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End-Organ Recovery Is Key to Success for Extracorporeal Membrane Oxygenation as a Bridge to Implantable Left Ventricular Assist Device

Durinka, Joel B.*; Bogar, Linda J.; Hirose, Hitoshi*; Brehm, Chris; Koerner, Michael M.; Pae, Walter E.; El-Banayosy, Aly; Stephenson, Edward R.; Cavarocchi, Nicholas C.*

doi: 10.1097/MAT.0000000000000043
Adult Circulatory Support

Preexisting organ dysfunctions are known factors of death after placement of implantable mechanical circulatory support (MCS). Extracorporeal membrane oxygenation (ECMO) may able to stabilize organ function in patients with cardiogenic shock before MCS implantation. Between 2008 and 2012, 17 patients with cardiogenic shock were supported with ECMO before implantable MCS placement. Patient’s end-organ functions were assessed by metabolic, cardiac, hepatic, renal, and respiratory parameters. Survival data after MCS implantations were analyzed for overall survival to discharge, complications, and breakpoint in days on ECMO to survival. Before MCS implantation, lactate, hepatic, and renal functions were improved and pulmonary edema was resolved. The interval between ECMO initiation and MCS placement was 12.1 ± 7.9 days. Overall survival rate to discharge after left ventricular assist device/total artificial heart placement was 76%. The survival of patients transitioned from ECMO to MCS within 14 days was 92% and was significantly better than the survival of patients from ECMO to MCS supported longer than 14 days, 25%, p < 0.05. ECMO support can immediately stabilize organ dysfunction in patients with cardiogenic shock. After improvement of organ function, MCS implantation should be done without delay, since the patients supported for longer than 14 days with ECMO had inferior survival compared to national data.

From the *Division of Cardiothoracic Surgery, Department of Surgery, Thomas Jefferson University, Philadelphia, Pennsylvania; Division of Cardiothoracic Surgery, Department of Surgery, Thomas Jefferson University, Philadelphia, Pennsylvania. Currently, Division of Cardiothoracic Surgery, Inova Health System, Falls Church, Virginia; and Heart and Vascular Institute, Penn State Hershey Medical Center, Hershey, Pennsylvania.

Submitted for consideration September 2013; accepted for publication in revised form November 2013.

Abstract was presented at ASAIO’s 59th Annual Conference. Chicago, IL. June 12–15, 2013.

Disclosure: The authors have no conflicts of interest to report.

Reprint Requests: Hitoshi Hirose, MD, Division of Cardiothoracic Surgery, Department of Surgery, Thomas Jefferson University, 1025 Walnut Street, Suite 605, Philadelphia, PA 19107. Email:

The use of the left ventricular assist device (LVAD) or total artificial heart (TAH) is becoming a viable clinical alternative to heart transplantation, not only as a bridge to transplantation but also as a destination therapy.1–3 Patients with severe heart failure, which is refractory to medical therapy, are potential candidates for LVAD/TAH implantation, and some of them may experience unpredictable, acute decompensated heart failure, including cardiogenic shock. Once these patients show sudden circulatory deterioration, multiple organ system failure may occur.

Preexisting organ dysfunction has unfavorably affected patient survival after ventricular assist device implantation, particular shown in the Interagency Registry for Mechanically Assisted Circulatory Support (INTERMACS) data, where class 1 survival is less than 45%.4 Although LVADs have been shown to be able to reverse end-organ failure in some patients,1–3,5–7 the pathophysiologic mechanism of end-organ failure and its recovery are not fully understood. Furthermore, the clinical markers and threshold beyond which recovery is unlikely to occur remain unknown. Extracorporeal membrane oxygenation (ECMO) support is a well-established technology that provides temporary circulatory support to recover end-organ function in patients who present with severe hemodynamic instability associated with multiple organ failure.1–3,5–7 Once hemodynamics are restored and organ function has recovered, long-term circulatory function can be maintained with an early bridge to a ventricular assist device1 or TAH. In patients with severe multiple organ failure not resolving on ECMO support, LVAD/TAH implantation is not recommended due to irreversible end-organ injury created during the insults of cardiogenic shock.7 This report presents our experience of using ECMO as a bridge to LVAD/TAH implantation at two university hospitals in patients with cardiogenic shock.

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Between September 2007 and July 2012, 58 consecutive patients presented with cardiogenic shock (INTERMACS class 1 in all patients) and were placed on VA-ECMO (veno-arterial ECMO) for circulatory support at our institutions. Among them, 17 (29%) were bridged to LVAD/TAH. The end-organ data and outcomes data from these patients were entered into a structured database approved for research by the individual local internal review board, and their demographic information is shown in Table 1.

Table 1

Table 1

Of the 58 ECMO patients, 13 (22%) recovered cardiac function and ECMO was removed successfully with optimal medical treatment without LVAD/TAH. None of the patients received cardiac transplants. Twenty-eight patients (48%) died on ECMO due to stroke (2), sepsis (6), anoxic brain injury (3), and others (17).

All patients were cannulated peripherally via percutaneous insertion of the ECMO cannula using the Seldinger technique. Femoral cannulation was the preferred placement in all patients on VA-ECMO. Distal arterial perfusion ports were placed in all patients. The arterial and venous HLS cannulae (Maquet San Jose, CA) were connected to a closed crystalloid primed circuit (~300 ml). The circuitry for ECMO consisted of the diffusion membrane hollow fiber oxygenator (Quadrox-D oxygenator, Maquet) and a Rotaflow (Maquet). Patients were anticoagulated to achieve a partial thromboplastin time between 50 and 60 seconds. Maintenance of adequate systemic blood flow was monitored by mean arterial pressure, blood lactate concentrations, central or mixed venous oxygen saturation, urine output, and cerebral oximetry. Mean arterial pressure was maintained between 60 and 80 mm Hg with vasopressor or vasodilator administration. Maintaining residual left ventricular ejection was also expected to reduce the risk of intracardiac clot formation. The patients were aggressively diuresed with a goal of aiming for baseline body weight and resolution of both peripheral and pulmonary edema.

Biological markers of stabilization and recovery included assessment of metabolic, liver, renal, and respiratory parameters. Once these parameters normalized and the patient had a normal neurological examination while sedation was held, the patient was assessed for LVAD/TAH implementation. Before LVAD/TAH placement, the patients were expected to be afebrile, alert without neurological deficit, euvolemic, and tolerant to 50% of oxygen support on both ECMO and ventilator. Weaning trials were performed using echocardiography to access left and right ventricular functions.8 Patients with isolated left ventricular dysfunction underwent implantable LVAD (HeartMate II, Thoratec, Pleasanton, CA) placement and patients with biventricular dysfunction underwent TAH (SynCardia Tucson, AZ) placement. Outcomes data after LVAD/TAH placement were studied until hospital discharge.

The data collected were expressed as a number with percentage or mean ± standard deviation. Categorical variables were compared using the χ 2 test or Fisher’s exact test, and continuous variables were compared using Standard t-test. p-value of less than 0.05 was considered significant.

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End-organ data before ECMO (pre-ECMO) and before LVAD/TAH placement (post-ECMO) are shown in Table 2.

Table 2

Table 2

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Lactate improved from 2.8 ± 2.5 mmol/L to 1.7 ± 1.1 mmol/L.

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Before initiation of ECMO, the liver enzymes were elevated in all 17 patients. During ECMO support, liver function improved; aspartate aminotransferase (AST) decreased from 166 ± 239 IU/L at the time of ECMO implantation to 61 ± 7 IU/L at the time of LVAD/TAH implantation. alanine aminotransferase (ALT) decreased from 140 ± 193 to 68 ± 65 IU/L and the total bilirubin decreased from 5.6 ± 7.2 to 2.0 ± 1.7 mg/dl.

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All patients had elevated creatinine and blood urea nitrogen levels before initiation of ECMO. With ECMO support, renal function improved: creatinine levels decreased from 1.7 ± 0.5 to 1.3 ± 0.7 mg/dl and none of the patients required dialysis.

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LVAD/TAH placement.

ECMO–LVAD/TAH time interval was 12.1 ± 7.9 days (range, 3–26 days). There were 14 complications while on ECMO support >14 days (Table 3); there were no complications in the patients on ECMO <14 days. Before the removal of ECMO (LVAD/TAH insertion), all patients on ECMO were hemodynamically stable, afebrile, euvolemic, and free of infection. In all patients, ECMO was removed in the operative room during LVAD or TAH implantation; there were no episodes of pulmonary or heart failure post-ECMO removal.

Table 3

Table 3

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Survival analyses

There were four patient deaths after LVAD/TAH placement (Table 3); all received LVADs. One patient who was on ECMO for 6 days died of an intracranial hemorrhage in the perioperative period. Three other deaths occurred in patients who were on ECMO support longer than 14 days; and all of these patients died from sepsis and multiple organ failure. There were no other post-ECMO complications contributing to mortality.

Overall survival to discharge after LVAD/TAH placement was 76% (13/17). The survival to discharge among those who transitioned off ECMO within 14 days was 92% (12/13), which was significantly better than the survival to discharge among those who were on ECMO longer than 14 days, 25% (1/4), p < 0.05. The survival rate of the patients who were supported on ECMO longer than 14 days (25%) was inferior to the LVAD survivals for the patients with INTERMACS class 1 (45%).

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Preexisting organ dysfunction has unfavorably affected patient survival after LVAD/TAH implantation particularly in INTERMACS class 1 patients.4 Although LVAD/TAHs have been shown to reverse end-organ failure in some patients,1–3,5–7 the pathophysiologic mechanism of end-organ failure and its recovery are not fully understood; clinical markers and thresholds beyond which recovery is unlikely to occur remain unknown. Ventricular assist devices have become an accepted and effective therapy as a bridge to cardiac transplantation and bridge to recovery. Left ventricular assist device and TAH are also used as a destination therapy for patients without the option for heart transplantation. However, there is a risk of dying from end-organ damage present at the time of implantation. In an effort to restore circulatory stability in these patients, we have instituted the early aggressive application of ECMO. Once circulatory hemodynamics were restored, our management focused on neurologic, metabolic, liver, kidney, and respiratory function. Metabolic, liver, and kidney functions were defined as the return of the transaminases and creatinine to near-normal limits during the ECMO support.1

In all of our patients, liver and kidney function improved during ECMO support. Because it is difficult to define the right time to implant an assist device, we think that a successful outcome after LVAD/TAH implantation requires the transaminases and creatinine to show near-normal values. In the literature, the bridge-to-bridge concept is still discussed in controversial terms. Magliato9 reported 26% survival rates in the bridge-to-bridge population and favored primary LVAD implantation. Pagani et al.10 described their experience with ECMO support followed by LVAD implantation, and they have found that ECMO can be used for assessment of the degree of end-organ recovery. Pennington et al.11 described consecutive mechanical circulatory support with ECMO and LVAD as “double-bridge resuscitation” to cardiac transplantation; 11 of their 23 patients died during ECMO support. Our results were superior to the preceding published cohorts, with our survival to discharge among those who transitioned off ECMO within 14 days of 92%. This may be due to a combination of patient selection and end-organ focused management.

The question then remains: Should we or should we not favor primary LVAD/TAH implantation in patients with cardiogenic shock? In our opinion, the immediate transfer to LVAD/TAH from cardiogenic shock may not acutely re-establish sufficient cardiac output to perfuse all vital organs and recover end-organ functions. At our institution, patients presenting with cardiogenic shock with end-organ injury are stabilized with ECMO support instead of insertion of VAD/TAH as a primary rescue device, since the outcomes of emergent LVAD/TAH with end-organ injury are dismal. Using this concept, we have achieved an overall survival rate of 76%, one of the highest reported to date in the literature and a survival rate of 92% in those patients who were successfully transitioned from ECMO–LVAD/TAH within 14 days.11 This is significantly better than the INTERMACS I patients who have primary LVAD placed with a resulting survival rate of less than 45%.3

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This study was limited due to the retrospective nature of the study and small sample size in two different institutions although the management of the patients in the two institutions was identical. Since the focus of this study was the effect of ECMO on cardiogenic shock, all patients fell into the category of INTERMACS class 1 before ECMO placement; therefore, we do not have data on the other classes of patients who were supported with ECMO. The pre-LVAD/TAH INTERMACS class was difficult to determine; thus, the pre-LVAD/TAH INTERMACS class was not studied in this series, instead we analyzed end-organ data.

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In summary, our results show that ECMO support can immediately stabilize circulation and provide organ perfusion in patients with cardiogenic shock. After improvement of metabolic, liver, kidney, and respiratory function, LVAD/TAH implantation can be performed successfully in these patients. Given the data shown in this study, patients who are successfully transitioned from ECMO to LVAD/TAH within 14 days have a higher survival rate and lower complication rate compared to ECMO support more than 14 days. Those outcomes on ECMO support more than 14 days were inferior to the national data of LVAD/TAH on INTERMACS class 1. Thus, we recommend LVAD/TAH placement as soon as end-organs recover in patients on ECMO for cardiogenic shock.

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left ventricular assist device; total artificial heart; extracorporeal membrane oxygenation; cardiogenic shock; bridge therapy

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