There were no significant statistical differences in the precannulation, postcannulation, and postdecannulation invasive hemodynamics (pulmonary artery systolic and diastolic pressures, pulmonary capillary wedge pressures) between the two cohorts. Notably, a numerically greater trend in the improvement of the CI in the ECPELLA cohort as compared with VA-ECMO alone was observed from precannulation (1.7 L/min × m2 [1.1–2.5] vs. 2.3 L/min × m2 [1.6–3.0]; p = 0.084) to 24 hour postdecannulation (3.3 L/min × m2 [2.9–3.4] vs. 2.8 L/min × m2 [1.9–3.3]; p = 0.244; Figure 3).
Refractory CS can occur after cardiac surgery, as an exacerbation of chronic heart failure with reduced ejection fraction, or from de novo heart failure, most commonly caused by acute coronary syndromes. In our series, approximately 46% of cases were associated with acute coronary syndrome of which about 44% received revascularization. This is in keeping with previous reports which suggest that up to 50% of CS is because of some form of acute coronary syndrome.1 Typically, in the setting of CS and ACS, IABPs were the preferred mode of mechanical support. However, in the contemporary IABP-SHOCK II trial, mortality was not improved by IABP and remained high at approximately 40% despite the use of a combination of inotropes, vasopressors, and IABP.30 With the advent of Tandem heart (Cardiac Assist, Pittsburgh, PA) and Impella, percutaneous mechanical circulatory support devices can now be safely and quickly implanted through peripheral vessels without surgical intervention. Nevertheless, in the current era, CS mortality remains extremely high. In fact, even though both Impella and Tandem Heart are capable of achieving superior hemodynamics compared with IABP in CS, no survival benefit has yet been demonstrated in randomized controlled trial.27 , 31 , 32 However, survival benefit with early initiation of support with Impella heart pumps in the setting of refractory CS complicating an AMI has been demonstrated in small single and multicenter observational studies,33 , 34 as well as in large multicenter observational studies.27 , 35 Furthermore, the use of early VA-ECMO has shown to reduce in-hospital mortality, and increase 30 day and 1 year survival in a recent small retrospective observational study.36 However, this study enrolled a heterogeneous patient population with a lower risk profile on admission compared with our patients.
Contrary to the European experience, our cohorts had relatively similar baseline characteristics, and a unified decision for the initiation or escalation of mechanical support was made by a Shock Team rather than a single clinician.24 The most significant finding in our study was that 30 day cumulative survival was greater in the ECPELLA versus VA-ECMO and extended to 1 year. Notably, the HR for overall mortality (ECPELLA versus VA-ECMO) was 0.52 (0.29–0.93; p = 0.027) suggesting a 50% mortality reduction from the addition of Impella to VA-ECMO. ST-elevation myocardial infarction and SAVE score did not significantly impact the benefit seen with ECPELLA, as evident by the lack of statistical interaction with respect to overall mortality. Although the mortality difference between the cohorts we report is unique, our overall cumulative survival rate is approximately 32% and 22% at 30 days and 1 year, respectively, for the entire cohort. These rates are similar to previously reported figures,5 , 6 despite the fact that prior studies excluded patients with specific characteristics such as a postcardiotomy state or those who had previous CPR42; conversely, the current study provides a real-world cohort of refractory CS to allow for an “all-comers” analysis. Further, the definition of “refractory” or “CS” is variable from study to study and thus the inclusion or exclusion of certain patients based on hemodynamics and clinical evaluations in these studies may alter survival rates; hence, we attempted to provide the most contemporary and meaningful definition of refractory CS to allow for some degree of applicability.
Nevertheless, we did observe a significant reduction in all-cause mortality at 30 days in the ECPELLA cohort. We believe these findings are related to several major observations. First and foremost, we report that only 58% of VA-ECMO patients (n = 21) had some form of venting (±IABP), as compared with 100% of the ECPELLA cohort (n = 30) which had Impella ± surgical vent (±IABP) supporting the association of left ventricular decompression and survival in our study. Along with the higher proportion of venting, the ECPELLA cohort demonstrated a numerical increase in CI from precannulation to postcannulation, and at decannulation as compared with the VA-ECMO cohort, despite using less inotropes. Similarly, a retrospective cohort of 121 patients reviewed for left ventricular distension while on VA-ECMO support revealed that the degree of clinically-defined left ventricular distention is inversely and significantly related to the degree of myocardial recovery, suggesting that lower degrees of distension through left ventricular decompression may result in improved cardiac function.29 Further, in the present report, the use of the ECPELLA strategy resulted in more patients being successfully weaned from VA-ECMO (70% vs. 44%; p = 0.048). In contrast, over half of those who were decannulated in the VA-ECMO cohort required secondary mechanical support. Although not statistically different, over 40% of patients in the ECPELLA cohort recovered myocardial function as opposed to only 22% in the VA-ECMO cohort. Taken together, these data suggest that the addition of Impella to VA-ECMO may promote myocardial recovery and translate to improved survival. Second, ECPELLA patients were more likely to have percutaneous support placed before or during VA-ECMO initiation (n = 26, 87%), thus resulting in early unloading. Correspondingly, a study of 287 patients with CS treated with Impella and stratified by time to support demonstrated that a shorter time to unloading correlated with improved survival.35 We hypothesize that a similar benefit is observed in patients who have early and effective unloading with combination Impella and VA-ECMO. Third, as noted above, the maximal inotropic score after day 1 was significantly higher in the VA-ECMO compared with the ECPELLA group. This suggests that the use of Impella may provide improved hemodynamic support as compared with the use of inotropes, while simultaneously reducing the use and harmful effects of these drugs (arrhythmias, progressive renal dysfunction, increase myocardial oxygen demand and ischemia, increased risk of cardiac death).43–45 Finally, the use of the ECPELLA strategy has the added clinical utility of providing a transitional strategy that allows earlier cessation of VA-ECMO. Indeed, a recent large meta-analysis has shown that VA-ECMO is associated with substantial morbidity.46 Furthermore, an analysis of outcomes of 4,658 patients from the national inpatient database in Japan supported with VA-ECMO for CS found excessive in-hospital mortality of 73.6% (77.1% in patients who sustained cardiac arrest [CA]). Of those, 40.3% expired after decannulation suggesting subsequent complications or lack of total native heart recovery.47
In terms of safety, there were no differences in major complications between ECPELLA and VA-ECMO alone. Any degree of bleeding, clinical hemolysis, stroke, and the need for dialysis were not different in either cohort. This confirms previous observations of comparable safety profiles in a small series comparing surgical decompression to Impella.28 We postulate that the low rate of observed complications is related to the adoption of contemporary management strategies for CS.48–50 In essence, our Shock Team has become seasoned in its approach and so to have the individual team members, including cardiothoracic surgery and interventional cardiology, who have become adept in large vessel access and closure, Impella placement and repositioning, and monitoring for and managing bleeding and hemolysis. Similarly, European experience has also found a favorable safety profile using a combination of Impella and VA-ECMO employing similar CS management strategies.24
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