hemodynamic status. The primary endpoint was the composite of death from any cause, resuscitated circulatory arrest, and implementation of another mechanical circulatory support device at 30 days. Results: A total of 122 patients were randomized; after excluding 5 patients due to the absence of informed consent, 117 subjects were included in the analysis, of whom 58 randomized to immediate VA-ECMO and 59 to no immediate VA-ECMO. The composite primary endpoint occurred in 37 (63.8%) and 42 (71.2%) of patients in the immediate VA-ECMO and the no early VA-ECMO groups, respectively (hazard ratio, 0.72; 95% confidence intervals [CI], 0.46 to 1.12; P=0.21). VA-ECMO was used in 23 (39%) of no early VA-ECMO patients. The 30-day incidence of resuscitated cardiac arrest (10.3. % vs. 13.6%; risk difference [RD], -3.2; 95% CI, -15.0 to 8.5), all-cause mortality (50.0% versus 47.5%; RD, 2.5; 95% CI, -15.6 to 20.7), serious adverse events (60.3% vs. 61.0%; RD, -0.7; 95% CI, -18.4 to 17.0), sepsis, pneumonia, stroke, leg ischemia, and bleeding was not statistically different between the immediate VA-ECMO and the no immediate VA-ECMO groups. Conclusions: Immediate implementation of VA-ECMO in patients with rapidly deteriorating or severe cardiogenic shock did not improve clinical outcomes compared with an early conservative strategy that permitted downstream use of VA-ECMO in case of worsening hemodynamic status. Clinical Trial Registration: URL: https://www.clinicaltrials.gov; Unique identifier NCT02301819.

IntroductionVeno-arterial extracorporeal life support (ECLS) is increasingly being used to treat rapidly progressing or severe cardiogenic shock. However, it has been repeatedly shown that increased afterload associated with ECLS significantly diminishes left ventricular (LV) performance. The objective of the present study was to compare LV function and coronary flow during standard continuous-flow ECLS support and electrocardiogram (ECG)-synchronized pulsatile ECLS flow in a porcine model of cardiogenic shock.MethodsSixteen female swine (mean body weight 45 kg) underwent ECLS implantation under general anesthesia and artificial ventilation. Subsequently, acute cardiogenic shock, with documented signs of tissue hypoperfusion, was induced by initiating global myocardial hypoxia. Hemodynamic cardiac performance variables and coronary flow were then measured at different rates of continuous or pulsatile ECLS flow (ranging from 1 L/min to 4 L/min) using arterial and venous catheters, a pulmonary artery catheter, an LV pressure-volume loop catheter, and a Doppler coronary guide-wire.ResultsMyocardial hypoxia resulted in declines in mean cardiac output to 1.7±0.7 L/min, systolic blood pressure to 64±22 mmHg, and LV ejection fraction (LVEF) to 22±7%. Synchronized pulsatile flow was associated with a significant reduction in LV end-systolic volume by 6.2 mL (6.7%), an increase in LV stroke volume by 5.0 mL (17.4%), higher LVEF by 4.5% (18.8% relative), cardiac output by 0.37 L/min (17.1%), and mean arterial pressure by 3.0 mmHg (5.5%) when compared with continuous ECLS flow at all ECLS flow rates (P<0.05). At selected ECLS flow rates, pulsatile flow also reduced LV end-diastolic pressure, end-diastolic volume, and systolic pressure. ECG-synchronized pulsatile flow was also associated with significantly increased (7% to 22%) coronary flow at all ECLS flow rates.ConclusionECG-synchronized pulsatile ECLS flow preserved LV function and coronary flow compared with standard continuous-flow ECLS in a porcine model of cardiogenic shock.

Aims Extracorporeal membrane oxygenation (ECMO) in veno‐arterial configuration represents an increasingly used method for circulatory support. ECMO in cardiogenic shock offers rapid improvement of circulatory status and significant increase in tissue perfusion. Current evidence on the use of ECMO in cardiogenic shock remains insufficient. The aim of the ECMO‐CS trial is to compare two recognized therapeutic approaches in the management of severe cardiogenic shock: early conservative therapy and early implantation of veno‐arterial ECMO on the background of standard care. Methods Eligible patients have either rapidly deteriorating or severe cardiogenic shock, defined using echocardiography, hemodynamic and metabolic criteria. Patients are randomized to the one of two arms: immediate veno‐arterial ECMO therapy or early conservative therapy. All other diagnostic and therapeutic procedures are performed as per current standard of care, including other cardiovascular interventions (i.e. percutaneous coronary intervention or cardiac surgery). Follow‐up includes visits at 30 days, 6 months and 12 months. Primary endpoint is a composite of death from any cause, resuscitated circulatory arrest, and implantation of another mechanical circulatory support device at 30 days. The sample size of 120 individuals (60 in each arm) provides 80% power to detect 50% reduction of primary endpoint, at alpha = 0.05. Patient recruitment started in October 2014. Conclusion The results of the ECMO‐CS trial may significantly influence current practice in the management of patients with severe and rapidly deteriorating cardiogenic shock. ECMO‐CS trial registration number is NCT02301819.

No abstract