Article Information

Corresponding author: Abdelmoniem Moustafa, M.D

Article Type : A Meta-Analysis

Volume : 3

Issue : 7

Received Date : 07 Sep ,2022


Accepted Date : 19 Sep ,2022

Published Date : 26 Sep ,2022


DOI : https://doi.org/10.38207/JCMPHR/2022/SEP030704101

Citation: Flaherty MP, Moustafa A, Khan MS, Khan AR, Basir MB, et al. (2022) Timing of Impella In Acute Myocardial Infarction complicated With Cardiogenic Shock Impacts Survival: A Meta-Analysis. J Comm Med and Pub Health Rep 3(07): https://doi.org/10.38207/JCMPHR/

Copyright: © 2022 Abdelmoniem Moustafa, M.D. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source a
  Timing of Impella In Acute Myocardial Infarction Complicated With Cardiogenic Shock Impacts Survival: A Meta-Analysis

Michael P. Flaherty, M.D., Ph.D1*, Abdelmoniem Moustafa, M.D2*, Mohammad Saud Khan, M.D3, Abdur R. Khan, M.D4, Mir B. Basir, D.O5, Navin K. Kapur, M.D6, Amir Kaki, M.D7, Theodore L. Schreiber M.D8, William W. O’Neill, M.D5

1Divisions of Cardiology, Baptist Health Systems - Heart & Vascular Center, Louisville, KY, USA

2Divisions of Cardiology, University of Toledo, Toledo, OH, USA

3Divisions of Cardiology, Western Kentucky Heart and Lung and Med Center Health, Bowling Green, KY, US

4Divisions of Cardiology, Massachusetts General Hospital, Boston, MA, USA

5Divisions of Cardiology, Henry Ford Hospital, Detroit, MI, USA

6Divisions of Cardiology, Tufts Medical Center, Boston, MA, USA

7Divisions of Cardiology, St. John's Hospital, Wayne State University, Detroit, MI, USA

8Divisions of Cardiology, St. John's McComb Hospital, Wayne State University, Detroit, MI, USA

*Dr Abdelmoniem Moustafa and Dr Michael Flaherty contributed equally

*Corresponding Author: Abdelmoniem Moustafa, M.D, Divisions of Cardiology, University of Toledo, Toledo, OH, USA.

Abstract
Background:
Acute myocardial infarction (AMI) complicated by cardiogenic shock (AMICS) is often fatal, despite early revascularization. We sought to analyze whether mortality could be favorably impacted by the early implementation of mechanical circulatory support (MCS) before revascularization during AMICS.

Methods and Results:
In this large study of 811 patients, the largest study to date, we performed a meta-analysis of eight studies comparing the impact of ‘Early’ versus ‘Late’ Impella implantation on early (In-hospital-to30 days) and late (6-12 month) mortality during AMICS. Pooled analysis showed significantly lower short-term mortality (RR: 0.61, 95 % CI: 0.49-0.75, p < 0.001, I2 = 0 %) and long-term mortality (RR: 0.64, 95 % CI: 0.48- 0.84, p=0.002, I2 = 0 %) with early Impella implantation compared to late Impella implantation.

Conclusion: Our findings suggest increased survival is associated with early implantation of Impella, before revascularization, in patients presenting with AMICS. Although further exploration of this finding is warranted, these data support a new protective strategy with Impella use in AMICS.

Non-standard Abbreviations and Acronyms
Percutaneous coronary intervention (PCI) Mechanical circulatory support (MCS) Acute myocardial infarction complicated by cardiogenic shock (AMICS)

Keywords: Acute myocardial infarction, cardiogenic shock, AMICS, Impella, pre PCI, Post PCI

Introduction
Mortality remains high (~50 %) in patients presenting with acute myocardial infarction (AMI) complicated by cardiogenic shock (AMICS) despite early revascularization. Decreased AMICS-related survival persists despite the addition of supportive therapies; in particular, the historical widespread use of intra-aortic balloon pumps (IABP) and the undirected, random use of partial percutaneous mechanical circulatory support (MCS). [1] However, when contemporary standardized AMICS protocols are deployed utilizing early MCS of the left and/or right ventricle(s) before revascularization, survival outcomes as high as ~77 % have been observed. [2] Yet, current guidelines do not provide specific guidance for the appropriate timing of MCS use in AMICS. [3] Therefore, we performed a meta-analysis of the current literature related to the use of Impella MCS in the treatment of AMICS to determine the overall survival impact of an early Impella implantation strategy.

Methods
This meta-analysis was performed following the guidelines of the Preferred Reporting Items for Systematic Review and Meta-Analysis. PubMed, Embase, and Cochrane Central databases were searched from inception till April 2022. Two reviewers (A.M., M.S.K) independently assessed the eligibility of the studies and extracted data. Studies reporting outcomes on ‘Early’ and ‘Late’ Impella implantation were included. Studies with overlapping patient populations were excluded. ‘Early’ and ‘Late’ Impella implantation were defined as Impella placement before or following coronary revascularization, respectively. The outcome assessed was mortality in short term (In-hospital or 30-day) and in long term (6-12 months). Risk ratios (RR) were calculated and the generic inverse variance method was used to pool data into a fixed effect model meta-analysis. Heterogeneity among studies was assessed using I2 statistics

Results
After applying the eligibility criteria, 8 studies were included in our analysis.1,4-10 Two studies were prospective [1,9] and the rest were observational in design. Of the 811 participants, 64 % were men, mean age was 65 years. Utilization of inotropes and the need for mechanical ventilation were prevalent, 85 % and 82 %, respectively. Cardiac arrest occurred in 54 % of all included patients. All 8 studies reported short-term mortality and 3 studies reported long-term mortality. [4,5,10] Cardiogenic shock was defined as systolic blood pressure (SBP) < 90 mm Hg or the need for inotropic support for more than 30 minutes to maintain SBP > 90 min despite adequate fluid loading. Exclusion criteria encompassed patients with severe aortoiliac disease and known severe aortic valve disease and patients who received Impella support after the first 24 hours following PCI.1,4-10 Patient demographics and studies' characteristics are summarized in Tables 1 and 2, respectively. Pooled analysis showed significantly lower short-term mortality (RR: 0.61, 95 % CI: 0.49- 0.75, p < 0.001, I2 = 0 %) and long-term mortality (RR: 0.64, 95 % CI: 0.48-0.84, p=0.002, I2 = 0 %) with early Impella implantation compared to late Impella implantation (Figure 1: A and B, respectively).

Methods
This meta-analysis was performed following the guidelines of the Preferred Reporting Items for Systematic Review and Meta-Analysis. PubMed, Embase, and Cochrane Central databases were searched from inception till April 2022. Two reviewers (A.M., M.S.K) independently assessed the eligibility of the studies and extracted data. Studies reporting outcomes on ‘Early’ and ‘Late’ Impella implantation were included. Studies with overlapping patient populations were excluded. ‘Early’ and ‘Late’ Impella implantation were defined as Impella placement before or following coronary revascularization, respectively. The outcome assessed was mortality in short term (In-hospital or 30-day) and in long term (6-12 months). Risk ratios (RR) were calculated and the generic inverse variance method was used to pool data into a fixed effect model meta-analysis. Heterogeneity among studies was assessed using I2 statistics 

Results
After applying the eligibility criteria, 8 studies were included in our analysis.1,4-10 Two studies were prospective [1,9] and the rest were observational in design. Of the 811 participants, 64 % were men, mean age was 65 years. Utilization of inotropes and the need for mechanical ventilation were prevalent, 85 % and 82 %, respectively. Cardiac arrest occurred in 54 % of all included patients. All 8 studies reported short-term mortality and 3 studies reported long-term mortality. [4,5,10] Cardiogenic shock was defined as systolic blood pressure (SBP) < 90 mm Hg or the need for inotropic support for more than 30 minutes to maintain SBP > 90 min despite adequate fluid loading. Exclusion criteria encompassed patients with severe aortoiliac disease and known severe aortic valve disease and patients who received Impella support after the first 24 hours following PCI.1,4-10 Patient demographics and studies' characteristics are summarized in Tables 1 and 2, respectively. Pooled analysis showed significantly lower short-term mortality (RR: 0.61, 95 % CI: 0.49- 0.75, p < 0.001, I2 = 0 %) and long-term mortality (RR: 0.64, 95 % CI: 0.48-0.84, p=0.002, I2 = 0 %) with early Impella implantation compared to late Impella implantation (Figure 1: A and B, respectively).

Table 1: Patient Clinical Characteristics and Demographics

 

O’Neill et al

(n=154)

Basir et al.

(n=287)

Schroeter et

al (n=68)

Ouweneel

et al (n=24)

Meraj et al

(n=36)

Loehn et

al (n=73)

Hemradj et

al (n=88)

Chatzis et

al (n=81)

Mean age

64

66

63

58

69

69

60

68

Male

110

219

49

18

28

53

72

68

Hypertension

119

193

NA

4

23

53

31

62

Diabetes Mellitus

68

117

16

2

13

28

14

27

Prior stroke

14

32

5

0

1

9

2

6

Prior MI

59

80

11

1

9

19

16

34

Mechanical ventilation

NA

218

55

24

26

55

78

81

Cardiac arrest

35

153

33

24

16

61

53

64

Inotropes/vasopressors

NA

230

NA

24

36

60

78

71

EF

26.4+/-13.4

25.3 +/- 12

27 +/-15

NA

24.6+/-12

29 +/-12

NA

32.9+/-7

Table 2: Studies characteristics

Study/Year

Design

Patients

(number)

Impella

Indication

O’Neill et al. 2014

Retrospective, observational, USpella registry

154

2.5

Cardiogenic shock due to Acute MI

Basir et al. 2016

Retrospective, observational, cVAD registry

287

2.5/CP

Cardiogenic shock due to Acute MI

Schroeter et al. 2016

Retrospective observational, single-center

68

2.5

Cardiogenic shock due to Acute MI

Ouweneel et al. 2016

Randomized Controlled Trail, Multi-center

48

CP

Cardiogenic shock due to Acute MI

Meraj et al. 2017

Retrospective, observational, cVAD registry

36

2.5

Cardiogenic shock due to Acute MI

Loehn et al. 2020

Retrospective Observational , single center

73

CP

Cardiogenic shock due to Acute MI

Hemredj et al. 2020

Prospective observational, single-center

88

2.5/CP/5

Cardiogenic shock due to Acute MI

Chatzis et al. 2021

Retrospective Observational , single center

81

2.5

Cardiogenic shock due to Acute MI

Figure 1: Forest Plot Comparing In-Hospital-30-Day (A) and 6-12 month (B) Mortality in “Early” vs. “Late” Impella use for AMICS.

Discussion
This analysis of 811 patients is currently the largest study investigating the role of percutaneous MCS timing in the treatment of AMICS. Our data suggest a significant survival benefit with early compared to late Impella implantation in patients presenting with AMICS. Early Impella initiation was associated with a 59 % reduction in short-term mortality (In-hospital/30 days) and a 36 % reduction in long-term mortality in AMICS patients. Early left ventricular unloading in AMICS demonstrated a reduction in infarction size as shown in animal models. [11] As previously reported, this early initiation of MCS may play a key role in halting the downward spiral of escalating vasopressor dosage, peripheral vasoconstriction, hypoperfusion, arrhythmias, systemic inflammatory response syndrome, and multi-organ failure. [5,6]

In line with our data, the Detroit Cardiogenic Shock Initiative Pilot Study demonstrated a significant improvement in survival to explant compared with historical data with early initiation of mechanical cardiac support. [12] Others demonstrate a well-documented proportional increase in survival rate with shorter doors to Impella times were observed in a retrospective study. [13] Whereas, contemporary data are scarce and mixed about the survival benefit from early use of other MCS devices compared to Impella. [1,14,15] Finally, O’Neill et al, in ostensibly the sickest non-AMICS cohorts studied to data, reported higher survival to explant with pre-PCI impeller support when compared to pre-PCI intra-aortic balloon pump use in a large cohort of AMICS.[16]

Study
Limitations:
There are several limitations in our analysis. Despite the lack of heterogeneity in our analysis, variability in the study population exists allowing for both known and unknown confounders. Outcomes-based on Impella initiation is subject to treatment bias wherein those treated late with Impella were treated as such due to a complication or unexpected hemodynamic compromise, therefore, self-selecting a higher risk cohort. These limitations can only be assessed by way of an individual patient-data meta-analysis or adequately powered randomized controlled trial. Additionally, we do not establish causation, due to the observational design and lack of a comparator group in the included studies, which makes our results purely hypothesis generating.

Conclusions
Collectively, when taken together with our data, the contemporary literature is replete with data underscoring the 'timing' of Impella support initiation as a crucial variable impacting outcome in AMICS. Our data are in line with previous analyses and other registry data reporting improved overall survival with an early MCS strategy as well as shorter door-to-MCS times.[12,17] However, larger adequately powered prospective studies (undoubtedly those aforementioned here) are needed to confirm our findings and alter future practice patterns.

Conflicts of Interest
Drs. Flaherty, Kapur, Kaki, Schreiber, and O'Neill receive modest speaker honoraria from Abiomed; Dr. Basir is a consultant and receives research funding from Abiomed; Drs. Moustafa, Khan MS, and Khan AR have no conflicts of interest to disclose.

Author's contribution
Conception and design: Abdelmoniem Moustafa, Michael Flaherty, Abdur R. Khan. Data collection and analysis: Abdelmoniem Moustafa, Mohammad Saud Khan. Writing: Michael Flaherty, Abdelmoniem Moustafa, Mohammad Saud Khan. Reviewing and Editing: Mir Basir, Navin Kapur, Amir Kaki, Theodore Schreiber, and William O’Neill

Source of Funding: There was no funding for this study.

References

  1. Ouweneel DM, Eriksen E, Sjauw KD, van Dongen IM, Hirsch A, et al. (2017) Percutaneous Mechanical Circulatory Support Versus Intra-Aortic Balloon Pump in Cardiogenic Shock After Acute Myocardial Infarction. Journal of the American College of Cardiology. 69(3): 278–287.
  2. Tehrani BN, Truesdell AG, Sherwood MW, Desai S, Tran HA, et al. (2019) Standardized Team-Based Care for Cardiogenic Shock. J Am Coll Cardiol. 73(13): 1659–1669.
  3. Rihal CS, Naidu SS, Givertz MM, Szeto WY, Burke JA, et al. (2015) 2015 SCAI/ACC/HFSA/STS Clinical Expert Consensus Statement on the Use of Percutaneous Mechanical Circulatory Support Devices in Cardiovascular Care (Endorsed by the American Heart Association, the Cardiological Society of India, and Sociedad Latino Americana de Cardiologia Intervencion; Affirmation of Value by the Canadian Association of Interventional Cardiology–Association Canadienne de Cardiologie d’intervention). J Am Coll Cardiol. 65(19): e7-e26.
  4. Schroeter MR, Köhler H, Wachter A, Bleckmann A, Hasenfuß G, et al. (2016) 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. 28(12): 467–472.
  5. Loehn T, O’Neill WW, Lange B, Pfluecke C, Schweigler T, et al. (2020) Long term survival after early unloading with Impella CP® in acute myocardial infarction complicated by cardiogenic shock. European Heart Journal: Acute Cardiovascular Care. 9(2): 149–157.
  6. Basir MB, Schreiber TL, Grines CL, Dixon SR, Moses JW, et al. (2017) Effect of Early Initiation of Mechanical Circulatory Support on Survival in Cardiogenic Shock. Am J Cardiol. 119(6): 845–851.
  7. O’neill WW, Schreiber T, Wohns DHW, Rihal C, Naidu SS, et al. (2014) The Current Use of Impella 2.5 in Acute Myocardial Infarction Complicated by Cardiogenic Shock: Results from the USpella Registry. Journal of Interventional Cardiology. 27(1): 1– 11.
  8. Meraj PM, Doshi R, Schreiber T, Maini B, O’Neill WW (2017) Impella 2.5 initiated prior to unprotected left main PCI in acute myocardial infarction complicated by cardiogenic shock improves early survival. J Interv Cardiol. 30(3): 256–263.
  9. Hemradj VV, Karami M, Sjauw KD, Engström AE, Ouweneel DM, et al. (2020) Pre-PCI versus immediate post-PCI Impella initiation in acute myocardial infarction complicated by cardiogenic shock. PLoS One. 15(7): e0235762.
  10. Chatzis G, Markus B, Luesebrink U, Ahrens H, Divchev D, et al. (2021) Early Impella Support in Postcardiac Arrest Cardiogenic Shock Complicating Acute Myocardial Infarction Improves Short- and Long-Term Survival. Critical Care Medicine. 49(6): 943-955.
  11. Kapur NK, Paruchuri V, Urbano-Morales JA, Mackey EE, Daly GH, et al. (2013) Mechanically unloading the left ventricle before coronary reperfusion reduces left ventricular wall stress and myocardial infarct size. Circulation. 128(4): 328–336.
  12. Basir MB, Schreiber T, Dixon S, Alaswad K, Patel K, et al. (2018) Feasibility of early mechanical circulatory support in acute myocardial infarction complicated by cardiogenic shock: The D etroit cardiogenic shock initiative. Catheter Cardiovasc Interv. 91(3): 454–461.
  13. Wilkins CE, Herrera TL, Nagahiro MK, Weathers LB, Girotra SV, et al. (2019) 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. J Invasive Cardiol. 31(2): E23–E29.
  14. Schrage B, Ibrahim K, Loehn T, Werner N, Sinning JM, et al. (2019) Impella Support for Acute Myocardial Infarction Complicated by Cardiogenic Shock: Matched-Pair IABP- SHOCK II Trial 30-Day Mortality Analysis. Circulation. 139(10): 1249–1258.
  15. Dhruva SS, Ross JS, Mortazavi BJ, Hurley NC, Krumholz HM, et al. (2020) Association of Use of an Intravascular Microaxial Left Ventricular Assist Device vs Intra-aortic Balloon Pump With In-Hospital Mortality and Major Bleeding Among Patients With Acute Myocardial Infarction Complicated by Cardiogenic Shock. JAMA. 323(8): 734-745.
  16. O'Neill WW, Grines C, Schreiber T, Moses J, Maini B, et al. (2018) Analysis of outcomes for 15,259 US patients with acute myocardial infarction cardiogenic shock (AMICS) supported with the Impella device. Am Heart J. 202: 33–38.
  17. Flaherty MP, Khan AR, O’Neill WW (2017) Early Initiation of Impella in Acute  Myocardial Infarction Complicated by Cardiogenic Shock Improves Survival: A Meta-Analysis. JACC Cardiovasc Interv. 10(17): 1805–1806.