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VA-ECMO With IABP is Associated With Better Outcome Than VA-ECMO Alone in the Treatment of Cardiogenic Shock in ST-Elevation Myocardial Infarction
Abstract: Objective. To assess whether combining venoarterial extracorporeal membrane oxygenation (VA-ECMO) with intra-aortic balloon pump (IABP) improves outcomes in ST-segment elevation myocardial infarction (STEMI) over VA-ECMO alone. Background. VA-ECMO is an upcoming technique in the treatment of cardiogenic shock (CS); however, it increases afterload. IABP + VA-ECMO has been suggested to reduce afterload and increase survival. Methods. A multicenter in-hospital registry was maintained on all patients undergoing VA-ECMO or VA-ECMO + IABP treatment for CS in STEMI. Results. Between 2015 and 2018, a total of 18 patients with STEMI underwent VA-ECMO ± IABP treatment for CS. The majority (n = 14; 78%) were male and median age was 59 years (interquartile range, 47-75 years). VA-ECMO + IABP was performed in 7 patients (39%) and VA-ECMO alone was performed in 11 patients (61%). The VA-ECMO + IABP group had more complex coronary anatomy and a higher number of patients with left main (LM) disease, LM + 3-vessel disease, or 3-vessel disease (VA-ECMO + IABP 86% vs VA-ECMO alone 18%; P=.03). The Survival After Veno-Arterial Extracorporeal Membrane Oxygenation (SAVE) score did not differ between the groups (VA-ECMO alone -5.9 ± 2.4 vs VA-ECMO + IABP -6.1 ± 2.6; P=.88). The SYNTAX score was higher in the VA-ECMO + IABP group (32 ± 13 vs 22 ± 14 in the VA-ECMO alone group). In the total group, a SAVE score of -6 had a predicted survival of 25%-35%. Survival in the VA-ECMO + IABP group was 100% (7/7) and survival in the VA-ECMO group was 55% (6/11); P=.04. Good neurological outcome was achieved in more patients in the VA-ECMO + IABP group (VA-ECMO alone 45% vs VA-ECMO + IABP 100%; P=.04). Conclusion. In STEMI complicated by CS, VA-ECMO + IABP leads to a lower observed mortality and higher observed good neurological outcome.
J INVASIVE CARDIOL 2021;33(5):E387-E392. Epub 2021 April 20.
Key words: IABP, intra-aortic balloon pump, primary PCI, VA-ECMO, venoarterial extracorporeal membrane oxygenation
ST-segment elevation myocardial infarction (STEMI) can cause great hemodynamic instability due to acute heart failure, and this is associated with poor outcome.1-3 Traditionally, intra-aortic balloon pump (IABP) was used for mechanical circulatory support but it has seen a decline in indication.4-8 Venoarterial extracorporeal membrane oxygenation (VA-ECMO) is an upcoming technique in the treatment of cardiogenic shock (CS) and the first studies with this technique have shown promising results.9-12 It has recently been introduced in the European Society of Cardiology guideline as a IIB indication for the treatment of CS.7,13 One of the drawbacks of VA-ECMO, however, is the increase of afterload for the left ventricle, especially in femoral-femoral percutaneous cannulation, which is almost always the case in the setting of STEMI.9 This increased afterload causes a higher oxygen consumption by the myocardium as well as increased left ventricular pressures, leading to injury upon insult of the already infarcted myocardium.14,15 Currently, there is much debate over whether left ventricular unloading is necessary. The use of Impella (Abiomed) (the so-called Ecmella), left ventricular venting, and concomitant VA-ECMO and IABP use have all been suggested to achieve this, but evidence on the best strategy is lacking.14,15 There are no physiological studies in this area and currently only computer simulations are available to give insight into the role of left ventricular unloading during VA-ECMO for CS.14 A combination of VA-ECMO + IABP has been suggested to reduce afterload and increase survival, but there is very little real-world evidence.9
Methods
A multicenter, in-hospital registry was kept on all patients undergoing VA-ECMO or VA-ECMO + IABP treatment for CS in addition to primary percutaneous coronary intervention (pPCI) in STEMI in 4 different hospitals in Europe. All patients were analyzed at baseline for age, sex, medical history, previous coronary artery disease, renal function, diabetes, body mass index (BMI), culprit lesion and target vessels, concomitant coronary artery disease, procedural characteristics including mode of cannulation, left ventricular ejection fraction (LVEF) before admission and after admission, patient-related complications (eg, bleeding at the cannula site, limb ischemia), VA-ECMO hardware-related complications (eg, pump failure, clot formation), length of VA-ECMO treatment and length of stay in the intensive care unit (ICU) and in hospital, hemodynamic parameters including cardiac arrest, mortality, and neurological outcome. Hematological parameters were also observed and included hemoglobin, hematocrit, platelet count, and lactate levels. CS was defined using the Killip class system.3
In order to assess coronary anatomy, the SYNTAX score was calculated using the online SYNTAX score calculator (https://www.syntaxscore.com/calculator/start.htm).16,17 The Survival After Veno-Arterial Extracorporeal Membrane Oxygenation (SAVE) score, an Extracorporeal Life Support Organization endorsed and validated score, was calculated to compare the predicted mortality with the actual mortality.18 This was done by using the online SAVE score calculator (https://www.save-score.com/). Neurological outcome was defined using the cerebral performance categories (CPC) scale where a CPC score of 1 and 2 was considered a good neurological outcome.19 Renal function was assessed using the estimated glomerular filtration rate (eGFR).20
Statistical analysis was performed using Chi-square and t-test to compare categorical and continuous variables.
Although approval of a medical ethical committee is not needed according to Dutch law (Wet Medisch Wetenschappelijk Onderzoek met Mensen), it was performed and there was no ethical conflict regarding this study. All patients were treated using the Maquet Cardiohelp, an integrated pump system that can generate flows of up to 7 L/minute and the Maquet CS300 IABP (Maquet/Gettinge Group), which has a pulsatile volume of 50 mL.
Results
Between 2015 and 2018, a total of 18 patients with STEMI underwent VA-ECMO ± IABP treatment for CS. The majority of patients (14/18; 78%) were male, with a median age of 59 years (interquartile range [IQR], 47-75 years). VA-ECMO + IABP was performed in 7/18 patients (39%) and VA-ECMO alone was performed in 11/18 patients (61%). All patients were in Killip class IV prior to admission and were on vasopressors and inotropes, and all patients received VA-ECMO support in the catheterization laboratory in addition to pPCI for STEMI. The patients in the IABP + VA-ECMO group received IABP support in the catheterization laboratory prior to PCI. Both the patients in the VA-ECMO group and the VA-ECMO + IABP group received VA-ECMO cannulation in the catheterization laboratory after PCI was performed. Indication for either procedure was made by the attending cardiologist. All patients underwent femoral-femoral cannulation.
Baseline. When comparing the VA-ECMO group vs the VA-ECMO + IABP group, there was no significant difference in age (59 ± 7 years vs 59 ± 7 years; P=.89), diabetes (9% vs 43%; P=.09), known coronary artery disease (36% vs 0%; P=.07), hypertension (45% vs 14%; P=.31), known reduced LVEF (0% vs 0%; P>.99), or eGFR (56 ± 27 mL/min/1.73 m² vs 59 ± 7 mL/min/1.73 m²; P=.88), respectively. There was, however, a difference in BMI, with patients in the VA-ECMO group being significantly heavier (29.1 ± 3.8 kg/m2 vs 24.5 ± 1.98 kg/m2 in the VA-ECMO + IABP group; P=.02). In both groups, a large number of patients suffered a cardiac arrest prior to or during admission (VA-ECMO 91% vs VA-ECMO + IABP 71%; P=.52). The SAVE score did not differ between the groups (VA-ECMO -5.9 ± 2.4 vs VA-ECMO + IABP -6.1 ± 2.6; P=.88). A SAVE score of -6 has a predicted survival of 25%-35% (Table 1).
Coronary anatomy. There was a significant difference in the coronary anatomy between the 2 groups. The VA-ECMO + IABP group tended to have more complex coronary anatomy when compared with the VA-ECMO group. This is represented by a higher amount of either LM disease, LM + 3-vessel disease, or 3-vessel disease (VA-ECMO 18% vs VA-ECMO + IABP 86%; P=.03). This was also represented by the higher SYNTAX score (VA-ECMO 22 ± 14% vs ECMO+IABP 32 ± 13%) (Table 2).
Outcome. Survival to discharge was 72% (13/18) in the overall cohort. Survival to discharge in the VA-ECMO + IABP group was significantly higher at 100% (7/7 patients) when compared with the VA-ECMO alone group, where survival to discharge was 55% (6/11 patients) (P=.04). A greater number of patients in the VA-ECMO + IABP group reached the 1-year survival point in the follow-up period (VA-ECMO, 36% vs VA-ECMO + IABP, 86%; P=.04). Of the 5 patients who died, 4 (80%) died on VA-ECMO and in the hospital. One of the patients in the VA-ECMO group suffered major neurological impairment due to prolonged resuscitation and died after discharge due to aspiration pneumonia. Good neurological outcome was achieved in more patients in the VA-ECMO + IABP group (VA-ECMO 45% vs VA-ECMO + IABP 100%; P=.04). However, if this is calculated for the survivors only (leaving out deceased patients), this difference was not significant (VA-ECMO 83% vs VA-ECMO + IABP 100%; P=.26). Complete revascularization was achieved equally in the 2 groups (82% vs 86%; P=.99). LVEF did not differ between the 2 groups, with only a small amount of patients having a preserved ejection fraction after treatment (9% vs 14%; P=.34) (Table 3).
Length of stay and laboratory findings. With regard to length of VA-ECMO treatment (4.9 ± 2.8 days vs 4.5 ± 2.1 days; P=.77), days spent in the ICU (21.5 ± 23.8 days vs 17.3 ± 12.6 days; P=.70), or length of hospitalization (27.3 ± 29.2 days vs 34.3 ± 26.9 days P=.65), there was no difference between the VA-ECMO group and the VA-ECMO + IABP group. There was also no difference in the hematocrit (0.39 ± 0.05 L/L vs 0.45 ± 0.06 L/L; P=.18), platelet count (205 ± 53 x109/L vs 267 ± 10 x109/L; P=.14), pH (7.14 ± 0.16 mmol/L vs 7.31 ± 0.11 mmol/L; P=.42), and lactate levels (8.57 ± 5.5 mmol/L vs 3.7±1.7 mmol/L; P=.06) post procedure. There was, however, a lower hemoglobin count in the VA-ECMO group (8.2 ± 1.1 mmol/L vs 10.1 ± 1.5 mmol/L in the VA-ECMO + IABP group; P<.01) (Table 4).
Safety aspects. From a safety perspective, there was no statistical difference between the 2 groups. Thromboembolic complications occurred in 27% of the VA-ECMO group, and 1 patient in that group also had an infected cannula. In the VA-ECMO + IABP group, there were no observed thromboembolic complications. However, this was not statistically significant (P=.55). Hemorrhagic complications occurred in 28% of the VA-ECMO group vs 43% of the VA-ECMO + IABP group (P=.28). There were no VA-ECMO hardware malfunctions observed in either group (Table 5).
Discussion
This study suggests that the combination of VA-ECMO + IABP is associated with better outcomes than VA-ECMO alone in the treatment of CS. The difference in outcomes between the 2 groups could be a result of the left ventricular unloading by the IABP. As all other organs are perfused by the VA-ECMO circuit, the IABP reduces the afterload for the left ventricle and this may reduce infarct size. There is, however, no difference in the postprocedural LVEF in this study. It could also improve survival through a mechanism of increased coronary perfusion with oxygenated blood from the VA-ECMO circuit. In the absence of an IABP, blood ejected from the heart goes through the pulmonary circulation. In the case of CS, there may be overt pulmonary congestion causing desaturated blood being ejected from the left ventricle into the coronary arteries. This can cause a harlequin effect and inadequate coronary perfusion. The use of an IABP may lead to better dispersion of oxygen-rich blood through the aorta, facilitating adequate coronary artery perfusion. This same mechanism may apply to cerebral perfusion. Concomitant IABP in addition to VA-ECMO may increase cerebral perfusion and result in a good neurological outcome. Although there was no statistically significant proof-of-principle, all study patients who underwent this technique had good neurological outcomes.
The SYNTAX score in the VA-ECMO + IABP group was higher than in the VA-ECMO alone group. A higher SYNTAX score aids in decision making between either PCI or coronary artery bypass surgery. In the case of STEMI, especially when there is profound CS, pPCI is the treatment of choice. The more complex anatomy in the VA-ECMO + IABP group did not lead to worse outcome or to less complete revascularization; this may be explained by the adequate hemodynamic support while a patient is on VA-ECMO, which may facilitate a more complex coronary intervention. A high SYNTAX score is also a predictor for major adverse cardiovascular and cerebral events, with a cut-off of 33. Yet, in this study, there is no observed difference between the 2 groups in regard to safety outcome. A possible explanation may be that concomitant use of VA-ECMO + IABP may lead to better overall hemodynamics, thus preventing complications.
The predicted mortality as assessed by the SAVE score in this study was equally high in both groups. All patients were in Killip class 4. These findings suggest a low predicted survival rate of between 25%-35%. Yet, in both groups, the actual survival was much higher. This may be an indication that both techniques may be successfully used in the treatment of CS in STEMI. A large number of patients suffered a cardiac arrest prior to receiving mechanical circulatory support, but the outcome was still good in the overall group, and more specifically, in the VA-ECMO + IABP group. Routine IABP implantation alone did not improve survival; therefore, VA-ECMO with concomitant IABP implantation may be the way forward in treating CS associated with STEMI.
The form of left ventricular unloading in this study is IABP. As mentioned before, other strategies are also possible. The advantage of using the IABP is that its use and availability are widespread and it is therefore readily available at many hospitals around the world. It is also relatively cheap compared with, for example, Impella. In addition, Impella is not reimbursed in many countries, which makes it a costly approach to left ventricular unloading. Furthermore, IABP is less invasive, specifically when compared with surgical left ventricular venting, and can even be used through the VA-ECMO cannula with off-label use of a Y-connector. IABP can also be used if there is severe aortic stenosis and it is difficult to pass the aortic valve.
The length of hospitalization and treatment did not differ between the 2 study groups. However, time spent in the hospital was considerable for both groups at nearly 1 month. This indicates that these highly complex patients with serious acute life-threatening disease should ideally be treated at dedicated tertiary-care centers with not only expertise in VA-ECMO, IABP, and PCI, but also in patient and family guidance as these treatments can be very traumatizing for patients and their families. In regard to the laboratory findings, there was a lower hemoglobin level in the VA-ECMO alone group. VA-ECMO can cause hemolysis and reduce hemoglobin, which could explain this finding. However, it was not observed in the VA-ECMO + IABP group. There is a trend toward lower lactate levels in the VA-ECMO + IABP group, which could be explained by the better hemodynamic support of this combined form of mechanical circulatory support. However, it could also be possible that the patients in the VA-ECMO + IABP group were less sick.
The complication rate is relatively low in this study group. Limb ischemia is a known complication and can be prevented by several techniques. First, cannulation should ideally be performed in both groins, with the arterial and venous cannulas each placed in a different groin to prevent simultaneous decreased perfusion of the leg due to arterial blockage and stasis of the blood due to venous occlusion by the cannula. Second, antegrade perfusion of the leg should be routinely performed to ensure perfusion of the leg. The distance between antegrade and retrograde arterial cannulas should be as short as possible to prevent clot formation at this site.
Recently, a meta-analysis was published by Russo et al demonstrating a benefit of left ventricular unloading for the treatment of CS. This study showed a benefit of all forms of unloading. However, it did not discern between the different etiologies of CS. Our study corroborates these data, and adds that in the specific case of STEMI, left ventricular unloading using the IABP in the setting of VA-ECMO support is beneficial.21
Study limitations. This is an observational study with a limited number of patients. Bias and unknown confounders may have caused the lower observed mortality in the VA-ECMO + IABP group. However, the lower mortality was observed even with the patients in the VA-ECMO + IABP group having more severe coronary artery disease. There is also operator bias in selecting patients eligible for mechanical circulatory support. Only comparative statistics were used in this study, making it difficult to establish causality. However, to our knowledge, this is the first study demonstrating a possible survival benefit of ECMO with concomitant IABP in the setting of STEMI complicated by CS. Future studies (preferably with a randomized controlled design) are required to establish the benefit of this technique in this group of patients. Interpretation of this study must be done with caution. It is hypothesis generating, but it is difficult to apply the results in daily practice. Hopefully, it will be possible to perform a randomized controlled trial in the future to establish a true survival benefit.
Conclusion
This small, observational study demonstrates that VA-ECMO might be able to improve survival in patients with CS due to STEMI even when in cardiac arrest. This observation suggests that VA-ECMO in combination with IABP is associated with higher survival than VA-ECMO alone and is also associated with good neurological outcome. It is also associated with better outcome in more complex coronary artery anatomy. However, the data presented are purely exploratory and warrant caution in their interpretation. Physiological studies are required to prove the effectiveness of this technique and to facilitate a future randomized controlled trial.
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From the 1Department of Cardiology, Medisch Centrum Leeuwarden, Leeuwarden, the Netherlands; 2Department of Cardiology, St. Antonius Ziekenhuis, Nieuwegein, the Netherlands; 3Department of Cardiology, Middelheim Ziekenhuis, Antwerpen, Belgium; 4Department of Cardiology, Haga Teaching Hospital, The Hague, the Netherlands; 5Department of Intensive Care, Medisch Centrum Alkmaar, Alkmaar, the Netherlands.
Disclosure: The authors have completed and returned the ICMJE Form for Disclosure of Potential Conflicts of Interest. The authors report no conflicts of interest regarding the content herein.
Manuscript accepted May 29, 2020.
Address for correspondence: Floris S. van den Brink, MD, Koopvaardersplantsoen 83, 1034KE, Amsterdam, The Netherlands. Email: floris.s.van.den.brink@gmail.com
