Original Contribution

Secular Trend in the Use and Implementation of Impella in High-Risk Percutaneous Coronary Intervention and Cardiogenic Shock: A Real-World Experience

Abdul Wahab Hritani, MD1;  Adil S. Wani, MD1;  Susan Olet, PhD2;  Claire J. Lauterbach2;  Suhail Q. Allaqaband, MD1;  Tanvir Bajwa, MD1;  M. Fuad Jan, MBBS, MD1

Abdul Wahab Hritani, MD1;  Adil S. Wani, MD1;  Susan Olet, PhD2;  Claire J. Lauterbach2;  Suhail Q. Allaqaband, MD1;  Tanvir Bajwa, MD1;  M. Fuad Jan, MBBS, MD1

Abstract: Objectives. Cardiogenic shock carries high mortality despite advancements in therapeutic interventions. Impella (Abiomed) is a mechanical circulatory support device that is being increasingly used in cardiogenic shock patients. Impella is also utilized in high-risk patients undergoing percutaneous coronary intervention (PCI). We review the trend of Impella use at a single tertiary-care center, retrospectively analyze the outcomes, and discuss the increasing use of this device in the United States. Methods. This a retrospective, observational study of Impella use for two indications, cardiogenic shock and high-risk PCI, at a tertiary-care center. The primary endpoint was the yearly implant rate of Impella and the secondary endpoint was periprocedural complications and major adverse cardiovascular events at 30 days. Results. Forty-four Impella devices were implanted between 2008 and June of 2017. The rate of Impella implantation has significantly increased since its introduction in our facility in 2008. The most common complication was acute renal dysfunction (23%) followed by vascular complications (20%). Mortality at 30 days was 75% in the cardiogenic shock group and 11% in the high-risk PCI group. Conclusion. The use of the Impella device as a mechanical circulatory support has increased since its introduction, although its acceptance rate remains low. Despite its theoretical hemodynamic advantage, the outcome in cardiogenic shock patients remains poor.

J INVASIVE CARDIOL 2019;31(9):E265-E270.

Key words: cardiogenic shock, mechanical circulatory support


In contemporary cardiology practice, percutaneous coronary intervention (PCI) is increasingly performed in patients with complex coronary artery disease (CAD) who cannot undergo coronary artery bypass surgery due to prohibitive risk. The majority of such high-risk patients are older and have concomitant severe left ventricular (LV) dysfunction, which increases periprocedural complications. Mortality has been reported up to 5 times higher in patients with severe LV dysfunction undergoing PCI than in patients with preserved LV function.1 In these clinical situations, mechanical circulatory support (MCS) devices have been proposed to reduce such risk.

Cardiogenic shock (CS) is a fatal complication of myocardial infarction (MI)2 that occurs in up to 10% of patients with ST-elevation myocardial infarction (STEMI) and 2.5% of patients with non-STEMI.2,3 It remains the leading cause of mortality in patients with acute MI, with an incidence of in-hospital death of close to 50%.4-6 The most commonly used MCS in current practice is the intra-aortic balloon pump (IABP); however, it has not been shown to offer a survival advantage.7

The use of the Impella system (Abiomed) has been suggested to improve outcomes in both animal and human studies. The improved hemodynamic profile noted with Impella use is due to two major mechanisms: improved end-organ perfusion and unloading of the myocardium for recovery. The Impella device has also been shown to increase coronary blood flow.8,9 In 2015, Impella was approved by the United States Food and Drug Administration (FDA) for use in high-risk PCI. In 2016, FDA approval was extended for use in acute MI and postcardiotomy CS, and in 2018, the indication was extended to CS caused by postpartum cardiomyopathy as well as myocarditis.10

Despite the paucity of randomized controlled data for the use of Impella as an MCS device in CS patients, there appears to be a national trend of increased utilization of this device in contemporary practice.3 Moreover, analysis of registry data shows an improvement in survival with early initiation of Impella in patients with CS secondary to acute MI.11

The purpose of our report is to review the trend of Impella use at our institution between 2008 and 2017, to review the indications, and to analyze the outcomes.

Methods

Study design and outcome. This study was a retrospective observational chart review of patients age 18 years and older who were treated at Aurora St. Luke’s Medical Center (the largest tertiary-care center in southeast Wisconsin) using the Impella system. The local Institutional Review Board approved the study. The cardiac catheterization procedure database was used to identify cases in which an Impella was placed between January 1, 2008 and June 30, 2017. The inclusion criterion was device insertion in the cardiac catheterization laboratory. Patients were excluded if they were referred to our facility with a device already in place.

The primary outcome measure was yearly rate of device placement by specific indication. Secondary outcomes were postprocedural vascular complications, acute renal failure, hemolysis, 30-day mortality rate, 30-day major adverse cardiovascular event (a composite of all-cause death, MI, and cerebrovascular accident) rate, and 1-year mortality rate. The primary safety outcome was device-related complications, including access-site complications, localized infection or bacteremia, hemolysis, acute renal dysfunction, and device malfunction.

Indications for Impella use. We considered two indications for device placement: CS secondary to acute MI or non-ischemic causes; and high-risk PCI.

Definitions. Acute MI was defined in accordance with the third universal definition of MI as the detection of a rise and/or fall of cardiac biomarkers (troponin T or I) with at least 1 value above the 99th percentile upper reference limit, with 1 or more of the following: anginal chest pain or anginal equivalent; new or presumed new ischemic electrocardiographic changes; pathologic Q-waves on electrocardiogram; imaging evidence of new loss of viable myocardium or new regional wall-motion abnormality; or identification of intracoronary thrombus by angiography.12 CS was defined based on clinical evidence of tissue hypoperfusion (such as hypoxia, altered mental status, oliguria, or cool, clammy skin) along with systolic blood pressure <90 mm Hg, systolic blood pressure <100 mm Hg despite vasopressors or inotropic therapy, and presence of adequate intravascular volume.2

High-risk PCI was determined based on clinical presentation with MI, severe LV dysfunction (LV ejection fraction <30%), and complex coronary lesions, including an unprotected left main coronary artery, three-vessel coronary intervention,13 or last remaining conduit.

Device. In brief, Impella is a non-pulsatile axial flow device that is placed inside the LV percutaneously and propels blood into the aorta. There are several types of Impella, such as the 2.5, 5, and CP, that each provide a different level of cardiac output augmentation. The pump is advanced retrogradely and placed across the aortic valve into the LV under fluoroscopic guidance.14 The current Impella devices used at our institution are the 2.5 and CP, which provide up to 2.5 L/min and 4.0 L/min of forward flow, respectively, directly in the ascending aorta.

Statistical analysis. Data are presented as counts and proportions for categorical variables and median (lower quartile [Q1] - upper quartile [Q3]) for continuous variables. The crude cumulative incidence of mortality is presented using a line graph for protected PCI and CS. Comparison between groups was done using Chi-square, Fisher’s exact, and Wilcoxon rank-sum tests, as appropriate. All tests were performed at a 5% level of significance using SAS version 9.4 (SAS Institute).

Results

Chart review identified 48 patients who had an Impella inserted in the cardiac catheterization laboratory between 2008 and 2017. Of these, a total of 27 patients (67.5%) had an Impella implanted for high-risk PCI and 13 patients (32.5%) had it implanted for CS. Eight patients had an Impella inserted as hemodynamic support during ventricular tachycardia ablation; these patients were not included in the analysis and discussion.

In our cohort, the majority of patients (70.0%) were males. Median patient age was 74 years and 77.5% were white. Significant comorbidities were present (Table 1).

Patients with high-risk PCI were more frequently associated with a history of prior CAD (81.5%), hypertension (59.3%), diabetes (55.6%), coronary artery bypass graft (29.6%), and cerebrovascular accident (25.9%). Patients with CS were more likely to have a past history of heart failure or new-onset heart failure (46.2%).

High-risk PCI. Among the 27 patients who underwent high-risk PCI under Impella support, a total of 3 had unstable angina and 24 had stable CAD. In all patients, the Impella device was removed following PCI and before the patient left the catheterization laboratory. Twenty-one patients (77.8%) had severe LV dysfunction (LV ejection fraction ≤35%), and 9 patients (33.3%) underwent PCI to an unprotected left main artery. All patients were discussed in a heart team approach15 and were deemed high risk for surgery. Twenty-two patients (81.5%) underwent multivessel PCI; a total of 64 stents were implanted in 27 patients (mean, 2.3 ± 1.0 stents).

Cardiogenic shock. A total of 13 patients had the Impella inserted for CS, with 8 secondary to acute MI and 5 for non-ischemic causes. Nine of our CS patients (69.2%) presented with cardiac arrest, 12 (92.3%) required vasopressors and inotropes, and 7 (53.8%) had an IABP inserted prior to the Impella.

Impella was used in all cases of CS secondary to acute MI for mechanical support during PCI and was limited only to the duration of PCI, except in 2 patients in whom the Impella device was removed the second day. One patient had severe aortic stenosis and required balloon aortic valvuloplasty as well, whereas the other required prolonged use of Impella due to refractory shock. Two of the patients with CS secondary to acute MI required stenting of the left main coronary artery.

There was an increase in Impella use from the time it was introduced in 2008, with 2 devices placed in 2008 and 10 placed in 2015 and 2016.

As expected, mortality at 30 days was extremely high in the CS group (10/13 patients; 76.9%) and lower in the high-risk PCI group (3/27 patients; 11.1%) (Table 2).

There were 16 device-related complications. The most common complication was acute renal dysfunction in 11 patients, of which 6 required hemodialysis. One patient had postimplantation hemolysis (detected by very high lactate dehydrogenase); removing the device led to resolution of the hemolysis. There were no postprocedural access-site infections or cases of bacteremia. There were no incidents of device malfunction (Table 3).

Discussion

In this observational retrospective study, we have examined our institutional use of the Impella device in patients with CS and high-risk PCI. Our study, although observational, might translate into other big centers within the United States. The mortality rate in our CS group was extremely high, probably reflecting the severity of the illness rather than the device efficacy itself. It appears that interventional cardiologists consider Impella use to be a higher level of care given that 50% of the CS patients started with IABP. Acute renal dysfunction was noted to be the most common complication (11/40; 27.5%) followed by vascular complications, which occurred in 2 of the 13 patients in the CS group (15.4%) and 6 of the 27 patients in the high-risk PCI group (22.2%) (Table 2).

The 2011 American College of Cardiology Foundation/American Heart Association (ACCF/AHA) PCI guidelines give a class IIb recommendation with level of evidence C for the elective insertion of a percutaneous MCS device as an adjunct to PCI in carefully selected high-risk patients, which may include those undergoing unprotected left main or last-remaining conduit PCI, those with severely depressed ejection fraction undergoing PCI of a vessel supplying a large territory, and/or those with CS.16

The 2013 ACCF/AHA guidelines give a class IIA recommendation for the use of IABP in the setting of CS with the option for other percutaneous MCS in the setting of refractory shock.17 In comparison, the European guidelines consider the routine use of percutaneous MCS a class III indication and advise these devices to be considered in refractory cases.18

In high-risk PCI, Impella has demonstrated a beneficial LV unloading effect with improved coronary perfusion. In contrast to Impella 2.5/CP, the Impella 5 system requires a surgical cut-down and is not truly percutaneous.8 The safety, feasibility, and usefulness of Impella in the setting of high-risk PCI has been reported by the Europella registry, which demonstrated no device-related mortality and a low device complication rate.19 The EUROSHOCK registry demonstrated access-site complications in up to 24% of the cohort patients, which is similar to our cohort.20

The first randomized trial on the use of Impella vs IABP in 25 patients with CS secondary to acute MI showed that the use of Impella was associated with significant improvement in cardiac output, mean arterial pressures, and lactic acid levels. The trial failed to show any mortality benefits at 30 days, which is probably due to the low number of patients.21,22 PROTECT II (A Prospective, Multicenter, Randomized Controlled Trial of the IMPELLA Recover LP 2.5 System Versus Intra-Aortic Balloon Pump in Patients Undergoing Non Emergent High Risk PCI) failed to demonstrate the superiority of Impella over IABP in patients undergoing high-risk PCI at 30 days or discharge (whichever came first). However, a prospectively planned outcome analysis of the trial at 90 days showed a superior major adverse event outcome with Impella (40% vs 51% with IABP; P=.02).23

In 2016, the IMPRESS (Impella CP Versus Intra-Aortic Balloon Pump in Acute Myocardial Infarction Complicated by Cardiogenic Shock) trial showed that Impella did not improve 30-day mortality when compared with IABP in patients with severe CS secondary to acute MI. However, the Impress trial population was extremely ill and only 5 patients in this study had Impella placed before PCI.24

Stretch et al22 reported a rapid upward national trend of percutaneous short-term MCS device use from 2004 to 2011. They reported a paradigm shift of short-term MCS use when comparing 2007 and earlier with the years after 2007. The availability of these devices with early placement prior to the onset of circulatory collapse has been shown to reduce hospital costs and lower mortality. Our observation of the upward trend of Impella use corresponds with the nationally reported trend.22

A trend of MCS use in patients with CS secondary to acute MI was reported by Sandhu et al,25 who found that only half of the patients undergoing PCI in the setting of CS were managed by MCS. They observed that the national trend of IABP use in this setting was on a slow downward trend, yet the use of other MCS devices, including Impella, was not significantly increasing. The authors postulated operator unfamiliarity, patient clinical status, and a lack of data showing improvement in patient outcomes as possible reasons for this observation about Impella use. They also noted that the use of newer MCS devices, including Impella, is clustered in a small minority of hospitals and the impact of these devices on patient outcomes is warranted.25

Iliodromitis et al26 reported the outcome of Impella use in 38 patients with acute coronary syndrome requiring high-risk PCI. They excluded patients with STEMI or CS. They reported acute renal dysfunction in 5% of patients, who did not require dialysis. Fifteen percent of their patients developed a femoral hematoma requiring prolonged immobilization. They required blood transfusion due to perioperative bleeding complications.

In the most recent analysis of patients with CS secondary to acute MI, a total of 237 patients treated with an Impella from large-volume European centers were matched to 237 patients from the IABP-SHOCK II trial.27 The use of an Impella device was not associated with lower 30-day mortality compared with matched patients from the IABP-SHOCK II trial treated with an IABP or medical therapy (48.5% vs 46.4%, respectively; P=.64). On the contrary, severe or life-threatening bleeding (8.5% vs 3.0%; P<.01) and peripheral vascular complications (9.8% vs 3.8%; P=.01) occurred significantly more often in the Impella group.

Ternus et al28 reported a trend of MCS use at Mayo Clinic after analyzing cases from 2009 to 2015, and reported no significant overall change in the total number of devices placed; however, Impella use was reported to be on a downward trend. The use of MCS devices prior to high-risk PCI also was noted to be on a downward trend. Furthermore, they concluded that there was an increase in complications related to Impella use vs IABP, without any improvement in composite outcome.28

In a recent review of cardiac shock centers by Rab et al,29 the authors pointed out that the National Cardiovascular Data Registry (NCDR) showed that MCS devices were used in only 0.7% of CS cases.30 The authors strongly advocate for the early recognition of CS secondary to acute MI and the early adoption of MCS devices using the motto of “door-to-support of <90 minutes.”29 A successful example is the Detroit Cardiogenic Shock Initiative (DCSI), which has been expanded to the National Cardiogenic Shock Initiative with more than 50 centers nationwide. The authors report 77% survival to discharge among 104 CS patients treated on such protocols.29 The protocol, in summary, involves emergency medical personnel screening patients for CS secondary to acute MI prior to arriving at the emergency department and trying to allocate those patients to a level 1 CS center – a center with MCS device capabilities. Thereafter, they should receive an MCS device – like the Impella – within 90 minutes and prior to attempting revascularization.29

Although this initiative portends exciting news for CS with acute MI, the data are non-randomized and limited to a few select centers, and at this time are not necessarily applicable to the general population.

Our center’s experience, along with our literature review, identified the major limitations to the use of Impella or other MCS devices in contemporary practice: (1) lack of high-volume randomized controlled trials showing major adverse cardiovascular event benefits; (2) excess rate of device-related complications, with the most common being access-site complications, renal dysfunction, and hemolysis; (3) lack of operator experience in using such devices, which might be related to number 1 and contribute to number 3; (4) perception of Impella as a higher level of care, which delays the use of this potentially highly beneficial hemodynamic device; and (5) the lack of universal availability of the Impella device in comparison with IABP.

Study limitations. This is a retrospective observational study with a small number of subjects, and conclusions should not be applied to all patients with CS or high-risk PCI. Patients fell under selection bias due to the nature of the study.

Conclusion

All recent data indicate that mortality in CS continues to be high, and whenever inotropes and pressors fail as a first-line therapy, clinicians turn to certain forms of MCS devices such as Impella or extracorporeal membrane oxygenation (ECMO). In many cases in the United States, this MCS device is still the IABP, although data do not support its use as first-line therapy and use of IABP in CS has been recently downgraded to a class II indication. Currently, very few institutions in the United States have an Impella-first or an ECMO-first strategy for CS, and protocols vary significantly. Optimizing myocardial recovery is the goal in CS patients, and Impella lends itself more naturally to this. In the case of high-risk PCI, on the other hand, protocols are generally uniform.

In this retrospective cohort study, we describe our center’s experience with the Impella device and the upward trend of its use over the past decade. There is still, however, a low adoption rate for this device. Future randomized trials – with volumes similar to the SHOCK 2 trial – might be needed to better answer the question of the utility of the Impella device. In addition, smaller sheaths, better operator training, proper patient selection, and the adoption of the cardiac shock center concept with earlier placement of Impella/MCS in CS patients might lead to better outcomes in such patients.

Acknowledgments. The authors are grateful to Jennifer Pfaff and Susan Nord of Aurora Cardiovascular Services for editorial preparation of the manuscript.

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From the 1Aurora Cardiovascular Services, Aurora Sinai/Aurora St. Luke’s Medical Centers, University of Wisconsin School of Medicine and Public Health, Milwaukee, Wisconsin; and 2Aurora Research Institute, Aurora Health Care, Milwaukee, Wisconsin.

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 submitted February 1, 2019, provisional acceptance given February 11, 2019, final version accepted March 11, 2019.

Address for correspondence: M. Fuad Jan, MBBS, MD, Aurora Cardiovascular Services, Aurora St. Luke’s Medical Center, 2801 W. Kinnickinnic River Parkway, Ste. 880, Milwaukee, WI 53215. Email: publishing18@aurora.org

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