Percutaneous Extracorporeal Life Support in Patients With Circulatory Failure: Results of the German Lifebridge Registry

Abstract: Objectives. Mortality rates remain high in patients with cardiogenic shock or acute refractory circulatory failure. Extracorporeal life support (ECLS) has been recently introduced into clinical practice for treatment of refractory hypotension in selected patients in combination with rapid restoration of gas exchange. The aim of this study was to evaluate the procedural performance and safety of the automated Lifebridge ECLS system (Zoll Lifebridge GmbH). Methods. A total of five tertiary cardiovascular centers located in Germany contributed data to this registry (n = 54 patients). Data were collected using a standardized case report form to record clinical characteristics, demographic, procedural, and follow-up data. Patients were included if they were in circulatory crisis (caused by cardiogenic shock or ongoing resuscitation) in an acute setting or in an elective setting during high-risk percutaneous intervention. Results. The Lifebridge device was successfully used in all patients. During elective use, no complications occurred besides 1 minor vascular injury. All elective patients were successfully weaned from the device and alive at the primary endpoint after 30 days. In the emergency setting, 85% of the patients were successfully weaned from the device and 49% of the patients were alive after 30 days. Relevant bleeding resulting in transfusion of red blood cells occurred in 5% of patients. Conclusion. In this observational study, we report data from the real-world use of a novel automated ECLS system. Elective use of Lifebridge was feasible and safe without major side effects. In the emergency setting, mortality rates were high; however, stabilization of the selected patients was safe and feasible.

J INVASIVE CARDIOL 2015;27(2):93-97

Key words: Lifebridge device, cardiogenic shock, resuscitation, emergency, ECMO, extracorporeal life support

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Despite recent advances in the treatment of patients with cardiogenic shock and acute refractory circulatory failure, mortality rates remain high.¹ The majority of patients with severe cardiogenic shock suffer from an acute myocardial infarction (AMI). However, intraaortic balloon pulsation (IABP) has often been used for postinterventional support of cardiac perfusion, but has failed to show any significant improvement in patient outcomes after successful revascularization.² As a consequence, clinical guidelines have been adapted for IABP use from class IB to class IIB recommendation for the treatment of refractory cardiogenic shock complicating myocardial infarction.³ 

In contrast to IABP, the concept of extracorporeal life support (ECLS) is based on the acute hemodynamic stabilization of refractory hypotension in combination with a rapid restoration of gas exchange. ECLS is capable of substantially improving survival among patients in circulatory arrest, especially if the duration of proceeding cardiopulmonary resuscitation is not too long.⁴ In addition, ECLS does not require any sustained left ventricular function and has the potential to reverse circulatory failure in patients with complete acute failure of cardiac function.⁵ Since mortality strongly increases with longer duration of cardiopulmonary resuscitation (CPR), rapid initiation of ECLS immediately reverses organ dysfunction improving outcome in such patients who would otherwise have an extremely impaired prognosis.

Another clinical situation in which mechanical cardiac assist devices have been used is during high-risk percutaneous coronary intervention (PCI).⁶ Although this remains controversial, mechanical assist devices may be considered in highly selected patients with impaired left ventricular function, significant ischemia risk affecting a large fraction of the myocardium, or impending hemodynamic instability.⁷ Numerous case reports and patient series as well as small non-randomized studies suggest a liberal prophylactic use,⁸ although this does not translate directly into reduced in-hospital mortality or reduced major cardiovascular event rate.⁹ 

The novel automated Lifebridge ECLS system (Zoll Lifebridge GmbH) is capable of rapid, secure initiation of full extracorporeal support. It allows mobile use of ECLS in non-specialized departments, intensive care units, and emergency rooms. This offers an option for rapid stabilization of patients in refractory circulatory arrest. The aim of this study was to evaluate the procedural performance and safety of the Lifebridge system in acute (cardiac arrest, severe, refractory cardiogenic shock) and elective (high-risk PCI) settings.

Methods

Study design and collection of data. A total of five tertiary cardiovascular centers located in Germany contributed data to the Lifebridge registry. The registry was designed to assess procedural characteristics and efficacy of use of the Lifebridge device. Data were collected at each site using a standardized case report form to record demographic and clinical characteristics, as well as procedural and follow-up data. Follow-up was obtained at 30 days, at the time of registry enrollment based on the medical records, and at physician or patient interviews. The investigators had full access to the data, the control of the data analysis and the final drafting of this article.

Inclusion criteria and treatment. All patients older than 18 years in need of hemodynamic support by the Lifebridge system were eligible for inclusion in this registry. This was independent of the main diagnosis that led to deterioration of circulation. In the acute setting, patients were included if they presented with: (1) systolic blood pressure ≤90 mm Hg for at least 30 minutes, ineffective vasopressor therapy, or ongoing resuscitation; (2) evidence of end-organ hypoperfusion (eg, urine output <30 mL or cold, diaphoretic extremities or altered mental status); and (3) evidence of elevated filling pressures (eg, pulmonary congestion on examination or chest radiograph), or impaired left ventricular function (LVEF ≤30%).

The decision for initiation of Lifebridge support was made at the discretion of the treating physician. Recommended exclusion criteria were: (1) patients with acute uncontrolled bleeding; (2) diseases that exclude the use of ECLS; and (3) patients who had been resuscitated for more than 2 hours. Inclusion criteria for the elective setting were: (1) planned high-risk PCI; and (2) severely impaired left ventricular function (LVEF ≤30%) or significant ischemia risk in a large fraction of the myocardium (>50% of vital myocardium at risk) or impending hemodynamic instability.

Device. The Lifebridge device is a miniaturized, compact, heart-lung support system. Its main advantages are portability due to its small dimensions and relatively low weight, rapid availability due to its “plug-and-play” design, and simple and safe applicability even for non-perfusionists due to its unique automated rapid priming and its incorporated security features. The modular construction consists of a disposable patient module with cardiopulmonary bypass circuit, control module, and base module with power supply, embedded PC, and user interface. The system weighs about 20 kg. It has incorporated a semiautomatic priming system that allows deployment within 5 minutes, and a 7-step air elimination program during priming and operation that prevents air embolization.

Procedure. The Lifebridge system was implanted via femoral access using 15-17 Fr arterial cannula and 17-21 Fr venous cannula according to the operators’ decision. After successful initiation of ECLS, the PCI was performed according to international standards by femoral or radial access.

Study endpoints. The primary study endpoint was all-cause mortality at 30 days. Secondary endpoints included procedural feasibility, the incidence of major cardiac and cerebral events (recurrent myocardial infarction, cardiovascular interventions, or stroke), device-related vascular complications (bleeding requiring transfusion or surgery), hemolysis, cardiac tamponade, and device dysfunction.

Statistical analysis. All statistical analyses including Kaplan-Meier curves were performed using SPSS statistic software, version 21.0 (SPSS, Inc). Continuous data are presented as mean ± standard deviation, while categorical variables are presented as numbers and percentages. All variables were tested for normal distribution with the Shapiro-Wilk test.

Results

Study population. Baseline characteristics of the study population are presented in Table 1. All patients were characterized by a high rate of comorbidities and cardiovascular risk factors. The majority of patients were male (76%) and overweight (body mass index >25). 

Primary study endpoint. All patients survived for at least 30 days following elective Lifebridge use. Despite poor prognosis of patients in severe hemodynamic crisis, 49% of the patients were alive at 30 days after emergency Lifebridge use. Information on successful weaning from the device as well as survival after 7 and 30 days is provided in Table 2 and Figure 1. In addition, a Kaplan-Meier curve was constructed for the emergency setting (Figure 2). 

Procedural results/safety and feasibility. Mean duration of circulatory support was 162 minutes (range, 20 minutes - 26 hours). Mean duration of support was 107 minutes (range, 20 minutes – 7 hours) in elective patients. Longer durations of Lifebridge use (mean duration time, 308 minutes) were observed in patients with acute circulatory crisis (range, 20 minutes – 26 hours). 

Procedural complication rate was very low in the elective group; only 1 vascular injury was documented without need for surgical repair.

In the emergency group, multi-organ failure occurred in 5 patients. Bleeding at the site of Lifebridge insertion occurred in 2 patients in whom transfusion of erythrocytes was required. Of note, no signs of relevant hemolysis were observed in any patient.

Discussion

In this observational study, we report data of a real-world registry evaluating a novel automated mobile ECLS system. In case of emergency ECLS implantation, we found a 30-day mortality rate of 51% in hemodynamically compromised patients. Taking into consideration that emergency ECLS was used in the setting of resuscitation and critical circulatory crisis, the data suggest an improvement of a predominantly worse prognosis. However, the limited data of this registry do not allow any final conclusions. 

Our data suggest that a strategy of prophylactic ECLS implementation in selected high-risk patients appears to be both safe and feasible. The elective use of ECLS for procedural support was associated with no significant complications and a 100% 30-day survival rate. Due to this excellent performance, this might be superior compared to other mechanical assist devices. In contrast to other methods used for periprocedural support, such as IABP and transaortic pumps,^10,11 ECLS can provide a full substitution of left ventricular function and allows physiological gas exchange during procedural support. Recently, the use of an Impella device could not demonstrate any improvement in the outcome of patients with procedural mechanical support during PCI compared to IABP.¹² Impella and IABP seem to support, at least, a moderate cardiac function. In contrast, ECLS provides an immediate treatment of hypoperfusion by establishing physiological mean arterial pressures as well as gas exchange.^13,14 This helps to preserve organ function and allows advanced treatment algorithms to address the underlying disease. Especially in the setting of acute cardiac care centers without on-site cardiac surgery, new devices such as Lifebridge might provide additional safety. In the current registry, there were no major vascular complications because of the additional cannulation of the femoral vessels with large-bore cannulae in the setting of prophylactic ECLS. This is in line with data reported by Husser et al. This group implemented a veno-arterial ECMO in selected patients with a very high-risk situation before transcutaneous aortic valve implantation.¹⁵ Hitherto, it remains unclear whether the prophylactic use of ECLS translates into improved survival rates.

In contrast, the survival after 30 days in the emergency group was 50%. Using ECLS in 10 patients in an emergency setting, Arlt et al also reported a survival of 50%.¹⁶ In reports on ECLS-supported acute settings, the outcome depends on the duration of mechanical CPR before the onset of ECLS.⁴ If resuscitation had to be performed for more than 60 minutes, the outcome was very poor. Unfortunately, data about the duration of resuscitation before ECLS were not collected systematically in our registry. In general, ECLS devices such as the Lifebridge allow the immediate start of postresuscitation care, such as the realization of mild hypothermia.¹⁷ Of note, the procedural success of Lifebridge use in the catheterization laboratory was very high, with a procedural success in 100% of the cases and a high rate of effectively weaned patients. In daily practice, implementation is very easily available since the arterial (and venous) access have already been established in the majority of patients. In our registry, percutaneous cannulation was successful in all patients; however, 2 cases of relevant bleeding requiring erythrocyte transfusion had to be observed. Nevertheless, new miniaturized ECLS systems such as Lifebridge can be highly effective and safe in emergency settings, in elective clinical settings, and in non-specialized departments. Particularly for patients in need of cardiac surgery, patient transfer to extracorporeal assistance can be more easily processed by using miniaturized ECMO systems. Proper patient selection and ECLS according to up-to-date standards is crucial for ECLS to become an effective resuscitation tool for patients in acute cardiac, pulmonary, and cardiopulmonary failure.

Study limitations. The prophylactic elective ECLS strategy was used in five centers with profound experience in treatment of critically ill patients and hemodynamic support. Therefore, the influence of experience and learning curve on the low complications cannot be excluded. Nevertheless, good clinical results seem feasible and can be safely achieved by a dedicated heart team including cardiologists, cardiac surgeons, perfusionists, and anesthesiologists. A limitation of this observational study is that we did not systematically collect the hemodynamic and vasopressor requirement in these patient populations. In addition, the current study is not randomized and cannot assess true effectiveness.

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From 1Friedrich-Schiller-University, Clinic of Internal Medicine I, Jena, Germany; 2Division of Cardiology, Bergmannsheil Hospital, Postdam, Germany; 3Städtisches Klinikum München GmbH, Klinikum Neuperlach, Department of Cardiology, Pneumology and Internal Intensive Care Medicine; 4Clinic for Thoracic Surgery, University Hospital, Ulm, Germany; 5Cardio Centrum Berlin, Charité University Medicine Berlin, Germany;  6Clinic for Thoracic Surgery, Clemenshospital, Münster, Germany; 7Clinic for Thoracic Surgery, University Hospital Mainz, Germany; 8Zoll Lifebridge GmbH, Ampfing, Germany;  9HSK, Dr Horst Schmidt Kliniken GmbH, Clinic of Internal Medicine I, Wiesbaden, Germany.

Disclosure: The authors have completed and returned the ICMJE Form for Disclosure of Potential Conflicts of Interest. Dr Bruns reports he is an employee for Zoll Medical. Dr Ferrari reports speaker honoraria from Lifebridge AG. The remaining authors report conflicts of interest regarding the content herein.

Manuscript submitted February 11, 2014, provisional acceptance given April 14, 2014, final version accepted May 9, 2014.

Address for correspondence: Christian Jung, MD, Clinic of Internal Medicine I, Friedrich-Schiller-University, Erlanger Allee 101, D–07747 Jena, Germany. Email: christian.jung@med.uni-jena.de