Cardiogenic shock is defined as a state of reduced cardiac output with clinical evidence of end-organ hypoperfusion (despite adequate intracardiac filling pressures) that complicates 5-10% of acute myocardial infarctions (MI). Prior to routine implementation of therapeutic strategies to achieve early coronary artery reperfusion, MI with cardiogenic shock was associated with an early mortality of 70-80%.¹ The first major advance in the management of cardiogenic shock came from the landmark SHOCK (Should We Emergently Revascularize Occluded Coronaries for Cardiogenic Shock?) trial.² The SHOCK trial randomly assigned 302 patients with ST-segment elevation myocardial infarction (STEMI) and cardiogenic shock to routine invasive strategy with early cardiac catheterization and coronary artery revascularization or initial medical stabilization followed by clinically selected catheterization and revascularization. The median time to revascularization was 1.4 hours in the revascularization group and 102.8 hours in the medical stabilization group. Although there was no significant difference in mortality at 30 days, early revascularization of the culprit (infarct) artery significantly reduced all-cause mortality at 6 months compared with initial medical stabilization (50.3% vs. 63.1%, p = 0.027). Clinical practice guidelines quickly incorporated the results of the SHOCK trial, and the American Heart Association and American College of Cardiology percutaneous coronary intervention (PCI) and STEMI guidelines assigned a Class 1B recommendation to emergent infarct-related artery revascularization in patients with MI complicated by cardiogenic shock.^3,4

Although the benefits of infarct-related artery revascularization are clear, management of severe non-culprit bystander coronary artery disease (CAD) in the setting of cardiogenic shock remains controversial. In the SHOCK trial, multi-vessel CAD was present in 87% of patients, 3-vessel disease in 65%, and left main disease in 20%.² In the absence of evidence from randomized trials addressing non-culprit revascularization, guidelines have stated that PCI of severe stenoses in non-infarct artery "should be considered" to improve myocardial perfusion and hemodynamic stability. Despite the theoretical benefits of this approach, the small subgroup that underwent initial multi-vessel PCI in the SHOCK trial had higher mortality than those that underwent culprit-lesion-only PCI (adjusted hazard ratio 2.75; 95% confidence interval, 1.05-7.25; p = 0.04).⁵ A subsequent meta-analysis also indicated that multi-vessel PCI in cardiogenic shock was associated with increased mortality compared with culprit-lesion-only PCI (37.5% vs. 28.8%, p = 0.001).⁶ These data led to the design of the CULPRIT-SHOCK (Culprit Lesion Only PCI Versus Multivessel PCI in Cardiogenic Shock) trial, which randomly assigned 706 patients with MI, multi-vessel CAD, and cardiogenic shock to culprit-lesion-only PCI versus immediate PCI of all obstructive lesions.⁷ Complete revascularization was strongly encouraged in the multi-vessel PCI arm, and operators were encouraged to perform PCI of chronic total occlusions when feasible. Complete revascularization was achieved in 81.0% of patients in the multi-vessel PCI arm, with staged revascularization of non-infarct vessels in only 17.7% of the patients assigned to culprit-lesion-only PCI. However, the CUPLRIT-SHOCK trial investigators reported that multi-vessel PCI was associated with a greater hazard for death compared with infarct-vessel-only PCI (51.6% vs. 43.3%, p = 0.03). Recently published results demonstrated that these differences persisted at 1 year.⁸ Based on these results, culprit-lesion-only PCI remains the preferred strategy in the setting of MI with multi-vessel CAD and cardiogenic shock.

The findings from the CULPRIT-SHOCK trial are discordant with recent trials that report lower mortality associated with multi-vessel PCI compared with culprit-lesion-only PCI in patients with STEMI without cardiogenic shock.^9,10 The mechanism of this difference is unknown. Cardiogenic shock is associated with an inflammatory and prothrombotic state, which might increase the risk of harm due to greater periprocedural myocardial injury during revascularization of non-culprit coronary vessels. This injury would likely have much greater negative hemodynamic consequences in patients with low cardiac output. Multi-vessel PCI might also confer a greater risk of contrast-induced nephrotoxicity in shock patients with renal hypoperfusion in comparison to those with uncomplicated MI.

In the CULPRIT-SHOCK trial, mechanical circulatory support was used in 28.3% of patients. The group randomly assigned to culprit-lesion-only coronary revascularization had a trend towards greater frequency of Impella CP (Abiomed; Danvers, MA) percutaneous ventricular assist device use (30.3% vs. 18.9%, p = 0.07), and numerically fewer patients received extracorporeal membrane oxygenation (18.2% vs. 28.4%, p = 0.09). In the absence of adequately powered randomized controlled trials evaluating circulatory support strategies, the impact of the differential application of circulatory support devices in the CULPRIT-SHOCK trial remains uncertain.

The results of the CULPRIT-SHOCK trial highlight the limitations of contemporary approaches to the management of shock, despite decades of improvements in PCI technique, stent design, antithrombotic pharmacology, and mechanical support devices. In fact, 30-day mortality rates were nearly identical among patients assigned to culprit-lesion-only PCI in the CULPRIT-SHOCK trial (published in 2017) and those assigned to early revascularization in the original SHOCK trial (published in 1999).^2,7 Consequently, development of novel approaches to the management of cardiogenic shock is necessary to further improve patient outcomes.

Data derived from a subgroup of the original SHOCK trial may help chart a path forward. In the SHOCK trial, immediate emergency coronary artery bypass grafting (CABG) after randomization and catheterization was recommended for early revascularization in patients with severe left main or multi-vessel CAD, although the method of revascularization was ultimately determined by the treating physicians. Among patients assigned to early revascularization, coronary angioplasty of the infarct artery was performed in 54.6% of participants, and CABG was performed in 37.5% of participants. Participants referred for early CABG in the SHOCK trial had a greater burden of CAD and twice the prevalence of diabetes mellitus in comparison to those who were referred for early PCI. However, survival was similar for trial participants who underwent PCI compared with those who underwent CABG.¹¹ Other studies suggest that CABG may be beneficial in the setting of multi-vessel CAD and cardiogenic shock. In a small propensity-matched study of 88 patients with STEMI and cardiogenic shock, PCI followed by CABG was associated with lower mortality at 30 days than PCI alone (20.5% vs. 40.9%, p = 0.03).¹² In an observational study using data from the Society of Thoracic Surgeons National Database, 5,496 patients with MI and cardiogenic shock who were referred for CABG had a 30-day mortality rate of 18.7% overall, with 37.2% mortality in the group that required pre-operative mechanical circulatory support and 58.4% in those who required post-operative circulatory support, suggesting that CABG is feasible in this setting and that outcomes may be as good or better than those associated with PCI.¹³

Although non-randomized data are confounded by indication for bypass surgery, selection bias, and survivor bias, these preliminary data provide compelling evidence to support further investigation of CABG for revascularization in cardiogenic shock with multi-vessel CAD. There are plausible explanations for the potential benefit of CABG in comparison to PCI in this setting. First, immediate complete revascularization is feasible with CABG, even in patients with chronic total occlusions or complex or calcified CAD. Second, on-pump CABG involves arresting the heart with cardioplegia, initiating of cardiopulmonary bypass for complete circulatory and hemodynamic support, ventricular unloading, and myocardial cooling. These maneuvers decrease myocardial oxygen requirements and provide myocardial rest for a sustained period during surgery. This combination of complete coronary revascularization and ventricular unloading may salvage at-risk ischemic myocardium. Cardiopulmonary bypass also sustains perfusion to internal organs, reversing the global ischemia that is believed to promote the cascade of events leading to systemic inflammation and progressive hemodynamic decline in shock.

Of course, there are challenges to this approach. In the contemporary era, many interventional cardiologists would be unwilling to refer a patient for CABG with a closed culprit artery in the setting of MI in cardiogenic shock. Thus, a strategy of emergent balloon angioplasty (without stenting) using rapid-acting intravenous antiplatelet or antithrombotic therapy (such as cangrelor and intravenous heparin) could be considered as a bridge to emergency CABG. Unique risks of CABG in this population must also be considered. Rates of stroke are consistently higher early after CABG compared with PCI.^14,15 Patients with biventricular dysfunction may have difficulties weaning from cardiopulmonary bypass and may require prolonged circulatory support. Cardiac surgery is also associated with risks of perioperative atrial fibrillation, post-operative pleural effusions, and surgical-site infections and poor wound healing. Thus, an adequately powered, randomized controlled trial is needed to characterize the risks and benefits of these different coronary revascularization strategies in the setting of MI with cardiogenic shock.

In conclusion, multi-vessel PCI does not lower mortality in patients with MI and cardiogenic shock, but complete revascularization with CABG may be a promising path forward. A randomized trial of infarct-only PCI versus balloon angioplasty followed by emergent CABG in patients with MI, multi-vessel CAD, and cardiogenic shock will provide insight into the optimal management of this devastating clinical scenario.

References

1. Goldberg RJ, Gore JM, Alpert JS, et al. Cardiogenic shock after acute myocardial infarction. Incidence and mortality from a community-wide perspective, 1975 to 1988. N Engl J Med 1991;325:1117-22.
2. Hochman JS, Sleeper LA, Webb JG, et al. Early revascularization in acute myocardial infarction complicated by cardiogenic shock. SHOCK Investigators. Should We Emergently Revascularize Occluded Coronaries for Cardiogenic Shock. N Engl J Med 1999;341:625-34.
3. Levine GN, Bates ER, Blankenship JC, et al. 2011 ACCF/AHA/SCAI Guideline for Percutaneous Coronary Intervention. A report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines and the Society for Cardiovascular Angiography and Interventions. J Am Coll Cardiol 2011;58:e44-122.
4. O'Gara PT, Kushner FG, Ascheim DD, 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:e78-140.
5. Webb JG, Lowe AM, Sanborn TA, et al. Percutaneous coronary intervention for cardiogenic shock in the SHOCK trial. J Am Coll Cardiol 2003;42:1380-6.
6. de Waha S, Jobs A, Eitel I, et al. Multivessel versus culprit lesion only percutaneous coronary intervention in cardiogenic shock complicating acute myocardial infarction: A systematic review and meta-analysis. Eur Heart J Acute Cardiovasc Care 2018;7:28-37.
7. Thiele H, Akin I, Sandri M, et al. PCI Strategies in Patients with Acute Myocardial Infarction and Cardiogenic Shock. N Engl J Med 2017;377:2419-32.
8. Thiele H, Akin I, Sandri M, et al. One-Year Outcomes after PCI Strategies in Cardiogenic Shock. N Engl J Med 2018;Aug 25:[Epub ahead of print].
9. Pasceri V, Patti G, Pelliccia F, et al. Complete Revascularization During Primary Percutaneous Coronary Intervention Reduces Death and Myocardial Infarction in Patients With Multivessel Disease: Meta-Analysis and Meta-Regression of Randomized Trials. JACC Cardiovasc Interv 2018;11:833-43.
10. Bravo CA, Hirji SA, Bhatt DL, et al. Complete versus culprit-only revascularisation in ST elevation myocardial infarction with multi-vessel disease. Cochrane Database Syst Rev 2017;5:CD011986.
11. White HD, Assmann SF, Sanborn TA, et al. Comparison of percutaneous coronary intervention and coronary artery bypass grafting after acute myocardial infarction complicated by cardiogenic shock: results from the Should We Emergently Revascularize Occluded Coronaries for Cardiogenic Shock (SHOCK) trial. Circulation 2005;112:1992-2001.
12. Chiu FC, Chang SN, Lin JW, Hwang JJ, Chen YS. Coronary artery bypass graft surgery provides better survival in patients with acute coronary syndrome or ST-segment elevation myocardial infarction experiencing cardiogenic shock after percutaneous coronary intervention: a propensity score analysis. J Thorac Cardiovasc Surg 2009;138:1326-30.
13. Acharya D, Gulack BC, Loyaga-Rendon RY, et al. Clinical Characteristics and Outcomes of Patients With Myocardial Infarction and Cardiogenic Shock Undergoing Coronary Artery Bypass Surgery: Data From The Society of Thoracic Surgeons National Database. Ann Thorac Surg 2016;101:558-66.
14. Farkouh ME, Domanski M, Sleeper LA, et al. Strategies for multivessel revascularization in patients with diabetes. N Engl J Med 2012;367:2375-84.
15. Stone GW, Sabik JF, Serruys PW, et al. Everolimus-Eluting Stents or Bypass Surgery for Left Main Coronary Artery Disease. N Engl J Med 2016;375:2223-35.

Keywords: Acute Coronary Syndrome, Shock, Cardiogenic, Myocardial Infarction, Cardiac Catheterization, Myocardial Revascularization, Percutaneous Coronary Intervention, Coronary Artery Disease

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