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Usefulness of Intra-aortic Balloon Pump Counterpulsation

Lokien X. van Nunen, MDa, Marko Noc, MD, PhDb, Navin K. Kapur, MDc, Manesh R. Patel, MDd,Divaka Perera, MDe, and Nico H.J. Pijls, MD, PhDa,*

Intra-aortic balloon pump (IABP) counterpulsation is the most widely used mechanical

tment orlands;enter, Lenter, Bedicinenter, Dart Fout Thomeptemb, 2015.g: This(Stichti052.ge 474spondin5.addres

/15/$ -i.org/1

circulatory support device because of its ease of use, low complication rate, and fast mannerof insertion. Its benefit is still subject of debate, and a considerable gap exists betweenguidelines and clinical practice. Retrospective nonrandomized studies and animal experi-ments show benefits of IABP therapy. However, recent large randomized trials do not showbenefit of IABP therapy, which has led to a downgrading in the guidelines. In our view, thisdichotomy between trials and practice might be the result of insufficient understanding ofthe prerequisites needed for effective IABP therapy, that is, exhausted autoregulation, andof not including the right patient population in trials. The population included in recentlarge randomized trials has been heterogeneous, also including patients in whom benefit ofIABP could not be expected. The clinical condition in which most benefit is expected, that ispersistent ischemia in acute ST-elevation myocardial infarction, is discussed in this review.In conclusion, this review aims to explain the physiological principles needed for effectiveIABP therapy, to reflect critically on the large randomized trials, and to solve some of thecontroversies in this field. � 2016 Elsevier Inc. All rights reserved. (Am J Cardiol2016;117:469e476)

Appropriate use of intra-aortic balloon pump (IABP)counterpulsation has been subject to heavy debate over thepast years.1e4 Use of IABP is generally confined to 3 groupsof patients, that is, high-risk percutaneous coronary inter-vention (PCI), acute myocardial infarction, and cardiogenicshock. There have been large randomized trials for all 3indications, which will be discussed in the following sec-tions. However, before analyzing these trials in detail, it ismandatory to better understand the presumed physiologicalprinciples of IABP counterpulsation and the prerequisitesneeded for adequate effect (or absence of effect) of IABP.

Physiological Principles and the Role of CoronaryAutoregulation

The IABP, positioned in the descending thoracic aortathrough the femoral artery, inflates and deflates in syn-chrony with the cardiac cycle. By inflating in the diastolicphase of the cardiac cycle, the diastolic aortic pressure is

f Cardiology, Catharina Hospital Eindhoven, Eindhoven,bCenter for Intensive Internal Medicine, Universityjubljana, Slovenia; cThe Cardiovascular Center, Tuftsoston, Massachusetts; dDivision of Cardiology, Depart-e, Duke Clinical Research Institute, Duke Universityurham, North Carolina; and eCardiovascular Division,ndation Centre of Research Excellence, Kings Collegeas’ Hospital, London, United Kingdom. Manuscript

er 14, 2015; revised manuscript received and accepted

work was supported by the Dutch Technology Founda-ng voor de Technische Wetenschappen) under project

for disclosure information.g author: Tel: (þ31) 40 2397004; fax: (þ31)

s: Nico.Pijls@inter.nl.net (N.H.J. Pijls).

see front matter � 2016 Elsevier Inc. All rights reserved.0.1016/j.amjcard.2015.10.063

augmented, resulting in higher coronary perfusion pressure(Figure 1). This could theoretically lead to improved coro-nary blood flow and thereby increase of myocardial oxygensupply.6,7

Early in systole, the balloon rapidly deflates, reducing theafterload of the left ventricle (Figure 1). In turn, this isbelieved to decrease myocardial workload and oxygen de-mand.8 However, the supposed direct mechanical effect ofcounterpulsation on coronary blood flow can be easily un-done by the reactive vasoconstriction of the coronary andmyocardial bed, known as coronary autoregulation. Undernormal physiological circumstances, sphincters at theentrance of coronary arterioles constrict or dilate in responseto coronary perfusion pressure, thereby guaranteeing con-stant myocardial blood flow over a wide range of aorticpressures (60 to 140 mm Hg).9 Therefore, in physiologicconditions with intact coronary autoregulation, myocardialblood flow is not dependent on perfusion pressure, and it isillusionary to expect increased coronary blood flow becauseof higher perfusion pressure by IABP counterpulsation.Thus, improved coronary blood flow by IABP can only beexpected in situations with exhausted autoregulation.

Recently, De Silva et al10 performed intracoronary flowand pressure measurements during IABP counterpulsationwith “switched on” and “switched off” coronary autor-egulation using intravenous adenosine infusion for mini-mizing coronary vascular resistance. The investigatorsshowed that the effect of IABP on coronary flow is directlydependent on coronary autoregulation. With intact autor-egulation, balloon pump augmentation did lead to anincrease in coronary pressure and also to a reactive increasein microvascular resistance, and as a result unchanged cor-onary blood flow. In contrast, with “switched off” autor-egulation, the balloon pump augmentation led to an increasein distal coronary pressure and coronary blood flow,whereas the microvascular resistance remained unchanged.

www.ajconline.org

Figure 1. Hemodynamic effects of intra-aortic balloon pump counter-pulsation. Waveform of an unassisted and assisted heartbeat. After theaortic valve closes, the IABP inflates, increasing the diastolic pressure.Before systole, the balloon deflates, resulting in lower end-diastolic pres-sure, reflecting afterload for the left ventricle. Reproduced from Myat et al5

with permission from the publisher.

470 The American Journal of Cardiology (www.ajconline.org)

Also in recent studies performed in the isolated beating pigheart, it was documented that with exhausted autoregulation,a linear relation between diastolic aortic pressure and cor-onary blood flow is present and that IABP increases coro-nary blood flow by up to 50% in the presence of pumpfailure because of ongoing myocardial ischemia.11,12

In short, only when autoregulation is exhausted, coronaryblood flow is directly dependent on perfusion pressure, andeffects of IABP on coronary blood flow can be expected.This is the case in the following clinical situations: (1) in theperfusion territory of a critical, subtotal stenosis; (2) inischemic myocardium, including “stunning” after myocar-dial infarction or during weaning from extracorporeal cir-culation; and (3) in patients with low mean aortic pressuresoutside the autoregulatory range (<60 mm Hg).

The importance of autoregulation when assessing theeffect of IABP was neither fully understood nor investigateduntil recently and is not reflected in the inclusion criteria inthe large randomized clinical trials, including acutemyocardial infarction and cardiogenic shock.

High-Risk PCI

IABP is often used as circulatory support system toprevent major complications during high-risk PCI.13 Pa-tients with severe left ventricular dysfunction undergoingPCI are at higher risk of morbidity and mortality.14,15 Thisrisk increases when the target lesion is supplying a sub-stantial proportion of the myocardium. By inducingischemia during PCI, left ventricular function will furtherdeteriorate, and patients are at risk of entering a downwardspiral of myocardial ischemia, hemodynamic compromise,cardiogenic shock, and ultimately death. Especially if asubtotal stenosis is present in a large contralateral coronaryartery, secondary ischemia of the contralateral myocardialterritory due to compensatory hyperkinesia might induce adownward spiral with deleterious outcome.

Until 2010, evidence supporting use of IABP in suchpatients consisted of several retrospective obser-vational and small randomized studies.16e19 The Balloon

PumpeAssisted Coronary Intervention Study (BCIS-1)randomized 301 patients scheduled to undergo high-risksingle-vessel or multivessel PCI to either IABP insertionbefore PCI or no planned IABP insertion.20 On the basis ofthe predicted and actual event rates, the study wasadequately powered. Outcome at hospital discharge wassimilar between the 2 groups, without significant differencesin myocardial infarction, death, cerebrovascular accident, orfurther revascularization. In the control group, 12% of thepatients needed rescue IABP insertion because of intra-procedural complications, mainly hypotension. Six-monthmortality was 4.6% in the IABP group and 7.4% in thecontrol group (p ¼ 0.32). Although not statistically signif-icant at first, this relative risk reduction of 38% remainedconstant over time, resulting in a significant benefit in favorof IABP over long-term follow-up, with a hazard ratio of0.66 (95% confidence interval 0.44 to 0.98; p ¼ 0.039).21

This consistent relative risk reduction by 1/3 is of hugeimpact in a patient population in which 1 out of every 3patients died within the long-term follow-up period(Figure 2). The constant hazard ratio during follow-up im-plies that this is attributable to an early treatment effect, thatis, IABP insertion before PCI. There were no other detect-able procedural differences between the 2 groups in terms ofnumber of vessels treated, success rate, and proportion ofleft main or proximal left anterior descending coronary ar-teries stented.

Explanation of this difference in outcome could be thereduction of ischemia by IABP during high-risk PCI and theprevention of intraprocedural complications. Effects ofIABP on coronary blood flow is not undone by coronaryautoregulation in these patients because autoregulation iscompletely exhausted in the coronary tree distal to a sig-nificant stenosis and in the presence of ischemic myocar-dium during and shortly after balloon inflation. Even smallperiprocedural myocardial infarctions, only measured byelevated troponin levels, have shown to affect outcome incardiac patients.22 In patients with severe ischemic cardio-myopathy as included in BCIS-1, this effect might be morepronounced, causing this significant difference in long-termoutcome. It is well conceivable that better protection of themyocardium during the procedure itself will result in adecrease in mortality in the long term, explaining the lateresults of BCIS-1.

Acute Myocardial Infarction

Primary PCI in patients presenting with ST-segmentelevation myocardial infarction (STEMI) has resulted inan impressive improvement in outcome.23 During the lastdecade, however, despite optimizing time intervals, outcomehas not further improved. This may be ascribed to “reper-fusion injury,” “no-reflow,” or “persistent ischemia,” whichoccurs in up to 30% of the patients and is caused by avariety of factors including microembolization of athero-thrombotic debris, vasospasm, and external compression ofthe capillaries due to intramyocardial edema, hemorrhage,and other factors, suppressing adequate myocardial perfu-sion after successful epicardial stenting.24 In such patients,this “ongoing” or “persistent” ischemia leads to reducedsalvage of myocardium, even if the occluded epicardial

Figure 2. Long-term outcome of BCIS-1. Panel A shows the KaplaneMeier curves of patients treated with and without elective IABP support in the BCIS-1trial, with 42 deaths in the elective IABP group versus 58 deaths in the control group (HR 0.66; 95% CI, 0.44 to 0.98; p ¼ 0.039). Panel B shows the hazardratios at different lengths of follow-up, showing a consistent hazard ratio over time. CI ¼ confidence interval; HR ¼ hazard ratio. Reproduced from Pereraet al21 with permission from the publisher.

Review/IABP 471

coronary artery has been opened successfully by primaryPCI.

Animal experiments have shown that IABP is effective inreducing no-reflow, improves myocardial salvage, anddecreases infarct size.25,26 A clinical registry in nearly 1,500consecutive patients showed prophylactic insertion of IABPto be associated with fewer events in all high-risk patientspresenting with acute myocardial infarction.27

The Counterpulsation to Reduce Infarct Size Pre-PCIAcute Myocardial Infarction (CRISP AMI) trial sought todetermine if routine IABP therapy before primary PCI inpatients with anterior STEMI without shock reduces infarctsize as assessed on cardiac magnetic resonance imaging(CMR) and randomized 337 patients.28 The study wasdesigned and powered to detect a 25% reduction in infarctsize in the IABP group. Final infarct size as assessed byCMR after 3 to 5 days showed no difference and a trendtoward larger infarctions in the IABP group (42.1% vs37.5%, p ¼ 0.06). All-cause mortality at 6 months occurredless frequent in the IABP group, although not statisticallysignificant (2% vs 5%, p ¼ 0.12). The exploratory com-posite end point of death, shock, or new or worsening heartfailure did reach statistical significance in favor of the IABPgroup (5% vs 12%, p ¼ 0.03). So, in CRISP AMI, theprimary end point was not achieved, and some confusionoriginated with respect to other end points.

However, 40% of the population in CRISP AMI hadsummed ST-elevation <6 mm, representing a cohort of pa-tients with relatively small infarctions with a good prognosisanyway, whether treated with IABP or any other additionaltherapy.29 It is unlikely that in these patients, any of the pre-defined end points like death or congestive heart failure wouldbe reached anyway, irrespective if and how they were treated.This is corroborated by the systolic and diastolic bloodpressure and heart rate of the study population, not suggestinga very sick trial population. Inclusion of these patients mostlikely diluted a possible effect of IABP insertion by under-powering the study. A recent substudy of CRISP AMI inpatients with large myocardial infarction (summed ST-deviation �15 mm) and persistent ischemia (ST-resolution

after PCI <50%) showed a significant reduction in mortalitydespite a much smaller patient population (Figure 3).30

Furthermore, in CRISP AMI, there was a considerableand asymmetrical crossover from control group to IABPgroup (8%), because of sustained hypotension or cardio-genic shock, failed PCI, or continued chest pain. The impactof this asymmetrical crossover will be discussed later in thisreport.

Finally, the primary end point was infarct size as assessedat 3 to 5 days using CMR. Using CMR in a patient populationwith the highest event rate in the first days will automaticallycreate bias because patients (mainly without IABP) who diedin the first days or were too unstable to undergo CMR are notincluded in this analysis of infarct size.

More in general, it is questionable if CMR 3 to 5 daysafter acute myocardial infarction is a reliable method topredict the ultimate infarct size and ejection fraction.Considerable further recovery is reported by consecutiveCMR examinations at later follow-up.31,32

Overall, use of IABP is not indicated routinely in acutemyocardial infarction. Especially in patients with relativelysmall infarctions or fast successful reperfusion, reflected bycomplete ST-resolution, there is no effect to be expected byIABP counterpulsation. However, in patients with largemyocardial infarction complicated by persistent ischemia(ongoing pain or insufficient ST-resolution), a significantdecrease of mortality was observed, which fits with the path-ophysiological considerations mentioned previously. Thisdecrease of outcome was observed in a substudy, with all itslimitations. Therefore, a prospective randomized controlledtrial in such patients has been started recently to investigatethis standpoint (SEMPER FI study: Survival in patients withExtensive Myocardial infarction complicated by PERsistentischemia Following IABP insertion; NCT02125526).

Cardiogenic Shock

Treatment of cardiogenic shock complicating acutemyocardial infarction remains a challenge with persistinghigh mortality rates.33,34 Pharmacological therapy often fails

Figure 3. All-cause mortality at 6 months in different (sub)populations of the CRISP AMI trial. All-cause mortality rates at 6 months in all patients receivingIABP as adjunct to PCI (blue line) or PCI alone (red line) in the CRISP AMI population (3 vs 9 deaths; log-rank p ¼ 0.12; A); in patients with large myocardialinfarction (1 vs 6 deaths; log-rank p ¼ 0.10; B); in patients with large myocardial infarction complicated by persistent ischemia (0 vs 5 deaths; log-rank p ¼0.046; C). IABP indicates intra-aortic balloon pump. ST-D, ST-deviation; ST-R, ST-resolution. Reproduced from EuroIntervention 2015, van Nunen LX et al,Intra-aortic balloon counterpulsation reduces mortality in large anterior myocardial infarction complicated by persistent ischaemia: a CRISP-AMI substudy,2015;11:286e292, with permission from Europa Digital & Publishing.30

472 The American Journal of Cardiology (www.ajconline.org)

to stabilize the patient in cardiogenic shock and carries theadditional risk of increasing myocardial ischemia because ofincreased myocardial oxygen demand. This is the reasonwhy physicians attempted to improve treatment of thesepatients by the use of mechanical circulatory supportdevices, one of them being the IABP.

Most trials with favorable results regarding IABP use inacute myocardial infarction complicated by cardiogenicshock were performed in the thrombolytic era.35,36 Registriesand retrospective studies in the era of primary PCI showedno difference in outcome by the use of IABP.37,38 TheIntraaortic Balloon Pump in Cardiogenic Shock II (IABP-SHOCK II) trial prospectively randomized 600 patients withacute myocardial infarction (with or without ST-segmentelevation) complicated by cardiogenic shock to primaryPCI with adjunctive IABP support or PCI alone.34 Thislandmark study showed no reduction in short-term andlong-term mortality (30-day mortality 39.7% vs 41.3%;1-year mortality 52% vs 51%, respectively; Figure 4).39

Strengths and limitations of this landmark trial have beendiscussed extensively. It is the largest randomized trialperformed in patients with cardiogenic shock, including 600patients in 32 months, and with a very high percentage offollow-up (1-year follow-up completed in 99.2%). Apartfrom that the study was underpowered because of a lowerevent rate in the control group than anticipated, several otherimportant limitations were present in this study, questioningits conclusions.

First, there was a large asymmetrical crossover fromcontrol group to the IABP group and an increase in the use ofleft ventricular assist devices in the control group of together17.4% of the patients not randomized to IABP. The impactof this high and asymmetrical crossover on statistical analysisand conclusions of the study will be discussed further on.

Second, almost half the patients randomized were resus-citated before PCI, and almost 40% received induced

hypothermia after PCI. Outcome in these patients is poorirrespective of the use of IABP and primarily dependent onneurologic recovery rather than myocardial salvage by IABP.

Finally, the time windows in these patients were verywide; patients could be included up to 12 hours after onsetof cardiogenic shock. If a patient with acute myocardialinfarction complicated by cardiogenic shock presents toolate (i.e., there is no persisting ischemia, neither viablemyocardium in the infarcted area anymore), no salvage ofmyocardium leading to a better prognosis can be expectedanyway. In such patients, in the best case, IABP therapy willlead to temporary relief and stabilization of hemodynamics.Volume pumps are more effective to increase output in suchpatients, but these effects are temporary as well and willdisappear as soon as the device is removed.

Although IABP-SHOCK II definitely questions theroutine use of IABP in patients presenting with acutemyocardial infarction complicated by cardiogenic shock,these limitations exemplify the difficulties in interpretingrandomized open trials involving very sick patients. Thequestion is if outcome would be different by including amore specific group of patients with STEMI, rather than aheterogeneous group of patients with respect to the presenceof persistent ischemia, time intervals, concomitant neuro-logic deficits, and the use of or crossover to additionalmechanical support strategies.

Cardiogenic shock should not be seen as a yes-or-nophenomenon such as cardiac arrest but rather as a veryheterogenous condition which requires a tailored treatment.By solely including the patients presenting with STEMIcomplicated by cardiogenic shock with still viablemyocardium and persistent ischemia as reflected by ongoingchest pain and persisting ST-deviation, and by excludingresuscitated patients, IABP therapy could be expected to bemore effective based on pathophysiological grounds, asdiscussed here previously.

Figure 4. One-year all-cause mortality of the IABP-SHOCK II Trial. One-year follow-up of the IABP-SHOCK II Trial. IABP indicates intra-aortic balloonpump. Reproduced from Thiele et al39 with permission from the publisher.

Review/IABP 473

A recent study in the isolated beating pig heart simulatedlarge myocardial infarction whether complicated bycardiogenic shock, and tested the effects of IABP counter-pulsation in healthy state, preshock state, and shock state,with and without superimposed myocardial ischemia.12

These experiments showed a strong increase by IABP ofcoronary flow (up to 50%), cardiac output (up to 20%), andmyocardial oxygen utilization (up to 25%) in largemyocardial infarction, cardiogenic shock, and ongoingischemia (Figures 5 and 6).

Statistical Limitations of Prospective Randomized IABPTrials

In both the CRISP AMI and IABP-SHOCK II trials,there was a large percentage of crossover from control groupto IABP group. One can wonder why the treating physicianin such open trials decides for crossover from the controlgroup to the IABP group, and in which patients this hap-pens. It is likely that the patients in whom crossoveroccurred were those in the worst condition, that is, at highestrisk for events. This crossover also occurs in other largerandomized open studies in critically ill patients in intensivecare units (such as the use of steroids in septic shock) and isalmost inevitable in patients randomized to the controlgroup (“back-against-the-wall” situations), but it hamperscorrect interpretation of data.

It is impossible to fully comprehend the effect of such ahigh asymmetrical crossover on trial results, but it should beclearly recognized that this high asymmetrical crossover inan open trial is prohibitive for an intention-to-treat analysis.Any possible positive effect of a study drug or device willautomatically be masked when the worst patients in thecontrol group are subject to crossover and receive thedevice, in this case IABP.

In an attempt to avoid such bias, the investigators of theIABP-SHOCK II trial also performed a per-protocol analysisand as-treated analysis. However, in a per-protocol analysis,the crossover patients (i.e., those at highest risk) areexcluded for analysis and the control group is most likely in

more healthy baseline condition in comparison with theIABP group. In addition, when using an as-treated analysis,all crossover patients are included in the IABP group,thereby creating a less-healthy IABP group at baseline.Absence of a difference in such analyses, in 2 groups withdifferent characteristics, cannot exclude effectiveness of thestudy device.

Thus, conclusions from such open randomized trials incritically ill patients with a high and asymmetrical crossoverrate remain controversial.

Recent Guidelines, Recommendations, and Conclusions

The IABP is a therapeutic device advocated to be used incritically ill patients with cardiogenic shock or myocardialinfarction. After 40 years, despite clear improvement inindividual patients, there are still extensive discussionsabout its potential benefits. Most likely, it is too good tosimply abandon but not good enough to recommend withoutrestrictions in patients with cardiogenic shock or myocardialinfarction in general.

A key issue in this respect is the better understanding ofthe underlying physiological principles and more specif-ically the role of coronary autoregulation, which wasinsufficiently recognized and investigated until recently.

Recent guidelines by the European Society of Cardiologydowngraded routine use of IABP in patients with cardio-genic shock (Class of Recommendation III, Level of Evi-dence A).40

Undoubtedly, routine use of IABP in cardiogenic shockwithout ischemia is not indicated. In such patients, hemo-dynamic support using flow-driven support devices such asImpella or LVAD is more effective.41 Similarly, IABP is notindicated as a routine device in STEMI, as learned from theCRISP AMI trial. However, in subgroup analysis of this trialbased on recent pathophysiological insights from experi-mental and human studies, a decrease of mortality by IABPand improved outcome was observed. Especially, in case ofpatients with persistent ischemia and large myocardialinfarction (whether complicated by cardiogenic shock),

Figure 5. Effect of IABP on hemodynamic parameters in the isolated beating pig heart. Effect of IABP on hemodynamic parameters in a beating pig heart inpreshock. Without ischemia (left part of the figure), cardiac output equals 4.6 l/min (red dot), blood pressure equals 76 mm Hg (black dot), left atrial pressureequals 16 mm Hg (blue dot), and coronary blood flow equals 1.2 l/min (green dot). Hereafter, additional global ischemia is slowly created by decreasing arterialoxygen saturation in the extracorporeal circulation. This is accompanied by a slow decrease of cardiac output, coronary blood flow, and blood pressure and anincrease in left atrial pressure. At a particular point in time (called t ¼ 0 minutes), the downward spiral is accelerated and progressive deterioration occurs. Next,without any change in external oxygen supply or any of the other controllable parameters, the IABP is switched on (t z 5 minutes) and within 2 minutes, asignificant improvement of cardiac output, coronary blood flow and blood pressure occurs, whereas left atrial pressure decreases dramatically. All parametersstabilize within a few minutes. At tz 10 minutes, the IABP is switched off again without any change in any of the controllable parameters, whereafter the heartrapidly deteriorates and enters the negative vicious circle again. By switching on the IABP (t z 15 minutes), significant improvement and stabilization occursagain. Reproduced from Schampaert et al12 with permission from the publisher.

Figure 6. Effect of IABP on coronary blood flow, cardiac output, and myocardial oxygen consumption in 12 beating pig hearts. Mean change (�standard error)by IABP support compared to the status without IABP of coronary blood flow (A), cardiac output (B), and myocardial oxygen consumption (C) for differentclinical scenarios, ranging from healthy to cardiogenic shock, whether (hatched) or not (solid) in the presence of global myocardial ischemia. Reproduced fromSchampaert et al12 with permission from the publisher.

474 The American Journal of Cardiology (www.ajconline.org)

there are arguments for the effectiveness of IABP to reduceischemia, leading to salvage of myocardium, decreasedmortality, and improved long-term outcome.

The key message of this discussion is that in selectingpatients who might benefit from IABP therapy, a moretailored and patient-specific approach is paramount. Pres-ence of ischemia, whether in high-risk PCI, acute myocar-dial infarction, or cardiogenic shock, seems to be the keyfactor in selecting patients who might benefit from IABPtherapy. The rationale for effective IABP therapy is thetrinity of exhausted autoregulation, persistent ischemia, andstill viable myocardium. We should be careful not to throwout the baby with the bathwater.

Disclosures

Dr. van Nunen received reimbursement for travel ex-penses and speaker fees from Maquet. Dr. Noc receivedspeaker fees from Maquet, Astra Zeneca, Ely Lilly, andKrka and is on the advisory board for Zoll. Dr. Kapurreceived institutional research funding from Abiomed,Cardiac Assist, and Maquet and received speaker fees fromAbiomed, Cardiac Assist, Maquet, Thoratec, and Heartware.Dr. Patel received institutional research funding and reim-bursement for travel expenses from Maquet. Dr. Pererareceived institutional research funding from Maquet. Dr.Pijls received institutional research funding, reimbursementsfor travel expenses, and speaker fees from Maquet.

Review/IABP 475

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