Use of the Impella Device for Acute Coronary Syndrome Complicated by Cardiogenic Shock – Experience From a Single Heart Center With Analysis of Long-term Mortality

Abstract: Aims. Impella is a microaxial rotary pump that is placed across the aortic valve to expel aspirated blood from the left ventricle into the ascending aorta; it can be used in cardiogenic shock. While previous studies have evaluated the efficacy and safety of the Impella device, more clinically relevant data are necessary, especially with regard to outcomes. Methods and Results. We screened our database of Impella patients in our heart center and found 68 consecutive patients who underwent Impella implantation due to acute coronary syndrome (ACS) complicated by cardiogenic shock. Data were evaluated with regard to baseline and procedural characteristics and also included an assessment of the short-term and long-term outcomes. The majority of patients (74%) suffered from an ST-elevation myocardial infarction, and 59% of patients received the Impella device during the initial coronary angiography. In the remaining cases, Impella implantation was performed at a later time, most commonly after IABP implantation. Patient characteristics were not significantly different between both groups. The predominantly implanted device was an Impella 2.5. Mortality in the severely ill patient population remained high, but univariate/multivariate analyses identified significant risk factors. Interestingly, delayed initiation of Impella support was an independent predictor of higher long-term mortality (hazard ratio, 2.157; P=.04) within the Impella patient cohort. Conclusion. This large series of patients with ACS complicated by cardiogenic shock who underwent Impella implantation provides information on the relevant risk factors for mortality. Early (compared with delayed) initiation of Impella support was a predictor of improved survival in this population of patients.

J INVASIVE CARDIOL 2016;28(12):467-472. Epub 2016 August 15.

Key words: acute coronary syndromes, coronary heart disease, acute heart failure, cardiogenic shock, Impella device

The Impella (Abiomed) is a microaxial rotary pump that is placed across the aortic valve and expels aspirated blood from the left ventricle (LV) into the ascending aorta.¹ Impella 2.5 and Impella CP can provide 2.5 to 3.5 L/min and can be percutaneously inserted. Impella 5.0 can deliver up to 5.0 L/min, but it requires a surgical cutdown of the femoral artery. Several studies have demonstrated that the Impella device is feasible and safe in ST-elevation myocardial infarction (STEMI)^2,3 or in high-risk percutaneous coronary intervention (PCI) patients,^4,5 but in the field of cardiogenic shock, only a few studies with ample patients have been reported.^6-8 In addition, studies differed in the selected patient group, eg, the study by Lemaire et al mostly analyzed patients with postcardiotomy cardiogenic shock. Initially, Meyns et al demonstrated the safety and feasibility of the Impella in 6 patients with severe cardiogenic shock after maximal inotropic support and IABP (intraaortic balloon pump) therapy.⁹ In addition, a randomized trial compared the IABP with Impella 2.5 in patients with cardiogenic shock.¹⁰ However, in most studies, the duration of the follow-up period was limited to the in-hospital phase or 30-day mortality, and long-term follow-up data were not obtained. The long-term effects of the Impella device used after PCI due to STEMI have been described in 10 patients. The patients had no evidence of aortic valve abnormalities and LV ejection fraction recovery was greater compared with control patients.³ Recently, the multicenter Impella EUROSHOCK registry demonstrated the feasibility of using the Impella 2.5 device in cases of cardiogenic shock and also documented improvement in some parameters suggesting improved blood perfusion. However, the 30-day mortality remained high, and two predictors (patient age and lactate level) of short-term mortality were identified.⁶ 

The present study sought to provide more clinically relevant data about the Impella device in a real-world scenario including a follow-up analysis of the long-term outcome in a severely ill patient population with acute coronary syndrome (ACS) with cardiogenic shock.

Methods

We performed a retrospective record review of all documented patients (n = 88) who underwent implantation of an Impella device at our heart center between 2006 and 2014. To evaluate a homogenous and comparable patient group, we focused on 68 consecutive patients who underwent Impella implantation due to ACS complicated by cardiogenic shock. Records were evaluated for data regarding baseline patient characteristics including indications, procedural characteristics, and complications of the Impella device. Moreover, on the basis of available records and/or telephone interviews with the patients or their relatives (after written consent), short-term and long-term outcome data were evaluated. Long-term outcome data were available for 64 patients. The conduct of this study was approved by the Ethics Commission of the University of Goettingen.

The Impella devices (2.5, CP, 5.0) have been described in detail elsewhere. Briefly, the Impella 2.5 and CP are 12-13 Fr microaxial pumps mounted on a 9 Fr catheter. They can be inserted under fluoroscopic control through the femoral artery using a modified Seldinger technique. The Impella 5.0 is 21 Fr in diameter and is mounted on a 9 Fr catheter shaft. It requires a surgical cutdown of the femoral artery. The Impella pumps are powered and controlled by an Impella console. An activated clotting time >250 seconds is required during Impella pump insertion intraoperatively, and the administration of a heparinized purge solution is subsequently necessary. Because of a lack of official guidelines to dictate center-specific standards, inclusion criteria for the use of the Impella device at our heart center were left to the discretion of the treating cardiologist/cardiac surgeon. “Early” Impella support was defined as device implantation during the initial coronary angiography. “Late” Impella support was any device implantation performed at a later time, most commonly after initial IABP implantation. The postprocedure support for the Impella device was managed in an experienced intensive care unit.

Primary PCI was performed using standard equipment and techniques with the use of drug-eluting or bare-metal stents as well as antiplatelet therapy at the discretion of the treating cardiologist. Multivessel coronary artery disease was defined as the presence of a coronary stenosis (stenosis degree >50%) in >1 main coronary artery. 

Cardiogenic shock was defined as the presence of a systolic blood pressure <90 mm Hg and/or a need for catecholamine therapy and impaired end-organ perfusion. The amount of fluid administration and inotropes/vasopressors was based on current guidelines as well as on individual experience and institutional policy. Based on recommendations for patients with ACS and cardiogenic shock and at the discretion of the treating cardiologist, IABP support was performed after primary PCI in a subset of patients. 

Data are expressed as mean ± standard deviation or frequencies and percentages, as appropriate. Statistical analysis was performed with the statistical computing software R version 3.1.3 (www.r-project.org). Survival analysis was conducted on time-to-event data (ie, time to death of any cause) for the described baseline characteristics with the R package “survival.” Sixty-eight patients were included in univariate and multivariate analyses for the assessment of 30-day mortality. Of these, 64 patients with available 1-year survival data were included in univariate and multivariate analyses for the assessment of 1-year mortality. Patients lost to follow-up were not included in the 1-year survival analysis due to the restricted dataset size in order to keep the dataset as consistent as possible. If a minimum of available clinical annotations was not reached, parameters were not considered in the multivariate analysis at all due to the limited dataset. Surviving patients were censored at 1 year. Survival data were visualized by Kaplan-Meier plots, and significance was calculated by the log-rank test (for two-group comparisons). The risk stratifiers found to be significant in the univariate analyses (P<.05) were included in the multivariate analyses. The initiation time of Impella support was inserted into the model as a target parameter. For multivariate models, the Cox proportional hazards model was used.

Results

Complete baseline characteristics are shown in Table 1. A total of 68 patients were analyzed. Mean age was 63 years, and 72% were male. Mean LV ejection fraction was 27 ± 14%. At the time of Impella implantation, 40% of the patients were already on IAPB support, and 49% had been resuscitated for cardiac arrest prior to Impella support.

The interventional treated coronary lesion (“culprit lesion”) was mostly located in the left anterior descending artery, followed by the right coronary artery and ramus circumflexus. In 9 cases, PCI of the left main coronary artery was performed, and a bypass graft was treated by PCI in only 2 cases. In the majority of cases (85%), an Impella 2.5 device was implanted. The overall average duration of support with Impella device was 4.6 ± 4.0 days (median, 3.0 days). Table 2 offers an overview of procedural characteristics.

The most common blood alteration/complication was a mild thrombocytopenia that generally required no specific therapeutic treatment. Significant heparin-induced thrombocytopenia (HIT) was identified in only 1% of patients. Significant hemolysis was present in 7% of patients with Impella support. Bleeding requiring a blood transfusion occurred in 24% of patients, but severe bleeding according to the GUSTO criteria occurred in only 6% of cases. These complications, although not insignificant, did not result in any deaths and could not always be definitively linked to the Impella device. However, in 15% of the cases, the operator decided to perform an early explantation of the Impella because of a suspected device complication (Table 3).

Due to the severity of illness in this patient population, 34% of the patients died during the hospital stay. The short-term 30-day mortality in our study population was 54%, and the longer-term 1-year mortality reached 63%.

The short-term and long-term mortality were not dependent on gender or the type of Impella device. As expected, an older age (≥70 years) was a significant predictor of a higher short-term and long-term mortality (hazard ratio [HR], 2.7; P=.01 and HR, 2.32; P=.01). An elevated body mass index (>25 kg/m²) tended to result in a higher 30-day and 1-year mortality, and a body size ≥1.80 m was associated with better long-term survival in our patient cohort (HR, 0.47; P=.02). An initial heart rate ≥90 bpm was significantly associated with a higher mortality after 30 days (HR, 2.8; P=.01) and after 1 year (HR, 2.5; P=.01). A QRS elevation ≥110 ms was associated only with a higher short-term mortality (HR, 2.0; P=.049), and the absence of a STEMI was a significant predictor of a higher long-term mortality. In a subset of patients #14 to #28, hemodynamic (pressure) parameters were available, and their influence on the mortality could be analyzed (but were non-significant). For complete univariate analysis parameters of 1-year mortality, see Supplementary Table 1.

The significant univariate risk factors were subsequently evaluated in multivariate analyses (Tables 4 and 5). The parameters age ≥70 years (HR, 3.1; P=.01) and initial heart rate ≥90 bpm (HR, 2.5; P=.02) were independent predictors of a higher short-term mortality. However, short-term mortality after 30 days was not significantly altered based on the timing of Impella implantation (HR, 1.6; P=.23;) (Table 4).

Delayed Impella implantation was an independent predictor of a higher long-term mortality (HR, 2.2; P=.04; n = 27) compared with an early implantation (n = 37). Baseline characteristics and risk factors were not significantly different between these two groups at the time of Impella implantation (Impella early vs Impella late; see Supplementary Table 2).

In addition, age ≥70 years (HR, 3.1; P=.01) and heart rate ≥90 bpm (HR, 3.1; P=.01) were associated with a significantly higher long-term mortality in the multivariate analysis (Table 5). Kaplan-Meier curves for age and timing of Impella support are shown in Figure 1.

Discussion

The present study includes a relatively large series of patients undergoing Impella device implantation at one center. Only some larger multicenter register studies have already been published.^6,7 The short-term and long-term mortality rates in our study are comparable and in line with those reported in these previous Impella studies. Nevertheless, the overall mortality of our patients remained on a high level and the analysis implicated no survival benefit of the entire patient population compared to previous historical clinical trials examining cardiogenic shock patients who were treated without cardiac devices or with the IABP device.^11,12 This may be related to the severity of illness of our patients, eg, a high proportion of patients (49%) had been resuscitated following a cardiac arrest prior to Impella implantation and severe cardiogenic shock. However, our patient population had a higher survival rate after 30 days and after 1 year compared with patients studied in the multicenter Impella EUROSHOCK registry (<30% long-term survival).⁶ 

In fact, the medical management of refractory cardiogenic shock is still associated with a significant reduction in survival rates despite improved revascularization strategies in patients with ACS.¹³ Consequently, a promising alternative for providing hemodynamic support for patients with cardiogenic shock is percutaneous devices that improve ventricular function/unloading^1,13 and the Impella devices are recently Food and Drug Administration (FDA)-approved concerning this indication. In our study, Impella 2.5 was the most frequently used device, and in the case of ACS, it can be implanted during coronary angiography/intervention. Certain studies with low patient numbers and only a few studies with greater patient numbers have shown an improvement in hemodynamic pressure parameters and a reduction of lactate levels after Impella 2.5 support.^6,10 In fact, a decrease in pulmonary capillary wedge pressure reflects effective LV unloading and decongestion. It is noteworthy that LV decongestion with Impella support in STEMI patients has been associated with improved acute and sustained LV recovery compared with routine patient care.² Moreover, Lauten et al identified a previous myocardial infarction, cardiopulmonary resuscitation, systolic blood pressure <90 mm Hg, and lactate >3.8 mmol as significant predictors of 30-day mortality after Impella 2.5 support in cases of cardiogenic shock after acute myocardial infarction (tested by univariate analysis with P<.05). Subsequent multivariate analysis revealed that the parameters of age >65 years and lactate >3.8 mmol were independent predictors for 30-day mortality in their registry study and analysis model.⁶ In our cohort, we identified some comparable and certain additional predictors of short-term and long-term survival/mortality with a univariate analysis, eg, age ≥70 years. Moreover, in our ACS patient group, the presence of an elevated heart rate, a smaller body size, and absence of STEMI were significantly associated with a higher 1-year mortality.

In other studies, it could be shown that initial tachycardia is an independent predictor for heart failure in patients with ACS¹⁴ and is associated with higher cardiovascular mortality in patients with coronary artery disease and myocardial infarction as well as with heart failure.¹⁵ Interestingly, a 2007 study employing multivariable analysis to identify risk factors for death in patients with STEMI and cardiogenic shock indicated that age was less strongly related to death in patients with a heart rate >100 bpm in whom the prognosis was uniformly poor.¹⁶ Cardiogenic shock in patients with STEMI was associated with a lower mortality risk compared with non-STEMI patients.¹⁷ The underlying causes included co-morbidities in mostly older non-STEMI patients and a higher revascularization rate in STEMI patients. These findings could explain the significantly higher long-term survival rates in our study population with STEMI compared with those without STEMI (or rather non-STEMI). Furthermore, the findings are in line with our finding that absence of STEMI was not an independent predictor of higher mortality (non-significant in multivariate analysis).

In our study cohort, the time of device support was divided into a group of ACS patients who received the Impella device within the initial coronary angiography (early Impella support) and patients with Impella implantation at a later time, most commonly performed after initial IABP support (late Impella implantation). It should be stressed that both patient groups had comparable baseline characteristics and risk factors at the time of Impella implantation. The results of the USpella registry, a multicenter study in the United States that compared patients who received Impella 2.5 support before PCI vs patients who received it after PCI in cases of acute myocardial infarction complicated by cardiogenic shock found that early initiation of hemodynamic support before PCI was associated with a higher survival rate after 30 days, but the duration of follow-up was limited.⁷ In our registry, Impella implantation in the ACS patients was always performed post PCI or as described at a later time. However, in multivariate analysis, the long-term survival was significantly better if Impella implantation was performed as early as possible in our ACS patient population. The survival curves for age and timing of Impella support emphasized that especially in patients aged ≥70 years, long-term mortality was higher if the Impella support had not been initiated as early as possible (with a limitation of low patient numbers in the respective groups). One could speculate that early LV decongestion by Impella support translated into a better long-term outcome, while the short-term outcome was more influenced by the high risk profile of the patients, eg, post cardiac arrest syndrome. Future (prospective) studies with the Impella device need to be conducted to evaluate mid-term to long-term mortality and further investigate these findings. Moreover, randomized controlled studies directly comparing cardiac shock patients with and without Impella devices are needed in regard to the long-term outcome/mortality rates and initiation of the Impella support as early as possible.

Study limitations. Our study has some limitations to consider. (1) The observational approach of our investigation cannot infer a causal relationship between the use of Impella and subsequently reduced mortality in a heterogeneous group of patients with ACS. Data were limited to comparisons within the Impella group, with no control group without the Impella device for comparison. Thus, our results will need to be confirmed with prospective investigations. (2) We cannot fully exclude the presence of potential patient or adjunctive treatment selection biases. (3) We cannot discriminate among the different Impella devices with higher hemodynamic support due to mostly implanted Impella 2.5 devices.

Conclusion

This large cohort of patients from a single-center real-world registry with the Impella device provides interesting insights and clinically relevant data about the Impella device that may contribute to optimizing patient selection and the timing of implantation to reduce mortality in this high-risk patient population. Our data indicate that early initiation of Impella support is a predictor of improved long-term survival in patients with ACS complicated by cardiogenic shock and should be considered at the time of the first cardiac intervention. Further study under this presupposition in future clinical trials is warranted.

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From the ¹University of Goettingen, Heart Center, Department of Cardiology and Pneumology, Goettingen, Germany; ²Department of Medical Statistics, University Medical Center Goettingen, Germany; ³Albert-Schweitzer-Clinic Northeim, Germany.

Disclosure: The authors have completed and returned the ICMJE Form for Disclosure of Potential Conflicts of Interest. Dr Schroeter and Dr Schillinger report personal fees and non-financial support from Abiomed during the conduct of this study. Dr Schillinger reports personal fees from St. Jude Medical, Abbott Vascular, and Astra Zeneca outside the submitted work. The remaining authors report no conflicts of interest regarding the content herein.

Manuscript submitted April 5, 2016, provisional acceptance given April 27, 2016, final version accepted May 17, 2016.

Address for correspondence: PD Dr med Marco R. Schroeter, Senior Physician, University of Goettingen, Heart Center, Department of Cardiology and Pneumology, Robert-Koch-Str. 40, D-37099 Goettingen, Germany. Email: mschroeter@med.uni-goettingen.de