Original Contribution

Contemporary Use of Veno-Arterial Extracorporeal Membrane Oxygenation for Refractory Cardiogenic Shock in Acute Coronary Syndrome

Smita I. Negi, MD;  Mladen Sokolovic, MD;  Edward Koifman, MD;  Sarkis Kiramijyan, MD;  Rebecca Torguson, MPH;  Joseph Lindsay, MD;  Itsik Ben-Dor, MD;  William Suddath, MD;  Augusto Pichard, MD;  Lowell Satler, MD;  Ron Waksman, MD

Smita I. Negi, MD;  Mladen Sokolovic, MD;  Edward Koifman, MD;  Sarkis Kiramijyan, MD;  Rebecca Torguson, MPH;  Joseph Lindsay, MD;  Itsik Ben-Dor, MD;  William Suddath, MD;  Augusto Pichard, MD;  Lowell Satler, MD;  Ron Waksman, MD

Abstract: Background. Refractory cardiogenic shock (RCS) in acute myocardial infarction (AMI) is associated with high rates of mortality. Smaller ventricular assist devices, such as the intraaortic balloon pump, provide limited support. Venoarterial extracorporeal membrane oxygenation (VA-ECMO) offers more robust mechanical ventricular support, but is not widely utilized by interventional cardiologists. This study aimed to evaluate the patient characteristics and outcomes of VA-ECMO with RCS in the setting of AMI. Methods and Results. A retrospective chart review of all VA-ECMO cannulations between 2009 and 2014 was performed, and patients with an indication of RCS in AMI were identified. A total of 15 patients underwent VA-ECMO placement for AMI with RCS. One-third of these patients presented with out-of-hospital cardiac arrest, and 60% had ST-elevation myocardial infarction. The Intraaortic balloon pump was placed in addition to VA-ECMO in 60% of patients. Median duration of VA-ECMO support was 45 hours. Successful wean off VA-ECMO was obtained in 50% of the patients, and vascular complications occurred in 53% of patients. The survival rate at discharge was 47%, and all survivors were alive at 30 days post discharge. Conclusion. VA-ECMO is infrequently used in patients for cardiopulmonary resuscitation in the AMI setting. When used judiciously, it has good clinical outcomes in this group of patients. However, use of VA-ECMO should be individualized based on vascular anatomy for best results. Close cooperation among interventional cardiologists, cardiovascular surgeons, cardiologists, cardiac intensivists, and perfusionists is essential for success of this therapy for RCS in AMI.

J INVASIVE CARDIOL 2016;28(2):52-57. Epub 2015 December 15. 

Key words: acute coronary syndrome, refractory cardiogenic shock, extracorporeal membrane oxygenation

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Refractory cardiogenic shock (RCS), which is defined as hypotension with failure in cardiac output resulting in global severe organ hypoperfusion refractory to conventional medical management, 1 complicates about 20% of acute myocardial infarction (AMI) cases. It is associated with significant mortality2,3 in spite of early revascularization, advanced medical therapies, and mechanical support devices. Although commonly used in the RCS setting because of its size and physician familiarity, the intraaortic balloon pump (IABP) has limited benefit, as shown in recent randomized trials.4-6

Mechanical circulatory support system with extracorporeal membrane oxygenation (ECMO) is a percutaneous support strategy primarily utilized in critical care medicine for management of severe acute respiratory distress syndrome unresponsive to mechanical ventilation.7,8 The advantage of venoarterial (VA)-ECMO over other percutaneous devices, such as IABP, TandemHeart (Cardiac Assist, Inc), and Impella devices (Abiomed), lies in the robust left ventricular (LV) support it provides, with concomitant right ventricular support and improvement in tissue oxygenation. In spite of these advantages, use of VA-ECMO has remained limited in the AMI population. This is primarily because of the lack of familiarity with the device among interventional cardiologists. In addition, there are limited data available to support its use in this subset of patients.1,9-11 Most large studies that evaluated the use of VA-ECMO included heterogeneous patients with non-cardiogenic shock, advanced heart failure, myocarditis, and unstable malignant ventricular arrhythmias. These are diverse pathophysiologies, with varying rapidity of onset, acuity of presentation, and reversibility of cause. These conditions are also not comparable in terms of their clinical outcomes. So far, very few studies have looked exclusively at the use of VA-ECMO in the AMI population.     

With this current series, the authors attempt to focus on the use of VA-ECMO by interventional cardiologists in the cardiac catheterization laboratory for RCS complicated by AMI and to determine the characteristics and outcomes of patients who were assigned to this treatment.  

Methods

Consecutive VA-ECMO insertions performed at the MedStar Washington Hospital Center in Washington, DC, during 2009-2014 were retrospectively screened from a cardiopulmonary support database. Patients undergoing VA-ECMO placement for an indication of RCS or cardiopulmonary resuscitation in the AMI setting or out-of-hospital cardiac arrest (OHCA) were included. Those undergoing ECMO placement for non-cardiogenic shock, fulminant myocarditis, decompensated heart failure, pulmonary embolism, or malignant arrhythmias without a presentation of AMI, or with a life expectancy of <1 month were excluded from the analysis (Figure 1).

The VA-ECMO was set up using standard techniques. A cardiothoracic vascular surgery team and perfusionist were present in the cardiac catheterization lab during cannulation. The femoral VA access route was accessed either percutaneously or by cut-down. The arterial cannula was placed in the distal aorta, proximal to the iliac bifurcation. The tip of the venous cannula was placed at the junction of inferior vena cava and the right atrium. Where needed, an antegrade arterial access was established to prevent distal limb ischemia in the cannulated lower extremity. Intravenous unfractionated heparin was utilized as the initial agent for anticoagulant in all cases.  

Coronary angiography was performed in all patients either before or after VA-ECMO insertion. Based on the coronary anatomy seen on angiogram, percutaneous coronary intervention (PCI), referral for coronary bypass artery grafting, or deferral of intervention and medical management were performed at the discretion of the interventional cardiologist and the heart team. All patients were started on standard post-AMI therapy unless contraindicated. 

AMI was defined as a combination of clinical signs and symptoms with presence of ST-segment elevation on electrocardiogram and/or elevated cardiac biomarkers per universal definition.12 PCI was performed in patients who were found to have significant coronary artery luminal stenosis believed to be the culprit lesion responsible for the clinical presentation or findings suggestive of an unstable lesion. RCS was defined as cardiogenic shock and hypotension unresponsive to conventional medical therapy: systolic blood pressure <90 mm Hg (or mean arterial pressure <60 mm Hg) and evidence of end-organ hypoperfusion in the presence of ≥2 parenteral inotropes or use of IABP or Impella. While on VA-ECMO, patients were closely monitored by a team of cardiac intensivists, nurse practitioners, and perfusionists. Successful weaning was defined as patients who were taken off ECMO during hospitalization. Those unable to be weaned off VA-ECMO were upgraded to a surgical left ventricular assist device (LVAD) and followed up by the advanced heart failure team. 

Baseline demographic, clinical, and laboratory data were collected through a retrospective chart review process. Procedural data, in-hospital complications, and disposition/discharge and outpatient follow-up status were recorded. 

Statistical analysis. Continuous variables were presented as mean ± standard deviation or median (range), where appropriate, and categorical variables were presented as percentages. The study protocol was approved by the Institutional Review Board for MedStar Washington Hospital Center.

Results

A total of 15 patients underwent VA-ECMO cannulation for AMI with RCS during the study period (Table 1). The mean age of the population was 57 ± 13 years. Sixty percent were male. None of the patients had significant valvular heart disease, history of a prior cerebrovascular event, or presence of end-stage renal disease at presentation (Table 2). One-third of patients presented with OHCA. Sixty percent presented with ST-segment elevation myocardial infarction (STEMI), and the median door-to-balloon time for STEMI patients was 60 minutes. Peak troponin I concentration was 82 ± 64 ng/L, and peak lactate was 21 ± 27 mmol/L during hospitalization. Median time to presentation with shock to VA-ECMO insertion was 95 minutes. The majority of patients had VA-ECMO placed post PCI. Ninety-three percent of patients were on two or more inotropes at the time of VA-ECMO placement, and 60% of patients had an IABP device placed prior to VA-ECMO. All patients undergoing PCI of the culprit lesion had procedural success and Thrombolysis in Myocardial Infarction (TIMI) grade-3 flow post intervention. Median duration of VA-ECMO support was 45 hours. Vascular complications related to VA-ECMO occurred in 53% of patients. Over 50% of patients were weaned off VA-ECMO, and 47% survived to discharge. One patient was transitioned to a surgical LVAD. None of the patients required transition to biventricular ventricular assist device. Similarly, none of the patients needed transitioning to IABP or Impella device after weaning off VA-ECMO. 

The majority (87%) of those weaned off VA-ECMO survived to discharge. However, vascular complications, such as limb ischemia and bleeding requiring surgery, were common and occurred in 53% of patients. Of those patients who survived to discharge, all were alive at 1-month follow-up (Table 3).

Discussion

The present study is one of the few contemporary series that has specifically looked at the experience with VA-ECMO use in AMI populations (Table 4).1,9-11 Our study found similar 30-day survival rates in RCS-AMI patients treated with VA-ECMO compared with other studies looking at this population.  

In this series, the authors found a little less than one-half of patients with VA-ECMO placement survived to discharge. These results are more encouraging than those from other studies utilizing a similar patient population.1,9-11 Overall, survival rates in this study reflect the present survival rates of AMI with RCS in general.2 Females had a better rate of survival than men in our cohort. This is contrary to what has been shown in previous studies.13 As would be expected, the deceased had more comorbidities and a higher prevalence of left main or multivessel coronary artery disease. These represented sicker patients with larger infarct sizes, as suggested by higher peak troponin levels attained. Additionally, those who survived had less severe degree of shock as evidenced by lower lactate levels. Overall, these survival rates are better that those seen with other forms of cardiogenic shock in non-AMI populations. This is likely because of the potential reversibility of etiology in AMI patients.

An interesting finding of this study was the lack of association of presentation with cardiac arrest to survival. This suggests that clinical presentation does not affect survival once refractory shock sets in and is consistent with other studies.13

Complications occurred more frequently in the deceased group, except for vascular complications, such as bleeding requiring surgery, compartment syndrome, and limb ischemia, which were more frequent in the group who survived. A possible explanation for this could be the survival bias, as most of these complications occurred at least 24-48 hours after VA-ECMO insertion, by which time the majority of patients in the non-survivor group were already dead. In the present series, higher bleeding complication rates with VA-ECMO were recorded when compared with previous studies.10,11 This may be the result of employing more aggressive antiplatelet and antithrombotic agent strategies in the present era for AMI. 

Intraaortic balloon counterpulsation was the first mechanical support device utilized in the majority of subjects in this study. This is in keeping with the current management of RCS with AMI.1,9-11 In this study, IABP insertion was seen more frequently in the non-survivor group, which was likely a marker of a more severe degree of shock. This is contrary to some previous studies where use of IABP with VA-ECMO was associated with better outcomes.11 It can be argued that placing IABP in these individuals cost time and led to a delay in initiating more definitive LV support in the form of VA-ECMO. However, VA-ECMO by itself may not reduce ventricular wall stress and thus not reduce the size of ischemic myocardium. In this situation, additional LV unloading with an IABP or Impella may provide myocardial protection and improve coronary blood flow.14

The major impediment in the utilization of ECMO in AMI is concern over the cumbersomeness of the procedure. However, VA-ECMO is easily inserted and provides a robust support in RCS when compared with smaller support devices, such as IABP or Impella.15 In addition, IABP and Impella are contraindicated in the presence of aortic valve disease, such as aortic insufficiency and severe aortic stenosis and mechanical aortic valve. Another advantage of VA-ECMO is biventricular support, and this may be especially beneficial in patients with right ventricular infarctions. In addition, VA-ECMO is especially suited for cases of RCS with impaired oxygenation. Outcomes of IABP use in AMI have been discouraging based on recent clinical trials.5 Similarly, use of Impella 2.5 in RCS has not shown any survival benefit.16 Results of Impella 5.0 vs 2.5 showed improved survival in the 5.0 group. This may be due to both better mechanical support as well as marked reduction in oxygen demand, which preserves myocardial function.17 However, currently no head-to-head comparison is available between Impella 5.0 vs ECMO in the AMI population. Similarly, no large-scale study has looked at the use of VA-ECMO in AMI, and existing knowledge is primarily based on small case series.       

Vascular complications continue to be seen in a high proportion of patients undergoing VA-ECMO placement in AMI and are one of the major drivers of morbidity and mortality in these patients. In our study, we found that almost 40% of patients developed vascular complications post VA-ECMO insertion. This is consistent with the vascular complication rate seen in recent studies.10 For this reason, patients with severe peripheral vascular disease should not undergo peripheral cannulation. Antegrade arterial sheath distal to the site of cannulation may be used to prevent limb ischemia. Similarly, both access-site and non-access site bleeding are common with VA-ECMO use and are related to anticoagulants used to prevent thrombosis of the oxygenator and the cannulae. In addition, most AMI patients also receive potent antiplatelet agents, which further increase bleeding risk. The timing of VA-ECMO insertion before vs after PCI had no impact on survival. This finding is in contrast to IABP, where both preclinical18 and clinical19,20 studies have shown that pre-PCI insertion improves outcomes. Similarly, pre-PCI initiation of hemodynamic support with Impella 2.5 has been associated with more complete revascularization and improved survival in RCS with AMI. This may be because patients with VA-ECMO had larger infarcts and were sicker, with a severe degree of shock. Moreover, VA-ECMO was inserted as a salvage measure after IABP had failed to provide optimal support. 

In this study, the median time between presentation with shock or arrest to VA-ECMO insertion was 95 minutes. Consistent and timely use of VA-ECMO in AMI or OHCA patients requires a round-the-clock cardiothoracic surgery back-up, a mature and skilled cardiac intensive care service, and preferably an advanced heart failure program set-up. An established advanced heart failure center may implant an LVAD in cases where weaning off VA-ECMO fails.

Study limitations. The major limitation of this study was the small number of patients and the retrospective, single-center study design. There was no direct comparison with any other treatment strategy, such as Impella 3.5 and TandemHeart. However, the current use and reported outcomes of patients undergoing VA-ECMO in RCS with AMI are sparse. 

Conclusion

The use of VA-ECMO is a feasible option in the cardiac catheterization lab setting and should be considered in patients with AMI complicated by RCS. Consistent improvement in survival is being observed with the use of this device in this population. Careful patient selection and timely insertion of this device can further improve the outcomes. A special team consisting of an interventional cardiologist, vascular surgeon, and perfusionist, as well as cardiac intensivists, should be trained to manage these patients with well-defined protocols. Additionally, special prophylactic management of arterial perfusion should be applied during the procedure. The use of VA-ECMO should continue to be refined to optimize outcomes in this complex patient population. 

References

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19.     Bergh N, Angerås O, Albertsson P, et al. Does the timing of treatment with intra-aortic balloon counterpulsation in cardiogenic shock due to ST-elevation myocardial infarction affect survival? Acute Card Care. 2014;16:57-62. 

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From the Section of Interventional Cardiology, MedStar Washington Hospital Center, Washington, DC.

Disclosure: The authors have completed and returned the ICMJE Form for Disclosure of Potential Conflicts of Interest. Dr Satler reports speakers fees from Abbott, AstraZeneca, and Boston Scientific. Dr Waksman reports personal fees from Biotronik, Medtronic, AstraZeneca, Boston Scientific, Abbott Vascular, and St. Jude Medical; grants from AstraZeneca, Boston Scientific, The Medicines Company, and Edwards Lifesciences. The remaining authors report no conflicts of interest regarding the content herein.

Manuscript submitted April 22, 2015, provisional acceptance given June 3, 2015, final version accepted July 31, 2015.

Address for correspondence: Ron Waksman, MD, FACC, FSCAI, Section of Interventional Cardiology, MedStar Washington Hospital Center/Georgetown University, 110 Irving Street NW, Suite 4B-1, Washington DC, 20010. Email: ron.waksman@medstar.net

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