2005;79:872-880 Ann Thorac SurgBovelander and Ottavio Alfieri

Jan J. Schreuder, Francesco Maisano, Andrea Donelli, Jos R.C. Jansen, Pat Hanlon, Jan Performance in Patients With Low Ejection Fraction

Beat-to-Beat Effects of Intraaortic Balloon Pump Timing on Left Ventricular

http://ats.ctsnetjournals.org/cgi/content/full/79/3/872located on the World Wide Web at:

The online version of this article, along with updated information and services, is

Print ISSN: 0003-4975; eISSN: 1552-6259. Southern Thoracic Surgical Association. Copyright © 2005 by The Society of Thoracic Surgeons.

is the official journal of The Society of Thoracic Surgeons and theThe Annals of Thoracic Surgery

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eat-to-Beat Effects of Intraaortic Balloon Pumpiming on Left Ventricular Performance in Patientsith Low Ejection Fraction

an J. Schreuder, MD, PhD, Francesco Maisano, MD, Andrea Donelli, MS,os R. C. Jansen, PhD, Pat Hanlon, RN, Jan Bovelander, CRNA, and Ottavio Alfieri, MDepartment of Cardiac Surgery, San Raffaele University Hospital, Milan, Italy; Department of Intensive Care, Leiden University

edical Center, Leiden, The Netherlands; Arrow International, Reading, Pennsylvania

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Background. Intraaortic balloon counterpulsationIABP) timing errors during arrhythmia may result infterload increases which may negatively influence leftentricular (LV) ejection and LV mechanical dyssyn-hrony. The aim of our study was to determine beat-to-eat effects of properly timed IABP, premature IAB

nflation, and late IAB deflation on LV performance andV mechanical dyssynchrony in heart failure patientsndergoing cardiac surgery.Methods. In 15 patients, LV pressure-volume relations

nd LV dyssynchrony were measured by conductanceolume catheter. Properly timed IABP was evaluated at a:1 assist ratio within a 10 seconds time-span. PrematureAB inflation and late IAB deflation were evaluated at a:4 assist ratio.Results. Properly timed 1:1 IABP acutely decreased LV

nd-systolic volume by 6.1% (p < 0.0001) and LV end-

ystolic pressure by 17.5% (p < 0.0001) due to decreased

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ery, San Raffaele University Hospital, Via Olgettina 60, 20132 Milan,taly; e-mail: schreuder@libero.it.

2005 by The Society of Thoracic Surgeonsublished by Elsevier Inc

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ortic impedance. Stroke volume (SV) increased by 14%p < 0.0001), which correlated markedly with a decreasef LV mechanical dyssynchrony (p < 0.0001). The largestV increases occurred in patients with lowest contractiletate. Premature IAB inflation decreased SV by 20% (p <.0001) due to abrupt increase of LV afterload during latejection. Late IAB deflation increased SV and strokeork by 18% (p < 0.0001) and 16% (p < 0.01) respectively,ue to increased afterload during early ejection andecreased afterload during late ejection.Conclusions. Left ventricular performance during IABP

s causally related to changes in LV afterload, and theiming of these changes in relation to contraction orelaxation phases, to LV mechanical dyssynchrony and toontractile state.

(Ann Thorac Surg 2005;79:872–80)

© 2005 by The Society of Thoracic Surgeons

ntraaortic balloon counterpulsation (IABP) to supportcardiac function has been well documented during

he last three decades [1–7]. Primary effects of properlyimed IABP are diastolic aortic pressure augmentationnd left ventricular (LV) afterload reduction by decreas-ng impedance to LV ejection [3, 4]. LV volume and LVnd-diastolic pressure (EDP) have been demonstrated to

See page 1017

ecrease in patients treated with IABP, whereas cardiacutput, ejection fraction (EF), and coronary flow may

ncrease [2–6]. However, arrhythmic episodes often re-ult in incorrect IABP timing decreasing its efficacy [7].remature IAB inflation may increase aortic impedancend therefore LV afterload late in the ejection phase,hereas late IAB deflation may increase afterload during

arly ejection. Acute load increases applied during contrac-ion or relaxation in heart muscle preparations or in intactnimal ventricles induced increases or decreases in ejection

ccepted for publication July 29, 2004.

ddress reprint requests to Dr Schreuder, Department of Cardiac Sur-

hase duration, respectively [8–11]. Moreover, altered load-ng conditions may result in dyssynchronous relaxation ofhe LV [11, 12]. Myocardial relaxation is known to beensitive to afterload and to LV dyssynchrony in patientsith dilated cardiomyopathy [13]. LV mechanical dyssyn-

hrony in these patients decreased due to reduction in walltress induced by interventions such as vasodilators, car-iomyoplasty, or LV ventricular reduction surgery [13–16].ecently we demonstrated a close relationship betweenardiac performance and intraventricular mechanical dys-ynchrony in patients undergoing LV restoration by theor procedure [16]. Hence we hypothesized that IABP

iming in patients with low EF may considerably influenceardiac performance by acute afterload changes and con-omitant changes in LV mechanical dyssynchrony. Effectsf IABP on LV performance and LV mechanical dyssyn-hrony were analyzed beat-to-beat from the pressure-olume plane during conventionally timed IABP, prema-

Dr Schreuder, Mr Bovelander and Ms Hanlon disclosethat they have a financial relationship with ArrowInternational; Dr Schreuder also has a financial rela-

tionship with CD Leycom.

0003-4975/05/$30.00doi:10.1016/j.athoracsur.2004.07.073

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ure IAB inflation and late IAB deflation, using theonductance volume catheter technique [14–23]. The beat-o-beat measurements were performed within a time spanf 10 seconds after an IABP change to exclude cardiovascu-

ar compensatory reflexes and or metabolic effects fromossible increases in coronary flow [4]. Beat-to-beathanges of cardiac performance with IABP may then berimarily attributed to acute changes in aortic impedance.

atients and Methods

atientsifteen patients, New York Heart Association (NYHA)lass II–IV, 48 to 64 years old, EF 21.5% � 8.5%, under-oing cardiac surgery requiring prophylactic IABP, weretudied. Eight patients underwent LV aneurysmectomy6 patients with coronary artery bypass graft [CABG]),patients underwent CABG (1 with mitral valve repair),

nd 1 patient underwent mitral valve repair. Open chestemodynamic evaluations of acute effects of IABP wereerformed before cardiopulmonary bypass.The study protocol was approved by the local ethics

ommittee and written informed patient consent wasbtained.

nstrumentationll patients received high dose opioid anesthesia. Fiveatients belonging to NYHA class III-IV received smallteady-state dosages of inotropics (dobutamine � 5 u ·g�1 · min�1).The IAB catheters (Narrowflex; Arrow International,

eading, PA) were positioned under transesophagealcho control in the descending thoracic aorta at 2-cmistal to the left subclavian artery. Thermodilution cath-ters (Edwards Lifesciences, Inc., Irvine, CA) were in-erted into the pulmonary artery and micromanometer-onductance catheters (F7; CD Leycom, Zoetermeer, Theetherlands) into the LV through a pulmonary vein.The cardiac function analyzer (Leycom CFL512; CD

eycom) uses a conductance catheter to measure ventric-lar volumes at a dual-field excitation mode [17, 21]. Theethod is based on measuring time-varying electrical

Abbreviations and Acronyms

EDP � end-diastolic pressureEDV � end-diastolic volumeEes � end-systolic elastanceEF � ejection fractionESPVR � end-systolic pressure-volume

relationshipESV � end-systolic volumeESP � end-systolic pressureIABP � intraaortic balloon counterpulsationLV � left ventricleSV � stroke volumeSW � stroke work

onductance of 5 to 7 ventricular blood segments, delin- p

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ated by selected catheter electrodes. Correct positioningf the conductance catheter was verified by transesoph-geal echocardiography and by inspection of the seg-ental conductance signals. The feasibility of the con-uctance catheter method to measure real-timeentricular volume has been demonstrated in animal andlinical studies [14–23]. Reproducibility of conductanceatheter measurements was demonstrated in patientsndergoing cardiac surgery [19]. Beat-to-beat stroke vol-me changes were validated by pulse contour analysis

20]. Time-varying segmental conductance reflects time-arying segmental LV volume as obtained and validatedy cine-angiography in canine hearts [21].Parallel conductance was assessed by injection of 10 ml

ypertonic saline (6%) into the pulmonary artery [17].ffective conductance stroke volume (SV) was defined asifference between conductance volumes at the times ofdP/dtmax and �dP/dtmax, which largely eliminates con-

ribution of possible regurgitant flows. Absolute LV vol-mes were calculated by matching effective conductanceV with simultaneously measured thermodilution SVnd by subtracting parallel conductance from total con-uctance volume.

echanical Ventricular Dyssynchronyentricular dyssynchrony assessment from segmentalV volume signals has been previously described forine-angiography and the conductance catheter [14, 23,4]. The conductance catheter measures volume seg-ents located perpendicular to the long heart-axis. A

olume segment was defined dyssynchronous when theolume change in that segment was in opposite directiondyskinetic) or showed no change (akinetic) compared tootal LV volume change. Segmental dyssynchrony wasuantified by percent time a segment was dyssynchro-ous in relation to total volume change, total dyssyn-hrony was the average of segmental dyssynchrony in allegments [14, 23]. Systolic dyssynchrony was calculatedrom R-wave to �dP/dtmax and diastolic dyssynchronyrom �dP/dtmax to R-wave.

ata Analysislectrocardiogram (ECG), LV pressure, aortic pressurend volume signals were digitized at a sampling rate of50 Hz. The following variables were calculated: Tau,ndex of LV pressure relaxation, defined as time requiredrom LV pressure at �dP/dtmax to be reduced by half [25];eak ejection rate calculated as maximal �dV/dt; End-ystolic elastance (Ees), representing a load independentndex of contractile state, was determined from unas-isted beats and first 8 seconds of IABP (Fig 1); Ees1ncluded last unassisted beat (arrow) and first 3 assistedeats; Ees2 included last unassisted beat and three latestssisted beats prior to10 seconds after IABP initiation.Values are mean � standard deviation (SD) of at least

our heart cycles. Comparisons between different IABPodes were assessed with a paired t-test. Statistical

elations between variables were tested by least-squaresinear regression. Statistical significance was assumed at

less than 0.05.

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easurement Protocolffects of properly timed IABP (inflation at the dicroticotch, deflation inducing end-diastolic aortic pressureecrease) were measured during 15 seconds ventilatorytop, the first 5 seconds without IABP followed by assistt a 1:1 ratio (Fig 1). All measurements were made underteady state conditions.

Premature IAB inflation was set 130 to190ms beforehe dicrotic notch to produce an abrupt afterloadncrease in the second part of the ejection phase (Fig 2A, b]).

Late IAB deflation was set 110 to180ms after the-wave, around the start of the ejection phase, to pro-uce a clear afterload increase in the first part of thejection phase (Fig 2 [B, c]). Both timing errors werevaluated at a 1:4 assist ratio during a 15 seconds venti-atory stop.

esults

emodynamic Response to Conventionally TimedABPhe acute effects of proper IABP timing at a 1:1 assistatio are illustrated by two typical examples (Fig 1).

ig 1. Effects of regular 1:1 IABP initiation (arrows), with IAB inflatecrease in end-diastolic Pao in patient A (NYHA III, EF 14%) and preases by decreasing LV end-systolic pressure (P) and volume (V), dereases. Numbers 1–10 represent first 10 beats after IABP initiation.alloon pump; LV � left ventricular; NYHA � New York Heart AssoLV � left ventricular volume.)

he largest decreases in LV pressure, LV end-systolic i

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olume (ESV), LV end-diastolic volume (EDV) andoncomitant increases in SV are observed within 4ssisted beats. Decreases in LVESV and LV end-ystolic pressure (ESP) delineate the end-systolic P-Velationship and its slope, the Ees, representing a loadndependent index of contractile state. The averageemodynamic responses to 1:1 IABP are presented inable 1. Heart rate (HR) and Tau did not changeignificantly. SV increased (p � 0.0001) by a mean of4% ranging from 2% to 34%. Stroke work (SW) de-reased by a mean of 5% (p � 0.01). LVESV, LVESP,VEDV, and LVEDP decreased by a mean of 6% (p �.0001), 16 mm Hg (p � 0.0001), 2% (p � 0.001) and 1.6m Hg (p � 0.001), respectively. IABP decreaseddP/dtmax by 8% (p � 0.01) and �dP/dtmax by 17.5% (p0.0001). Mean aortic pressure increased by 15.5% (p0.0001). Peak ejection rate and EF increased by 9% (p0.03) and 3% (p � 0.001, net increase), respectively.End-systolic elastance appeared to be nonlinear, the

lope determined over the first 8 seconds after IABPnitiation at 1:1 assist was 1.6 � 0.85 mm Hg/mL; Ees1,etermined from the first three assisted beats was signif-

cantly (p � 0.01) steeper than Ees2, using the lastnassisted loops and those from 4 to 8 seconds after IABP

erformed near the dicrotic notch of the Pao and deflation effectingt B (NYHA III, EF 22%). IABP induced acute stroke volume in-ting nonlinear Ees (dotted lines) followed by end-diastolic P-V de-� end-systolic elastance; EF � ejection fraction; IABP � intraaorticn; Pao � mean aortic pressure; PLV � left ventricular pressure;

ion patienlinea(Eesciatio

nitiation (Table 1 and Fig 1).

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ig 2. Premature IAB inflation (A) applied 150 ms (arrows, b) before the dicrotic notch of the aortic pressure (Pao) generated abrupt increasesn LV afterload in late ejection with impairment of LV volume (VLV) ejection in NYHA II patient (EF 33%). Late IAB deflation (B) increasednd-diastolic Pao (arrows, b) and increased afterload during early ejection (c) followed by decreased afterload in late ejection increasingtroke volume in NYHA III patient (EF 24%); a, b, and c represent beats analyzed according to Tables 2 and 3. (EF � ejection fraction; LV �

eft ventricular; NYHA � New York Heart Association; PLV � left ventricular pressure.)

able 1. Effects of IABP at 1:1

Off On p Value

R beats/min 76 � 19 76 � 18I L/min/m2 2.24 � 0.6 2.55 � 0.6 0.0001V mL 53.3 � 15 60.5 � 14 0.0001W mm Hg · mL 4387 � 1801 4170 � 1795 0.01DV mL 272 � 72 266 � 69 0.001SV mL 212 � 70 199 � 67 0.0001F % 21.5 � 8 24.9 � 8 0.0001DP mm Hg 11.3 � 3 9.7 � 3 0.001SP mm Hg 92 � 21 76 � 20 0.0001ao mm Hg 71 � 11 82 � 9 0.0001dP/dtmax mm Hg/s 957 � 363 880 � 366 0.01dP/dtmax mm Hg/s �789 � 209 �672 � 230 0.0001au ms 51.2 � 10 53.4 � 13 0.07ER mL/s 564 � 172 614 � 166 0.03ysDys % 31.7 � 5 29.7 � 5 0.02iaDys % 38.5 � 5.5 36.1 � 5 0.001es1-2 mm Hg/mL 1.80 � 0.9 1.54 � 0.9 0.01

I � cardiac index; DiaDys � diastolic dyssynchrony; EDP � end-diastolic pressure; EDV � end-diastolic volume; Ees � end-systoliclastance; EF � ejection fraction; ESP � end-systolic pressure; ESV � end-systolic volume; HR � heart rate; Pao � mean aorticressure; PER � peak ejection rate; SV � stroke volume; SW � stroke work; SysDys � systolic dyssynchrony.

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emodynamic Response to Premature IAB Inflationhe adverse effects of premature inflation are illustrated

n Figure 2A. Abrupt increases in LV afterload late in LVjection, as a result from increased aortic impedance,nduced premature closure of the aortic valve and im-aired LV ejection. Table 2 provides average data, beforeremature inflation (a), during premature IAB inflationpplied at 130 to 190 ms before the dicrotic notch (b), andfter IAB assist (c). LVESP, or end-systolic afterload,ncreased (p � 0.0001) during premature IAB inflation by

mean of 14 mm Hg. SV decreased (p � 0.0001) by 20%,anging from –6% to –55%, with concomitant increase inVESV (p � 0.0001). Stroke work decreased by a mean of

able 2. Early IAB Inflation

Prea

R beats/min 75 � 18V mL 52.3 � 16 41W mm Hg · mL 3875 � 1785 29DV mL 253 � 66 2SV mL 191 � 59 2F % 22.6 � 11 17DP mm Hg 11.2 � 5 11SP mm Hg 84 � 24dP/dtmax mm Hg/s 787 � 238 7dP/dtmax mm Hg/s �676 � 203 �6au ms 55.5 � 10ysDys % 30.9 � 5.6 32iaDys % 37.7 � 6.9 38

iaDys � diastolic dyssynchrony; EDP � end-diastolic pressure; Eressure; ESV � end-systolic volume; HR � heart rate; IAB �

systolic dyssynchrony.

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Prea

R beats/min 78 � 18V mL 51.8 � 14W mm Hg · mL 3875 � 969DV mL 247 � 66SV mL 187 � 60F % 22.7 � 10DP mm Hg 11.2 � 4SP mm Hg 86 � 14dP/dtmax mm Hg/s 846 � 253dP/dtmax mm Hg/s �693 � 160au ms 56.1 � 6ysDys % 30.5 � 3iaDys % 37.7 � 7

iaDys � diastolic dyssynchrony; EDP � end-diastolic pressure; Eressure; ESV � end-systolic volume; HR � heart rate; IAB �

systolic dyssynchrony.

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5% (p � 0.002). Tau increased by 44% (p � 0.0001),ndicating deterioration of LV relaxation. The 16% meanncrease (p � 0.05) in SV in the postassisted beat com-ared with the preassisted beat did not compensate for

he 20% SV decrease of the preceding beat.

emodynamic Response to Late IAB Deflationigure 2B depicts an example of late deflation causing

ncreased end-diastolic aortic pressure and aortic imped-nce, which increased LV afterload during early ejectionc), followed by a reduction in afterload due to IABeflation during late ejection. Table 3 presents averageata of late IAB deflation initiated 110 to 180ms after the

ring p Values Post p Valuesa-b c a-c

18 75.5 � 1815 0.0001 60.7 � 18 0.00011137 0.002 3836 � 145868 255 � 67 0.0563 0.0001 186 � 60 0.0059 0.001 25.8 � 11 0.0026 12.2 � 6 0.0128 0.0001 74 � 19 0.0002233 684 � 189 0.04181 0.08 �608 � 205 0.000217 0.0001 57.2 � 10 0.055.5 0.03 29.5 � 6.57.3 36.9 � 7.9

end-diastolic volume; EF � ejection fraction; ESP � end-systolicortic balloon; SV � stroke volume; SW � stroke work; SysDys

During Post p Valuesb c a-c

78 � 19 77 � 1851.9 � 15 61.1 � 15 0.00013958 � 1024 4490 � 932 0.01248 � 67 249 � 67189 � 60 180 � 58 0.000122.7 � 10 26.3 � 10 0.000111.4 � 5 11.5 � 5

87 � 17 78 � 16 0.02858 � 261 911 � 269 0.001

�702 � 149 �694 � 23456.9 � 6 50.7 � 7 0.0130.6 � 3 29.6 � 4 0.1138.6 � 7 36.9 � 8

end-diastolic volume; EF � ejection fraction; ESP � end-systolicortic balloon; SV � stroke volume; SW � stroke work; SysDys

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-wave. SV increased (p � 0.0001) by a mean of 18% inhe postassisted beat (c) ranging from 2 to 49% due toecreases in LVESV (p � 0.0001) compared with preas-isted beats (a). Peak �dP/dt increased (p � 0.0001) by 8%ue to late IAB deflation, whereas Tau was shorter (p �.005). SW increased by 16% (p � 0.01) in contrast toonventional timed IABP.

V Performance and Mechanical Dyssynchronyigure 3 displays segmental and total volume tracingshowing a reduction in LV dyssynchrony after IABPnitiation at 1:1 assist. Systolic and diastolic dyssynchronyecreased in all patients by a net mean of 2% (p � 0.02nd p � 0.001, Table 1) within 8 seconds of initiationABP. Percent SV change was inversely correlated withotal LV dyssynchrony change (p � 0.00003, Fig 4A),mphasizing its relation with LVESV and LVEDV, whichodetermine alterations in SV. The percent increase inV during IABP assist at 1:1 inversely correlated with Ees

p � 0.008, Fig 4B), indicating that largest increases in SVccurred in the patients with lowest contractile state.Systolic dyssynchrony increased abruptly during

remature inflation by a net mean of 1.5% (Table 2, p �.03), although diastolic dyssynchrony and LVEDVemained unchanged. During late IAB deflation sys-olic and diastolic dyssynchrony did not change signif-

ig 3. Five LV segmental volume tracings (s1-s5) and TVLV usedor Dys analysis in patient A (Fig 1). Pronounced paradoxical seg-ental volume movements are located in the apex (s1-s2). The cal-

ulated Dys decreased immediately after initiation of IABP at a 1:1atio (arrow). (Dys � dyssynchrony; IABP � intraaortic balloonump; LV � left ventricular; TVLV � total volume tracing.)

cantly (Table 3). The combined results of the prema- d

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ure inflation and late deflation data revealed a markednverse correlation between changes in SV and systolic

ig 4. (A, B) Regression diagrams from IABP at 1:1 assist ratio androm (C) early/late IAB inflation/deflation at 1:4 assist ratio demon-trating: (A) percent change in SV (%�SV) versus LV TDys�TDys); (B) %�SV versus Ees; and (C) %�SV versus change inystolic dyssynchrony (�SysDys). Dotted lines represent 95% pre-iction limits. (Ees � end-systolic elastance; IABP � intraaorticalloon pump; LV � left ventricular; SV � stroke volume; TDys �otal dyssynchrony.)

yssynchrony (Fig 4C, p � 0.00001).

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omment

his study demonstrates acute beneficial effects of prop-rly timed IABP at a 1:1 ratio in heart failure patients.ecreases in aortic impedance resulted in instantaneous

ncreases in SV by LV afterload reduction with concom-tant decreases in LVESV, LVEDV, and LV mechanicalyssynchrony. The decreases in LVESV and LVESP de-

ineated the slope (Ees) of the end-systolic P-V relation-hip. The largest increases in SV occurred in the patientsith the lowest contractile state.Premature IAB inflation acutely impaired LV ejection

ue to abrupt afterload increase during late ejection,ncreasing systolic dyssynchrony, and Tau impairing

yocardial relaxation. Late IAB deflation induced a dualffect, afterload increase during early ejection and de-rease in late ejection, combined these increased SV andmproved LV relaxation, but at increased SW.

emodynamics Conventionally Timed IABPhort-term effectiveness of IABP was demonstrated byichols and colleagues [3], using multigated cardiaclood pool imaging. Cardiac output increased by 10%,0 minutes after initiation of IABP. Our study shows in allatients, despite the heterogeneous population, beat-to-eat SV increases due to decreases in LVESV, precedingecreases in LVEDV and LVEDP. Similar changes werebserved in animals with heart failure using LV pres-ure-volume loops [5]. Beat-to-beat improvement of car-iac performance with IABP, as demonstrated byheung and coworkers [4] and confirmed in the present

tudy, may be primarily attributed to acute decreases inortic impedance reducing LV afterload, because cardio-ascular compensatory reflexes and metabolic effectsrom possible increases in coronary flow can be excludedithin the measurement time of 10 seconds.The decreases in LVESV and LVESP determine the

nd-systolic elastance (Ees) as slope of the end-systolic-V relationship, which implies that the lower the slope

he larger the decrease in LVESV. The inverse correlationetween Ees and SV indicates that patients with the

owest contractile state will show the largest increases inV with IABP (Fig 4B). The significant nonlinear convexes (Fig 1, Table 1) is related to low contractile state asas demonstrated by Burkhoff and associates [26] in

nimal studies.Decreases in wall motion abnormalities have been

emonstrated 10 minutes after IABP initiation [3]. Dys-ynchrony of wall motion reduces mechanical efficiencyf ventricular ejection by inducing premature onset and

mpaired relaxation [10]. LV mechanical dyssynchrony,s demonstrated in patients with dilated cardiomyopathynd LBBB using tagged MRI, was shown to be a keyredictor for multi site pacing efficacy [27]. Patients withilated cardiomyopathy and marked LV dyssynchronyhowed decreases in LV mechanical dyssynchrony byall stress reduction following vasodilator administra-

ion, cardiomyoplasty or LV reduction surgery [13–16].he acute decreases in both systolic and diastolic dys-

ynchrony with IABP point to a similar mechanism, p

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ased on decreases in impedance reducing LV afterloadith concomitant decreases in LVESV and preload, im-roving LV mechanical efficiency. Reductions in LV totalyssynchrony showed a strong inverse correlation with

ncreases in SV induced by IABP assist at 1:1 (Fig 4A). Theargest increases in SV with IABP result from largestecreases in LVESV combined with smallest decreases inVEDV. Therefore increases in SV with conventional

ABP are causally related to decreases in LV afterload,reload, contractile state and concomitant changes in

otal LV mechanical dyssynchrony.

remature IAB Inflation-Late IAB Deflationhe present study shows that abrupt increases in aortic

mpedance, and therefore in LV afterload, imposed dur-ng late ejection result in shortened ejection phases, asas demonstrated in isolated cardiac muscle experi-ents and in vivo animal experiments [8–11]. Premature

AB inflation performed 130 to 190 ms before the dicroticotch resulted in increased LVESP, Tau, and decreasedV. These findings agree with the animal study by Zilend Gaasch [9] where IAB inflation was applied 80 msefore the dicrotic notch. Factors such as IAB positioningnd pulse-wave velocity from IAB to LV can explainifferences in timing between man and animal resultsnd the variance observed in the current patient popu-ation. The pulse-wave velocity will also vary withhanges in cardiac output or aortic compliance. IABnflation performed in animals 20 ms before the dicroticotch revealed no change in contraction duration whilearly relaxation rate increased [9]. In the present studye observed that premature IAB inflation applied less

han 50 ms before the dicrotic notch did not change SV.he significant increase in systolic dyssynchrony duringremature IAB inflation is analogous to increase in dys-ynchronous relaxation due to altered loading condi-ions, as described in animal studies by Gaasch andssociates [11] and Schafer and colleagues [12].Conventional IAB deflation should produce a clear re-

uction in end-diastolic aortic pressure. However, Kern andoworkers [28] demonstrated in a clinical IABP study thatAB deflation might be performed later in diastole withoutdverse hemodynamic effects. Our study shows that inci-ental late IAB deflation at a 1:4 assist ratio may result in

mmediate increases in SV, although at increased SW.nimal experiments showed that afterload increase applieduring early ejection prolongs ejection phase duration sim-

lar to a decrease in afterload applied in late ejection [8–10].nitial afterload increase in early ejection and decrease inate ejection due to late IAB deflation may explain theelatively large mean SV increase of 18% SV in a singleABP assisted beat (Fig 2 [B, c]).

Late IAB deflation induced a significantly higher SW inwo ways, by increasing PLV in early ejection and byncreased SV. Possible beneficial effects of late IAB de-ation applied at a 1:1 ratio should be investigated inpecific patient conditions. On the other hand, incidentalate deflation which may occur during IABP due torrhythmia should have no detrimental effects on cardiac

erformance.

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The marked beat-to-beat SV alterations due to after-oad changes applied at different times in the cardiacycle with premature inflation or late deflation markedlyorrelated with systolic dyssynchrony changes (Fig 4C).rutsaert’s hypothesis that LV mechanical dyssynchronyr nonuniformity may act as a modulator of cardiacerformance together with heart rate, contractile state,reload and afterload may therefore be applicable ineart failure patients [29]. In a previous study we dem-nstrated a direct relationship between increases in con-ractile state (Ees) and decreases in intraventricular dys-ynchrony in patients undergoing LV restoration by theor procedure [16].

imitations of the Studye analyzed acute hemodynamic effects occurring within

0 seconds after initiation of IABP in heart failure patientsith open chest under general anesthesia. Longer-term

nalysis may show differences due to metabolic effects byossible increases in coronary flow and or resulting fromompensatory cardiovascular reflexes. NYHA class III-IVatients received small constant dosages of inotropic agentshich may have changed their contractile state and theagnitude of the responses to IABP.The applied LV mechanical dyssynchrony analysis is

ot discriminative between slow paradoxical wall mo-ions as known from LV aneurysms or fast wall motionsnown from dilated cardiomyopathy or left bundleranch block [14, 16, 23, 27]. We assume that, mechanis-

ically, both will have similar effects on LV performance.The population we studied included patients with

schemic heart disease and mitral valve dysfunction, andid not include all potential IABP indications.

onclusionsrecisely timed IABP in heart failure patients is highlyffective in generating beat-to-beat improvements inystolic and diastolic LV performance as demonstratedy beat-to-beat increases in SV and decreases in LVfterload, LVESV, preload and LV mechanical dyssyn-hrony. These beat-to-beat improvements are due toecreases in aortic impedance, were generally estab-

ished within four beats after IABP initiation, becauseetabolic effects due to possible changes in coronary

ow and cardiovascular compensatory reflexes may bexcluded in this time frame. Decreases in LVESV andVESP delineated the ESPVR and its slope, the Ees,

mplying that the largest SV increases occur in patientsith lowest contractile state.Premature IAB inflation markedly impaired LV ejec-

ion and relaxation by afterload increase and concomi-ant LV mechanical dyssynchrony increase during theecond part of the ejection phase, indicating that prema-ure IAB inflation, as may occur during arrhythmia, mayave detrimental effects on cardiac performance in heart

ailure patients. Late IAB deflation resulted in increasedV and increased SW by afterload increase during early

jection and afterload decrease in late ejection, indicating

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hat incidental late IAB deflation will not negatively affectardiac performance.

e wish to thank Professor Attilio Maseri, MD, PhD, for hiseview of this manuscript. This study was funded by the Depart-ent of Cardiac Surgery, San Raffaele University Hospital

Milan, Italy) and Arrow International (Reading, PA).

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2005;79:872-880 Ann Thorac SurgBovelander and Ottavio Alfieri

Jan J. Schreuder, Francesco Maisano, Andrea Donelli, Jos R.C. Jansen, Pat Hanlon, Jan Performance in Patients With Low Ejection Fraction

Beat-to-Beat Effects of Intraaortic Balloon Pump Timing on Left Ventricular

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