PMC9674118_01
Timeline ("chain of survival") with data on the episodes of care. The timeline ("chain of survival") reflects the pre-, intra- and post-hospital course of the cardiac arrest patient, which includes the period from onset of patient symptoms for suspected STE-ACS to hospital discharge and follow-up assessment in the ECPR Outpatient Care Program of the Cardiac Arrest Center. Each location is displayed at the bottom (light yellow color). Each critical clinical diagnosis is highlighted with red arrows (and lightning symbols) at the timeline. The provided medical procedures are colorized by organ system: cardiovascular system (red), pulmonary system (dark yellow), renal system (green) and non-specific (blue). The image scaling does not correlate with the actual time. Abbreviations: acute lung injury (ALI); cardiopulmonary resuscitation (CPR); emergency medical service (EMS); left ventricle (LV); ST-segment elevation acute coronary syndrome (STE-ACS); veno-arterial extracorporeal membrane oxygenation (VA ECMO); veno-arterio-venous ECMO (VAV ECMO).
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F1
Upon discretion of the ECPR team, VA ECMO support was initiated after 32 min of total low-flow time (Figures 1, 2A). ECMO revealed a proximal occlusion of the right coronary artery, which was successfully revascularized with two drug eluting stents. Echocardiographic LV distension was detected in the asystolic patient, wherefore a LV micro-axial pump (Impella CP ) was inserted transfemorally to ensure LV unloading and increase cardiac output (Figures 1, 2B) (ECMELLA). Metabolic homeostasis, i.e., pH and lactate levels, was reached within days, while kidney function recovered and infection, i.e., leukocytes and C-reactive protein levels, diminished after antibiotic treatment (Supplementary Figure 1 in Supplementary material).
(A-C) Diagram on configurations of percutaneous mechanical circulatory support devices. (A) Peripheral VA ECMO. Poorly oxygenated blood is drawn from the femoral vein, oxygenated in a membrane oxygenator and returned by a centrifugal pump via the common femoral artery. (B) VA ECMO and Impella  pump ("ECMELLA"). The Impella  pump is placed across the aortic valve to provide continuous blood flow from the LV into the proximal ascending aorta. (C) VAV ECMO and Impella . VAV ECMO is a triple cannulation technique by "upgrading" the VA ECMO configuration. A third cannula is inserted into the jugular or subclavian vein. The ECMO outflow with oxygenated blood is diverted into two cannulas by a Y-connector, one cannula toward the aorta via the common femoral artery and one toward the right atrium via the jugular or subclavian vein. Flow regulators control blood flow into the arterial and venous circuit, respectively. Abbreviations: left ventricle (LV); veno-arterial extracorporeal membrane oxygenation (VA ECMO); veno-arterio-venous ECMO (VAV ECMO).
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F2
Upon discretion of the ECPR team, VA ECMO support was initiated after 32 min of total low-flow time (Figures 1, 2A). ECMO revealed a proximal occlusion of the right coronary artery, which was successfully revascularized with two drug eluting stents. Echocardiographic LV distension was detected in the asystolic patient, wherefore a LV micro-axial pump (Impella CP ) was inserted transfemorally to ensure LV unloading and increase cardiac output (Figures 1, 2B) (ECMELLA). Optimization of ventilator settings were not sufficient, wherefore - according to guidelines by the Extracorporeal Life Support Organization (ELSO) guidelines - VA ECMO was converted to VAV ECMO via the right jugular vein, while continuing concomitant Impella  support (Figure 2C).
(A-E) Left-ventricular unloading in a patient with out-of-hospital cardiac arrest treated with VAV ECMO and Impella  pump. Raw data were retrospectively retrieved from the Impella CP  console (Abiomed, Danvers, USA). For each given time point after initiation of ECMELLA therapy (T0) the estimated left-ventricular pressure (LVP in mmHg), aortic pressure (AoP in mmHg, derived from Impella  pressure sensor) or mean arterial pressure (MAP in mmHg), as well as Impella  motor current (milliampere, mA), Impella  motor speed (rotations per minute, rpm) and Impella  pump flow (liters per minute, L/min) are displayed. LVP was estimated based on AoP and pressure gradient (DeltaP in mmHg, derived from Impella  motor current) as follows: LVP = AoP -DeltaP. (A) Impella CP  was inserted transfemorally in an asystolic patient with pre-existing VA ECMO. Displayed are the first 34 s after start of Impella CP  indicated by increasing motor current and motor speed. Depending on the Impella CP  flow (up to 2 L/min), the estimated LVP decreased to 9 mmHg (i.e., LV unloading indicated by red arrow). Therefore, despite asystole, the patient exhibited physiologic AoP (i.e., 75 mmHg) provided by VA ECMO flow of 4 L/min with sufficient unloading of the LV (physiologic LVP - LVEDP of 9 mmHg). (B) The patient remained in asystole without ROSC for approximately two hours after initiation of ECMELLA therapy indicated by static AoP and estimated LVP (no pulsatility). In this case, an Impella  pump flow of 1 L/min was sufficient to unload the LV (estimated LVP, i.e., LVEDP under asystole of 9mmHg) while a VA ECMO flow of 4 L/min provided a sufficient hemodynamic support (i.e., MAP 100 mmHg). (C) ROSC with sinus rhythm was achieved after approximately two hours following initiation of ECMELLA therapy as being indicated by undulating estimated LVP (pulsatility indicating cardiac contractions). Flat AoP (greater than estimated LVP) indicates lack of aortic valve opening. Of note, Impella  pump flow was set to 2.5 L/min which reduced LV preload. VA ECMO flow was set to 4 L/min. (D) Two days after ICU admission, VA ECMO therapy was advanced to VAV ECMO therapy while the Impella  pump remained inserted. Induction of VAV ECMO therapy (i.e., reduction of ECMO outflow to the aorta and therefore reduction in LV afterload) was associated with increased mean Impella  pump flow (increase in Impella  pump flow of 0,48 L/min, indicated by red line) with given constant pump settings (Impella  motor current). Impella pump flow was 2.7 L/min, VA ECMO flow was 2.5 L/min and VAV ECMO flow was 1.5 L/min. (E) Differential hypoxemia was successfully reversed by VAV-ECMELLA. LV function fully recovered over the next days. Estimated LVP was now greater than AoP resulting in opening of aortic valve and pulsatile aortic pressures (MAP 75 mmHg) despite unloading (Impella  pump flow 2 L/min). ECMO flow was 1.5 L/min. Abbreviations: ECMELLA (VA ECMO plus Impella CP ); intensive care unit (ICU); left-ventricular (LV); return of spontaneous circulation (ROSC); veno-arterial extracorporeal membrane oxygenation (VA ECMO); VAV-ECMELLA (VAV ECMO plus Impella CP ).
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F3
Upon addition of Impella  support, the estimated mean intracavitary left-ventricular pressure (LVP) decreased from 78 to 9 mmHg within 20 seconds (Figure 3A). Despite coronary revascularization, the patient remained in asystole while ECMELLA provided adequate systemic hemodynamic support, i.e., aortic pressure of approximately 70mmHg, while assuring optimal LV loading conditions at a level comparable to physiological diastolic LVPs (Figure 3B). ROSC (sinus rhythm with pulsatile LVPs) was ultimately observed approximately two hours after ECMELLA initiation (Figure 3C). This resulted in reduced LV afterload and increased Impella  pump flow (Figure 3D). Finally, the patient recovered clinically and hemodynamically including increasing LVPs, aortic valve re-opening and improved LV ejection fraction (LVEF) (Figure 3E), allowing for stepwise weaning from VAV ECMO and Impella .
(A-D) Occurrence and treatment of differential hypoxemia during VA ECMO treatment. (A)
No cardiac function. Systemic perfusion with oxygenated blood (indicated by dark red color) is solely dependent from VA ECMO flow which is infused retrogradely toward the heart. (B) Recovery of cardiac function with impaired pulmonary gas exchange. The LV starts ejecting poorly oxygenated blood from the pulmonary circulation (indicated by blue color) that mixes with oxygenated blood from the VA ECMO ("watershed" or "mixing cloud"). The location of the "watershed" depends on the LV function and the VA ECMO flow. With severe myocardial dysfunction (e.g., due to cardiac arrest), the watershed is close to or at (if asystolic patient) the aortic valve. (C)
Harlequin phenomenon. With improving LV function, the "watershed" may move more distally in the aortic arch. As a result, given impaired pulmonary function, poorly oxygenated blood from the LV is ejected into the aortic arch, coronary and cerebral arteries, resulting in ischemia and cyanosis of the upper body (in this case, right upper body), while the lower body is sufficiently oxygenated by the VA ECMO circuit. This phenomenon is known as differential hypoxemia, watershed phenomenon, two-circulation syndrome or Harlequin phenomenon. (D)
VAV ECMO. The Harlequin phenomenon (Figure 3C) can be treated by converting VA ECMO to VAV ECMO. Thus, ECMO-oxygenated blood (indicated by lighter red color) is infused from a third ECMO cannula via the jugular or subclavian vein through and the pulmonary circulation into the LV and upper body (see Figure 1C). Abbreviations: left ventricle (LV); veno-arterial extracorporeal membrane oxygenation (VA ECMO); veno-arterio-venous ECMO (VAV ECMO).
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NIRS readings and right radial arterial blood oxygen saturation remained impaired, indicating hypoxemia of the upper body compatible with differential hypoxemia (Figures 4A-C). As a result, NIRS readings and right radial oxygen saturations normalized (Figure 4D).