Treatment and prognosis of cardiogenic shock complicating acute myocardial infarction

INTRODUCTION — 

Cardiogenic shock is a clinical condition of inadequate tissue (end-organ) perfusion due to cardiac dysfunction.

The treatment and prognosis of cardiogenic shock complicating acute myocardial infarction (MI) will be reviewed here. The pathophysiology, clinical manifestations, and diagnosis of this disorder are discussed separately. (See "Clinical manifestations and diagnosis of cardiogenic shock in acute myocardial infarction".)

The initial approach to reperfusion, including patients with cardiogenic shock, is discussed separately. (See "Acute ST-elevation myocardial infarction: Selecting a reperfusion strategy", section on 'Cardiogenic shock'.)

GENERAL MEASURES

Empiric therapies for MI and systolic dysfunction — In patients with acute MI and cardiogenic shock, the goal of management is to restore perfusion. As such, agents that decrease inotropy or may worsen hypotension should be avoided and include beta blockers, angiotensin converting enzyme inhibitors, angiotensin II receptor blockers, sacubitril-valsartan, and mineralocorticoid receptor antagonists. While these agents have benefits in stable patients with MI or in stable patients with left ventricular (LV) systolic dysfunction, these agents are likely to worsen cardiogenic shock.

Pulmonary artery catheterization — Pulmonary artery catheters may be used to guide management of patients with cardiogenic shock, including temporary mechanical circulatory support (tMCS) device selection and deescalation of tMCS devices or vasoactive agents [1,2]. Experts have differing views on the utility of pulmonary artery catheterization. Observational data suggest an association between pulmonary artery catheter placement and survival in Society for Cardiovascular Angiography and Interventions (SCAI) shock stages C, D, and E, but these findings are prone to bias and have not been confirmed with randomized trials [3,4].

Ventilatory support — Ventilatory support may be required in cardiogenic shock to achieve the following (see "Overview of initiating invasive mechanical ventilation in adults in the intensive care unit"):

●Protect the airway and maintain oxygen supply in patients with a deterioration in consciousness or cardiac arrest.

●Treat acute respiratory failure, most often due to cardiogenic pulmonary edema. (See "Treatment of acute decompensated heart failure: General considerations".)

●Raise the arterial pH in metabolic acidosis. (See "Bicarbonate therapy in lactic acidosis".)

Shock teams — Incorporation of a multidisciplinary shock team in management and decision making may help improve outcomes [5,6]. Shock teams typically provide the expertise, resources, and personnel (interventional cardiologists, cardiac surgeons, advanced heart failure cardiologists) required for management of cardiogenic shock.

Management of arrhythmias — In patients with acute MI and cardiogenic shock, arrhythmias may provoke or complicate management. The management of arrhythmias in this setting is discussed separately. (See "Ventricular arrhythmias during acute myocardial infarction: Prevention and treatment" and "Conduction abnormalities after myocardial infarction" and "Supraventricular arrhythmias after myocardial infarction".)

INITIAL APPROACH TO MANAGEMENT

Reperfusion strategy and antithrombotic therapy — Patients with cardiogenic shock benefit from early reperfusion (algorithm 1). The approach to selecting an approach to reperfusion is discussed separately. (See "Acute ST-elevation myocardial infarction: Selecting a reperfusion strategy", section on 'Cardiogenic shock'.)

The approaches to choosing a P2Y₁₂ inhibitor and an anticoagulant depend on which reperfusion therapy is most appropriate (eg, percutaneous coronary intervention, fibrinolysis) and are similar to the approaches in patients without cardiogenic shock, as discussed separately (algorithm 2). In general, potent P2Y₁₂ inhibitors, oral or intravenous (IV), should be preferred based on the slow gastroenteral resorption in cardiogenic shock. In addition, unfractionated heparin should be given IV. (See "Acute ST-elevation myocardial infarction: Initial antiplatelet therapy" and "Acute ST-elevation myocardial infarction: Management of anticoagulation".)

Volume status — In patients with acute MI complicated by cardiogenic shock, volume management requires an individualized approach, and both diuresis and volume resuscitation should be managed with frequent reassessment to mitigate unintended adverse effects. Patients with cardiogenic shock and acute MI may have hypovolemia, hypervolemia, inappropriate vasodilation, mechanical complications of MI, or a combination of features [7]:

●Pulmonary edema or other evidence of congestion – Patients with acute MI and cardiogenic shock who have evidence of congestion (eg, elevated jugular venous distension, pulmonary edema, respiratory distress) typically require diuresis. In addition to therapies required to maintain ventilation and oxygenation, diuresis with a low dose of IV furosemide is a reasonable approach.

●Suspected hypovolemia or vasodilation – In patients with suspected hypovolemia (eg, absence of jugular venous distension, frequent emesis, fever) who do not have pulmonary edema, it is reasonable to administer an empiric IV volume challenge of 250 mL of isotonic saline [8]. Overly vigorous fluid challenge in patients with extensive LV infarction, particularly older adults, is likely to result in pulmonary edema and should be avoided.

●Right ventricular infarction – Cardiogenic shock and hypotension may be secondary to right ventricular MI. Volume repletion has a role in patients who have low right-sided filling pressures with hypovolemia, which is discussed separately. (See "Right ventricular myocardial infarction", section on 'Optimization of right ventricular preload'.)

Hypotension — In patients with ST-elevation MI (STEMI) and hypotension (ie, systolic blood pressure <80 mmHg) attributable to LV systolic dysfunction or right ventricular systolic dysfunction, we suggest initial therapy with norepinephrine rather than other vasopressors. Other reasonable choices for initial therapy for hypotension include dopamine, phenylephrine, and vasopressin. We avoid therapy with epinephrine. We use the lowest dose of vasopressor that restores blood pressure (table 1). If additional agents are required, we attempt to minimize the number of agents and their dose. (See "Use of vasopressors and inotropes".)

In patients with mechanical complications of MI or other factors contributing to hypotension, management of hypotension may require additional therapies (eg, pericardiocentesis, volume resuscitation). (See "Acute myocardial infarction: Mechanical complications".)

Our preference for norepinephrine is based on our clinical experience with its effectiveness, its ability to provide vasopressor and mild inotropic effects, and weak data that suggest a lower rate of adverse effects compared with dopamine and epinephrine. In a trial of 1679 patients with circulatory shock due to varying etiologies (eg, septic, hypovolemic, and cardiogenic shock) who were randomly assigned to initial therapy with either dopamine or norepinephrine, the subgroup of 280 patients with cardiogenic shock treated with dopamine had a higher rate of death and arrhythmias (predominantly atrial fibrillation) at 28 days compared with those treated with norepinephrine [9]. Epinephrine is generally avoided based on results of a trial that was stopped early due to a higher rate of deterioration in patients randomly assigned to epinephrine compared with norepinephrine (37 versus 7 percent) [10].

Inotropic support — In patients whose blood pressure has been stabilized but who have ongoing evidence of malperfusion, we suggest addition of an inotrope. If the patient cannot receive an inotrope (eg, ventricular arrhythmias) or rapid correction of severe malperfusion is required, it may be reasonable to place a temporary mechanical circulatory support device. (See 'Temporary mechanical circulatory support' below.)

The choice of inotrope depends on the patient's characteristics. In patients with impaired kidney function, dobutamine is typically used; milrinone is cleared via the kidneys. Dobutamine has a shorter half-life compared with milrinone. We start inotropic therapy with a low dose and without a bolus (table 1).

A trial that compared dobutamine with milrinone in 192 patients with cardiogenic shock from diverse causes found similar rates of outcomes that included death, transplantation, and mechanical circulatory support [11]. We do not use levosimendan in this population; studies that evaluated its safety and efficacy are discussed separately. (See "Inotropic agents in heart failure with reduced ejection fraction", section on 'Intravenous calcium-sensitizing agents'.)

MANAGEMENT OF REFRACTORY SHOCK

Identification of complications — Patients with acute MI and cardiogenic shock who do not respond to reperfusion, volume management, and appropriate support with vasopressors or inotropes should be evaluated for complications of MI or other causes of shock with urgent echocardiography. (See "Acute myocardial infarction: Mechanical complications" and "Evaluation of and initial approach to the adult patient with undifferentiated hypotension and shock".)

Vasoactive agents – In patients with acceptable blood pressure, evidence of malperfusion despite vasopressor and inotropic support, and signs of high systemic vascular resistance, one option for therapy is addition of a vasodilator (eg, intravenous nitroglycerin, nitroprusside). This approach requires supervision from a clinician experienced in the management of cardiogenic shock.

Temporary mechanical circulatory support — In patients with cardiogenic shock refractory to volume management and vasoactive agents, placement of a temporary mechanical circulatory support (tMCS) device can be used to increase cardiac output. In our practices, we reserve use of such devices for patients with Society for Cardiovascular Angiography and Interventions (SCAI) stages D and E cardiogenic shock [12]. Support with such devices is characterized by a high likelihood of complications (eg, renal replacement therapy, limb ischemia, bleeding).

The choice of device is individualized to the patient's characteristics, local experience with device management, and device availability. The options for tMCS include veno-arterial extracorporeal life-support (ECLS), intraaortic balloon pumps (IABPs), percutaneous microaxial pumps, and paracorporeal centrifugal pumps combined with percutaneously placed catheters (eg, TandemHeart device). Aspects of device selection and management are discussed separately. (See "Short-term mechanical circulatory assist devices".)

This approach is consistent with professional guidelines, though European guidelines recommend against IABP use [13-15].

There are no definitive studies that address the relative efficacy of various tMCS devices [16]. Trials of individual devices versus management without such devices are difficult to compare due to factors that include differences in patients enrolled (eg, fraction of patients who received cardiopulmonary resuscitation, differing rates of mortality in control groups) and trial protocols (eg, device management, weaning parameters) [17]. In trials of individual tMCS devices versus usual care, the risk of complications was higher in patients treated with tMCS devices, and the effect of tMCS device use on mortality varied [18]:

●The DanGer-Shock trial investigated the relative efficacy of early use of the Impella CP microaxial pump plus standard care versus standard care alone in 355 highly selected patients with cardiogenic shock related to STEMI without risk of hypoxic brain injury [19]. Patients assigned to the Impella CP group had lower rates of all-cause mortality at 180 days (46 versus 59 percent; hazard ratio [HR] 0.74, 95% CI 0.55-0.99) despite a higher risk of device-related adverse events (severe bleeding, limb ischemia, hemolysis, device failure, worsening aortic regurgitation; HR 4.74, 95% CI 2.36-9.55) and renal replacement therapy (HR 1.98, 95% CI 1.27-3.09). The reasons for the beneficial effect of the Impella CP in this trial include exclusion of right ventricular failure, exclusion of hypoxic brain injury, the device itself, and treatment bias (eg, unusually high mortality rate in the control group, shortest ICU duration ever reported in a control group, unusually high rate of renal replacement in the active microaxial flow pump group).

●In a trial (IABP-SHOCK II) that included 600 patients with cardiogenic shock complicating acute MI, the rates of mortality in patients assigned to IABP or no IABP were similar (40 versus 41 percent; relative risk [RR] 0.96, 95% CI 0.79-1.17) [20]. There were no significant differences in secondary endpoints such as length of stay in the intensive care unit, kidney function, rates of major bleeding, peripheral ischemic complications, sepsis, or stroke. Mortality rates were similar at long-term follow-up of 12 months and 6.2 years (52 versus 51 and 66 versus 67 percent, respectively) [21,22]. A 2015 meta-analysis of seven studies, including IABP-SHOCK II, came to similar conclusions [23].

●Trials that studied percutaneous ECLS in acute MI-related cardiogenic shock suggest that its routine use in this population is not associated with a survival benefit. In the largest trial (ECLS-SHOCK) that included 420 patients with advanced acute MI-related cardiogenic shock (ie, lactate of >3 mmol/L required for inclusion), the rate of 30-day mortality was similar in patients assigned to ECLS and usual care (49 versus 48 percent in the group assigned to ECLS; RR 0.98, 95% CI 0.80-1.19) [24]. Ischemic complications occurred more frequently in the ECLS group (RR 2.86; 95% CI 1.31-6.25). At one year, all-cause mortality was similar (55 percent in the ECLS group and 55.8 percent in usual care) [25]. These findings were consistent with those of a subsequent meta-analysis [26].

PROGNOSIS

Short-term — The short-term prognosis of cardiogenic shock is directly related to the severity of the hemodynamic disorder. Patients most commonly succumb to multiorgan dysfunction due to ongoing hypoperfusion [27]. In-hospital mortality is over 50 percent [28,29].

In 2019, the Society for Cardiovascular Angiography and Intervention (SCAI) proposed a classification scheme for patients admitted to a cardiac intensive care unit with cardiogenic shock [30]. This system is designed to provide a standardized framework for assessing the severity of cardiogenic shock and guiding clinical management. The stages are as follows:

●Stage A – "At risk" for cardiogenic shock but without clinical evidence of shock

●Stage B – "Beginning" shock, characterized by hypotension or tachycardia without hypoperfusion

●Stage C – "Classic" cardiogenic shock, with hypotension and hypoperfusion

●Stage D – "Deteriorating" shock, where initial interventions have failed to restore stability and adequate perfusion

●Stage E – "Extremis," indicating a highly unstable patient, often with cardiovascular collapse [30]

This classification system was endorsed by multiple societies, including the American College of Cardiology, the American Heart Association, the Society of Critical Care Medicine, and the Society of Thoracic Surgeons [30].

One study found that SCAI stages correlated with hospital mortality rates; unadjusted hospital mortality rates increased progressively from SCAI Stage A (3 percent) to Stage E (67 percent) [31].

In subsequent validation studies, patients were categorized into one of five stages of cardiogenic shock severity based on the presence or absence of hypotension, tachycardia, hypoperfusion, clinical deterioration, or refractory shock [12,31]. Each higher stage of cardiogenic shock was significantly associated with increased hospital mortality.

Long-term — Long-term survival in patients with MI complicated by cardiogenic shock is improved with timely revascularization in the acute setting, and functional status and quality of life in most survivors are excellent [32,33]. However, in the Intraventricular Aortic Balloon Pump Cardiogenic Shock (IABP-SHOCK) trial, mortality was approximately 67 percent at nearly six years [22]. (See 'Temporary mechanical circulatory support' above.)

The following have been identified as risk factors for short- or long-term mortality in cardiogenic shock:

●Increasing age; clinical signs of severe hypoperfusion such as oliguria, cold or clammy extremities, or biochemical evidence such as increasing lactate [34,35]; elevated creatinine; and neurologic involvement such as history of stroke [20,22,36] and anoxic damage [37].

●Abnormal hemodynamic parameters such as reduced mean arterial pressure (MAP) despite supportive therapies, reduced cardiac output (CO), cardiac index, and cardiac power index (MAP x CO/451 x body surface area in m²) [38].

●Possible non-ST-elevation MI as opposed to STEMI [39].

●Mortality varies significantly with the location of the culprit lesion and is higher in patients with a left main coronary artery or saphenous vein graft lesion than in those with circumflex, left anterior descending, or right coronary artery lesions (79 and 70 percent versus 37 to 42 percent). Right coronary culprit lesions were associated with the best prognosis [40]. Multivessel disease or prior coronary artery bypass graft surgery are also risk factors for mortality [20,37].

●Echocardiographic predictors of outcome are reduced LV ejection fraction and worsening severity of mitral regurgitation [40,41].

●The time from symptom onset to reperfusion is an important determinant of mortality in patients with STEMI who undergo primary percutaneous coronary intervention [42,43].

●The intracellular aminopeptidase dipeptidyl peptidase 3 (DPP3), which degrades angiotensin II and inhibits angiotensin II-mediated signal transduction, may be involved in cardiogenic shock pathophysiology. High circulating DPP3 levels after acute MI are associated with cardiogenic shock development [44].

SOCIETY GUIDELINE LINKS — 

Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Non-ST-elevation acute coronary syndromes (non-ST-elevation myocardial infarction)" and "Society guideline links: ST-elevation myocardial infarction (STEMI)" and "Society guideline links: Percutaneous coronary intervention" and "Society guideline links: Mechanical circulatory support".)

SUMMARY AND RECOMMENDATIONS

●General measures

•Empiric therapies for MI and systolic dysfunction - In patients with acute myocardial infarction (MI) and cardiogenic shock, the goal of management is to restore perfusion. As such, agents that decrease inotropy or may worsen hypotension should be avoided and include beta blockers, angiotensin converting enzyme inhibitors, angiotensin II receptor blockers, sacubitril-valsartan, and mineralocorticoid receptor antagonists. (See 'Empiric therapies for MI and systolic dysfunction' above.)

•Pulmonary artery catheterization – Pulmonary artery catheters may be used to guide management of patients with shock. (See 'Pulmonary artery catheterization' above.)

•Ventilatory support - Ventilatory support may be required in cardiogenic shock. (See "Overview of initiating invasive mechanical ventilation in adults in the intensive care unit".)

•Shock teams – Incorporation of a multidisciplinary shock team in management and decision making may help improve outcomes. (See 'Shock teams' above.)

•Management of arrhythmias – In patients with acute MI and cardiogenic shock, arrhythmias may provoke or complicate management. The management of arrhythmias in this setting is discussed separately. (See "Ventricular arrhythmias during acute myocardial infarction: Prevention and treatment" and "Conduction abnormalities after myocardial infarction" and "Supraventricular arrhythmias after myocardial infarction".)

●Initial approach to management

•Reperfusion – Patients with cardiogenic shock benefit from early reperfusion. The approach to selecting an approach to reperfusion is discussed separately (algorithm 1). (See "Acute ST-elevation myocardial infarction: Selecting a reperfusion strategy", section on 'Cardiogenic shock'.)

The approaches to choosing a P2Y₁₂ inhibitor and an anticoagulant depend on which reperfusion therapy is most appropriate (eg, percutaneous coronary intervention, fibrinolysis) and are similar to the approaches in patients without cardiogenic shock, as discussed separately (algorithm 2). (See "Acute ST-elevation myocardial infarction: Initial antiplatelet therapy" and "Acute ST-elevation myocardial infarction: Management of anticoagulation".)

•Volume status – In patients with acute MI complicated by cardiogenic shock, volume management requires an individualized approach, and both diuresis and volume resuscitation should be managed with frequent reassessment to mitigate unintended adverse effects. Patients with cardiogenic shock and acute MI may have hypovolemia, hypervolemia, inappropriate vasodilation, mechanical complications of MI, or a combination of features. (See 'Volume status' above.)

•Hypotension – In patients with ST-elevation MI (STEMI) and hypotension (ie, systolic blood pressure <80 mmHg) attributable to cardiogenic shock, we suggest initial therapy with norepinephrine rather than other vasopressors (Grade 2C). Other reasonable choices for initial therapy for hypotension include dopamine, phenylephrine, and vasopressin. We avoid therapy with epinephrine. (See 'Hypotension' above.)

•Inotropic support – In patients whose blood pressure has been stabilized but who have ongoing evidence of malperfusion, we suggest addition of an inotrope (Grade 2C). If the patient cannot receive an inotrope (eg, ventricular arrhythmias) or rapid correction of malperfusion is required, it may be reasonable to place a temporary mechanical circulatory support (tMCS) device. (See 'Temporary mechanical circulatory support' above and 'Inotropic support' above.)

●Management of refractory shock

•Identification of complications – Patients with acute MI and cardiogenic shock who do not respond to reperfusion, volume management, and appropriate support with vasopressors or inotropes should be evaluated for complications of MI or other causes of shock with echocardiography and possibly a pulmonary artery catheter. (See "Acute myocardial infarction: Mechanical complications" and "Evaluation of and initial approach to the adult patient with undifferentiated hypotension and shock".)

•Temporary mechanical circulatory support – In patients with cardiogenic shock refractory to volume management and vasoactive agents, placement of a tMCS device can be used to increase cardiac output. In our practices, we reserve use of such devices for patients with Society for Cardiovascular Angiography and Interventions (SCAI) stages D and E cardiogenic shock with no evidence of hypoxic brain injury. Support with such devices is characterized by a high likelihood of complications (eg, renal replacement therapy, limb ischemia, bleeding). (See 'Temporary mechanical circulatory support' above.)

The choice of device is individualized to the patient's characteristics and local experience with device management. (See "Short-term mechanical circulatory assist devices".)

●Prognosis – The risk of mortality is directly related to the cause and severity of shock. (See 'Prognosis' above.)

ACKNOWLEDGMENTS — 

The UpToDate editorial staff acknowledges Venu Menon, MD, Judith Hochman, MD, and Duane Pinto, MD, MPH, who contributed to previous versions of this topic review.