Clinical review: mechanical circulatory support for cardiogenic shock complicating acute myocardial infarction
© BioMed Central Ltd 2010
Published: 14 October 2010
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© BioMed Central Ltd 2010
Published: 14 October 2010
Acute myocardial infarction is one of the 10 leading reasons for admission to adult critical care units. In-hospital mortality for this condition has remained static in recent years, and this is related primarily to the development of cardiogenic shock. Recent advances in reperfusion therapies have had little impact on the mortality of cardiogenic shock. This may be attributable to the underutilization of life support technology that may assist or completely supplant the patient's own cardiac output until adequate myocardial recovery is established or long-term therapy can be initiated. Clinicians working in the intensive care environment are increasingly likely to be exposed to these technologies. The purpose of this review is to outline the various techniques of mechanical circulatory support and discuss the latest evidence for their use in cardiogenic shock complicating acute myocardial infarction.
The in-hospital mortality for acute myocardial infarction (AMI) is currently around 7% . Death is related predominantly to the development of cardiogenic shock, which affects 5% to 10% of all cases of AMI and has a mortality rate of 50% to 90% [2, 3]. Patients who develop cardiogenic shock frequently require critical care services, and AMI is one of the 10 leading causes for admission to adult critical care units . Over the past three decades, revascularization therapy has revolutionized care for these patients. Recent studies support prompt percutaneous coronary intervention (PCI) when there is electrocardiographic evidence of an AMI , and if PCI is not available within 90 minutes, fibrinolysis should be delivered within 30 minutes [6, 7].
Despite these developments, there has been little progress in reducing mortality from cardiogenic shock complicating an AMI . Part of the reason for this is that impaired cardiac contractility may persist many hours after revascularization, an observation described as myocardial stunning . Interventions that can assist or completely supplant the patient's own cardiac output may support these patients until the stunned myocardium recovers (bridge to recovery). Recovery can be predicted using peak serum creatinine kinase levels  or contrast echocardiography , but even when recovery does not occur, mechanical circulatory support may provide time to determine whether longer- term therapies are appropriate (bridge to decision). In this review, we will outline the various techniques of mechanical circulatory support and discuss the evidence for their use in cardiogenic shock complicating AMI.
Cardiogenic shock criteria
Systolic blood pressure (SBP) of less than 90 mm Hg for greater than 30 minutes
SBP drop of greater than 30 mm Hg below basal for greater than 30 minutes in patients with hypertension
Use of vasopressors and inotropes to keep SBP greater than 90 mm Hg
Cardiac index of less than 2.2 L/min per m2
Pulmonary artery occlusion pressure of greater than 15 mm Hg
Signs of tissue hypoperfusion
Pale, cool, and clammy peripheries
Prolonged capillary refill times
Altered mental status/confusion
Mixed venous saturation of less than 65%
Inflation timing is determined using either the electrocardiogram or the arterial pressure waveform. In the latest devices, inflation timing can be controlled with a physiologic timing algorithm that predicts aortic valve closure. When combined with R wave or pressure predictive deflation, this method maintains balloon synchrony even in patients with severe tachyarrhythmias .
As well as providing improved synchrony, modern IABPs have reduced vascular complications. Data from the Benchmark registry, which has collected outcomes for over 37,000 patient episodes , demonstrate that smaller (8 to 9.5 French) catheter sheaths have reduced the total complication rate to 2.6% and cut major complications, including limb, bowel, and renal ischemia, to under 0.5%. As a result, mortality directly attributable to IABP use is currently less than 0.05% . Owing to a higher risk of limb ischemia, these devices, even with smaller catheters, should be used cautiously in patients with severe peripheral vascular disease. IABPs are not suitable for all patients and are specifically contra-indicated in those with severe aortic regurgitation, aortic dissection, or large aneurysms.
Attempts to study IABP use in cardiogenic shock have been affected by poor recruitment. This may reflect the difficulty of obtaining timely consent and randomization in the critically ill. For example, the SMASH (Swiss Multicenter Evaluation of Early Angioplasty for Shock Following Myocardial Infarction) study was stopped after recruiting only 55 patients during a 4-year period . Similarly, the TACTICS (Thrombolysis and Counter-pulsation to Improve Survival in Myocardial Infarction Complicated by Hypotension and Suspected Cardiogenic Shock) trial was stopped after 3 years when only 57 out of a planned 538 patients were randomly assigned .
Mortality evidence supporting intra-aortic balloon pump use in cardiogenic shock complicating an acute myocardial infarction
O'Rourke et al.  (1981)
Flaherty et al.  (1985)
Kovack et al.  (1997)
GUSTO-I  (1997)
SHOCK  (2000)
NRMI-2  (2001)
Reperfusion by PCI
NRMI-2  (2001)
In 1997, Kovack and colleagues  demonstrated that patients who developed cardiogenic shock complicating an AMI were twice as likely to survive when an IABP was used in conjunction with pharmocological reperfusion strategies (Table 2). In the same year, the GUSTO-I (Global Utilization of Streptokinase and Tissue Plasmino-gen Activator for Occluded Coronary Arteries) trial reported that early IABP use was associated with a trend toward lower 30-day (47% versus 60%; P = 0.06) and 1-year (57% versus 67%; P = 0.04) mortality rates in patients who presented with cardiogenic shock complicating an AMI . Analysis of the larger SHOCK (Should We Emergently Revascularize Occluded Coronary Arteries for Cardiogenic Shock) trial (1,190 patients) confirmed this benefit, demonstrating statistically significant lower in-hospital mortality for cardiogenic shock patients who received IABP verses those who did not (50% versus 72%; P ≤0.0001) . However, a significant confounding factor in these studies was a higher number of revascularization procedures in the IABP group.
To eliminate confounding, the SHOCK data were re-evaluated comparing IABP plus fibrinolysis with fibrinolysis alone. In this analysis, in-hospital mortality was still improved by 25% (47% versus 63%; P = 0.007) . A similar benefit was observed in the larger National Registry of Myocardial Infarction 2 (NRMI-2) (n = 23,180 patients), in which the use of IABP as an adjunct to fibrinolysis, in cardiogenic shock, reduced in-hospital odds of death by 18% (odds ratio (OR) 0.82, 95% confidence interval (CI) 0.72 to 0.93) . A recent meta-analysis by Sjauw and colleagues  demonstrated that this benefit remains statistically significant beyond the in-hospital period, with an absolute decrease in 30-day mortality of 18% (95% CI 16% to 20%; P < 0.0001).
IABP benefits are less clear for cardiogenic shock patients who undergo primary PCI. In the SHOCK trial, revascularization with PCI resulted in a significant reduction of mortality when compared with medical therapy, including fibrinolysis. Importantly, IABP use was 86% in both groups, and mortality in the medical therapy group was lower than expected . This suggests that IABP plus medical therapy may result in lower mortality and that IABP plus PCI further improves mortality. In contrast, the NRMI-2 study observed that IABP as an adjunct to primary PCI resulted in a higher mortality (OR 1.27, 95% CI 1.07 to 1.50) in patients with cardiogenic shock complicating an AMI . This negative association is also evident in the recent meta-analysis by Sjauw and colleagues . However, for this part of their analysis, only two registries were used: the NRMI-2 study and the data of Sjauw and colleagues. In the absence of randomization, the trend may be confounded since patients receiving both PCI and an IABP in the NRMI-2 study were more likely to have cardiogenic shock complicated by previous PCI (OR 1.85, CI 1.64 to 2.09) and experience an inter-hospital transfer (OR 2.57, CI 2.40 to 2.75) .
A more recent study that randomly assigned patients with AMI complicated by cardiogenic shock to either IABP plus PCI or PCI alone did not demonstrate significant improvement in APACHE II (Acute Physiology and Chronic Health Evaluation II) scores or mortality over the first 4 days of admission (36.8% in the IABP group versus 28.6%) . However, this study was not powered to assess mortality. Large randomized clinical trials are required to resolve this issue and address whether the current American Heart Association and American College of Cardiology guidelines recommending PCI and IABP in the setting of cardiogenic shock complicating AMI require revision . In the meantime, we recommend IABP use in any patient meeting the criteria for cardiogenic shock in the setting of an AMI when inotrope therapy has been initiated, whether the patient has received PCI or thrombolysis or neither. IABPs are more widely available than more complex forms of mechanical circulatory support, have a low complication rate, and decrease myocardial oxygen demand. IABPs should be routinely available at centers treating patients with AMI.
When there is evidence of inadequate tissue oxygen delivery despite IABP, invasive ventilation, and inotropes, full circulatory support should be considered. Extracor-poreal membrane oxygenation (ECMO) can subsume the function of both heart and lungs and was first successfully used in adults in 1972 . De-oxygenated blood is removed from the body, pumped through an artificial oxygenator, and returned to the circulation. Modern oxygenators consist of multiple, small hollow fibers lined with polymethylpentene and allow gas but not liquid transfer. Oxygen and carbon dioxide exchange is achieved as blood runs through the center of the fibers and an oxygen/air mix flows on the outside. Blood flow is generated by a centrifugal pump, where a rotating impeller spins blood outwards, creating centrifugal acceleration. Since no compression is involved, high flow rates can be generated with minimal trauma to blood components.
Peripheral ECMO is less invasive, is easier to place, and can be placed percutaneously by surgeons or intensivists. It can be initiated quickly, making it more appropriate in emergencies. However, the cardiac output of the failing heart competes with retrograde ECMO flow from the femoral aortic cannula, producing admixing in the thoracic aorta and an increase in left ventricular wall tension. If there is concomitant respiratory failure, this can result in the delivery of inadequately oxygenated blood to the coronary and cerebral circulations and hinder recovery . Central ECMO is not associated with this problem but is slower to initiate and may have a higher complication rate with bleeding and infection. It is usually confined to the support of patients after surgical revascularization. Peripheral VA-ECMO is adequate for most forms of cardiogenic shock, but frequent echo-cardiography is necessary to monitor for progressive ventricular dilatation. If this develops, the left atrium can be vented either by changing the ECMO circuit configuration or by performing a percutaneous atrial septostomy [35–37].
VA-ECMO is associated with bleeding in 30% to 60% of cases [38, 39], sometimes requiring massive transfusions. New pumps and improved circuit biocompatibility allow lower levels of anticoagulation to be used and should reduce the impact of this complication. Clotting abnor-malities predispose to hemorrhagic stroke, which, combined with circuit embolic complications such as air bubbles or clots, results in an overall stroke rate of 3% to 12% [33, 40, 41]. Other complications include nosocomial infection in 50% to 60% [40, 41] and multi-organ dysfunction in 33% , although the contribution of ECMO is not easy to separate from the complications of severe critical illness. Device and circuit complications appear to be declining .
Evidence supporting extracorporeal membrane oxygenation use in cardiogenic shock complicating an acute myocardial infarction
Cardiogenic shock etiology
Golding et al.  (1992)
Muehrcke et al.  (1996)
Magovern et al.  (1999)
UA or CHF
Formica et al.  (2008)
Combes et al.  (2008)
ELSO  (2009)
The variable survival rates reflect that fact these are small single-center studies. The Extracorporeal Life Support Organization (ELSO) registry addresses this limitation by recording the experience of over 170 ECMO centers worldwide. ELSO has accumulated data on over 40,000 ECMO cases, of whom approximately 3,000 are adults. In 2009, ELSO reported a survival rate of 39% for adult cardiogenic shock .
Contraindications to full mechanical circulatory support
Prolonged cardiopulmonary resuscitation with inadequate perfusion
Existing organ dysfunction
Advanced chronic obstructive pulmonary disease
Interstitial lung disease
Previous stroke with significant disability
End-stage renal failure (relative)
Contraindication to anticoagulation (relative)
Contraindication to transplant (relative)
Classification of ventricular assist devices
TandemHeart (CardiacAssist, Inc., Pittsburgh, PA, USA)
Impella 2.5L (Abiomed, Aachen, Germany)
Impella 5L (Abiomed)
CentriMag (Levitronix LLC, Waltham, MA, USA)
Bio-Medicus (Eden Prairie, MN, USA)
DeltaStream (Medos Medizintechnik AG, Stolberg, Germany)
HeartMate II (Thoratec Corporation, Pleasanton, CA, USA)
Jarvik 2000 (Jarvik Heart Inc., New York, NY) and Incor(Berlin Heart AG, Berlin, Germany)
HeartAssist 5 (MicroMed Cardiovascular, Inc., Houston, TX, USA) and DuraHeart (Terumo Heart Inc., Ann Arbor, MI, USA)
In acute cardiogenic shock complicating an MI, percutaneous LVADs (pLVADs) hold the most promise. They can be initiated quickly and do not require a sternotomy. The two most studied devices are the TandemHeart (CardiacAssist, Inc., Pittsburgh, PA, USA) and Impella (Abiomed, Aachen, Germany).
Comparative data of studies into ventricular assist device use in cardiogenic shock complicating an acute myocardial infarction.
Δ Cardiac output, L/min
30-day survival, percentage
Thiele et al.  (2005)
Burkhoff et al.  (2006)
Seyfarth et al.  (2008)
John et al.  (2007)
Titrated for cardiac index > 2.2 L/min per m2
When these three studies are combined in a meta-analysis, it is still not possible to detect a mortality benefit . However, it is arguable that an overall number of 100 patients is still too small. In addition to offering no clear survival benefits, pLVADs provide only left ventricular support. Thus, they are inappropriate for cardiogenic shock due to right ventricular ischemia, and although successful cases of percutaneous right ventricular assist [56, 57] and even biventricular assist  have been reported, they required substantial modification of existing technology. Despite this, the improved hemo-dynamics are impressive and percutaneous devices are set to become increasingly important in the management of acute cardiogenic shock [59, 60], especially if larger studies demonstrate that these hemodynamic benefits translate into significant survival benefits.
In the acute setting of cardiogenic shock complicating AMI, surgical VAD placement has proven to be challenging. The additional trauma of surgery com-pounds the multi-organ dysfunction and coagulopathy associated with extracorporeal circuits. However, third-generation pumps have been successfully surgically placed in the acute setting by means of cannulas tunneled through the chest wall. In one study, the Centrimag (Levitronix LLC, Waltham, MA, USA) was used to provide temporary BiVAD for 12 patients presenting with refractory shock following AMI. Eight patients were successfully bridged to an implantable VAD, and two patients recovered allowing device explantation. Overall 1-year survival was 62.5% .
Implantable VADs allow patients to be discharged home, providing a bridge to transplant, bridge to recovery, or destination therapy. Destination therapy is particularly attractive since transplant demand greatly exceeds donor availability. Studies in the last decade have demonstrated that implantable pulsatile LVADs are superior to medical therapy in end-stage heart failure patients who are ineligible for a transplant [62, 63]. Recently, it was demonstrated that third-generation devices result in decreased mortality and greater reliability when compared with pulsatile LVADs .
VADs are susceptible to complications similar to those experienced with ECMO. Neurological insults affect 4% to 12% of patients, infection 20% to 30%, and bleeding 30% to 40% [52, 53, 65]. Device malfunction rates are improving; over a 2-year period, less than 10% of implantable third-generation pumps require replacement .
The decision to initiate VAD therapy should be made under the same circumstances as those described above for ECMO. The precise modality chosen depends on institutional experience and patient factors. For isolated left ventricular failure, with minimal respiratory disturbance, a pLVAD may be sufficient. Where there is concomitant respiratory failure or high ventilatory settings or when biventricular support is desired through a percutaneous approach, ECMO is more appropriate (Figure 3). Occasionally, the two may be used together . In patients between these extremes, the factors of institutional experience, likelihood of recovery, and whether surgical revascularization is required will dictate choice. Finally, pursuing this technology is not without controversy in terms of resource allocation and ethics . These issues vary substantially depending on healthcare infrastructure, financing sources, and donor (as well as blood product) availability.
When cardiogenic shock complicating AMI is refractory to medical therapy, the only options available for survival are mechanical support strategies. Mechanical support can be applied in a stepwise progression starting with IABP support, followed by either ECMO or an LVAD. In the acute setting, these devices may provide circulatory support until the benefits of revascularization are realized. In the event that weaning is not possible, these devices serve as a bridge to decision or transplant. In patients who are ineligible for transplant, implantable VADs hold the promise of viable destination therapy.
acute myocardial infarction
biventricular assist device
extracorporeal membrane oxygenation
Extracorporeal Life Support Organization
intra-aortic balloon pump
left ventricular assist device
National Registry of Myocardial Infarction 2
percutaneous coronary intervention
percutaneous left ventricular assist device
Should We Emergently Revascularize Occluded Coronary Arteries for Cardiogenic Shock
ventricular assist device
veno-arterial extracorporeal membrane oxygenation
veno-venous extracorporeal membrane oxygenation