Left Ventricular Unloading Is Associated With Lower Mortality in Patients With Cardiogenic Shock Treated With Venoarterial Extracorporeal Membrane Oxygenation: Results From an International, Multicenter Cohort Study

Benedikt Schrage, Peter Moritz Becher, Alexander Bernhardt, Hiram Bezerra, Stefan Blankenberg, Stefan Brunner, Pascal Colson, Gaston Cudemus Deseda, Salim Dabboura, Dennis Eckner, Matthias Eden, Ingo Eitel, Derk Frank, Norbert Frey, Masaki Funamoto, Alina Goßling, Tobias Graf, Christian Hagl, Paulus Kirchhof, Danny Kupka, Ulf Landmesser, Jerry Lipinski, Mathew Lopes, Nicolas Majunke, Octavian Maniuc, Daniel McGrath, Sven Möbius-Winkler, David A Morrow, Marc Mourad, Curt Noel, Peter Nordbeck, Martin Orban, Federico Pappalardo, Sandeep M Patel, Matthias Pauschinger, Vittorio Pazzanese, Hermann Reichenspurner, Marcus Sandri, P Christian Schulze, Robert H G Schwinger, Jan-Malte Sinning, Adem Aksoy, Carsten Skurk, Lukasz Szczanowicz, Holger Thiele, Franziska Tietz, Anubodh Varshney, Lukas Wechsler, Dirk Westermann, Benedikt Schrage, Peter Moritz Becher, Alexander Bernhardt, Hiram Bezerra, Stefan Blankenberg, Stefan Brunner, Pascal Colson, Gaston Cudemus Deseda, Salim Dabboura, Dennis Eckner, Matthias Eden, Ingo Eitel, Derk Frank, Norbert Frey, Masaki Funamoto, Alina Goßling, Tobias Graf, Christian Hagl, Paulus Kirchhof, Danny Kupka, Ulf Landmesser, Jerry Lipinski, Mathew Lopes, Nicolas Majunke, Octavian Maniuc, Daniel McGrath, Sven Möbius-Winkler, David A Morrow, Marc Mourad, Curt Noel, Peter Nordbeck, Martin Orban, Federico Pappalardo, Sandeep M Patel, Matthias Pauschinger, Vittorio Pazzanese, Hermann Reichenspurner, Marcus Sandri, P Christian Schulze, Robert H G Schwinger, Jan-Malte Sinning, Adem Aksoy, Carsten Skurk, Lukasz Szczanowicz, Holger Thiele, Franziska Tietz, Anubodh Varshney, Lukas Wechsler, Dirk Westermann

Abstract

Background: Venoarterial extracorporeal membrane oxygenation (VA-ECMO) is increasingly used to treat cardiogenic shock. However, VA-ECMO might hamper myocardial recovery. The Impella unloads the left ventricle. This study aimed to evaluate whether left ventricular unloading in patients with cardiogenic shock treated with VA-ECMO was associated with lower mortality.

Methods: Data from 686 consecutive patients with cardiogenic shock treated with VA-ECMO with or without left ventricular unloading using an Impella at 16 tertiary care centers in 4 countries were collected. The association between left ventricular unloading and 30-day mortality was assessed by Cox regression models in a 1:1 propensity score-matched cohort.

Results: Left ventricular unloading was used in 337 of the 686 patients (49%). After matching, 255 patients with left ventricular unloading were compared with 255 patients without left ventricular unloading. In the matched cohort, left ventricular unloading was associated with lower 30-day mortality (hazard ratio, 0.79 [95% CI, 0.63-0.98]; P=0.03) without differences in various subgroups. Complications occurred more frequently in patients with left ventricular unloading: severe bleeding in 98 (38.4%) versus 45 (17.9%), access site-related ischemia in 55 (21.6%) versus 31 (12.3%), abdominal compartment in 23 (9.4%) versus 9 (3.7%), and renal replacement therapy in 148 (58.5%) versus 99 (39.1%).

Conclusions: In this international, multicenter cohort study, left ventricular unloading was associated with lower mortality in patients with cardiogenic shock treated with VA-ECMO, despite higher complication rates. These findings support use of left ventricular unloading in patients with cardiogenic shock treated with VA-ECMO and call for further validation, ideally in a randomized, controlled trial.

Keywords: extracorporeal membrane oxygenation; shock, cardiogenic.

Figures

Figure 1.
Figure 1.
Kaplan-Meier curve of the unmatched study cohort. ECMELLA indicates Impella+extracorporeal membrane oxygenation; HR, hazard ratio; and VA-ECMO, venoarterial extracorporeal membrane oxygenation.
Figure 2.
Figure 2.
Kaplan-Meier curve of the matched study cohort. ECMELLA indicates Impella+extracorporeal membrane oxygenation; HR, hazard ratio; and VA-ECMO, venoarterial extracorporeal membrane oxygenation.
Figure 3.
Figure 3.
Association between ECMELLA use and 30-day all-cause mortality in prespecified subgroups. P interaction is 0.79 for age <52 years versus age 52 to 62 years, 0.95 for age <52 years versus age >62 years, and 0.82 for age 52 to 62 years versus age >62 years. P interaction is 0.23 for lactate <5 mmol/L versus 5 to 10.8 mmol/L, 0.20 for <5 mmol/L versus >10.8 mmol/L, and 0.90 for 5 to 10.8 mmol/L versus >10.8 mmol/L. P interaction is 0.55 for survival after venoarterial extracorporeal membrane oxygenation (SAVE) score >−6 versus −6 to −11, 0.99 for >−6 versus <−11, and 0.52 for −6 to −11 versus <−11. P interaction is 0.16 for Simplified Acute Physiology Score II (SAPS II) <52 versus −52 to 76, 0.21 for <52 versus >76, and 0.86 for 52 to 76 versus >76. AMI indicates acute myocardial infarction; CS, cardiogenic shock; ECMELLA, Impella+extracorporeal membrane oxygenation; eCPR, venoarterial extracorporeal membrane oxygenation–assisted cardiopulmonary resuscitation; HR, hazard ratio; NS, nonsignificant; and VA-ECMO, venoarterial extracorporeal membrane oxygenation.
Figure 4.
Figure 4.
Association between ECMELLA use and severe bleeding in prespecified subgroups. P interaction is 0.30 for age <52 years versus age 52 to 62 years, 0.11 for age <52 years versus age >62 years, and 0.50 for age 52 to 62 years versus age >62 years. P interaction is 0.21 for lactate <5 mmol/L versus 5 to 10.8 mmol/L, 0.77 for <5 mmol/L versus >10.8 mmol/L, and 0.32 for 5 to 10.8 mmol/L versus >10.8 mmol/L. P interaction is 0.74 for survival after venoarterial extracorporeal membrane oxygenation (SAVE) score >−6 versus −6 to −11, 0.72 for >−6 versus <−11, and 0.97 for −6 to −11 versus <−11. P interaction is 0.70 for Simplified Acute Physiology Score II (SAPS II) <52 versus −52 to 76, 0.67 for <52 versus >76, and 0.41 for 52 to 76 versus >76. AMI indicates acute myocardial infarction; CS, cardiogenic shock; ECMELLA, Impella+extracorporeal membrane oxygenation; eCPR, venoarterial extracorporeal membrane oxygenation–assisted cardiopulmonary resuscitation; OR, odds ratio; NS, nonsignificant; and VA-ECMO, venoarterial extracorporeal membrane oxygenation.
Figure 5.
Figure 5.
Association between ECMELLA use and intervention because of access site–related ischemia in prespecified subgroups. P interaction is 0.75 for age <52 years versus age 52 to 62 years, 0.95 for age <52 years versus age >62 years, and 0.82 for age 52 to 62 years versus age >62 years. P interaction is 0.62 for lactate <5 mmol/L versus 5 to 10.8 mmol/L, 0.52 for <5 mmol/L versus >10.8 mmol/L, and 0.23 for 5 to 10.8 mmol/L versus >10.8 mmol/L. P interaction is 0.58 for survival after venoarterial extracorporeal membrane oxygenation (SAVE) score >−6 versus −6 to −11, 0.51 for >−6 versus <−11, and 0.23 for −6 to −11 versus <−11. P interaction is 0.65 for Simplified Acute Physiology Score II (SAPS II) <52 versus −52 to 76, 0.64 for <52 versus >76, and 0.31 for 52 to 76 versus >76. AMI indicates acute myocardial infarction; CS, cardiogenic shock; ECMELLA, Impella+extracorporeal membrane oxygenation; eCPR, venoarterial extracorporeal membrane oxygenation–assisted cardiopulmonary resuscitation; NS, nonsignificant; OR, odds ratio; and VA-ECMO, venoarterial extracorporeal membrane oxygenation.
Figure 6.
Figure 6.
Kaplan-Meier curves for all-cause mortality in patients receiving ECMELLA treated with early LV unloading and delayed LV unloading versus matched patients treated with only VA-ECMO.A, Only patients receiving ECMELLA in whom the Impella was implanted before or within 2 hours after the VA-ECMO implantation were considered for the matching; eg, matching patients with early LV unloading versus patients treated with VA-ECMO only. B, Only patients receiving ECMELLA in whom the Impella was implanted >2 hours after the VA-ECMO implantation were considered; eg, matching patients with delayed LV unloading versus patients treated with VA-ECMO only. ECMELLA indicates Impella+extracorporeal membrane oxygenation; HR, hazard ratio; LV, left ventricular; and VA-ECMO, venoarterial extracorporeal membrane oxygenation.

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