Outcomes of Hemodynamic Support With Impella for Acute Myocardial Infarction Complicated by Cardiogenic Shock at a Rural Community Hospital Without On-Site Surgical Back-up

Abstract: Aims. Impella 2.5 and Impella CP (Abiomed) are percutaneous left ventricular assist devices that can be easily deployed in the cardiac catheterization laboratory without need for surgery and provide effective hemodynamic support. The utility of Impella devices for management of acute myocardial infarction complicated by cardiogenic shock (AMI-CS) at a rural community hospital without on-site surgical back-up has not been reported. Methods. We retrospectively reviewed all consecutive patients who underwent percutaneous coronary intervention (PCI) with Impella support between 2012 and 2017 for AMI-CS at our institution. Survival, in-hospital complications, and recovery of native heart function at follow-up were assessed. Results. A total of 90 consecutive patients (age, 63.8 ± 11.56 years; 28.8% female) with AMI-CS were supported with Impella and underwent PCI. At admission, 82.2% had cardiogenic shock and 32.2% sustained out-of-hospital cardiac arrest (OHCA). Survival rates at discharge, 30 days, 180 days, and 365 days were 61.1%, 60.0%, 57.7%, and 57.3%, respectively. Survivors were younger (P=.02) and had lower rates of OHCA (P<.01). Survival rate at 180 days was 72.4% when door-to-Impella support time was ≤48 minutes, 53.9% when Impella was initiated between 49 to 86 minutes, and 39.3% when Impella support was initiated after 86 minutes (P=.04). Recovery of native heart function was observed in 88.7% of 62 patients weaned off Impella support. Conclusions. Early hemodynamic support with the Impella percutaneous left ventricular assist device in severely ill patients with AMI-CS at a rural community hospital without on-site surgical back-up yielded very favorable survival outcomes, with recovery of native heart function.  

J INVASIVE CARDIOL 2019;31(2):E23-E29.

Key words: cardiogenic shock, Impella device, left ventricular assist device

Cardiogenic shock (CS) is a state of critical hypoperfusion of end-organs due to reduced cardiac output and occurs in up to 10% of patients with acute myocardial infarction (AMI).¹ Despite early revascularization with percutaneous coronary intervention (PCI), mortality associated with CS remains high at about 50%.^1,2

Mechanical circulatory support (MCS) devices have been shown to improve hemodynamics, cardiac output, and tissue perfusion.^3,4 The current United States and European guidelines suggest use of MCS in patients presenting with AMI-CS (class IIb recommendation).^5-7 Recent studies on trends in utilization of MCS in the United States for CS due to acute coronary syndromes report increasing use of short-term percutaneous MCS such as Impella devices (Abiomed, Inc).^8,9 In addition to the rapid hemodynamic benefits, Impella can be easily deployed in the cardiac catheterization laboratory without any surgical intervention.³ However, studies suggest greater use of MCS in young, male patients with MI, lower prevalence of comorbid conditions such as chronic renal failure or peripheral vascular disease, and presentation to large urban hospitals.^8,9 The usefulness of Impella support in recovering hearts of patients presenting at rural community hospitals without on-site surgical back-up has not been addressed.

San Juan Regional Medical Center (SJRMC), a 194-bed community hospital in northwest New Mexico, provides care to a quarter million people residing in the four-corners area of New Mexico, Arizona, Colorado, and Utah. It is 175 miles from the nearest tertiary medical facility and has no cardiovascular surgical back-up on-site. This study provides data on the use and clinical outcomes of hemodynamic support with Impella 2.5 and Impella CP for AMI-CS in patients presenting to SJRMC.

Methods

A retrospective review of all patients treated with Impella as MCS device from November 2011 to September 2017 at SJRMC was conducted. The study was approved by the SJRMC institutional review board.

At our institution, Impella 2.5 and Impella CP devices have been used as primary MCS for the management of AMI-CS, out-of-hospital cardiac arrest (OHCA) with return of spontaneous circulation (ROSC), and hemodynamically stable high-risk percutaneous coronary intervention (HR-PCI) since November 2011.

AMI diagnosis was confirmed based on electrocardiographic findings indicative of new or presumed new ischemia (new ST-T changes or new left bundle-branch block), detection of elevated cardiac biomarkers, or angiographic findings of an infarct-related artery on coronary angiogram in a clinical setting of myocardial ischemia (symptoms of ischemia). CS was defined based on clinical criteria including: (1) hypotension (systolic blood pressure <90 mm Hg for 30 minutes before inotropes/vasopressors or inotropes/vasopressors required to maintain systolic blood pressure >90 mm Hg); and (2) signs of end-organ hypoperfusion (cool extremities, oliguria with urine output of <30 mL/hour or anuria, and altered mental status). Successful weaning from Impella device was defined as survival to device explantation without need for additional MCS support. Recovery was defined as successful weaning with survival to discharge. Hemolysis was defined as presence of hemoglobinuria (“tea-colored urine”) and/or new or worsening of anemia with decrease in hematocrit or hemoglobin level that is out of proportion with levels explained by the patient’s condition. Limb ischemia was defined as new incidence of hypoperfusion of the leg marked by symptoms such as decreased skin temperature of the limb or decreased peripheral pulse, and requiring treatment.

Statistical analysis. Statistical analyses were performed with JMP software, version 10 (SAS Institute, Inc). Data are presented as mean ± standard deviation or median with interquartile range (IQR). Categorical variables are presented as number (percentage), and baseline categorical variables were tested using Pearson’s Chi-square test for contingency tables. Baseline, hemodynamic, and laboratory parameters between survivors and non-survivors were compared using t-test or non-parametric alternative. Changes in left ventricular ejection fraction from baseline at discharge and longest follow-up were compared via paired t-test. A two-sided P-value of <.05 was considered statistically significant.     

Results

Patient population. A total of 132 patients received hemodynamic support with Impella between November 8, 2011 and September 29, 2017 at our institution. Clinical indication for Impella support (Figure 1) was AMI-CS in 98 patients (74.2%), non-ischemic cardiomyopathy complicated by cardiogenic shock (NICM-CS) in 5 patients (3.8%), other etiologies causing CS in 9 patients (6.8%), HR-PCI in 18 patients (13.6%), and electrophysiology procedures in 2 patients (1.5%).

Of the 98 patients supported with Impella for AMI-CS, ninety patients underwent PCI and were included in this analysis (Figure 1). The mean age was 63.8 ± 11.56 years and 28.8% were female. Seventy-four patients (82.2%) presented with CS at the time of admission and 87.7% had ST-elevation myocardial infarction (STEMI). Also, twenty-nine patients had OHCA with initial rhythm of ventricular tachycardia/ventricular fibrillation (VT/VF) in 82.7%. Patients presented with average left ventricular ejection fraction of 36.6% ± 14.6% and signs of tissue hypoperfusion with median peak creatinine of 1.3 mg/dL (IQR, 1-2.35 mg/dL) (Table 1).

Prompt revascularization with PCI was performed with a median door-to-balloon time of 50 minutes (IQR, 30-64 minutes). Angiographic success with a Thrombolysis in Myocardial Infarction (TIMI) score of 3 post PCI was achieved in 88%. Hemodynamic support was initiated with Impella 2.5 in 82% and with Impella CP in 18%. Impella support was initiated prior to PCI in 46.6% and post PCI in 53.3%. The median door-to-Impella support was 59 minutes (IQR, 39-100 minutes) and duration of Impella support was 24 hours (IQR, 12-34 hours).

Successful weaning from Impella support without need for additional MCS was observed in 62/90 patients (68.8%). Of the 62 survivors to Impella explantation, a total of 7 died prior to discharge and 55 patients (88.7%) recovered their native heart function and survived to discharge. Overall rates of survival to discharge, 30 days, 180 days, and 365 days were 61.1% (55/90), 60% (54/90), 57.7% (52/90), and 57.3% (51/89), respectively. The baseline characteristics were similar among survivors and non-survivors except for age and occurrence of acute kidney injury (AKI) prior to Impella initiation (Table 1). The non-survivors presented with higher rate of OHCA (18.5% vs 52.7%; P<.01), had lower mean left ventricular ejection fraction at presentation (39.6% vs 31.0% P=.01), higher creatinine levels (1.2 mg/dL vs 2.3 mg/dL; P=.04), and required higher number of vasopressors (1.53 vs 2.08; P<.01). In addition, non-survivors more often required mechanical ventilation (27.7% vs 86.1%; P<.001). Decrease in survival rate at 30 days was observed with increasing number of vasopressors used. Survival rates at 30 days were 73.8%, 56.5%, and 40% in patients receiving ≤1, 2, or ≥3 vasopressors, respectively (Figure 2). Survivors had higher PCI success rate as measured by post-PCI TIMI grade flow 3 (94.4% vs 77.1%; P=.01). Interestingly, survivors showed a trend toward shorter median door-to-Impella support time (56.5 minutes vs 80 minutes; P=.07). In line with the above findings, patients with door-to-Impella support time of ≤48 minutes had a 180-day survival rate of 72.4%, compared to 53.9% for those who received Impella support within 49-86 minutes and 39.3% for those who received Impella support after 86 minutes (Figure 3). Moreover, survivors had longer median duration of Impella support than non-survivors (24 hours vs 12 hours; P=.02).

Functional heart recovery in the surviving patients was observed with significant improvement in left ventricular ejection fraction at follow-up compared to baseline. Mean left ventricular ejection fraction was 39.1% at baseline, which improved to 43.6% at discharge and to 54.1% at longest follow-up of up to 24 months (P<.001) (Figure 4). As suggested by previous real-world studies, occurrence of OHCA significantly impacted survival rates. Among 61 patients without OHCA, survival rates were 72.1%, 72.1%, 68.8%, and 68.3% at discharge, 30 days, 180 days, and 365 days compared to only 34.4% through 365 days among 29 patients with OHCA.

No difference in the rate of in-hospital complications was observed between survivors and non-survivors (Table 2). Bleeding requiring transfusion was the most frequent event for the entire cohort (22/89; 24.7%), with a numerically lower rate among the survivors (20.3% vs 31.4%; P=.31). Bleeding requiring surgery occurred in 2 patients (2.25%), and limb ischemia occurred in 1 patient (1.12%). Hemolysis was observed in 19 patients (21.5%), with 10 patients among those with OHCA.

Discussion

To the best of our knowledge, this study represents the largest single-center investigation to date on patients with AMI-CS supported with an Impella device at a community hospital without on-site surgical back-up. The main findings of our study are: (1) favorable survival in severely ill patients with AMI-CS at discharge, 30, 180, and 365 days following early hemodynamic support with Impella; (2) Impella support allowed functional recovery of the left ventricle, with significant improvement in ejection fraction; and (3) the utility of the Impella device without need for surgical intervention and acceptable complication rate in the emergency setting of AMI-CS at a rural community hospital.

The main goal of treatment in patients presenting with AMI-CS is the rapid restoration of tissue perfusion, thus enabling recovery of end-organ dysfunction.² Percutaneous MCS devices represent an attractive strategy to provide rapid hemodynamic support and include devices such as TandemHeart (TandemLife), extracorporeal membrane oxygenation (ECMO), and Impella.² Although the TandemHeart device can provide significant hemodynamic support, insertion requires transseptal puncture, with an average insertion time of 45-60 minutes, thus limiting its use in the emergent setting of AMI-CS.¹⁰ ECMO has been used to support patients in CS or cardiac arrest, but prolonged use is associated with poor outcomes and a high complication rate.¹¹ A recent retrospective analysis of a nationwide emergency department sample database in the United States suggested greater use of ECMO only in large metropolitan hospitals due to the complexity of procedures and a high risk of complications.¹²

In contrast to other percutaneous devices, the Impella 2.5 and CP are minimally invasive MCS devices that provide rapid hemodynamic support by unloading the left ventricle and promote myocardial recovery by replacing left ventricular function.³ The present study demonstrates the utility and clinical outcomes of the Impella 2.5 and CP devices at a rural community hospital without on-site surgical back-up for patients with AMI-CS requiring urgent hemodynamic support.

Patients in our cohort were severely ill (82.2% presented with CS at admission, 87.7% had STEMI, and 32.2% sustained OHCA). Despite the presence of these high-risk features, survival rates at 30 days (60.0%), 180 days (57.7%), and 365 days (57.3%) in our cohort were favorable compared to the IABP-SHOCK II trial (60.0% at 30 days, 51.0% at 180 days, and 48.0% at 365 days).^13,14 In fact, a higher proportion of patients in our study presented with STEMI (87.7% vs 68.6%; P<.001) and had poor hemodynamic profile with lower median systolic blood pressure than patients randomized in the IABP-SHOCK II trial (68.5 mm Hg [IQR, 53-80 mm Hg] vs 89.5 mm Hg [IQR, 79-107 mm Hg]). The 30-day survival rate observed in our study was favorable even when compared to a recent study from an experienced ECMO center in patients with AMI-CS (60.0% vs 36.8%; P<.01).¹⁵ Compared to patients treated with ECMO, patients in our study were older (63.8 years vs 52.7 years) and had higher incidence of diabetes (42.2% vs 20.9%; P<.01). However, the proportion of patients with cardiac arrest in our study was lower (46.7% vs 78.3%; P=.03), which might have contributed to the higher survival rate. Furthermore, survival rate at 30 days in our cohort was significantly higher in comparison to the EUROSHOCK Impella registry16 (60.0% vs 35.8%; P<.001), with a similar proportion of patients with OHCA (32.2% vs 40.8%; P=.20).

In our cohort, non-survivors had a higher incidence of OHCA, longer duration of cardiopulmonary resuscitation, and lower baseline left ventricular ejection fraction. All of these conditions are well documented to be associated with worse outcomes.^17-19 In fact, the survival rates in patients presenting without OHCA were 72.1%, 68.8%, and 68.3% at 30 days, 180 days, and 365 days (Figure 1). The favorable survival outcome in our study is likely due to early initiation of Impella support, with median door-to-Impella support time of 59 minutes. Indeed, survival was higher in patients with door-to-Impella support time within 48 minutes vs those who received Impella support after 48 minutes (Figure 3). Consistent with previous data from the cVAD registry, 4 survival rates in our study decreased significantly with increasing number of vasopressors (Figure 2). Overall, the results of the present analysis corroborate with recent studies of Impella in AMI-CS that demonstrated improved survival outcomes following prompt initiation of Impella support within 90 minutes of CS, prior to escalating doses of inotropes, and prior to PCI.^4,20

The most important finding our study is the recovery of native heart function with Impella support. Of the 62 patients weaned off Impella support, a total of 55 (88.7%) survived to discharge following recovery of native heart function. Among the 49 survivors with left ventricular ejection fraction measurement available at baseline, discharge, and longest follow-up of up to 24 months, mean left ventricular ejection fraction increased from 39.1% at baseline to 54.1% at longest follow-up (representing a 38% increase from baseline; P<.001) (Figure 4). This left ventricular unloading by Impella presents a major advantage when compared to venoarterial ECMO. Due to retrograde flow in the descending aorta, venoarterial ECMO increases afterload on the already failing heart, further increasing myocardial oxygen demand and ischemia, thus lowering the likelihood of native heart recovery.²¹ Results from preclinical studies suggest that early initiation of left ventricular unloading with Impella increases cardioprotective signaling, thus improving cell survival and limiting myocardial damage.^22,23 In keeping with preclinical studies, prompt hemodynamic support with Impella and early revascularization likely led to recovery of native heart function among survivors.

Previous studies have documented the safety of Impella use in AMI-CS patients, and complication rates observed in the present study are consistent with previous reports.^16,24,25 Recently, Cheng et al performed a meta-analysis of 1866 patients with CS or cardiac arrest and reported a high complication rate with venoarterial ECMO.¹¹ When compared with the cumulative complication rates reported for venoarterial ECMO by Cheng et al,¹¹ the Impella 2.5 and CP devices in the present study appear to have acceptable rates for limb ischemia (1.1% vs 16.5%; P<.05) and major bleeding (26.9% vs 46.1%; P<.05). The hemolysis rate of 21.5% in our study was higher than the previously reported rate of 10.3% with Impella 2.5.²⁵ However, none of the hemolysis events required removal of the device during our study. Interestingly, more than 50% of the patients experiencing hemolysis had OHCA and 63% had bleeding requiring blood transfusion; both of these complications may have contributed to the higher hemolysis rates.

Taken together, the results of the present analysis suggest that rapid hemodynamic support with Impella 2.5 and Impella CP is an effective and safe strategy to improve outcomes in patients presenting with AMI-CS. Compared with other short-term MCS devices, the ease of use and rapid hemodynamic support offered by Impella 2.5 and Impella CP make them very attractive and convenient MCS devices in the setting of a rural community hospital without on-site surgical back-up.

Study limitations. Limitations of our study include the retrospective nature of data collection, which is subject to confounding and bias, in addition to the selective availability of parameters such as hemodynamic improvement after Impella implantation. The observational nature of this study limits definitive conclusions regarding Impella use and observed survival outcomes. This is a single-center study with unique geographic and demographic characteristics and therefore results may not be generalizable.

Conclusion

Early hemodynamic support with Impella 2.5 and CP devices for severely ill patients with AMI-CS at a rural community hospital without on-site surgical back-up yielded very favorable survival outcomes with recovery of native heart function.

References

1. Thiele H, Desch S, de Waha S. Mechanical circulatory support: the last resort in cardiogenic shock? EuroIntervention. 2018;13:2099-2101.
2. Tewelde SZ, Liu SS, Winters ME. Cardiogenic shock. Cardiol Clin. 2018;36:53-61.
3. Chera HH, Nagar M, Chang NL, et al. Overview of Impella and mechanical devices in cardiogenic shock. Expert Rev Med Devices. 2018 Dec 18 (Epub Ahead of Print).
4. Basir MB, Schreiber TL, Grines CL, et al. Effect of early initiation of mechanical circulatory support on survival in cardiogenic shock. Am J Cardiol. 2017;119:845-851.
5. American College of Emergency Physicians, Society for Cardiovascular Angiography and Interventions, O’Gara PT, et al. 2013 ACCF/AHA guideline for the management of ST-elevation myocardial infarction: a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines. J Am Coll Cardiol. 2013;61:e78-e140.
6. Ponikowski P, Voors AA, Anker SD, et al. 2016 ESC guidelines for the diagnosis and treatment of acute and chronic heart failure: the task force for the diagnosis and treatment of acute and chronic heart failure of the European Society of Cardiology (ESC) developed with the special contribution of the Heart Failure Association (HFA) of the ESC. Eur Heart J. 2016;37:2129-2200.
7. Ibanez B JS, Agewall S, Antunes MJ, et al. 2017 ESC guidelines for the management of acute myocardial infarction in patients presenting with ST-segment elevation: the task force for the management of acute myocardial infarction in patients presenting with ST-segment elevation of the European Society of Cardiology (ESC). Eur Heart J. 2018;39:119-177.
8. Strom JB, Zhao Y, Shen C, et al. National trends, predictors of use, and in-hospital outcomes in the mechanical circulatory support for cardiogenic shock. EuroIntervention. 2018;13:e2152-e2159.
9. Agarwal S, Sud K, Martin JM, Menon V. Trends in the use of mechanical circulatory support devices in patients presenting with ST-segment elevation myocardial infarction. JACC Cardiovasc Interv. 2015;8:1772-1774.
10. Kar B, Adkins LE, Civitello AB, et al. Clinical experience with the TandemHeart percutaneous ventricular assist device. Tex Heart Inst J. 2006;33:111-115.
11. Cheng R, Hachamovitch R, Kittleson M, et al. Complications of extracorporeal  membrane oxygenation for treatment of cardiogenic shock and cardiac arrest: a meta-analysis of 1,866 adult patients. Ann Thorac Surg. 2014;97:610-616.
12. El Sibai R, Bachir R, El Sayed M. ECMO use and mortality in adult patients with cardiogenic shock: a retrospective observational study in U.S. hospitals. BMC Emerg Med. 2018;18:20.
13. Thiele H, Zeymer U, Neumann F-J, et al. Intraaortic balloon support for myocardial infarction with cardiogenic shock. N Engl J Med. 2012;367:1287-1296.
14. Thiele H, Zeymer U, Neumann F-J, et al. Intra-aortic balloon counterpulsation in acute myocardial infarction complicated by cardiogenic shock (IABP-SHOCK II): final 12 month results of a randomised, open-label trial. Lancet. 2013;382:1638-1645.
15. Overtchouk P, Pascal J, Lebreton G, et al. Outcome after revascularisation of acute myocardial infarction with cardiogenic shock on extracorporeal life support. EuroIntervention. 2018;13:e2160-e2168.
16. Lauten A, Engstrom AE, Jung C, et al. Percutaneous left ventricular support with the Impella 2.5 assist device in acute cardiogenic shock - results of the Impella EUROSHOCK-registry. Circ Heart Fail. 2013;6:23-30. Epub 2012 Dec 4.
17. Martinell L, Nielsen N, Herlitz J, et al. Early predictors of poor outcome after out-of-hospital cardiac arrest. Crit Care. 2017;21:96.
18. Karatolios K, Chatzis G, Markus B, et al. Impella support compared to medical treatment for post-cardiac arrest shock after out of hospital cardiac arrest. Resuscitation. 2018;126:104-110.
19. Sleeper LA, Reynolds HR, White HD, et al. A severity scoring system for risk assessment of patients with cardiogenic shock: a report from the SHOCK trial and registry. Am Heart J. 2010;160:443-450.
20. Basir MB, Schreiber T, Dixon S, et al. Feasibility of early mechanical circulatory support in acute myocardial infarction complicated by cardiogenic shock: the Detroit cardiogenic shock initiative. Catheter Cardiovasc Interv. 2018;91:454-461.
21. Lim HS. The effect of Impella CP on cardiopulmonary physiology during venoarterial extracorporeal membrane oxygenation support. Artif Organs. 2017;41:1109-1112. Epub 2017 Jun 7.
22. Esposito ML, Zhang Y, Qiao X, et al. Left ventricular unloading before reperfusion promotes functional recovery after acute myocardial infarction. J Am Coll Cardiol. 2018;72:501-514.
23. Kapur NK, Qiao X, Paruchuri V, et al. Mechanical pre-conditioning with acute circulatory support before reperfusion limits infarct size in acute myocardial infarction. JACC Heart Fail. 2015;3:873-882.
24. Schroeter M, Köhler H, Wachter A, et al. 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. J Invasive Cardiol. 2016;28:467-472.
25. O’Neill WW, Schreiber T, Wohns DH, et al. The current use of Impella 2.5 in acute myocardial infarction complicated by cardiogenic shock: results from the USpella registry. J Interv Cardiol. 2014;27:1-11.

From the ¹Montrose Memorial Hospital, Montrose, Colorado; and ²San Juan Regional Medical Center, Farmington, New Mexico.

Disclosure: The authors have completed and returned the ICMJE Form for Disclosure of Potential Conflicts of Interest. Dr Wilkins reports non-financial support (writing assistance) and personal fees from Abiomed. The remaining authors report no conflicts of interest regarding the content herein.

Manuscript submitted October 9, 2018 and accepted on October 25, 2018.

Address for correspondence: Charles Everett Wilkins, MD, Montrose Memorial Hospital, 801 South 3rd Street, Montrose, CO 81401. Email: cwilkins@montrosehospital.com