Advertisement

Implementation of a Comprehensive ST-Elevation Myocardial Infarction Protocol Improves Mortality Among Patients With ST-Elevation Myocardial Infarction and Cardiogenic Shock

Open AccessPublished:August 14, 2020DOI:https://doi.org/10.1016/j.amjcard.2020.08.012
      Mortality in patients with STEMI-associated cardiogenic shock (CS) is increasing. Whether a comprehensive ST-elevation myocardial infarction (STEMI) protocol (CSP) can improve their care delivery and mortality is unknown. We evaluated the impact of a CSP on incidence and outcomes in patients with STEMI-associated CS. We implemented a 4-step CSP including: (1) Emergency Department catheterization lab activation; (2) STEMI Safe Handoff Checklist; (3) immediate catheterization lab transfer; (4) and radial-first percutaneous coronary intervention (PCI). We studied 1,272 consecutive STEMI patients who underwent PCI and assessed for CS incidence per National Cardiovascular Data Registry definitions within 24-hours of PCI, care delivery, and mortality before (January 1, 2011, to July 14, 2014; n = 723) and after (July 15, 2014, to December 31, 2016; n = 549) CSP implementation. Following CSP implementation, CS incidence was reduced (13.0% vs 7.8%, p = 0.003). Of 137 CS patients, 43 (31.4%) were in the CSP group. CSP patients had greater IABP-Shock II risk scores (1.9 ± 1.8 vs 2.8 ± 2.2, p = 0.014) with otherwise similar hemodynamic and baseline characteristics, cardiac arrest incidence, and mechanical circulatory support use. Administration of guideline-directed medical therapy was similar (89.4% vs 97.7%, p = 0.172) with significant improvements in trans-radial PCI (9.6% vs 44.2%, p < 0.001) and door-to-balloon time (129.0 [89:160] vs 95.0 [81:116] minutes, p = 0.001) in the CSP group, translating to improvements in infarct size (CK-MB 220.9 ± 156.0 vs 151.5 ± 98.5 ng/ml, p = 0.005), ejection fraction (40.8 ± 14.5% vs 46.7 ± 14.6%, p = 0.037), and in-hospital mortality (30.9% vs 14.0%, p = 0.037). In conclusion, CSP implementation was associated with improvements in CS incidence, infarct size, ejection fraction, and in-hospital mortality in patients with STEMI-associated CS. This strategy offers a potential solution to bridging the historically elusive gap in their care.
      Cardiogenic shock (CS) is a common complication of ST-elevation myocardial infarction (STEMI), occurring in 5% to 13% of patients, and causes significant morbidity and mortality.
      • Backhaus T
      • Fach A
      • Schmucker J
      • Fiehn E
      • Garstka D
      • Stehmeier J
      • Hambrecht R
      • Wienbergen H
      Management and predictors of outcome in unselected patients with cardiogenic shock complicating acute ST-segment elevation myocardial infarction: results from the Bremen STEMI Registry.
      • Valle JA
      • Kaltenbach LA
      • Bradley SM
      • Yeh RW
      • Rao SV
      • Gurm HS
      • Armstrong EJ
      • Messenger JC
      • Waldo SW
      Variation in the adoption of transradial access for ST-segment elevation myocardial infarction: insights from the NCDR CathPCI Registry.
      • Wayangankar SA
      • Bangalore S
      • McCoy LA
      • Jneid H
      • Latif F
      • Karrowni W
      • Charitakis K
      • Feldman DN
      • Dakik HA
      • Mauri L
      • Peterson ED
      • Messenger J
      • Roe M
      • Mukherjee D
      • Klein A
      Temporal trends and outcomes of patients undergoing percutaneous coronary interventions for cardiogenic shock in the setting of acute myocardial infarction: a report from the CathPCI Registry.
      There is a wealth of data supporting the importance of timely reperfusion through percutaneous coronary intervention (PCI) and its association with improved survival in patients with STEMI and CS.
      • Moosvi AR
      • Khaja F
      • Villanueva L
      • Gheorghiade M
      • Douthat L
      • Goldstein S
      Early revascularization improves survival in cardiogenic shock complicating acute myocardial infarction.
      • Lee L
      • Erbel R
      • Brown TM
      • Laufer N
      • Meyer J
      • O'Neill WW
      Multicenter registry of angioplasty therapy of cardiogenic shock: initial and long-term survival.
      • Gacioch GM
      • Ellis SG
      • Lee L
      • Bates ER
      • Kirsh M
      • Walton JA
      • Topol EJ
      Cardiogenic shock complicating acute myocardial infarction: the use of coronary angioplasty and the integration of the new support devices into patient management.
      • Hochman JS
      • Sleeper LA
      • Webb JG
      • Sanborn TA
      • White HD
      • Talley JD
      • Buller CE
      • Jacobs AK
      • Slater JN
      • Col J
      • McKinlay SM
      • LeJemtel TH
      Early revascularization in acute myocardial infarction complicated by cardiogenic shock.
      Moreover, there is suggestion that a delay in door-to-balloon time (D2BT) results in increased mortality, supporting that rapid PCI may further improve outcomes in these patients. However, despite advances in STEMI care and national improvements in D2BT, mortality is increasing amongst those with STEMI and CS.
      • Wayangankar SA
      • Bangalore S
      • McCoy LA
      • Jneid H
      • Latif F
      • Karrowni W
      • Charitakis K
      • Feldman DN
      • Dakik HA
      • Mauri L
      • Peterson ED
      • Messenger J
      • Roe M
      • Mukherjee D
      • Klein A
      Temporal trends and outcomes of patients undergoing percutaneous coronary interventions for cardiogenic shock in the setting of acute myocardial infarction: a report from the CathPCI Registry.
      A recent study by Kochar et al.
      • Kochar A
      • Al-Khalidi HR
      • Hansen SM
      • Shavadia JS
      • Roettig ML
      • Fordyce CB
      • Doerfler S
      • Gersh BJ
      • Henry TD
      • Berger PB
      • Jollis JG
      • Granger CB
      Delays in primary percutaneous coronary intervention in ST-segment elevation myocardial infarction patients presenting with cardiogenic shock.
      demonstrated that patients with STEMI and CS had worse first medical contact-to-device time, were less likely to be revascularized, and had 10-fold higher in-hospital mortality compared to those without CS. In addition, implementation of the American Heart Association (AHA) Mission: Lifeline STEMI Systems Accelerator initiative, a regional system of care intervention aimed at improving D2BT, was associated with minimum improvement in D2BT in patients with STEMI and CS. As such, it remains unclear if the care of these critically ill patients is modifiable and if systems of care can be developed to reliably and quickly respond to them.
      • Khot UN
      • Huded CP.
      Systems for rapid revascularization in ST-segment elevation myocardial infarction with cardiogenic shock.
      We recently showed the complementary impact on mortality of guideline-directed medical therapy (GDMT), use of trans-radial access (TRA) for primary PCI, and lower D2BT in patients with STEMI.
      • Huded CP
      • Kumar A
      • Johnson M
      • Abdallah M
      • Ballout JA
      • Kravitz K
      • Menon V
      • Gullett TC
      • Hantz S
      • Ellis SG
      • Podolsky SR
      • Meldon SW
      • Kralovic DM
      • Brosovich D
      • Smith E
      • Kapadia SR
      • Khot UN
      Incremental prognostic value of guideline-directed medical therapy, transradial access, and door-to-balloon time on outcomes in ST-segment-elevation myocardial infarction.
      The value of systems of care focusing on improving these key issues for patients with STEMI and CS is unknown. Accordingly, we implemented a 4-step comprehensive STEMI protocol (CSP) aimed at systematically targeting these tenets of STEMI care and investigated its impact on (1) the incidence of CS in all patients with STEMI and (2) care delivery and outcomes in patients with STEMI and CS.

      Methods

      We performed a prospective, registry-based study of consecutive patients with STEMI treated with PCI at our center from January 1, 2011, to December 31, 2016. No patients were excluded. Baseline characteristics, care metrics, adverse events and mortality were adjudicated by the standards of the American College of Cardiology National Cardiovascular Data Registry CathPCI Registry by trained data abstractors.
      • Moussa I
      • Hermann A
      • Messenger JC
      • Dehmer GJ
      • Weaver WD
      • Rumsfeld JS
      • Masoudi FA
      The NCDR CathPCI Registry: a US national perspective on care and outcomes for percutaneous coronary intervention.
      Survival status was ascertained by medical record review and follow-up phone calls as needed. Survival status was complete in 98.7% (n = 1,255) of the population at 30 days and 90.9% (n = 1,156) at 1 year. In those with CS, survival status was complete in 100% (n = 137) and 98.5% (n = 135) at 30 days and 1 year, respectively.
      Our 4-step CSP has been described.
      • Huded CP
      • Johnson M
      • Kravitz K
      • Menon V
      • Abdallah M
      • Gullett TC
      • Hantz S
      • Ellis SG
      • Podolsky SR
      • Meldon SW
      • Kralovic DM
      • Brosovich D
      • Smith E
      • Kapadia SR
      • Khot UN
      4-Step protocol for disparities in STEMI care and outcomes in women.
      On July 15,2014, we implemented a CSP intending to minimize STEMI care variability by (1) enabling immediate Emergency Department physician activation of the catheterization laboratory without delay for Cardiology consultation, (2) using a STEMI Safe Handoff Checklist to standardize the early triage of patients including GDMT administration, (3) mandating transfer to an immediately available catheterization laboratory to avoid patient delays, and (4) employing a “radial-first” approach to PCI in suitable patients. Although use, timing, and type of mechanical circulatory support was not protocolized, all patients placed on veno-arterial extracorporeal membrane oxygenation remained in our cardiac intensive care unit rather than being transferred to a cardiothoracic intensive care unit. We identified patients who had CS, per the American College of Cardiology National Cardiovascular Data Registry definition of sustained (> 30 minutes) episode of systolic blood pressure < 90 mm Hg and/or cardiac index < 2.2 L/min/m2 determined to be secondary to cardiac dysfunction, and/or the requirement of parenteral inotropic or vasopressor agents or mechanical support to maintain blood pressure and cardiac index previously mentioned those specified levels, within 24-hours of PCI.
      • Moussa I
      • Hermann A
      • Messenger JC
      • Dehmer GJ
      • Weaver WD
      • Rumsfeld JS
      • Masoudi FA
      The NCDR CathPCI Registry: a US national perspective on care and outcomes for percutaneous coronary intervention.
      Patients treated from January 1, 2011, to July 14, 2014, were defined as the control group and those treated from July 15, 2014, to December 31, 2016, as the CSP group. First, we assessed for differences in care delivery and incidence of CS in all STEMI patients before and after the implementation of the 4-step CSP. Second, we assessed the impact of the 4-step CSP on these differences and mortality in those with STEMI and CS.
      Percentages and means ± standard deviation or median with interquartile range were computed for categorical and continuous variables, respectively. Categorical variables were compared using the Chi-square test or Fisher's exact tests whereas continuous variables were analyzed using the 2-tailed Student's t test or the Mann-Whitney U test, when appropriate. Logistic regression was performed to assess for predictors of in-hospital mortality; variables with a p-value <0.10 and those with clinical relevance were included in the final model. We used Kaplan-Meier life tables and the Log-rank test to compare mortality between those within the control and CSP groups. Lastly, we created quality control charts using statistical process control, a method utilizing time series analysis methods to graphically present data variability to support evidence of statistical change.
      • Benneyan JC
      • Lloyd RC
      • Plsek PE
      Statistical process control as a tool for research and healthcare improvement.
      Analyses were performed using R Software version 3.6.3 (R Foundation for Statistical Computing, Vienna, Austria) and JMP Pro version 14 (Cary, North Carolina). A p-value <0.05 was considered statistically significant. The authors declare that all supporting data are available within the article. The study protocol was approved by the Cleveland Clinic Foundation Institutional Review Board; need for informed consent was waived.

      Results

      Of the 1,272 STEMI patients treated with PCI, 723 (56.8%) were in the control group and 549 (43.2%) in the CSP group. Patients in the CSP group were less likely to have a history of previous MI (35.1% vs 21.9%, p <0.001) with no differences in previous revascularization. Baseline characteristics and use of mechanical circulatory support (13.6% vs 10.5%, p = 0.105) were otherwise similar. In the CSP group, there were significant improvements in administration of aspirin, anticoagulant, and P2Y12 inhibitor prior to sheath insertion for PCI (74.1% vs 82.5%, p < 0.001) and on admission following PCI (95.6% vs 97.6%, p = 0.049), use of TRA for PCI (19.1% vs 67.0%, p <0.001), median D2BT (106.0 [81:140] vs 89.5 [68:109] minutes, p <0.001), and D2BT at appropriate goal (59.7% vs 84.1%, p <0.001). Receipt of all 3 metrics (GDMT prior to sheath insertion, use of TRA for PCI, and D2BT at appropriate goal) was significantly increased in the CSP group (8.4% vs 47.0%, p < 0.001). The incidence of CS was significantly lower in the CSP group within 24 hours of PCI (13.0% vs 7.8%, p = 0.003) and within 24 hours post-PCI (7.6% vs 4.6%, p = 0.025).
      A total of 137 patients presented with STEMI and CS, with 94 (68.6%) patients in the control group and 43 patients (31.4%) in the CSP group (Table 1). Patients in the CSP group had higher IABP-Shock II risk scores (1.9 ± 1.8 vs 2.8 ± 2.2, p = 0.014); baseline characteristics were otherwise similar (Table 1). There were no differences in presenting hemodynamic parameters, initial serum lactate or creatinine, the incidence of cardiac arrest previous to PCI, left main or left anterior descending culprit vessel, or multivessel coronary artery disease.
      Table 1Baseline characteristics, presentation, and angiographic findings of STEMI patients with cardiogenic shock before and after implementation of a comprehensive STEMI protocol
      VariableNo protocol (n = 94)Protocol (n = 43)p Value
      Age (years)65.5 ± 11.962.9 ± 13.20.264
      Men57 (61%)28 (65%)0.706
      Body mass index (kg/m2)28.2 ± 5.730.5 ± 7.30.079
      White67 (77%)29 (74%)0.822
      Current or former smoker37 (39%)13 (30%)0.343
      Hypertension71 (76%)34 (79%)0.828
      Dyslipidemia71 (76%)33 (77%)1.000
      Diabetes mellitus32 (34%)22 (51%)0.057
      Previous myocardial infarction38 (40%)10 (23%)0.056
      Previous percutaneous coronary intervention24 (26%)13 (30%)0.679
      Previous coronary artery bypass grafting8 (9%)1 (2%)0.272
      Previous heart failure28 (30%)10 (23%)0.538
      Previous valve surgery3 (3%)1 (2%)1.000
      Previous cerebrovascular disease19 (20%)8 (19%)0.826
      Previous peripheral arterial disease19 (20%)9 (21%)1.000
      Chronic kidney disease0.438
       Glomerular filtration rate > 60 ml/min/1.73 m249 (57%)20 (54%)
       Glomerular filtration rate 30–60 ml/min/1.73 m230 (35%)11 (30%)
       Glomerular filtration rate < 30 ml/min/1.73 m23 (4%)4 (11%)
       Hemodialysis4 (5%)2 (5%)
      Chronic lung disease14 (15%)6 (14%)1.000
      Presentation
      Heart rate (beats per minute)94.6 ± 31.795.6 ± 30.20.886
      Systolic blood pressure (mm Hg)105 [89.5:129]109 [105:128]0.832
      Cardiac arrest50 (53%)21 (48.8%)0.714
      Creatinine (mg/dl)1.28 ± 1.021.63 ± 1.380.134
      Hemoglobin (g/dl)13.1 ± 2.513.5 ± 2.80.494
      Serum lactate (mmol/L)4.1 ± 3.54.9 ± 4.10.272
      Angiographic Findings
      Culprit coronary artery0.968
       Left main or left anterior descending49 (52%)23 (54%)
       Left circumflex19 (20%)9 (21%)
       Right coronary26 (28%)11 (26%)
      Fluoroscopy time (minutes)27.3 ± 18.531.9 ± 26.30.308
      Fluoroscopy dose (mGy)1670 [847:2899]1678 [1020:2491]0.052
      Contrast volume (ml)204.0 ± 105.5170.7 ± 78.80.066
      Administration of GDMT on admission (89.4% vs 97.7%, p = 0.172) was similar with significant improvements in the use of TRA for PCI (9.6% vs 44.2%, p < 0.001), median D2BT (129.0 [89:160] vs 95.0 [81:116] minutes, p = 0.001), and D2BT at appropriate goal (38.5% vs 72.1%, p < 0.001) in the CSP group (Figure 1). Quality control charts depicting semi-annual variation in the (A) administration of GDMT upon admission and (B) use of TRA for PCI and case-by-case variation in (C) D2BT are included in Figure 2. Receipt of all 3 metrics was significantly increased in the CSP group (1.1% vs 20.9%, p < 0.001); conversely, significantly fewer met no metrics (28.7% vs 11.6%, p <0.001). Use of mechanical circulatory support, including type of device, was similar between groups (Table 2).
      Figure 1
      Figure 1Improvements in utilization of radial access during percutaneous coronary intervention, door-to-balloon time, infarct size, and in-hospital mortality following implementation of a comprehensive STEMI protocol amongst patients with cardiogenic shock.
      Figure 2
      Figure 2Quality control chart depicting improvements in (A) administration of guideline-directed medical therapy upon admission (89.4% vs 97.7%), (B) use of radial access for primary PCI (9.6% vs 44.2%), and (C) door-to-balloon time (129.0 vs 95.0 minutes) following implementation of the comprehensive STEMI protocol.
      Table 2In-hospital treatment and outcomes of patients with STEMI and cardiogenic shock before and after implementation of a comprehensive STEMI protocol
      VariableNo protocol (n = 94)Protocol (n = 43)p Value
      Aspirin90 (97%)43 (100%)0.551
      P2Y12inhibitor< 0.0001
       Clopidogrel71 (76%)12 (28%)
       Prasugrel3 (3%)1 (2%)
       Ticagrelor11 (12%)29 (67%)
       None9 (10%)1 (2%)
      Unfractionated heparin or bivalrudin93 (99%)43 (100%)1.000
      Glycoprotein IIb/IIIa inhibitor24 (26%)11 (26%)1.000
      Drug eluting stent19 (20%)34 (79%)< 0.001
      Coronary artery bypass grafting7 (7%)2 (5%)0.720
      Mechanical circulatory support0.826
       Intra-aortic balloon pump62 (66%)29 (67%)
       Impella2 (2%)1 (2%)
       Tandem heart3 (3%)0 (0%)
       Extracorporeal membrane oxygenation8 (9%)5 (12%)
      In-hospital outcomes
      Postprocedure creatinine (mg/dl)2.10 ± 1.862.05 ± 1.670.879
      Postprocedure hemoglobin (g/dl)9.30 ± 2.0510.2 ± 2.060.014
      Peak troponin T (ng/ml)8.28 [2.88:13.3]6.48 [2.66:12.3]0.144
      Peak creatine kinase-MB (ng/ml)220.9 ± 156.0151.5 ± 98.50.005
      Recurrent myocardial infarction0 (0%)0 (0%)n/a
      Cerebrovascular accident2 (2%)1 (2%)1.000
      Major bleeding35 (37%)11 (26%)0.242
      Need for blood transfusion42 (45%)17 (40%)0.710
      Access site bleed22 (23%)5 (12%)0.262
      There were no differences in adverse outcomes between groups (Table 2). Patients in the CSP group had a significantly smaller infarct size (peak creatine kinase-MB 220.9 ± 156.0 ng/ml vs 151.1 ± 98.5, p = 0.005) and greater postinfarct ejection fraction (40.8 ± 14.5% vs 46.7 ± 14.6%, p = 0.037). Although there was no difference in length of stay, there was a trend toward increased rate of discharge to home (Table 3). In-hospital mortality (30.9% vs 14.0%, p = 0.037) was significantly reduced in patients in the CSP group. In a multivariable model including age, gender, race, chronic kidney disease, peripheral vascular disease, diabetes mellitus, use of drug eluting stent, and P2Y12 inhibitor, CSP was an independent predictor for hospital survival (OR: 5.6, 95% CI: 1.2 to 11.1, p = 0.035). Although numerically lower in the CSP group, the mortality reduction was non-significant at one-year (42.9% vs 34.2%, p = 0.113, Figure 3).
      Table 3Discharge characteristics and therapies of STEMI patients with cardiogenic shock before and after implementation of a comprehensive STEMI protocol
      Discharge characteristicsNo protocol (n = 94)Protocol (n = 43)p Value
      Postinfarct ejection fraction40.8 ± 14.546.7 ± 14.60.037
      Postinfarct ejection fraction ≤ 35%41 (44%)13 (30%)0.137
      Length of stay (days)13.0 ± 11.413.5 ± 11.20.818
      Discharged to home43 (46%)27 (63%)0.064
      Discharge Therapies
      Aspirin65 (100%)35 (95%)0.129
      P2Y12inhibitor0.141
       Clopidogrel41 (63%)19 (51%)
       Prasugrel6 (9%)2 (5%)
       Ticagrelor10 (15%)13 (35%)
       None8 (12%)3 (8%)
      ACE inhibitor or angiotensin receptor blocker41 (63%)20 (54%)0.406
      Beta blocker60 (92%)33 (89%)0.720
      Statin60 (92%)34 (92%)1.000
      Figure 3
      Figure 3One-year mortality of patients with STEMI and cardiogenic shock before and after implementation of a comprehensive STEMI protocol.

      Discussion

      In this study, we demonstrated that implementation of a 4-step CSP was associated with a reduction in the incidence of STEMI-associated CS by 40%. Amongst those with STEMI and CS, patients in the CSP group had improved guideline-recommended care delivery including > 4-fold increase in the use of TRA for PCI and > 25% reduction in D2BT. These improvements translated to a significant reduction in infarct size by > 30% and in-hospital mortality by > 50%. Although there was a trend towards less major bleeding, need for blood transfusion and overall trans-femoral access remained high due to substantial use of mechanical circulatory support. These findings quantify the positive impact of a formalized STEMI protocol on clinical outcomes in patients with CS, who are among the most critically ill patients encountered in patient care. However, despite these early improvements, long-term mortality remained severe.
      Numerous previously studied strategies have not improved outcomes in patients with STEMI and CS, including use of intra-aortic balloon pumps,
      • Thiele H
      • Zeymer U
      • Neumann FJ
      • Ferenc M
      • Olbrich HG
      • Hausleiter J
      • Richardt G
      • Hennersdorf M
      • Empen K
      • Fuernau G
      • Desch S
      • Eitel I
      • Hambrecht R
      • Fuhrmann J
      • Bohm M
      • Ebelt H
      • Schneider S
      • Schuler G
      • Werdan K
      IABP-SHOCK II Trial Investigators
      Intraaortic balloon support for myocardial infarction with cardiogenic shock.
      percutaneous left ventricular assist devices,
      • Thiele H
      • Sick P
      • Boudriot E
      • Diederich KW
      • Rainer H
      • Niebauer J
      • Schuler G
      Randomized comparison of intra-aortic balloon support with a percutaneous left ventricular assist device in patients with revascularized acute myocardial infarction complicated by cardiogenic shock.
      • Seyfarth M
      • Sibbing D
      • Bauer I
      • Frohlich G
      • Bott-Flugel L
      • Byrne R
      • Dirschinger J
      • Kastrati A
      • Schomig A
      A randomized clinical trial to evaluate the safety and efficacy of a percutaneous left ventricular device versus intra-aortic balloon pumping for treatment of cardiogenic shock caused by myocardial infarction.
      • Lauten A
      • Engström AE
      • Jung C
      • Empen K
      • Erne P
      • Cook S
      • Windecker S
      • Bergmann MW
      • Klingenberg R
      • Luscher TF
      • Haude M
      • Rulands D
      • Butter C
      • Ullman B
      • Hellgren L
      • Modena MG
      • Pedrazzini G
      • Henriques JPS
      • Figulla HR
      • Ferrari M
      Percutaneous left-ventricular support with the Impella-2.5-assist device in acute cardiogenic shock: results of the Impella-EUROSHOCK-registry.
      and multivessel revascularization.
      • Thiele H
      • Akin I
      • Sandri M
      • Fuernau G
      • de Waha S
      • Meyer-Saraei R
      • Nordbeck P
      • Geisler T
      • Landemesser U
      • Skurk C
      • Fach A
      • Lapp H
      • Piek JJ
      • Noc M
      • Goslar T
      • Felix SB
      • Maier LS
      • Stepinska J
      • Oldroyd K
      • Serpytis P
      • Montalescot G
      • Barthelemy O
      • Huber K
      • Windecker S
      • Savonitto S
      • Torremante P
      • Vrints C
      • Schneider S
      • Desch S
      • Zeymer U
      CULPRIT-SHOCK Investigators
      PCI strategies in patients with acute myocardial infarction and cardiogenic shock.
      To date, the only proven strategy to reduce mortality in patients with STEMI and CS is early reperfusion.
      • Hochman JS
      • Sleeper LA
      • Webb JG
      • Sanborn TA
      • White HD
      • Talley JD
      • Buller CE
      • Jacobs AK
      • Slater JN
      • Col J
      • McKinlay SM
      • LeJemtel TH
      Early revascularization in acute myocardial infarction complicated by cardiogenic shock.
      Recent studies, demonstrating improved outcomes among patients who underwent prompt reperfusion, called for a systems of care approach to improving D2BT.
      • Scholz KH
      • Maier SKG
      • Maier LS
      • Lengenfelder B
      • Jacobshagen C
      • Jung J
      • Fleischmann C
      • Werner GS
      • Olbrich HG
      • Ott R
      • Mudra H
      • Seidl K
      • Schulze PC
      • Weiss C
      • Haimerl J
      • Friede T
      • Meyer T
      Impact of treatment delay on mortality in ST-segment elevation myocardial infarction (STEMI) patients presenting with and without haemodynamic instability: results from the German prospective, multicentre FITT-STEMI trial.
      ,
      • Shavadia JS
      • Roe MT
      • Chen AY
      • Lucas J
      • Fanaroff AC
      • Kochar A
      • Fordyce CB
      • Jollis JG
      • Tamis-Holland J
      • Henry TD
      • Bagai A
      • Kontos MC
      • Granger CB
      • Wang TY
      Association between cardiac catheterization laboratory pre-activation and reperfusion timing metrics and outcomes in patients with ST-segment elevation myocardial infarction undergoing primary percutaneous coronary intervention: a report from the ACTION registry.
      This was studied by Kocher et al
      • Kochar A
      • Al-Khalidi HR
      • Hansen SM
      • Shavadia JS
      • Roettig ML
      • Fordyce CB
      • Doerfler S
      • Gersh BJ
      • Henry TD
      • Berger PB
      • Jollis JG
      • Granger CB
      Delays in primary percutaneous coronary intervention in ST-segment elevation myocardial infarction patients presenting with cardiogenic shock.
      who demonstrated that the AHA Mission: Lifeline STEMI Systems Accelerator project did not improve first medical contact-to-device time among patients with STEMI and CS. The authors concluded a “lack of specialized focus on high-risk STEMI patients with CS in the Accelerator program.” An AHA scientific statement on the contemporary management of CS advocated for a “model of high-volume hospitals used as hubs for regional systems of care dedicated to CS care.”
      • Shaefi S
      • O'Gara B
      • Kociol RD
      • Joynt K
      • Mueller A
      • Nizamuddin J
      • Mahmood E
      • Talmor D
      • Shahul S
      Effect of cardiogenic shock hospital volume on mortality in patients with cardiogenic shock.
      ,
      • van Diepen S
      • Katz JN
      • Albert NM
      • Henry TD
      • Jacobs AK
      • Kapur NK
      • Kilic A
      • Menon V
      • Ohman EM
      • Sweitzer NK
      • Thiele H
      • Washam JB
      • Cohen MG
      Contemporary management of cardiogenic shock: a scientific statement from the American Heart Association.
      However, our results highlight the importance of the specific manner in which a system of care is applied. Rather than implementing a system which focuses on care delivery specific to patients with STEMI and CS or diverting such patients to regional shock centers, we propose a paradigm shift supporting a systems of care which focuses more broadly on improving care at the STEMI-level. Cumulatively, by employing a comprehensive approach to all patients presenting with STEMI which focuses on early protocol-driven GDMT, increasing adoption of TRA for PCI, enabling rapid access to a cardiac catheterization laboratory, and providing centralized care in a modern cardiac intensive care unit, we were able to both decrease the incidence of STEMI-associated CS and improve care delivery and outcomes amongst this high-risk population. We have further demonstrated an association of our CSP with improved outcomes amongst women presenting with STEMI, another high-risk population subject to care disparities.
      • Huded CP
      • Johnson M
      • Kravitz K
      • Menon V
      • Abdallah M
      • Gullett TC
      • Hantz S
      • Ellis SG
      • Podolsky SR
      • Meldon SW
      • Kralovic DM
      • Brosovich D
      • Smith E
      • Kapadia SR
      • Khot UN
      4-Step protocol for disparities in STEMI care and outcomes in women.
      As a corollary to this, we found that the strategies previously mentioned improved D2BT resulting in guideline-recommended time to reperfusion for > 70% of patients with STEMI and CS. In a recent study investigating causes of non-system delays, it was shown that almost half of all STEMI patients with CS were excluded from D2BT public reporting with these patients having higher associated mortality even after adjusting for presentation characteristics.
      • Swaminathan RV
      • Wang TY
      • Kaltenbach LA
      • Kim LK
      • Minutello RM
      • Bergman G
      • Wong SC
      • Feldman DN
      Nonsystem reasons for delay in door-to-balloon time and associated in-hospital mortality: a report from the National Cardiovascular Data Registry.
      Although exclusion from public reporting acknowledges the barriers which physicians managing patients with STEMI and CS encounter––patient comorbidities, management of hemodynamic instability, frequent need for transfer to a tertiary care facility, care process variables––it supports the premise that CS complicating STEMI is a non-modifiable risk which precludes timely reperfusion. We demonstrated that implementation of a CSP can mitigate these challenges and expedite reperfusion for these high-risk patients. This raises the suggestion of a paradigm shift from acknowledging CS complicating STEMI to be a rigid obstacle to optimal care delivery to supporting the implementation of care processes which enable guideline-recommended D2BT for these patients. Future consideration should be given to creation of national metrics which, similarly to uncomplicated STEMI, assess care delivery for patients with STEMI-associated CS.
      It should be noted that although we found that CSP implementation was associated with early survival, this difference dissipated after discharge. The reasons why remain unclear, as a majority of patients in the CSP cohort underwent prompt revascularization and were discharged home with appropriate GDMT and preserved ejection fraction. There are data to suggest that among STEMI patients that survive the immediate postdischarge period, mortality is largely attributable to non-cardiac causes, namely infection, gastrointestinal bleeding, and malignancy.
      • Doost Hosseiny A
      • Moloi S
      • Chandrasekhar J
      • Farshid A
      Mortality pattern and cause of death in a long-term follow-up of patients with STEMI treated with primary PCI.
      ,
      • Yamashita Y
      • Shiomi H
      • Morimoto T
      • Yaku H
      • Furukawa Y
      • Nakagawa Y
      • Ando K
      • Kadota K
      • Mitsuru A
      • Nagao K
      • Shizuta S
      • Ono K
      • Kimura T
      CREDO-Kyoto AMI Registry Investigators
      Cardiac and noncardiac causes of long-term mortality in ST-segment-elevation acute myocardial infarction patients who underwent primary percutaneous coronary intervention.
      It remains unclear if hospital survivors of STEMI and CS have a greater predilection for these causes of non-cardiac death in comparison to their counterparts with uncomplicated STEMI. Further studies regarding the reasons for long-term mortality and impact of outpatient follow-up upon discharge are warranted.
      Our study has certain limitations. First, this is a nonrandomized, prepost study with small sample size and thus subject to confounding, including changes in standard of care (greater use of drug eluting stents or novel P2Y12 inhibitors). However, the CSP group was a predictor for in-hospital survival in multivariable analysis despite a higher IABP-SHOCK II risk score, a previously validated score strongly correlated with mortality among patients with infarct-related CS,
      • Pöss J
      • Köster J
      • Fuernau G
      • Fuernau G
      • Eitel I
      • de Waha S
      • Ouarrak T
      • Lassus J
      • Harjola VP
      • Zeymer U
      • Holger T
      • Desch S
      Risk stratification for patients in cardiogenic shock after acute myocardial infarction.
      supportive of the positive impact of the program. Second, our study is based at a single STEMI referral center and warrants further validation at similar. Although this may reduce generalizability to regions without a tertiary care center, we did not exclude any patients, and our population should reflect that of any large, urban area in the United States.
      In conclusion, implementation of a CSP significantly reduced the incidence of CS among patients with STEMI. Among those with STEMI and CS, care improvements with CSP were associated with improvements in infarct size, ejection fraction, and early mortality. This strategy offers an attractive solution to improve the care of these critically ill patients. However, long-term mortality remains significant in this patient population, highlighting the need for further improvements in care strategies in the outpatient setting.

      Author Contributions

      A Kumar: Dr. Kumar had full access to all the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis. Dr. Kumar contributed to the conception and design of the study, the data analysis, the data interpretation, the manuscript drafting, and the critical revision of the manuscript.
      CP Huded: Dr. Huded contributed to the the data analysis, the data interpretation, and the critical revision of the manuscript. L Zhou: Dr. Zhou contributed to the data interpretation and the critical revision of the manuscript. C Krittanawong: Dr. Krittanawong contributed to the data interpretation and critical revision of the manuscript. LD Young: Dr. Young contributed to the data interpretation and the critical revision of the manuscript. A Krishnaswamy: Dr. Krishnaswamy contributed to the data interpretation and the critical revision of the manuscript. V Menon: Dr. Menon contributed to the data interpretation and the critical revision of the manuscript. AM Lincoff: Dr. Lincoff contributed to the data interpretation and the critical revision of the manuscript. SG Ellis: Dr. Ellis contributed to the data interpretation and the critical revision of the manuscript. GW Reed: Dr. Reed contributed to the data interpretation and the critical revision of the manuscript. SR Kapadia: Dr. Kapadia contributed to the data interpretation and the critical revision of the manuscript. UN Khot: Dr. Khot contributed to the conception and design of the study, the supervision, the data analysis, the data interpretation, the manuscript drafting, and the critical revision of the manuscript. Dr. Khot is the corresponding author.

      Author Disclosures

      The authors have no relationships to industry or disclosures pertinent to this study to report.

      References

        • Backhaus T
        • Fach A
        • Schmucker J
        • Fiehn E
        • Garstka D
        • Stehmeier J
        • Hambrecht R
        • Wienbergen H
        Management and predictors of outcome in unselected patients with cardiogenic shock complicating acute ST-segment elevation myocardial infarction: results from the Bremen STEMI Registry.
        Clin Res Cardiol. 2018; 107: 371-379
        • Valle JA
        • Kaltenbach LA
        • Bradley SM
        • Yeh RW
        • Rao SV
        • Gurm HS
        • Armstrong EJ
        • Messenger JC
        • Waldo SW
        Variation in the adoption of transradial access for ST-segment elevation myocardial infarction: insights from the NCDR CathPCI Registry.
        J Am Coll Cardiol Intv. 2017; 10: 2242-2254
        • Wayangankar SA
        • Bangalore S
        • McCoy LA
        • Jneid H
        • Latif F
        • Karrowni W
        • Charitakis K
        • Feldman DN
        • Dakik HA
        • Mauri L
        • Peterson ED
        • Messenger J
        • Roe M
        • Mukherjee D
        • Klein A
        Temporal trends and outcomes of patients undergoing percutaneous coronary interventions for cardiogenic shock in the setting of acute myocardial infarction: a report from the CathPCI Registry.
        J Am Coll Cardiol Intv. 2016; 9: 341-351
        • Moosvi AR
        • Khaja F
        • Villanueva L
        • Gheorghiade M
        • Douthat L
        • Goldstein S
        Early revascularization improves survival in cardiogenic shock complicating acute myocardial infarction.
        J Am Coll Cardiol. 1992; 19: 907-914
        • Lee L
        • Erbel R
        • Brown TM
        • Laufer N
        • Meyer J
        • O'Neill WW
        Multicenter registry of angioplasty therapy of cardiogenic shock: initial and long-term survival.
        J Am Coll Cardiol. 1991; 17: 599-603
        • Gacioch GM
        • Ellis SG
        • Lee L
        • Bates ER
        • Kirsh M
        • Walton JA
        • Topol EJ
        Cardiogenic shock complicating acute myocardial infarction: the use of coronary angioplasty and the integration of the new support devices into patient management.
        J Am Coll Cardiol. 1992; 19: 647-653
        • Hochman JS
        • Sleeper LA
        • Webb JG
        • Sanborn TA
        • White HD
        • Talley JD
        • Buller CE
        • Jacobs AK
        • Slater JN
        • Col J
        • McKinlay SM
        • LeJemtel TH
        Early revascularization in acute myocardial infarction complicated by cardiogenic shock.
        N Engl J Med. 1999; 341: 625-634
        • Kochar A
        • Al-Khalidi HR
        • Hansen SM
        • Shavadia JS
        • Roettig ML
        • Fordyce CB
        • Doerfler S
        • Gersh BJ
        • Henry TD
        • Berger PB
        • Jollis JG
        • Granger CB
        Delays in primary percutaneous coronary intervention in ST-segment elevation myocardial infarction patients presenting with cardiogenic shock.
        J Am Coll Cardiol Intv. 2018; 11: 1824-1833
        • Khot UN
        • Huded CP.
        Systems for rapid revascularization in ST-segment elevation myocardial infarction with cardiogenic shock.
        J Am Coll Cardiol Intv. 2018; 11: 1834-1836
        • Huded CP
        • Kumar A
        • Johnson M
        • Abdallah M
        • Ballout JA
        • Kravitz K
        • Menon V
        • Gullett TC
        • Hantz S
        • Ellis SG
        • Podolsky SR
        • Meldon SW
        • Kralovic DM
        • Brosovich D
        • Smith E
        • Kapadia SR
        • Khot UN
        Incremental prognostic value of guideline-directed medical therapy, transradial access, and door-to-balloon time on outcomes in ST-segment-elevation myocardial infarction.
        Circ Cardiovasc Interv. 2019; 12e007101
        • Moussa I
        • Hermann A
        • Messenger JC
        • Dehmer GJ
        • Weaver WD
        • Rumsfeld JS
        • Masoudi FA
        The NCDR CathPCI Registry: a US national perspective on care and outcomes for percutaneous coronary intervention.
        Heart. 2013; 99: 297-303
        • Huded CP
        • Johnson M
        • Kravitz K
        • Menon V
        • Abdallah M
        • Gullett TC
        • Hantz S
        • Ellis SG
        • Podolsky SR
        • Meldon SW
        • Kralovic DM
        • Brosovich D
        • Smith E
        • Kapadia SR
        • Khot UN
        4-Step protocol for disparities in STEMI care and outcomes in women.
        J Am Coll Cardiol. 2018; 15: 2122-2132
        • Benneyan JC
        • Lloyd RC
        • Plsek PE
        Statistical process control as a tool for research and healthcare improvement.
        Qual Saf Health Care. 2003; 12: 458-464
        • Thiele H
        • Zeymer U
        • Neumann FJ
        • Ferenc M
        • Olbrich HG
        • Hausleiter J
        • Richardt G
        • Hennersdorf M
        • Empen K
        • Fuernau G
        • Desch S
        • Eitel I
        • Hambrecht R
        • Fuhrmann J
        • Bohm M
        • Ebelt H
        • Schneider S
        • Schuler G
        • Werdan K
        • IABP-SHOCK II Trial Investigators
        Intraaortic balloon support for myocardial infarction with cardiogenic shock.
        N Engl J Med. 2012; 367: 1287-1296
        • Thiele H
        • Sick P
        • Boudriot E
        • Diederich KW
        • Rainer H
        • Niebauer J
        • Schuler G
        Randomized comparison of intra-aortic balloon support with a percutaneous left ventricular assist device in patients with revascularized acute myocardial infarction complicated by cardiogenic shock.
        Eur Heart J. 2005; 26: 1276-1283
        • Seyfarth M
        • Sibbing D
        • Bauer I
        • Frohlich G
        • Bott-Flugel L
        • Byrne R
        • Dirschinger J
        • Kastrati A
        • Schomig A
        A randomized clinical trial to evaluate the safety and efficacy of a percutaneous left ventricular device versus intra-aortic balloon pumping for treatment of cardiogenic shock caused by myocardial infarction.
        J Am Coll Cardiol. 2008; 52: 1584-1588
        • Lauten A
        • Engström AE
        • Jung C
        • Empen K
        • Erne P
        • Cook S
        • Windecker S
        • Bergmann MW
        • Klingenberg R
        • Luscher TF
        • Haude M
        • Rulands D
        • Butter C
        • Ullman B
        • Hellgren L
        • Modena MG
        • Pedrazzini G
        • Henriques JPS
        • Figulla HR
        • Ferrari M
        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
        • Thiele H
        • Akin I
        • Sandri M
        • Fuernau G
        • de Waha S
        • Meyer-Saraei R
        • Nordbeck P
        • Geisler T
        • Landemesser U
        • Skurk C
        • Fach A
        • Lapp H
        • Piek JJ
        • Noc M
        • Goslar T
        • Felix SB
        • Maier LS
        • Stepinska J
        • Oldroyd K
        • Serpytis P
        • Montalescot G
        • Barthelemy O
        • Huber K
        • Windecker S
        • Savonitto S
        • Torremante P
        • Vrints C
        • Schneider S
        • Desch S
        • Zeymer U
        • CULPRIT-SHOCK Investigators
        PCI strategies in patients with acute myocardial infarction and cardiogenic shock.
        N Engl J Med. 2017; 377: 2419-2432
        • Scholz KH
        • Maier SKG
        • Maier LS
        • Lengenfelder B
        • Jacobshagen C
        • Jung J
        • Fleischmann C
        • Werner GS
        • Olbrich HG
        • Ott R
        • Mudra H
        • Seidl K
        • Schulze PC
        • Weiss C
        • Haimerl J
        • Friede T
        • Meyer T
        Impact of treatment delay on mortality in ST-segment elevation myocardial infarction (STEMI) patients presenting with and without haemodynamic instability: results from the German prospective, multicentre FITT-STEMI trial.
        Eur Heart J. 2018; 39: 1065-1074
        • Shavadia JS
        • Roe MT
        • Chen AY
        • Lucas J
        • Fanaroff AC
        • Kochar A
        • Fordyce CB
        • Jollis JG
        • Tamis-Holland J
        • Henry TD
        • Bagai A
        • Kontos MC
        • Granger CB
        • Wang TY
        Association between cardiac catheterization laboratory pre-activation and reperfusion timing metrics and outcomes in patients with ST-segment elevation myocardial infarction undergoing primary percutaneous coronary intervention: a report from the ACTION registry.
        JACC Cardiovasc Interv. 2018; 24: 1837-1847
        • Shaefi S
        • O'Gara B
        • Kociol RD
        • Joynt K
        • Mueller A
        • Nizamuddin J
        • Mahmood E
        • Talmor D
        • Shahul S
        Effect of cardiogenic shock hospital volume on mortality in patients with cardiogenic shock.
        J Am Heart Assoc. 2015; 4e001462
        • van Diepen S
        • Katz JN
        • Albert NM
        • Henry TD
        • Jacobs AK
        • Kapur NK
        • Kilic A
        • Menon V
        • Ohman EM
        • Sweitzer NK
        • Thiele H
        • Washam JB
        • Cohen MG
        Contemporary management of cardiogenic shock: a scientific statement from the American Heart Association.
        Circulation. 2017; 136: e232-e268
        • Swaminathan RV
        • Wang TY
        • Kaltenbach LA
        • Kim LK
        • Minutello RM
        • Bergman G
        • Wong SC
        • Feldman DN
        Nonsystem reasons for delay in door-to-balloon time and associated in-hospital mortality: a report from the National Cardiovascular Data Registry.
        J Am Coll Cardiol. 2013; 61: 1688-1695
        • Doost Hosseiny A
        • Moloi S
        • Chandrasekhar J
        • Farshid A
        Mortality pattern and cause of death in a long-term follow-up of patients with STEMI treated with primary PCI.
        Open Heart. 2016; 3e000405
        • Yamashita Y
        • Shiomi H
        • Morimoto T
        • Yaku H
        • Furukawa Y
        • Nakagawa Y
        • Ando K
        • Kadota K
        • Mitsuru A
        • Nagao K
        • Shizuta S
        • Ono K
        • Kimura T
        • CREDO-Kyoto AMI Registry Investigators
        Cardiac and noncardiac causes of long-term mortality in ST-segment-elevation acute myocardial infarction patients who underwent primary percutaneous coronary intervention.
        Circ Cardiovasc Qual Outcomes. 2017; 10e002790
        • Pöss J
        • Köster J
        • Fuernau G
        • Fuernau G
        • Eitel I
        • de Waha S
        • Ouarrak T
        • Lassus J
        • Harjola VP
        • Zeymer U
        • Holger T
        • Desch S
        Risk stratification for patients in cardiogenic shock after acute myocardial infarction.
        J Am Coll Cardiol. 2017; 69: 1913-1920