INTRODUCTION

Approximately every 40 seconds, someone in the United States experiences a myocardial infarction. Acute myocardial infarction (AMI) accounts for roughly 80 of patients in cardiogenic shock (CS).1 In this scenario, CS commonly manifests with left ventricular failure. However, in 20 of cases, CS is due to a complication associated with AMI, such as acute mitral regurgitation, ventricular septal defect, or subacute or acute free wall rupture. Right heart failure may also contribute to CS and is more commonly associated with right ventricular myocardial infarction.

Of the 805,000 heart attacks that occur each year in the United States, an estimated 38 are due to ST-elevation myocardial infarction (STEMI).2 Electrocardiographic criteria for STEMI have been well defined by the American College of Cardiology, American Heart Association, European Society of Cardiology, and World Heart Federation (Table 1).3,4 STEMI is associated with a 2-fold increased risk for developing CS.5

Table 1.

Definition of myocardial infarction.3,4

ST-ELEVATION MYOCARDIAL INFARCTION (STEMI)
The American College of Cardiology, American Heart Association, European Society of Cardiology, and World Heart Federation committee established the following electrocardiogram (ECG) criteria for STEMI:
  • New ST-segment elevation at the J point in two contiguous leads, with the cutoff point as > 0.1 mV in all leads other than V2 or V3
  • In leads V2V3, the cutoff point is > 0.2 mV in men older than 40 years and > 0.25 mV in men younger than 40 years, and > 0.15 mV in women
A new left bundle branch block is considered a STEMI equivalent. Patients with a pre-existing left bundle branch block can be further evaluated using Scarbossa's criteria:
  • ST-segment elevation of 1 mm or more that is concordant with (in the same direction as) the QRS complex
  • ST-segment depression of 1 mm or more in lead V1, V2, or V3
  • ST-segment elevation of 5 mm or more that is discordant with (in the opposite direction) the QRS complex
NONST-ELEVATION MYOCARDIAL INFARCTION (NSTEMI)
NSTEMI is diagnosed in patients who have symptoms consistent with acute cardiogenic shock and troponin elevation but without ECG changes consistent with STEMI. Unstable angina and NSTEMI differ primarily in the presence or absence of detectable troponin leak. Myocardial injury is expected at troponin levels exceeding the 99th percentile upper reference limit, which is specified for each individual assay. Specific cutoffs can be found in manufacturers' package inserts, in peer-reviewed publications, and on the International Federation of Clinical Chemistry and Laboratory Medicine website.

PATIENT OUTCOMES IN CARDIOGENIC SHOCK

Recent analyses of the National Inpatient Sample report that the incidence of CS among STEMI patients increased from 6.5 to 10.1 between 2003 and 2010. It further showed that in-hospital mortality for these patients decreased from 44.6 to 33.8 over the same time period.6 Similar findings were reported in an analysis of the same database from 2003 to 2011. In this analysis, the National Cardiovascular Data Registry (NCDR) reported that 12.2 of STEMI patients experienced CS between 2007 and 2011, with an in-hospital mortality rate of 33.1 for STEMI complicated by CS. The authors also observed that CS was less prevalent (4.3) among non-STEMI patients but was associated with a higher in-hospital mortality rate of 40.8.7

Despite these registry data, randomized clinical trials continue to report mortality rates between 40 and 60 for patients with AMI and shock (Table 2). In 1999, the SHOCK (Should we Emergently Revascularize Occluded Coronaries for Cardiogenic Shock) trial reported 30-day mortality rates of 41 for patients younger than age 75 who received early revascularization and 75 for patients older than 75. While the SHOCK trial failed to show improvement in its primary end point of 30-day mortality, it was the first trial to report improved 6-month outcomes (secondary end point) associated with early revascularization among the entire patient cohort. However, among patients older than age 75, both 30-day and 6-month mortality were worse when receiving early revascularization compared to medical therapy alone.8 The long-term benefits of early revascularization were confirmed by the same group at 10 years of follow-up.9

Table 2.

Recent clinical trials evaluating treatment options in cardiogenic shock. IABP: intra-aortic balloon pump; PCI: percutaneous coronary intervention; RRT: renal replacement therapy; SHOCK: Should we Emergently Revascularize Occluded Coronaries for Cardiogenic Shock trial; IABP-SHOCK II: Intra-Aortic Balloon Pump Support for Myocardial Infarction with Cardiogenic Shock trial; IMPRESS: Impella Versus IABP Reduces Mortality in STEMI Patients Treated with Primary PCI in Severe Cardiogenic Shock trial; CULPRIT SHOCK: Culprit Lesion-Only PCI Versus Multivessel PCI in Cardiogenic Shock trial; DCSI: Detroit Cardiogenic Shock Initiative

TRIAL YEAR PATIENTS PATIENT POPULATION TREATMENT ARMS PRIMARY END POINT(S) RESULTS
SHOCK 1999 302 Shock due to left ventricular failure complicating myocardial infarction Emergency revascularization or initial medical stabilization 30-day all-cause mortality No significant difference in mortality between treatment groups (46.7% vs 56.0%; P .11)
IABP SHOCK II 2012 600 Shock complicating acute myocardial infarction Intra-aortic balloon counterpulsation or no intra-aortic balloon counterpulsation 30-day all-cause mortality No significant difference in mortality between treatment groups (39.7% vs 41.3%; P .69)
IMPRESS 2016 48 Severe shock complicating acute myocardial infarction Impella CP or intra-aortic balloon pump 30-day all-cause mortality No significant different in mortality between Impella CP and IABP (46% vs 50%, P .96)
CULPRIT SHOCK 2017 706 Shock presenting with multivessel disease and acute myocardial infarction Culprit-lesion-only PCI or immediate multivessel PCI 30-day mortality and renal failure requiring RRT Culprit-lesion-only PCI was associated with slightly decreased risk of mortality (OR: 0.84, P .03) compared to multivessel PCI, but the risk of RRT did not differ (OR: 0.71, P .07)
DCSI 2018 41 Acute myocardial infarction complicated by cardiogenic shock Single treatment arm of invasive hemodynamic monitoring and rapid initiation of non-IABP MCS Survival to explant and change in CPO Survival to explant was 85% vs 51% in historical controls (P < .001), and post-procedure CPO increased 67% compared to pre-procedure CPO (P < .001)

More recently, the IABP-SHOCK II (Intra-Aortic Balloon Pump Support for Myocardial Infarction with Cardiogenic Shock) trial reported that the use of an intra-aortic balloon pump for AMI (both STEMI and non-STEMI) was not superior to medical therapy alone in reducing 30-day mortality. Mortality rates in this trial ranged between 39.7 and 41.3 in both treatment arms. In 2017, the CULPRIT SHOCK (Culprit Lesion Only PCI Versus Multivessel PCI in Cardiogenic Shock) trial reported that culprit-lesion-only intervention was associated with reduced 30-day mortality (43.3) compared to multivessel intervention (51.6) for AMI complicated by CS (AMI-CS) (P .03).10 The Detroit Cardiogenic Shock Initiative, a single-arm trial, found that early mechanical circulatory support (MCS) intervention was associated with improved survival to explant compared to historical controls (85 vs 51, P < .001).11 Despite this promising risk reduction, collective trial data are not conclusive and suggest that mortality due to AMI with CS remains largely unchanged over the past two decades.

CLASSIFICATION OF CARDIOGENIC SHOCK

One explanation for varying results for AMI-CS outcomes in clinical trials may be the lack of clear definitions for CS severity. The original Killip and Diamond-Forrester classifications for shock severity in AMI used physical exam findings and hemodynamic data to assess perfusion and congestion. The more recent Diamond-Forrester classification defined four clinical subsets of shock: (I) no pulmonary congestion or peripheral hypoperfusion, (II) isolated pulmonary congestion, (III) isolated peripheral hypoperfusion, and (IV) both pulmonary congestion and hypoperfusion. These subsets correlated with cardiac index and pulmonary capillary wedge pressure and were associated with increasing mortality (Table 3).12,13 Since the initial development of this classification system, several consensus statements have highlighted a further need for improved definitions for diagnosing CS, additional classification systems to gauge the severity of CS, algorithms for using acute MCS (AMCS) devices, and a better understanding of hemodynamic-guided decision making in CS.

Table 3.

The Diamond-Forrester Classification for shock severity in acute myocardial infarction.12,13

CLASS CARDIAC INDEX (MM/MIN) PCWP (MM HG) MORTALITY (%)
I > 2 < 18 3
II > 2 > 18 9
III < 2 < 18 23
IV < 2 > 18 51
I > 2 < 18 3
II > 2 > 18 9
III < 2 < 18 23
IV < 2 > 18 51

In response to these unmet needs, the Society for Cardiovascular Angiography and Interventions (SCAI) recently proposed a staging system for CS based on expert consensus opinion. The purpose of the SCAI classification scheme is to facilitate patient care and research in CS by providing a uniform system for identifying patients who have an increased risk of dying (Table 4).14 The SCAI system included five classes of CS: (A) at risk for CS, (B) beginning CS, (C) classic CS, (D) deteriorating CS, and (E) extreme CS. Each stage is defined by a physical exam along with biochemical and hemodynamic findings. These definitions were intentionally left more general to accommodate the variability of clinical parameters available at the time of presentation. Stages C, D, and E include patients who require inotrope, vasopressor, or short-term MCS therapy for CS. Stage D patients represent Stage C patients with clinical deterioration, and Stage E patients are those who have deteriorated even further.14 The clinical utility of the SCAI staging system is currently under investigation.

Table 4.

The Society for Cardiovascular Angiography and Interventions classification scheme.13 CS: cardiogenic shock; JVP: jugular venous pressure; SBP: systolic blood pressure; CVP: central venous pressure; PA sat: pulmonary artery saturation; BNP: brain natriuretic peptide; MAP: mean arterial pressure; PCWP: pulmonary capillary wedge pressure; RAP: right atrial pressure; PAPI: pulmonary artery pulsatility index; GFR: glomerular filtration rate; LFT: liver function test; CPR: cardiopulmonary resuscitation; ECMO: extracorporeal membrane oxygenation; BiPaP: bilevel positive airway pressure

STAGE DESCRIPTION PHYSICAL EXAM/BEDSIDE FINDINGS BIOCHEMICAL MARKERS HEMODYNAMICS
A At risk Patient is not currently experiencing signs or symptoms of CS but is at risk for its development. Patient may have large acute myocardial infarction or prior infarction and/or acute on chronic heart failure symptoms.
  • Normal JVP
  • Lung sounds clear
  • Warm and well perfused
  • Strong distal pulses
  • Normal mentation
  • Normal labs
  • Normal renal function
  • Normal lactic acid
Normotensive (SBP 100 mm Hg or normal) If hemodynamics done:
  • Cardiac index 2.5
  • CVP < 10 mm Hg
  • PA sat 65%
B Beginning CS Patient has clinical evidence of relative hypotension or tachycardia without hypoperfusion.
  • Elevated JVP
  • Rales in lung fields
  • Warm and well perfused
  • Strong distal pulses
  • Normal mentation
  • Normal lactate
  • Minimal renal function impairment
  • Elevated BNP
SBP < 90 mm Hg or MAP < 60 mm Hg or > 30 mm Hg drop from baseline Pulse 100 If hemodynamics done:
  • Cardiac index 2.2
  • PA sat 65%
C Classic CS Patient manifests with hypoperfusion that requires intervention (inotrope, pressor, or mechanical support, including ECMO) beyond volume resuscitation to restore perfusion. These patients typically present with relative hypotension. May include:
  • Looks unwell
  • Panicked
  • Ashen, mottled, dusky
  • Volume overload
  • Extensive rales
  • Killip class 3 or 4
  • BiPap or mechanical ventilation
  • Cold, clammy
  • Acute alteration in mental status
  • Urine output < 30 mL/h
May include:
  • Lactate 2 mmol/L
  • Creatinine doubling or > 50% drop in GFR
  • Increased LFTs
  • Elevated BNP
May include: SBP < 90 mm Hg or MAP < 60 mm Hg or > 30 mm Hg drop from baseline and drugs/device used to maintain BP above these targets Hemodynamics:
  • Cardiac index < 2.2
  • PCWP > 15 mm Hg
  • RAP/PCWP 0.8
  • PAPI < 1.85
  • Cardiac power output 0.6 W
D Deteriorating/doom Patient is similar to category C but is getting worse and failing to respond to initial interventions. Any of stage C Any of Stage C and: deteriorating Any of Stage C and: requiring multiple pressors or addition of mechanical circulatory support devices to maintain perfusion
E Extremis Patient is experiencing cardiac arrest with ongoing CPR and/or ECMO, being supported by multiple interventions.
  • Near pulselessness
  • Cardiac collapse
  • Mechanical ventilation
  • Defibrillator used
Trying to die CPR (A-modifier) pH 7.2 Lactate 5 mmol/L
  • No SBP without resuscitation
  • PEA or refractory VT/VF
  • Hypotension despite
  • maximal support

Several registries have also begun to provide new insight into CS. The Cardiogenic Shock Working Group (CSWG) is a national multicenter retrospective registry that uses real-world experiences of patients with CS. Initiated in 2017, the CSWG registry now includes more than 1,500 patients and contains hemodynamic data for analysis of more than 1,000 patients. This is the largest contemporary US registry for any-cause CS and includes experiences with all AMCS device platforms. Due to its diverse patient profile and availability of hemodynamic data, this registry could provide valuable insight by stratifying mortality risk by different etiologies, comorbidities, and treatments of shock to inform future randomized clinical trials.15

The National Cardiogenic Shock Initiative (NCSI) is a prospective registry that will determine if implementation of an algorithm to identify CSusing hemodynamic data and early initiation of AMCS with the Impella CP deviceimproves clinical outcomes among patients with AMI-CS. A recent analysis from the NCSI registry involving 171 patients with AMI-CS reported 72 survival-to-discharge rate; it also identified predictors of in-hospital mortality, including age > 70 years, creatinine > 2.0, lactate > 4.0, and cardiac power output < 0.6 W.16

More recently, a group of physicians at the Inova Heart and Vascular Institute tested whether an algorithm focused on identification, stratification, and early initiation of AMCS in CS improves clinical outcomes (Figure 1).17 One year after implementing the algorithm, they reported a significant increase in 30-day survival (44 to 82) among patients presenting with AMI-CS. They further determined that elevated lactate levels, vasopressor use, diabetes, dialysis, age, and low cardiac power output or pulmonary artery pulsatility index levels were associated with increased 30-day mortality.

Figure 1. 

Cardiogenic Shock Algorithm developed by the INOVA Heart and Vascular Institute. Republished with permission of Elsevier Science & Technology Journals, from Standardized Team-Based Care for Cardiogenic Shock, Tehrani et al., 73(13), 2019.17

SUMMARY

The relatively minor improvements in CS outcomes over the past decades warrant a more rigorous scientific exploration of the syndrome. Past studies have helped identify elements necessary to specify and validate the optimal treatment of CS; these include integration of hemodynamic and metabolic data for diagnosis and risk stratification, early evaluation and appropriate initiation of AMCS devices, and an organized algorithmic approach to decision making. The lack of a standard CS treatment protocol may be a barrier to widespread use of a single classification system, but the diversity of classification systems being developed is no doubt a step towards broader implementation of CS classification. Recent initiatives, such as the SCAI Shock Classification Scheme, the Cardiogenic Shock Working Group Registry, the National Cardiogenic Shock Initiative, and the Inova Heart and Vascular Institute prospective registry, will provide much needed insight that may improve patient outcomes and the development of prospective studies testing the clinical utility of various treatment approaches.

KEY POINTS

  • Despite advances in pharmacologic and device-based approaches to support patients in cardiogenic shock, no significant improvement in mortality has been observed over the past 20 years.
  • Randomized clinical trials have failed to show clear superiority of therapeutic strategies. The heterogeneity of trial and registry data is due to an unmet need for appropriate shock classification criteria.
  • Key elements for the optimal treatment of cardiogenic shock include integration of hemodynamic and metabolic data for diagnosis and risk stratification, early evaluation and appropriate initiation of acute mechanical circulatory support devices, and an organized algorithmic approach to decision making.