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Cardiogenic Shock

Published:September 23, 2013DOI:https://doi.org/10.1016/j.ccl.2013.07.009

      Keywords

      Key points

      • Cardiogenic shock is a final common pathway defined by a marked reduction in cardiac output and inadequate end-organ perfusion, which can result from an array of cardiac insults.
      • Cardiogenic shock is a systemic disease involving a vicious cycle of inflammation, ischemia, and progressive myocardial dysfunction, which often results in death.
      • Cardiogenic shock is the leading cause of death from acute myocardial infarction; urgent revascularization favorably impacts mortality.
      • Cardiogenic shock is a life-threatening emergency that requires intensive monitoring accompanied by aggressive hemodynamic support with vasopressors, inotropes, and/or mechanical circulatory support.
      • Novel therapeutic strategies are required to reduce the unacceptably high mortality rates currently associated with cardiogenic shock.

      Introduction

      Cardiogenic shock (CS) is a dramatic and highly lethal condition that has long presented a challenge to those who care for patients in the cardiac intensive care unit (CICU). CS represents the final common pathway of a large number of pathologic conditions, leading to a marked impairment of cardiac output and consequently a state of inadequate end-organ perfusion. As a result, a vicious cycle of inflammation, ischemia, and progressive myocardial dysfunction ensues, which often results in death. Despite decades of study, the mortality rate associated with CS remains stubbornly high. Indeed, recent studies have called into question the role of interventions previously believed to be of significant benefit. Nevertheless, an expanding understanding of the pathophysiology of this condition, and the availability of increasingly sophisticated pharmacologic and mechanical therapies, are likely to result in substantially improved outcomes for patients with CS in the years ahead.

      Etiology

      The cause of CS may be left ventricular (LV) or right ventricular (RV) pump failure, severe valvular regurgitation, or ventricular disruption, alone or in combination (Box 1). Although sometimes included as a type of CS, obstructive shock (eg, valvular obstruction, pulmonary embolism, cardiac tamponade) is not discussed in this review. The inciting event precipitating CS may be abrupt in origin, as is the case for acute myocardial infarction (AMI) or fulminant myocarditis, or may be the rapid decompensation of a chronic disorder, such as dilated cardiomyopathy. No large-scale registries of CS exist, and therefore reliable data regarding the relative contribution of these various etiologies are not available. Fig. 1 displays the experience of our tertiary CICU during 2012.
      Etiologies of cardiogenic shock
      • 1.
        Left ventricular pump failure
        • a.
          Acute myocardial infarction (STEMI, non-STEMI)
        • b.
          Acute myocarditis
        • c.
          Tako-tsubo cardiomyopathy
        • d.
          Cardiac contusion
        • e.
          End-stage cardiomyopathy
        • f.
          Prolonged cardiopulmonary bypass
        • g.
          Septic shock with severe myocardial depression
      • 2.
        Right ventricular pump failure
        • a.
          Right ventricular infarction
        • b.
          End-stage pulmonary hypertension
      • 3.
        Acute valvular regurgitation
        • a.
          Ischemic mitral regurgitation
        • b.
          Papillary muscle rupture
        • c.
          Myxomatous degeneration of the mitral valve with rupture of chordae tendinae
        • d.
          Infective endocarditis
        • e.
          Aortic dissection
        • f.
          Trauma
      • 4.
        Ventricular disruption
        • a.
          Ventricular septal rupture
        • b.
          Free wall rupture
      Figure thumbnail gr1
      Fig. 1Etiology of CS in 34 consecutive patients with CS treated in the Cardiac Intensive Care Unit of the Medstar Washington Hospital Center in 2012.

      Incidence

      Because of the wide spectrum of causes of CS, the true incidence of this condition is unknown; however, the most common cause of CS remains AMI, for which the incidence has been well described. CS occurs in 5% to 8% of patients hospitalized with AMI, and is more common among patients presenting with ST-segment elevation myocardial infarction (STEMI) than among those with non-STEMI.
      • Reynolds H.R.
      • Hochman J.S.
      Cardiogenic shock: current concepts and improving outcomes.
      The incidence of CS complicating AMI remained stable for many years, but recently appears to have decreased in parallel with the adoption of primary percutaneous coronary intervention (PCI) for STEMI. For example, in a large population-based registry of acute coronary syndromes, the overall incidence of CS fell from 12.9% in 1997 to 5.5% in 2006.
      • Jeger R.V.
      • Radovanovic D.
      • Hunziker P.R.
      • et al.
      Ten-year trends in the incidence and treatment of cardiogenic shock.
      Importantly, only a minority of patients with AMI with CS arrive at the hospital with an established clinical syndrome of organ hypoperfusion. In most (>70%) cases, shock develops following hospital admission.
      • Hochman J.S.
      • Sleeper L.A.
      • Webb J.G.
      • et al.
      Early revascularization in acute myocardial infarction complicated by cardiogenic shock. SHOCK Investigators. Should We Emergently Revascularize Occluded Coronaries for Cardiogenic Shock.
      • Webb J.G.
      • Sleeper L.A.
      • Buller C.E.
      • et al.
      Implications of the timing of onset of cardiogenic shock after acute myocardial infarction: a report from the SHOCK Trial Registry. SHould we emergently revascularize Occluded Coronaries for cardiogenic shocK?.

      Outcomes

      Although the mortality rate associated with CS likely varies depending on the etiology, systematic data on outcomes are available only for CS resulting from AMI. CS is the most common cause of death in patients hospitalized with AMI, and short-term mortality rates have been slow to improve. Earlier studies reported mortality rates as high as 80%.
      • Hollenberg S.M.
      • Kavinsky C.J.
      • Parrillo J.E.
      Cardiogenic shock.
      In-hospital mortality in the SHould we emergently revascularize Occluded Coronaries for CS (SHOCK) Trial Registry was 60%, similar to the 59.4% rate reported from the Global Registry of Acute Coronary Events (GRACE) registry.
      • Hochman J.S.
      • Buller C.E.
      • Sleeper L.A.
      • et al.
      Cardiogenic shock complicating acute myocardial infarction—etiologies, management and outcome: a report from the SHOCK Trial Registry. Should we emergently revascularize Occluded Coronaries for cardiogenic shocK?.
      • Awad H.H.
      • Anderson Jr., F.A.
      • Gore J.M.
      • et al.
      Cardiogenic shock complicating acute coronary syndromes: insights from the Global Registry of Acute Coronary Events.
      In some recent reports, however, in-hospital mortality rates of less than 50% have been achieved.
      • Jeger R.V.
      • Radovanovic D.
      • Hunziker P.R.
      • et al.
      Ten-year trends in the incidence and treatment of cardiogenic shock.
      • Babaev A.
      • Frederick P.D.
      • Pasta D.J.
      • et al.
      Trends in management and outcomes of patients with acute myocardial infarction complicated by cardiogenic shock.
      • Thiele H.
      • Zeymer U.
      • Neumann F.J.
      • et al.
      Intraaortic balloon support for myocardial infarction with cardiogenic shock.
      In our CICU, we treated 438 patients with post-MI CS from 2006 to 2012, with an in-hospital mortality rate of 37%. Importantly, several studies have demonstrated that among CS survivors, long-term outcomes are quite favorable.
      • Singh M.
      • White J.
      • Hasdai D.
      • et al.
      Long-term outcome and its predictors among patients with ST-segment elevation myocardial infarction complicated by shock: insights from the GUSTO-I trial.
      • Hochman J.S.
      • Sleeper L.A.
      • Webb J.G.
      • et al.
      Early revascularization and long-term survival in cardiogenic shock complicating acute myocardial infarction.
      • Holmes Jr., D.R.
      • Bates E.R.
      • Kleiman N.S.
      • et al.
      Contemporary reperfusion therapy for cardiogenic shock: the GUSTO-i trial experience. The GUSTO-I Investigators. Global Utilization of Streptokinase and Tissue Plasminogen Activator for Occluded Coronary Arteries.

      Pathophysiology

      Investigations into the pathophysiology of CS in the early twentieth century concluded, in general, that “shock… is largely, and probably solely, a manifestation of heart failure.”
      • Boyer N.
      Cardiogenic shock.
      However, even then, the possibility that mechanisms other than pump dysfunction contributed to the shock state was seriously considered. Indeed, Boyer wrote in 1944 that “…it is still conceivable that peripheral mechanisms play a contributory role.”
      • Boyer N.
      Cardiogenic shock.
      Over the ensuing decades, a clearer understanding of the complex interplay between forces local and systemic, mechanical and biochemical, has begun to emerge.
      A more contemporary understanding of CS considers it to be the final common pathway of a number of derangements that affect the entire circulatory system (Fig. 2). CS is initiated by a severe reduction in cardiac output, lowering perfusion of the coronary arteries, which may already be compromised by atherosclerotic lesions. This leads to ischemia, further worsening of myocardial performance, and hence the perpetuation of a vicious cycle within the heart. Further myocardial necrosis and/or stunning may result from distal embolization and/or reperfusion injury when fibrinolytics therapy or primary PCI is undertaken, or from reocclusion of the infarct artery. Right ventricular failure may be the primary cause of CS, but more commonly is a contributing factor.
      Figure thumbnail gr2
      Fig. 2Modern paradigm of CS in acute myocardial infarction. LVEDP, left ventricular end-diastolic pressure.
      (From Antman EM, Braunwald E. Acute myocardial infarction. In: Braunwald E, Fauci A, Kasper D, et al, editors. Harrison’s Principles of Internal Medicine. 15th edition. New York: McGraw-Hill; 2001. p. 1395; with permission.)
      As a response to this central circulatory derangement, compensatory neurohumoral responses occur, including activation of the sympathetic and angiotensin-renin systems. These may temporarily increase contractility and induce peripheral vasoconstriction in an attempt to maintain central blood pressure and sustain flow to vital organs. However, the ultimate result is worsening myocardial ischemia, further peripheral organ hypoperfusion, and an increase in the risk of ventricular arrhythmias. Catecholamines (intrinsic or pharmacologic) increase myocardial oxygen demand and may also be directly myocardiotoxic. Neurohumoral activation leads to salt and water retention, resulting in pulmonary edema, worsening hypoxia, and further ischemia. When these compensatory mechanisms are overwhelmed, anaerobic metabolism and lactic acidosis ensue, further depressing myocardial function.
      • Bates E.R.
      Cardiogenic shock.
      Inflammatory mediators, including interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-α), are frequently elevated in CS and have a negative inotropic effect. In addition, cytokines lead to the production of high levels of nitric oxide (NO) through induction of inducible nitric oxide synthase (iNOS). This may result in a state of inappropriate vasodilation, worsening hypotension, and lactic acidosis.
      • Reynolds H.R.
      • Hochman J.S.
      Cardiogenic shock: current concepts and improving outcomes.
      Consistent with these observations, approximately 20% of patients in the SHOCK trial demonstrated findings characteristic of the systemic inflammatory response syndrome, with low systemic vascular resistance, fever, leukocytosis, and elevated inflammatory markers, such as C-reactive protein.
      • Kohsaka S.
      • Menon V.
      • Lowe A.M.
      • et al.
      Systemic inflammatory response syndrome after acute myocardial infarction complicated by cardiogenic shock.
      However, despite intensive investigation, it remains unclear whether these mechanisms are important contributors to the shock state or merely represent an epiphenomenon.
      • Reynolds H.R.
      • Hochman J.S.
      Cardiogenic shock: current concepts and improving outcomes.

      Diagnosis

      A constellation of findings reflecting hypotension, low cardiac output, hypoperfusion, and congestion is required to make the diagnosis of CS. The assessment of hypotension may be performed noninvasively or with the use of an intra-arterial catheter. Findings of low cardiac output may include tachycardia, low pulse pressure, faint pulses, distant heart sounds, displaced apical impulse, and third or fourth heart sounds. The presence of a systolic murmur may suggest the presence of mitral regurgitation or ventricular septal defect. Electrocardiography, coronary and LV angiography, and, particularly, echocardiography are useful to confirm the presence of LV and/or RV dysfunction, valvular regurgitation, or cardiac disruption. Hypoperfusion may manifest as agitation, disorientation, or lethargy from cerebral hypoperfusion; cool, clammy, or cyanotic extremities from peripheral hypoperfusion; and oliguria from renal hypoperfusion. The presence of an elevated serum lactate level can provide confirmatory evidence of visceral hypoperfusion. Congestion may be manifest by elevation of the jugular venous pressure or pulmonary rales. Chest radiography may reveal pulmonary venous congestion or frank pulmonary edema, and serum natriuretic peptide levels are generally elevated.
      Various sets of diagnostic criteria for CS have been proposed, each of which relies on invasive hemodynamic measurements obtained from a pulmonary artery catheter (PAC), in addition to clinical findings. There is no consensus as to which of these invasive criteria represent the diagnostic “gold standard,” but the criteria used for entry into the SHOCK trial are generally accepted (Box 2).
      Diagnostic criteria for cardiogenic shock
      • 1.
        Systolic blood pressure <90 mm Hg for at least 30 minutes or the need for supportive measures to maintain a systolic blood pressure ≥90 mm Hg
      • 2.
        Cool extremities or a urine output <30 mL per hour
      • 3.
        Heart rate ≥60 beats per minute
      • 4.
        Cardiac index ≤2.2 L/min per square meter of body surface area
      • 5.
        Pulmonary capillary occlusion pressure ≥15 mm Hg

      General considerations, monitoring, and therapy

      General Considerations

      CS is a life-threatening emergency. Hence, once the diagnosis of CS is established, the clinician must immediately seek to understand the cause of the clinical condition as well as initiate therapy before irreversible injury to vital organs ensues. Meticulous patient monitoring in a cardiac intensive care unit is essential, as rapid changes often occur throughout the clinical course. Frequent clinical assessment should be performed by an expert team composed of, at a minimum, a cardiac intensivist, cardiac critical care nurse, and respiratory therapist. All patients should undergo 12-lead electrocardiography (with right-sided leads when RV infarction is suspected), followed by continuous electrocardiographic monitoring. Blood pressure should be monitored with an intra-arterial catheter, and a central venous line should be inserted for administration of vasopressor agents. Continuous measurement of arterial oxygen saturation with pulse oximetry should be initiated. Catheter drainage of the bladder with hourly measurement of urine output is required. Frequent laboratory analysis of electrolytes and arterial blood gases is also important. All patients should undergo comprehensive transthoracic and, if necessary, transesophageal echocardiography as soon as feasible.

      Hemodynamic Monitoring

      The role of invasive hemodynamic monitoring with a PAC in patients with CS is uncertain. No clinical trial has yet established a clinical benefit with the use of this modality in this clinical setting. Less invasive or noninvasive alternatives, such as transpulmonary thermodilution, pulse contour analysis, thoracic electrical bioimpedance, and bedside Doppler echocardiography are being used with increasing frequency.
      • Marik P.E.
      • Baram M.
      Noninvasive hemodynamic monitoring in the intensive care unit.
      Nevertheless, monitoring with a PAC may serve multiple important functions in the setting of CS (Box 3), and most authorities continue to recommend the insertion of a PAC in patients with CS.
      • O'Gara P.T.
      • Kushner F.G.
      • Ascheim D.D.
      • et al.
      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.
      When a PAC is used, clinical judgment is essential to avoid potentially catastrophic complications (eg, pulmonary artery rupture).
      Role of the pulmonary artery catheter in cardiogenic shock
      • Eliminate diagnostic uncertainty
      • Distinguish among various hemodynamic profiles
        • Left ventricular failure: high PAOP, low cardiac output, high SVR
        • Right ventricular failure: high RA pressure and a ratio of right atrial/PAOP >0.8
        • Mitral regurgitation: large v-wave in the PAOP tracing
        • Ventricular septal rupture: significant step-up in oxygen saturation between the RA and the pulmonary artery
      • Guide fluid and inotropic therapy
      • Provide prognostic data (eg, cardiac power)
      Abbreviations: PAOP, pulmonary artery occlusion pressure; RA, right atrium; SVR, systemic vascular resistance.

      Initial Therapy

      Limited initial fluid resuscitation is reasonable unless frank pulmonary edema is present. The maintenance of adequate oxygenation and airway protection is essential, and mechanical intubation is frequently required. Care should be taken to avoid oxygen toxicity and unnecessarily high levels of positive end-expiratory pressure. Moderate hyperventilation may assist in correcting acidemia. Hypokalemia and hypomagnesemia predispose patients to ventricular arrhythmia and should be aggressively corrected. If sustained atrial or ventricular arrhythmias are present, prompt electrical cardioversion should be performed. Amiodarone is useful to prevent arrhythmia recurrence. Inappropriate bradycardia, which can be due to excess vagotonia, heart block, or drug effects, should be corrected pharmacologically or with temporary transvenous pacing. Narcotic analgesics in moderate doses are useful to limit pain and anxiety, as well as reduce preload, afterload, and sympathetic activity. Diuretics can be used to decrease filling pressures and relieve pulmonary congestion. Beta blockers and calcium channel blockers should be avoided, as they have negative inotropic properties and may worsen shock.
      • Chen Z.M.
      • Pan H.C.
      • Chen Y.P.
      • et al.
      Early intravenous then oral metoprolol in 45,852 patients with acute myocardial infarction: randomised placebo-controlled trial.
      Marked hyperglycemia (and any hypoglycemia) should be avoided, and an insulin infusion may be required.

      Reperfusion

      When the etiology of CS is AMI, rapid relief of ischemia is essential. Standard, guideline-recommended medical therapy should be initiated, with the exception that medications that lower blood pressure (beta blockers, nitrates) should be omitted. In the setting of STEMI, fibrinolytic therapy has been shown to reduce the incidence of CS; however, no study has demonstrated a beneficial effect of fibrinolytic therapy on mortality once CS is established.
      • Holmes Jr., D.R.
      • Bates E.R.
      • Kleiman N.S.
      • et al.
      Contemporary reperfusion therapy for cardiogenic shock: the GUSTO-i trial experience. The GUSTO-I Investigators. Global Utilization of Streptokinase and Tissue Plasminogen Activator for Occluded Coronary Arteries.
      Effectiveness of intravenous thrombolytic treatment in acute myocardial infarction. Gruppo Italiano per lo Studio della Streptochinasi nell'Infarto Miocardico (GISSI).
      In-hospital mortality and clinical course of 20,891 patients with suspected acute myocardial infarction randomised between alteplase and streptokinase with or without heparin. The International Study Group.
      The landmark SHOCK trial randomized 302 patients with CS complicating STEMI to either initial medical stabilization or emergency revascularization. Medical therapy included administration of fibrinolytic therapy and the insertion of an intra-aortic balloon pump (IABP) in most patients. Patients in the revascularization arm underwent angioplasty or coronary artery bypass graft (CABG) surgery as soon as possible and within 6 hours of randomization. The primary end point was all-cause mortality at 30 days, and was not significantly different in the medical therapy and revascularization groups (56.0% vs 46.7%, P = .11). However, mortality was significantly reduced in the revascularization group at 6 months and 1 year by an absolute 13% at both time points.
      • Hochman J.S.
      • Sleeper L.A.
      • Webb J.G.
      • et al.
      Early revascularization in acute myocardial infarction complicated by cardiogenic shock. SHOCK Investigators. Should We Emergently Revascularize Occluded Coronaries for Cardiogenic Shock.
      Based on these results, emergency revascularization in suitable patients with CS is recommended, irrespective of time delay.
      • O'Gara P.T.
      • Kushner F.G.
      • Ascheim D.D.
      • et al.
      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.
      The use of CABG surgery for CS was first reported in 1972.
      • Dunkman W.B.
      • Leinbach R.C.
      • Buckley M.J.
      • et al.
      Clinical and hemodynamic results of intraaortic balloon pumping and surgery for cardiogenic shock.
      In the SHOCK trial, one-third of the patients in the randomized early revascularization arm were treated with a surgical approach. Outcomes were similar to those treated with PCI.
      • Hochman J.S.
      • Sleeper L.A.
      • Webb J.G.
      • et al.
      Early revascularization in acute myocardial infarction complicated by cardiogenic shock. SHOCK Investigators. Should We Emergently Revascularize Occluded Coronaries for Cardiogenic Shock.
      However, rates of CABG surgery in the setting of CS are decreasing because of inherent time delays, increasingly favorable results with PCI, and the hesitancy of many surgeons to operate on patients with high operative mortality in the era of public reporting of surgical outcomes.
      • Thiele H.
      • Zeymer U.
      • Neumann F.J.
      • et al.
      Intraaortic balloon support for myocardial infarction with cardiogenic shock.
      • Bates E.R.
      Cardiogenic shock.
      In the recent Intraaortic Balloon Pump in CS (IABP-SHOCK II) trial (see later in this article), only 3% of patients with CS in the setting of AMI underwent immediate CABG surgery.
      • Thiele H.
      • Zeymer U.
      • Neumann F.J.
      • et al.
      Intraaortic balloon support for myocardial infarction with cardiogenic shock.

      Pharmacologic Therapy

      The major goals of pharmacologic therapy in CS are to maintain adequate arterial pressure and cardiac output to allow for adequate tissue perfusion and thereby maintain tissue viability. Unfortunately, both inotropes and vasopressors, although frequently required, increase myocardial oxygen demand and have other adverse effects on the failing heart. Not surprisingly, higher vasopressor doses are associated with worse outcomes, likely due to both more severe hemodynamic derangement as well as direct toxic effects.
      • Valente S.
      • Lazzeri C.
      • Vecchio S.
      • et al.
      Predictors of in-hospital mortality after percutaneous coronary intervention for cardiogenic shock.
      Therefore, the lowest possible doses should be used, and frequent adjustments should be made based on measured hemodynamic parameters.
      Randomized trial data informing the choice of vasoactive agents in CS are extremely limited. A recent multicenter trial randomized 1679 patients with shock of any cause to initial treatment with either dopamine or norepinephrine in a double-blind fashion. In the overall trial, there was no significant difference in mortality at 28 days. In a subgroup of 280 patients with CS, mortality was significantly higher among patients treated with dopamine; however, there was no significant interaction between treatment effect and shock subgroup, so this may be a chance finding within a small subgroup.
      • De Backer D.
      • Biston P.
      • Devriendt J.
      • et al.
      Comparison of dopamine and norepinephrine in the treatment of shock.
      The American College of Cardiology Foundation/American Heart Association (ACCF/AHA) guidelines no longer recommend the use of any particular agent(s), although they do note that the use of dopamine may be associated with excess hazard.
      • O'Gara P.T.
      • Kushner F.G.
      • Ascheim D.D.
      • et al.
      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.
      Therefore, until further trial data become available, treatment decisions must be based on clinical experience and individual hemodynamic profiles. Table 1 includes the pharmacologic effects of commonly used inotropic and vasopressor agents, as well as our recommendations regarding the clinical situations in which each of these may be used preferentially.
      Table 1Vasoactive agents in cardiogenic shock
      Vasoactive AgentMechanism of ActionPreferred Use
      DobutamineBeta-1 agonistTo increase cardiac output in an unstable patient when blood pressure is not critically low (systolic blood pressure ≥100 mm Hg).
      MilrinonePhosphodiesterase-3 inhibitorTo increase cardiac output in a patient who is not critically unstable and the blood pressure is not critically low.
      DopamineLow dose: Dopamine receptor agonist

      Beta-1 agonist

      High dose: Alpha agonist
      To increase cardiac output and blood pressure when the heart rate is not extremely high (≥100–110 beats per minute).
      NorepinephrineAlpha agonist

      Limited beta-1 agonist
      To increase blood pressure and cardiac output when the blood pressure is critically low (systolic blood pressure <90 mm Hg) and/or the heart rate is extremely high (>110 beats per minute).
      EpinephrineAlpha agonist

      Beta-1 agonist

      Beta-2 agonist
      To increase heart rate, contractility, and blood pressure in extremely critical situations (usually near cardiac arrest).
      IsoproterenolBeta-1 agonist

      Beta-2 agonist
      To increase heart rate when the blood pressure is not compromised (systolic blood pressure ≥120 mm Hg).
      PhenylephrineAlpha agonistTo increase blood pressure when it is critically low (systolic blood pressure <90 mm Hg) and myocardial contractility is not compromised. Not recommended in cardiogenic shock.

      IABP

      The IABP is the most widely used form of mechanical hemodynamic support in patients with CS. Introduced in the 1960s, the IABP consists of a balloon inserted into the descending aorta between the arch vessels and the renal arteries (Fig. 3A). The balloon inflates after cardiac ejection and deflates before the onset of the following systole. Balloon inflation displaces blood proximally (toward the heart), increasing coronary perfusion pressure and raising diastolic aortic pressure. Deflation of the balloon during systole reduces end-diastolic pressure and LV afterload. IABP use is associated with hemodynamic improvement, increased perfusion of vital organs, maintenance of infarct artery patency, and reduction in myocardial oxygen consumption.
      • O'Connor C.M.
      • Rogers J.G.
      Evidence for overturning the guidelines in cardiogenic shock.
      However, results of recent observational studies have been mixed with regard to the clinical benefit of IABP.
      • Taylor J.
      ESC guidelines on acute myocardial infarction (STEMI).
      Therefore, recommendations regarding the use of IABP in CS were recently downgraded from Class I (“is recommended”) to Class IIa (“can be useful”) in the ACCF/AHA guidelines and to Class IIb (“may be considered”) in the European Society of Cardiology guidelines.
      • O'Gara P.T.
      • Kushner F.G.
      • Ascheim D.D.
      • et al.
      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.
      • Taylor J.
      ESC guidelines on acute myocardial infarction (STEMI).
      Figure thumbnail gr3
      Fig. 3Schematic representation of selected mechanical circulatory support devices. (A) Intra-aortic balloon pump. (B) Impella Recover 2.5. (C) TandemHeart.
      (From Desai NR, Bhatt DL. Evaluating percutaneous support for cardiogenic shock: data shock and sticker shock. Eur Heart J 2009;30:2073–5; with permission.)
      After both of these guideline updates, however, the results of the IABP-SHOCK II trial were published. This multicenter randomized trial assigned 600 patients with CS complicating AMI to treatment with or without IABP. All patients were expected to undergo early revascularization and receive modern medical therapy. At 30 days, mortality was similar among patients in the IABP group and those in the control group (39.7% and 41.3%, P = .69). No subgroup could be identified in which IABP reduced short-term mortality. Fortunately, peripheral ischemic and bleeding complications were uncommon and not different between the groups. Potential limitations of the trial include a relatively small sample size, lower-than-expected mortality in the control group, and a 10% crossover rate to IABP in the control group.
      • Thiele H.
      • Zeymer U.
      • Neumann F.J.
      • et al.
      Intraaortic balloon support for myocardial infarction with cardiogenic shock.
      The impact of these results on clinical practice and authoritative guidelines is yet to be determined. Given the ease of implantation and the excellent safety profile of the IABP, however, it is likely that its use in CS will remain substantial. However, these disappointing results provide greater impetus to evaluate other forms of mechanical support in patients with refractory CS.

      Advanced Mechanical Circulatory Support

      Percutaneous LV assist devices

      In patients with CS who are refractory to standard therapy, it has been hypothesized that devices that provide greater mechanical circulatory support may lead to better clinical outcomes. Currently, 2 short-term percutaneously implanted ventricular assist devices (pVADs) are available that can be deployed in the catheterization laboratory. These are the TandemHeart (CardiacAssist, Inc, Pittsburgh, PA) and the Impella Recover 2.5 (Abiomed, Aachen, Germany) (see Fig. 3B, C).

      TandemHeart

      The TandemHeart consists of an external centrifugal blood pump, a 21-French inflow cannula placed into the left atrium via transseptal puncture, and a 17-French outflow cannula inserted into the femoral artery. This system provides 4 to 5 L per minute of flow to support the failing LV. Risks include leg ischemia and potentially catastrophic displacement of the inflow cannula into the right atrium.
      Initial trials confirmed the hemodynamic efficacy of the TandemHeart system. For example, Thiele and colleagues
      • Thiele H.
      • Lauer B.
      • Hambrecht R.
      • et al.
      Reversal of cardiogenic shock by percutaneous left atrial-to-femoral arterial bypass assistance.
      showed an improvement in cardiac index from 1.7 ± 0.3 L/min to 2.4 ± 0.6 L/min, mean arterial pressure from 63 ± 8 mm Hg to 80 ± 9 mm Hg, and pulmonary artery occlusion pressure (PAOP) from 21 ± 4 mm Hg to 14 ± 4 mm Hg in 18 patients. A later report from the Texas Heart Institute described the clinical course of 117 patients with refractory CS in whom the TandemHeart system was implanted. Patients were at extremely high risk, and half had undergone cardiopulmonary resuscitation before or at the time of device implantation. Survival to hospital discharge was 60% (50% in the STEMI subgroup).
      • Kar B.
      • Basra S.S.
      • Shah N.R.
      • et al.
      Percutaneous circulatory support in cardiogenic shock: interventional bridge to recovery.

      Impella recover 2.5

      The Impella Recover 2.5 consists of a catheter-based 12-French pump motor inserted via the femoral artery and positioned across the aortic valve. The pump pulls blood from the LV through an inlet area near the tip of the catheter, and expels blood into the proximal ascending aorta, providing up to 2.5 L/min of flow (see Fig. 3). Risks include leg ischemia and displacement of the catheter out of the LV. The device cannot be used in patients with aortic stenosis, aortic regurgitation, or a mechanical prosthetic aortic valve.
      Several small, early studies demonstrated significant hemodynamic improvements with the Impella Recover 2.5 system. For example, Meyns and colleagues
      • Meyns B.
      • Dens J.
      • Sergeant P.
      • et al.
      Initial experiences with the Impella device in patients with cardiogenic shock—Impella support for cardiogenic shock.
      reported on 16 patients with CS treated with this device. Improvements in cardiac output (4.1 ± 1.3 L/min to 5.9 ± 1.9 L/min), mean arterial pressure (57.4 ± 13 mm Hg to 80.6 ± 17 mm Hg), and PAOP (29 ± 10 mm Hg to 18 ± 7 mm Hg) were seen after 6 hours of support. More recently, a report from a prospective European registry in 120 consecutive patients showed that plasma lactate decreased from 5.8 ± 5.0 mmol/L on admission to 2.5 ± 2.6 mmol/L at 48 hours.
      • Lauten A.
      • Engstrom A.E.
      • Jung C.
      • et al.
      Percutaneous left-ventricular support with the Impella-2.5-assist device in acute cardiogenic shock: results of the Impella-EUROSHOCK-registry.

      Randomized trials of pVADs

      Notwithstanding encouraging preliminary studies and clear improvements in hemodynamics with each of these pVADs, randomized controlled trials versus IABP are required to prove a clinical benefit in the setting of CS. Three such trials have been conducted to date (2 with the TandemHeart and 1 with the Impella Recover 2.5).
      • Thiele H.
      • Sick P.
      • Boudriot E.
      • et al.
      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.
      • Burkhoff D.
      • Cohen H.
      • Brunckhorst C.
      • et al.
      A randomized multicenter clinical study to evaluate the safety and efficacy of the TandemHeart percutaneous ventricular assist device versus conventional therapy with intraaortic balloon pumping for treatment of cardiogenic shock.
      • Seyfarth M.
      • Sibbing D.
      • Bauer I.
      • et al.
      A randomized clinical trial to evaluate the safety and efficacy of a percutaneous left ventricular assist device versus intra-aortic balloon pumping for treatment of cardiogenic shock caused by myocardial infarction.
      A meta-analysis of these trials included a total of 100 patients. The pVADs provided superior hemodynamic support when compared with IABP. However, 30-day survival was similar in the pVAD and IABP groups (55% vs 57%, relative risk 1.06, 95% confidence interval 0.68–1.66, P = .8). In addition, the IABP had a better safety profile, whereas the pVADs were associated with higher equipment costs.
      • Cheng J.M.
      • den Uil C.A.
      • Hoeks S.E.
      • et al.
      Percutaneous left ventricular assist devices vs intra-aortic balloon pump counterpulsation for treatment of cardiogenic shock: a meta-analysis of controlled trials.
      Based on these disappointing results, the current ACCF/AHA guidelines provide only a IIb recommendation (“may be considered”) for the use of alternative LV assist devices for patients with refractory CS.
      • O'Gara P.T.
      • Kushner F.G.
      • Ascheim D.D.
      • et al.
      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.

      Extracorporeal membrane oxygenation

      Veno-arterial (V-A) extracorporeal membrane oxygenation (ECMO) also can be used to support the circulation in patients with CS. The ECMO circuit consists of a centrifugal blood pump, a heater, and a membrane oxygenator. ECMO can be deployed centrally via a sternotomy, or much more rapidly via percutaneously inserted cannulae placed in the right atrium (via the femoral vein) and the descending aorta (via the femoral artery). Flow of approximately 4 L/min can be established quickly and maintained for up to several weeks. Pulmonary support for hypoxic patients is also provided. Complications include limb ischemia, a systemic inflammatory response, and bleeding.
      The use of V-A ECMO provides rapid hemodynamic stabilization and resolution of organ dysfunction due to hypoperfusion. Patients presenting with cardiac arrest can be allowed time to demonstrate neurologic recovery. This period of support can be used to bridge a patient to myocardial recovery, LV assist device implantation, or cardiac transplantation. For example, Tang and colleagues
      • Tang G.H.
      • Malekan R.
      • Kai M.
      • et al.
      Peripheral venoarterial extracorporeal membrane oxygenation improves survival in myocardial infarction with cardiogenic shock.
      recently reported their experience with 21 consecutive patients with CS following AMI, all of whom failed initial therapy with an IABP or Impella Recover 2.5. ECMO support was maintained for 9.0 ± 7.5 days (range 1–25 days). Two patients were bridged to LVAD and subsequent transplantation, whereas 14 were able to be weaned from ECMO. Survival at 30 days was a remarkable 76%. This and other reports suggest that ECMO may be a reasonable management option for patients with refractory CS, but to date, compelling clinical evidence is lacking and no randomized trials have been conducted.

      CentriMag

      The CentriMag VAD (Thoratec, Pleasanton, CA) is a surgically implanted centrifugal pump with a magnetically levitated rotor that can provide up to 10 L/min of blood flow. For LV support, the inlet cannula is placed in the LV apex and the outlet cannula delivers blood to the ascending aorta. The pump is highly reliable, and support durations of up to 3 months have been reported.
      • Slaughter M.S.
      • Tsui S.S.
      • El-Banayosy A.
      • et al.
      Results of a multicenter clinical trial with the Thoratec Implantable Ventricular Assist Device.
      Left, right, or biventricular support can be established with 1 or 2 CentriMag devices. In a recent multicenter report, 38 patients with CS (14 post-AMI) were supported for 1 to 60 days (mean, 13 days). Survival at 30 days following device removal was 47%. Complications were relatively uncommon, and included bleeding, infection, and neurologic dysfunction.
      • John R.
      • Long J.W.
      • Massey H.T.
      • et al.
      Outcomes of a multicenter trial of the Levitronix CentriMag ventricular assist system for short-term circulatory support.
      No randomized trials involving CentriMag implantation in patients with CS have yet been conducted.

      Mechanical complications of AMI

      Although CS is usually associated with poor LV contractility, there are several special situations in which the cardiac cause of shock is related to a disruption in the heart’s anatomy.

      Free Wall Rupture

      LV free wall rupture is a rare complication of AMI, occurring in 1% to 3% of patients.
      • Hochman J.S.
      • Buller C.E.
      • Sleeper L.A.
      • et al.
      Cardiogenic shock complicating acute myocardial infarction—etiologies, management and outcome: a report from the SHOCK Trial Registry. Should we emergently revascularize Occluded Coronaries for cardiogenic shocK?.
      In the SHOCK trial registry, free wall rupture accounted for 1.4% of cases of CS.
      • Slater J.
      • Brown R.J.
      • Antonelli T.A.
      • et al.
      Cardiogenic shock due to cardiac free-wall rupture or tamponade after acute myocardial infarction: a report from the SHOCK Trial Registry. Should we emergently revascularize occluded coronaries for cardiogenic shock?.
      Free wall rupture usually presents in catastrophic fashion, with recurrent chest pain followed by pulseless electrical activity and death. However, a minority of patients survive the initial rupture, in which case, salvage is possible if the diagnosis is made rapidly. Most commonly, bedside echocardiography is used, which demonstrates a significant pericardial effusion containing echodense material consistent with blood. The actual rupture site is rarely identified, but contrast echocardiography may reveal passage of contrast into the pericardial space and thereby confirm the diagnosis.
      • Mittle S.
      • Makaryus A.N.
      • Mangion J.
      Role of contrast echocardiography in the assessment of myocardial rupture.
      Hemodynamic stability can be restored with pericardiocentesis, with or without percutaneous cardiopulmonary support (ie, ECMO).
      • Abedi-Valugerdi G.
      • Gabrielsen A.
      • Fux T.
      • et al.
      Management of left ventricular rupture after myocardial infarction solely with ECMO.
      • Anastasiadis K.
      • Antonitsis P.
      • Hadjimiltiades S.
      • et al.
      Management of left ventricular free wall rupture under extracorporeal membrane oxygenation support.
      Subsequently, prompt surgical repair of the rupture site is essential. A recent report of 25 consecutive patients with postinfarction free wall rupture operated on at a single center demonstrated a remarkable 84% survival at 6 months.
      • Zoffoli G.
      • Battaglia F.
      • Venturini A.
      • et al.
      A novel approach to ventricular rupture: clinical needs and surgical technique.

      Ventricular Septal Rupture

      The incidence of ventricular septal rupture has decreased to less than 1% in the reperfusion era, with the rupture generally occurring within 24 hours of presentation with STEMI.
      • Gueret P.
      • Khalife K.
      • Jobic Y.
      • et al.
      Echocardiographic assessment of the incidence of mechanical complications during the early phase of myocardial infarction in the reperfusion era: a French multicentre prospective registry.
      An international randomized trial comparing four thrombolytic strategies for acute myocardial infarction. The GUSTO investigators.
      • Yip H.K.
      • Fang C.Y.
      • Tsai K.T.
      • et al.
      The potential impact of primary percutaneous coronary intervention on ventricular septal rupture complicating acute myocardial infarction.
      The rupture may be apical and simple or posterobasal and complex. Diagnosis is made with echocardiography. Postinfarction ventricular septal rupture produces a sudden left-to-right shunt, which frequently results in profound heart failure or frank CS. Temporization may be approached with vasodilators, inotropes, and IABP support. In medically treated patients, however, mortality rates exceed 90%.
      • Crenshaw B.S.
      • Granger C.B.
      • Birnbaum Y.
      • et al.
      Risk factors, angiographic patterns, and outcomes in patients with ventricular septal defect complicating acute myocardial infarction. GUSTO-I (Global Utilization of Streptokinase and TPA for Occluded Coronary Arteries) Trial Investigators.
      Surgical repair, although carrying a very high mortality rate, is associated with improved results. For example, in a recent report on 2876 consecutively operated patients with postinfarction ventricular septal rupture from the Society of Thoracic Surgeons National Database, survival to 30 days was 48.1%.
      • Arnaoutakis G.J.
      • Zhao Y.
      • George T.J.
      • et al.
      Surgical repair of ventricular septal defect after myocardial infarction: outcomes from the Society of Thoracic Surgeons National Database.
      For this reason, emergency surgical repair is currently recommended in the ACCF/AHA guidelines.
      • O'Gara P.T.
      • Kushner F.G.
      • Ascheim D.D.
      • et al.
      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.
      However, earlier surgical repair is technically more challenging because of the presence of friable tissues and is associated with higher mortality than delayed repair.
      • Arnaoutakis G.J.
      • Zhao Y.
      • George T.J.
      • et al.
      Surgical repair of ventricular septal defect after myocardial infarction: outcomes from the Society of Thoracic Surgeons National Database.
      Therefore, support with percutaneous LVAD or ECMO for several days to allow for tissue healing before surgery may be an alternative approach.
      • Tsai M.T.
      • Wu H.Y.
      • Chan S.H.
      • et al.
      Extracorporeal membrane oxygenation as a bridge to definite surgery in recurrent postinfarction ventricular septal defect.
      • Rohn V.
      • Spacek M.
      • Belohlavek J.
      • et al.
      Cardiogenic shock in patient with posterior postinfarction septal rupture—successful treatment with extracorporeal membrane oxygenation (ECMO) as a ventricular assist device.
      • Gregoric I.D.
      • Bieniarz M.C.
      • Arora H.
      • et al.
      Percutaneous ventricular assist device support in a patient with a postinfarction ventricular septal defect.
      Recently, successful transcatheter closure using septal occluder devices in selected patients has been reported.
      • Assenza G.E.
      • McElhinney D.B.
      • Valente A.M.
      • et al.
      Transcatheter closure of post-myocardial infarction ventricular septal rupture.

      Papillary Muscle Rupture

      Papillary muscle rupture leading to acute, severe mitral regurgitation occurs in approximately 1% of patients with AMI and accounted for 6.9% of cases of CS in the SHOCK trial registry.
      • Gueret P.
      • Khalife K.
      • Jobic Y.
      • et al.
      Echocardiographic assessment of the incidence of mechanical complications during the early phase of myocardial infarction in the reperfusion era: a French multicentre prospective registry.
      • Thompson C.R.
      • Buller C.E.
      • Sleeper L.A.
      • et al.
      Cardiogenic shock due to acute severe mitral regurgitation complicating acute myocardial infarction: a report from the SHOCK Trial Registry. Should we use emergently revascularize Occluded Coronaries in cardiogenic shocK?.
      This complication is more likely to occur in inferoposterior MI than in anterior MI because of the single blood supply from the posterior descending artery to the posteromedial papillary muscle. The presentation is similar to ventricular septal rupture, and the diagnosis is readily made with echocardiography. Treatment consists of vasodilation, inotropic support, and IABP, followed by urgent mitral valve repair, or more commonly, replacement. In patients undergoing urgent surgical intervention, 30-day survival rates of 61% to 82% have been reported in recent case series.
      • Schroeter T.
      • Lehmann S.
      • Misfeld M.
      • et al.
      Clinical outcome after mitral valve surgery due to ischemic papillary muscle rupture.
      • Russo A.
      • Suri R.M.
      • Grigioni F.
      • et al.
      Clinical outcome after surgical correction of mitral regurgitation due to papillary muscle rupture.

      RV infarction

      Hemodynamically significant RV infarction occurs as a result of occlusion of the right coronary artery proximal to the acute marginal branches, complicating 10% to 15% of cases of acute inferior STEMI. Acute RV dysfunction leads to decreased LV preload, decreased cardiac output, and, when profound, CS. In the SHOCK trial registry, RV infarction accounted for 2.8% of cases of CS.
      • Hochman J.S.
      • Buller C.E.
      • Sleeper L.A.
      • et al.
      Cardiogenic shock complicating acute myocardial infarction—etiologies, management and outcome: a report from the SHOCK Trial Registry. Should we emergently revascularize Occluded Coronaries for cardiogenic shocK?.
      The diagnosis is suggested clinically by the classic trial of hypotension, clear lung fields, and elevated jugular venous pressure. Although ST segment elevation in the right-sided electrocardiographic leads (V3R and V4R) has a high sensitivity for the presence of RV infarction, this finding does not predict the magnitude of RV dysfunction. Echocardiography is much more reliable in this regard.
      • Goldstein J.A.
      Acute right ventricular infarction.
      Following reperfusion therapy, RV preload should be optimized by monitoring the central venous pressure and assessing the response of cardiac output to volume challenges. In RV infarction, cardiac output becomes highly sensitive to both heart rate and atrioventricular synchrony. Therefore, patients with significant bradycardia may require atrially based pacing and tachyarrhythmias should be treated with prompt cardioversion. Hemodynamic support with inotropes, particularly dobutamine, should be initiated if shock persists. The role of IABP in RV infarction is uncertain, but counterpulsation may improve both RV and LV function by augmenting coronary perfusion. Recent reports suggest that temporary percutaneous or surgical right ventricular assist devices (RVADs) may provide a bridge to recovery in severely compromised patients.
      • Prutkin J.M.
      • Strote J.A.
      • Stout K.K.
      Percutaneous right ventricular assist device as support for cardiogenic shock due to right ventricular infarction.
      • Marquez T.T.
      • D'Cunha J.
      • John R.
      • et al.
      Mechanical support for acute right ventricular failure: evolving surgical paradigms.
      • Kiernan M.S.
      • Krishnamurthy B.
      • Kapur N.K.
      Percutaneous right ventricular assist via the internal jugular vein in cardiogenic shock complicating an acute inferior myocardial infarction.
      Most patients with RV infarction will have spontaneous recovery of RV function, although this may occur slowly. Therefore, aggressive support to prevent early death and irreversible organ failure often results in favorable long-term outcomes.

      Future directions

      Comparative Effective Research

      Although there are multiple treatment options available for patients with CS, few have been subjected to adequately powered clinical trials, leaving clinicians with little solid evidence on which to base their treatment decisions. Given the very high event rate in this population, definitive comparative effectiveness trials of existing therapies could be performed with relatively small sample sizes. A consortium of high-volume centers, rapidly cycling though a series of focused, pragmatic trials, would likely bring about dramatic progress in this field. Because of the enormous implications of CS for the public health, federal funding of such an effort should be a priority.

      Novel Therapies

      Anti-inflammatory therapies

      In terms of novel therapies for CS, many opportunities present themselves for further investigation. In the sizable subset of patients with a demonstrable systemic inflammatory response, therapies targeting specific inflammatory mediators, such as IL-6 and TNF-α, might prove to be of benefit. Alternatively, more general inhibitors of inflammation could be investigated, in a manner analogous to the role of corticosteroids in septic shock.
      • Shpektor A.
      Cardiogenic shock: the role of inflammation.

      NO inhibition

      The role of NO overproduction as a result of induction of iNOS by inflammatory stimuli in the setting of CS remains unresolved. However, the Tilarginine Acetate Injection in a Randomized International Study in Unstable Acute Myocardial Infarction Patients with CS (TRIUMPH) trial did not show a benefit of nonselective NO synthase inhibition in a relatively unselected group of patients with CS.
      • Alexander J.H.
      • Reynolds H.R.
      • Stebbins A.L.
      • et al.
      Effect of tilarginine acetate in patients with acute myocardial infarction and cardiogenic shock: the TRIUMPH randomized controlled trial.
      Further work characterizing the role of NO in CS is required, but it is possible that earlier initiation of therapy, more selective inhibition of iNOS, or the targeting of therapy to patients with the highest degree of iNOS activation may result in greater therapeutic efficacy.
      • Bailey A.
      • Pope T.W.
      • Moore S.A.
      • et al.
      The tragedy of TRIUMPH for nitric oxide synthesis inhibition in cardiogenic shock: where do we go from here?.

      Therapeutic hypothermia

      Therapeutic hypothermia has recently been proposed as a possible systemic treatment for CS.
      • Stegman B.M.
      • Newby L.K.
      • Hochman J.S.
      • et al.
      Post-myocardial infarction cardiogenic shock is a systemic illness in need of systemic treatment: is therapeutic hypothermia one possibility?.
      This widely available treatment decreases the metabolic rate and oxygen consumption, limits reperfusion injury in the heart and other organs, and may reduce infarct size.
      • Gotberg M.
      • Olivecrona G.K.
      • Koul S.
      • et al.
      A pilot study of rapid cooling by cold saline and endovascular cooling before reperfusion in patients with ST-elevation myocardial infarction.
      Furthermore, hypothermia reduces the production of multiple proinflammatory cytokines (Fig. 4).
      • Polderman K.H.
      Application of therapeutic hypothermia in the intensive care unit. Opportunities and pitfalls of a promising treatment modality—Part 2: practical aspects and side effects.
      In a case series of 10 adult patients with post cardiac surgery CS refractory to medical therapy, moderate hypothermia was associated with improved hemodynamics and an unexpectedly high survival rate.
      • Yahagi N.
      • Kumon K.
      • Watanabe Y.
      • et al.
      Value of mild hypothermia in patients who have severe circulatory insufficiency even after intra-aortic balloon pump.
      In another study, moderate hypothermia was associated with increased cardiac index and mean arterial pressure in 28 patients with CS following cardiac arrest.
      • Skulec R.
      • Kovarnik T.
      • Dostalova G.
      • et al.
      Induction of mild hypothermia in cardiac arrest survivors presenting with cardiogenic shock syndrome.
      Further investigation of this therapy in CS is therefore clearly warranted.
      Figure thumbnail gr4
      Fig. 4Pathways potentially affected by therapeutic hypothermia. SV, stroke volume.
      (From Stegman BM, Newby KL, Hochman JS, et al. Post-myocardial infarction cardiogenic shock is a systemic illness in need of systemic treatment: is therapeutic hypothermia one possibility? J Am Coll Cardiol 2012;59:646; with permission.)

      Mechanical circulatory support

      Recent advances in mechanical circulatory support have been impressive but require further improvement. Surgically implanted systems provide high flow rates but are limited by the invasiveness of the procedure and the significant risk of postoperative complications. Current percutaneous devices are safer and simpler to implant but provide limited flows. Next-generation percutaneously implanted support devices that aim to be simple to implant and maintain, have low complication rates, and provide high flow rates are currently under development.
      • Kar B.
      • Basra S.S.
      • Shah N.R.
      • et al.
      Percutaneous circulatory support in cardiogenic shock: interventional bridge to recovery.

      Summary

      CS is a condition in which a marked reduction in cardiac output and inadequate end-organ perfusion results from an array of cardiac insults, the most common of which is AMI. CS is a systemic disease involving a vicious cycle of inflammation, ischemia, and progressive myocardial dysfunction, which often results in death. This life-threatening emergency requires intensive monitoring accompanied by aggressive hemodynamic support with vasopressors, inotropes, and/or mechanical circulatory support. Other therapies are tailored to the specific pathophysiology, including urgent revascularization for AMI and surgical repair for mechanical disruption. The development of novel therapeutic strategies is urgently required to reduce the unacceptably high mortality rates currently associated with CS.

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