a b s t r a c t

Introduction: The role of circulatory support in the post-cardiac arrest period remains controversial. Our objective was to investigate the association between treatment with a percutaneous hemodynamic support device and outcome after admission for cardiac arrest.

Methods: We performed a retrospective study of adult patients with admission diagnosis of cardiac arrest or ven- tricular fibrillation (VF) from the Michigan Inpatient Database, treated between July 1, 2010, and June 30, 2013. Patient demographics, clinical characteristics, treatments, and disposition were electronically abstracted based on ICD-9 codes at the hospital level. Mixed-effects logistic regression models were fit to test the effect of percu- taneous hemodynamic support device defined as either percutaneous left ventricular assist device (pLVAD) or intra-aortic balloon pump on survival. These models controlled for age, sex, VF, myocardial infarction (MI), and cardiogenic shock with hospital modeled as a random effect.

Results: A total of 103 hospitals contributed 4393 patients for analysis, predominately male (58.8%) with a mean age of 64.1 years (SD 15.5). On univariate analysis, younger age, male sex, VF as the initial rhythm, acute MI, per- cutaneous coronary intervention, percutaneous hemodynamic support device, and absence of cardiogenic shock were associated with survival to discharge (each p b 0.001). Mixed-effects logistic regressions revealed use of percutaneous hemodynamic support device was significantly associated with survival among all patients (OR

1.8 (1.28-2.54)), and especially in those with acute MI (OR 1.95 (1.31-2.93)) or cardiogenic shock (OR 1.96

(1.29-2.98)).

Conclusion: Treatment with percutaneous hemodynamic support device in the post-arrest period may provide left ventricular support and improve outcome.

(C) 2017

1. Introduction

The benefit of circulatory support in the post-cardiac arrest period remains controversial. Historically, intra-aortic balloon pumps (IABP) have been used as the primary circulatory support device for myocardial infarction (MI) complicated by cardiogenic shock [1]. However, a con- temporary prospective, randomized controlled trial has revealed no Mortality benefit with this therapy at one month or one year for patients in cardiogenic shock after MI [2]. While use of IABP for cardiogenic shock in the setting of acute MI was once a level 1b recommendation in America, it has recently been downgraded to a level 2b

? Sources of support: This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.

* Corresponding author at: William Beaumont Hospital, 3601 W. 13 Mile Rd, Royal Oak, MI 48073, United States.

E-mail address: [email protected] (R. Swor).

recommendation [1,3]. Advances in technology have allowed for me- chanical support using percutaneous left ventricular assist devices (pLVAD). While numerous studies have shown improved hemodynam- ics with these devices, no randomized controlled trial has been per- formed to assess overall mortality benefit [4,5,6]. Furthermore, studies assessing both IABP and pLVAD use in patients resuscitated from out- of-hospital cardiac arrest (OHCA) are limited given the difficulty in studying this patient population [7].

Data from IABP use to treat post-cardiac arrest cardiogenic shock are more readily available than data from other pLVADs. Two studies retro- spectively studying the subject have found that IABP use was strongly associated with Neurologically intact survival [8,9]. However, a further prospective study found IABP use associated with increased mortality in MI patients complicated by cardiac arrest [10]. There have been promising porcine studies evaluating the use of pLVAD during cardiac arrest resuscitation, doubling the rate of return of spontaneous circula- tion (ROSC) compared to Standard care [11]. In human subjects, studies

https://doi.org/10.1016/j.ajem.2017.10.036

0735-6757/(C) 2017

A. Pressman et al. / American Journal of Emergency Medicine 36 (2018) 834–837 835

assessing pLVAD use in cardiac arrest have been limited to case series. These series showed that pLVAD use was associated with a sicker pa- tient populations but found no difference in neurologically intact sur- vival [12,13].

It is clear that little literature exists studying pLVAD and IABP use in Post cardiac arrest patients across larger populations. The objective of this study was to investigate whether, in a statewide cohort of post car- diac arrest patients, use of percutaneous hemodynamic support device was associated with survival.

1. Methods

We performed a retrospective study of adult (age >= 18 years) pa- tients with an admission diagnosis of cardiac arrest (ICD-CM 427.5) or ventricular fibrillation (ICD-9 CM 427.41) from the Michigan Inpatient Database (MIDB), treated between July 1, 2010, and June 30, 2013. This definition of cardiac arrest includes both OHCA patients that sur- vived to hospital admission, as well as those who arrested in the ED and survived to admission. No patient with CPR in progress is included in this cohort of patients. The MIDB is run by the Michigan Health & Hos- pital Association and has been collecting data on patients requiring in- patient admission since the 1980s. It currently collects data on 1.3 million admitted patients annually from N 100 hospitals across Michigan [14,15]. This database collects information on all patients who survived to admission into an acute care hospital, including patient demo- graphics, receiving facility, discharge diagnoses, procedures performed, and patient outcomes. Patient outcomes recorded included survival to hospital discharge and discharge destination (home, short term rehabil- itation, skilled nursing facility, hospital). For this study we defined sur- viving to hospital discharge as any patient discharged from the hospital to home or another facility other than hospice. Data on patient demographics (age, sex), clinical characteristics (arrest rhythm of ven- tricular fibrillation (VF), cardiogenic shock (ICD-9 CM 98551), myocar- dial infarction (ICD-9 CM, 41000-41010)), procedures performed (e.g. percutaneous coronary intervention (PCI), percutaneous hemodynamic support device placement), and outcome (survived to discharge) were electronically abstracted based on ICD-9 codes at the hospital level. Per- cutaneous hemodynamic support device was defined as either IABP or pLVAD (Impella 2.5). Duplicate cases, patients b 18 years old, and cases with missing data were excluded.

Univariate relationships with outcome were compared using a

Welch’s two-sample t-test for continuous data and a chi-squared test of independence for categorical data. Mixed-effects logistic regression models were fit to test the effect of percutaneous hemodynamic support device on outcome, with hospital modeled as a random effect. In the mixed-effects logistic regression, we controlled for those variables known to have an effect on survival from our univariate analysis (age, sex, VF, MI, and cardiogenic shock), but also attempted to control for specific hospital effect on survival. This study was approved by the Wil- liam Beaumont Hospital Institutional Review Board. All data cleaning and analysis was performed using R (version 3.2.1) and RStudio (ver- sion 0.99.467).

1. Results

A total of 103 hospitals in Michigan contributed 4393 patients for analysis with a mean age of 64.1 years (SD 15.5) and 41% being female. From the total, 1422 patients (32.4%) had a diagnosis of VF, 1174 (26.7%) with MI, and 779 (17.7%) cardiogenic shock. Only 197 (4.5%) patients received a percutaneous hemodynamic support device, of which most were IABP (182 (4.1%)). These were placed in 35 different hospitals, with only 20 hospitals placing them more than once a year. Table 1 and Fig. 1 highlight the results of the univariate analyses, reveal- ing that younger age, male sex, VF initial rhythm, acute MI, PCI, percuta- neous hemodynamic support device, and absence of cardiogenic shock were associated with survival to discharge. This effect was most notable

Table 1

Univariate analysis of factors associated with survival to hospital discharge.

Patient variables	Survival	Deaths	p-Value
	(n = 1688)	(n = 2705)
Age, mean (SD)	61.5 (15.3)	65.7 (15.5)	b 0.001a
Male sex, n(%)	1083 (64.2)	1499 (55.4)	b 0.001b
VF initial rhythm, n(%)	821 (48.6)	601 (22.2)	b 0.001b
Acute MI, n(%)	510 (30.2)	664 (24.5)	b 0.001b
Cardiogenic shock, n(%)	220 (13.0)	559 (20.7)	b 0.001b
Received PCI, n(%)	278 (16.5)	122 (4.5)	b 0.001b
Hemodynamic support device, n(%)	103 (6.1)	94 (3.5)	b 0.001b

VF-ventricular fibrillation; MI-myocardial infarction; PCI-percutaneous intervention.

^a Compared using Welch’s two-sample t-test.

^b Compared using chi-squared test of independence.

for an initial rhythm of VF (OR, 3.3, 95% CI, 2.9-3.8) and receiving PCI (OR, 4.2, 95% CI, 3.3-5.2) but was still significant for those receiving a percutaneous hemodynamic support device (OR, 1.8, 95% CI, 1.4-2.4). As would be expected, cardiogenic shock was negatively associated with survival (OR, 0.6, 95% CI, 0.5-0.7).

Fig. 2 shows results of the mixed-effects logistic regression model assessing the association of percutaneous hemodynamic support device on survivability in all patients, acute MI patients, and patients compli- cated by cardiogenic shock. The mixed-effects logistic regression model attempted to control for variables found in our univariate analy- sis such as age, sex, VF initial rhythm, cardiogenic shock and presence of MI while also taking into account a theoretical hospital effect towards survivability. While controlling for these variables, use of a percutane- ous hemodynamic support device was associated with survival in all pa- tients (OR, 1.8, 95% CI, 1.3-2.5) and even more so when applied to acute MI patients (OR, 1.9, 95% CI, 1.3-2.9) and those in cardiogenic shock (OR, 2.0, 95% CI, 1.3-3.0).

1. Discussion

These data identify that the use of percutaneous hemodynamic sup- port device in post cardiac arrest patients admitted to Michigan hospi- tals was associated with an improved survival. This was true in all patients, patients who had a diagnosis of MI, and patients with a diagno- sis of cardiogenic shock. While an improved outcome was observed for all patients, the association was even stronger with those who had suf- fered an acute MI or suffered from cardiogenic shock. To our knowledge this is the largest dataset that has evaluated use of percutaneous hemo- dynamic support device in the post arrest population.

Our findings are important, as the literature specifically evaluating percutaneous hemodynamic support device use in cardiac arrest pa- tients is sparse [7]. While existing literature evaluating IABP use in MI patients suffering from cardiogenic shock found no mortality benefit, there is some data to suggest that IABP use is positively associated with Neurologically intact survival in post arrest patients [1,8,9]. In the largest prospective trial assessing IABP use in MI patients complicated by cardiac arrest, IABP was associated with higher mortality [10]. Be- cause IABP was used in a sicker population, and the primary outcome of mortality did not assess for neurologic status, results were likely neg- atively biased. It is possible that these variables as well as our inclusion of pLVAD use could account for our positive association with survival. Furthermore, this study did not delineate between in hospital and OHCA while our study specifically looked at those admitted for cardiac arrest. In human subjects, very little data exists specifically addressing pLVAD use in OHCA. A single study compared IABP use to pLVAD (Impella 2.5) use in OHCA patients and found no difference in neurolog- ically intact survival at 28 days. However, no comparison was made be- tween patients that received either LVAD device to those that received neither [12,13]. Our findings expand the literature as our patient popu- lation represented patients who suffered either OHCA or Emergency

836 A. Pressman et al. / American Journal of Emergency Medicine 36 (2018) 834–837

Fig. 1. Unadjusted odds ratios of factors associated with survival to hospital discharge.

Department (ED) arrest and compared those receiving either percuta- neous hemodynamic support device to those that received neither.

Overall, few patients from the MIDB were treated with percutaneous hemodynamic support device after being admitted to the hospital for cardiac arrest. Our findings suggest a positive association between sur- vival to discharge and percutaneous hemodynamic support device use defined as either IABP or pLVAD. Although retrospective and hypothesis generating, this study is important given the absence of prospective data on this therapy. A body of literature has evolved calling for the de- velopment of post cardiac arrest centers, which may provide interven- tions (emergent PCI, Targeted temperature management, percutaneous hemodynamic support device) to post arrest patients [16-22]. This literature is mixed with respect to showing improved out- comes in such centers. Our data indicates that percutaneous hemody- namic support devices were placed in a small subset of hospitals across the state, and an even smaller subset of these placed them more frequently than once a year. This may further support the utiliza- tion of post cardiac arrest centers that have more experience with crit- ically ill patients that may benefit from these devices. Data supporting identification of subsets of patients and therapies such as percutaneous hemodynamic support device placement are needed to guide decisions regarding the triage of post arrest patients.

There is also growing literature showing that other novel innova-

tions such as mechanical CPR and extracorporeal membrane oxygena- tion (ECMO) may improve outcomes in OHCA [23,24]. Mechanical CPR and ECMO CPR may serve as a “bridge-to-therapy”, giving the patient uninterrupted Mechanical support until the appropriate therapeutic in- tervention (e.g. PCI) may be performed. Our findings suggest that the percutaneous hemodynamic support devices we studied may also be considered as a bridge-to-therapy while awaiting the targeted interven- tion that may resolve the cause of arrest. Furthermore, while most stud- ies consider a positive outcome as survival or a neurologically intact state, further research may show that these bridge-to-therapy devices may also increase survival to Organ donation [25]. While survival of the patient remains the foremost priority, in cases where neurologically intact survival is not possible, percutaneous hemodynamic support

devices may provide the necessary support to keep organs perfused while the subject of organ donation may be broached.

Prospective data regarding the use of percutaneous hemodynamic support devices post arrest is needed, however, the relative infrequency of cardiogenic shock in this population (17.7% in this study) and limited number of centers that perform emergent percutaneous hemodynamic support device placement (b 33% in this study) make it unlikely that large prospective Multi-center trials will be performed to definitively answer the question of whether pLVAD therapy improves outcome. Fur- thermore, it would be difficult to implement a randomized control trial in this population as it would be unethical to withhold or place percuta- neous hemodynamic support devices if felt there could be a benefit or harm for specific patients. In the interim, data from registries and ad- ministrative datasets play an important role in guiding clinicians and policy makers.

Limitations

Use of ICD-9 CM coding is a fundamental limitation of this study, as we do not have physiological data to assess clinical characteristics and comorbidities of this population. All diagnoses are identified upon hos- pital discharge and we are unable to identify which clinical entities were present upon hospital admission. More in-depth analysis of the data- base subjects in regards to cardiac arrest type, MI type, total Ischemic time, Time to intervention with the percutaneous hemodynamic sup- port device, and specifics about post-arrest hemodynamics were not possible and would have been of great interest. The vast majority of our population with percutaneous hemodynamic support devices re- ceived IABPs. Although pLVADs are relatively new devices that generate greater flow than IABPs, we are unable to assess the independent asso- ciation of either technology alone to improve outcome. This dataset rep- resents patients who were admitted to the hospital after resuscitation and have a continued perfusing rhythm, and who have an admission di- agnosis of cardiac arrest. As such, patients who may have arrested in an ED are included in our population along with OHCA patients. This pop- ulation may be more similar to out of hospital patients than inpatient

Fig. 2. Mixed-effects regression model testing effect of pLVAD use on survival to hospital discharge.

A. Pressman et al. / American Journal of Emergency Medicine 36 (2018) 834–837 837

cardiac arrests, but the relative number of these patients in our study cohort is not known. Our inclusion population does not include patients who have CPR in progress who received some sort of immediate circu- latory support, such as extracorporeal membrane oxygenation . While this immediate type of support is being implemented with in- creasing frequency and is an intriguing evolution of resuscitative care, it does not address our population. Finally, patients who expired prior to admission were not included in the MIDB and therefore are also not in our analysis.

Our findings could possibly be confounded by survival bias as pa- tients who survived long enough to receive percutaneous hemodynam- ic support device may have been more likely to survive overall. However, we feel this is unlikely, as numerous other studies have found that cardiac arrest patients are more likely to receive IABP and pLVAD if they have worse left ventricular function and hemodynamics [8,9,10]. Furthermore, unlike PCI, which is often performed after the pa- tient may have awakened and their outcome status is clearer, IABP would typically be performed earlier in a patient’s course, before an out- come can be anticipated. Finally we used survival to hospital discharge as our outcome and did not attempt to use any measures of quality of survival (e.g. Discharge home vs skilled nursing, etc) in our analysis. Other measures of positive outcome, such as survival to organ trans- plantation or neurologically intact survival, should also be considered in the future.

Conclusion

In this statewide population, treatment with percutaneous hemody- namic support device in the post-arrest period was associated with an improved survival to hospital discharge. These data support the need for further prospective work to assess the benefit of percutaneous he- modynamic support devices in post cardiac arrest patients.

Acknowledgments

This study adhered to the conditions approved by the William Beau- mont Hospital Institutional Review Board. The authors would like to ac- knowledge the work of the providers and hospitals that contribute their data to the MIDB.

Author disclosure statement

No competing financial interests exist. This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.

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