Beat-to-Beat Effects of Intraaortic Balloon Pump Timing on Left Ventricular Performance in Patients With Low Ejection Fraction

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1 Beat-to-Beat Effects of Intraaortic Balloon Pump Timing on Left Ventricular Performance in Patients With Low Ejection Fraction Jan J. Schreuder, MD, PhD, Francesco Maisano, MD, Andrea Donelli, MS, Jos R. C. Jansen, PhD, Pat Hanlon, RN, Jan Bovelander, CRNA, and Ottavio Alfieri, MD Department of Cardiac Surgery, San Raffaele University Hospital, Milan, Italy; Department of Intensive Care, Leiden University Medical Center, Leiden, The Netherlands; Arrow International, Reading, Pennsylvania Background. Intraaortic balloon counterpulsation (IABP) timing errors during arrhythmia may result in afterload increases which may negatively influence left ventricular (LV) ejection and LV mechanical dyssynchrony. The aim of our study was to determine beat-tobeat effects of properly timed IABP, premature IAB inflation, and late IAB deflation on LV performance and LV mechanical dyssynchrony in heart failure patients undergoing cardiac surgery. Methods. In 15 patients, LV pressure-volume relations and LV dyssynchrony were measured by conductance volume catheter. Properly timed IABP was evaluated at a 1:1 assist ratio within a 10 seconds time-span. Premature IAB inflation and late IAB deflation were evaluated at a 1:4 assist ratio. Results. Properly timed 1:1 IABP acutely decreased LV end-systolic volume by 6.1% (p < ) and LV endsystolic pressure by 17.5% (p < ) due to decreased aortic impedance. Stroke volume (SV) increased by 14% (p < ), which correlated markedly with a decrease of LV mechanical dyssynchrony (p < ). The largest SV increases occurred in patients with lowest contractile state. Premature IAB inflation decreased SV by 20% (p < ) due to abrupt increase of LV afterload during late ejection. Late IAB deflation increased SV and stroke work by 18% (p < ) and 16% (p < 0.01) respectively, due to increased afterload during early ejection and decreased afterload during late ejection. Conclusions. Left ventricular performance during IABP is causally related to changes in LV afterload, and the timing of these changes in relation to contraction or relaxation phases, to LV mechanical dyssynchrony and to contractile state. (Ann Thorac Surg 2005;79:872 80) 2005 by The Society of Thoracic Surgeons Intraaortic balloon counterpulsation (IABP) to support cardiac function has been well documented during the last three decades [1 7]. Primary effects of properly timed IABP are diastolic aortic pressure augmentation and left ventricular (LV) afterload reduction by decreasing impedance to LV ejection [3, 4]. LV volume and LV end-diastolic pressure (EDP) have been demonstrated to See page 1017 decrease in patients treated with IABP, whereas cardiac output, ejection fraction (EF), and coronary flow may increase [2 6]. However, arrhythmic episodes often result in incorrect IABP timing decreasing its efficacy [7]. Premature IAB inflation may increase aortic impedance and therefore LV afterload late in the ejection phase, whereas late IAB deflation may increase afterload during early ejection. Acute load increases applied during contraction or relaxation in heart muscle preparations or in intact animal ventricles induced increases or decreases in ejection Accepted for publication July 29, Address reprint requests to Dr Schreuder, Department of Cardiac Surgery, San Raffaele University Hospital, Via Olgettina 60, Milan, Italy; schreuder@libero.it. phase duration, respectively [8 11]. Moreover, altered loading conditions may result in dyssynchronous relaxation of the LV [11, 12]. Myocardial relaxation is known to be sensitive to afterload and to LV dyssynchrony in patients with dilated cardiomyopathy [13]. LV mechanical dyssynchrony in these patients decreased due to reduction in wall stress induced by interventions such as vasodilators, cardiomyoplasty, or LV ventricular reduction surgery [13 16]. Recently we demonstrated a close relationship between cardiac performance and intraventricular mechanical dyssynchrony in patients undergoing LV restoration by the Dor procedure [16]. Hence we hypothesized that IABP timing in patients with low EF may considerably influence cardiac performance by acute afterload changes and concomitant changes in LV mechanical dyssynchrony. Effects of IABP on LV performance and LV mechanical dyssynchrony were analyzed beat-to-beat from the pressurevolume plane during conventionally timed IABP, prema- Dr Schreuder, Mr Bovelander and Ms Hanlon disclose that they have a financial relationship with Arrow International; Dr Schreuder also has a financial relationship with CD Leycom by The Society of Thoracic Surgeons /05/$30.00 Published by Elsevier Inc doi: /j.athoracsur

2 Ann Thorac Surg SCHREUDER ET AL 2005;79: LEFT VENTRICULAR PERFORMANCE AND IABP TIMING Abbreviations and Acronyms EDP end-diastolic pressure EDV end-diastolic volume Ees end-systolic elastance EF ejection fraction ESPVR end-systolic pressure-volume relationship ESV end-systolic volume ESP end-systolic pressure IABP intraaortic balloon counterpulsation LV left ventricle SV stroke volume SW stroke work ture IAB inflation and late IAB deflation, using the conductance volume catheter technique [14 23]. The beatto-beat measurements were performed within a time span of 10 seconds after an IABP change to exclude cardiovascular compensatory reflexes and or metabolic effects from possible increases in coronary flow [4]. Beat-to-beat changes of cardiac performance with IABP may then be primarily attributed to acute changes in aortic impedance. Patients and Methods Patients Fifteen patients, New York Heart Association (NYHA) class II IV, 48 to 64 years old, EF 21.5% 8.5%, undergoing cardiac surgery requiring prophylactic IABP, were studied. Eight patients underwent LV aneurysmectomy (6 patients with coronary artery bypass graft [CABG]), 6 patients underwent CABG (1 with mitral valve repair), and 1 patient underwent mitral valve repair. Open chest hemodynamic evaluations of acute effects of IABP were performed before cardiopulmonary bypass. The study protocol was approved by the local ethics committee and written informed patient consent was obtained. 873 Instrumentation All patients received high dose opioid anesthesia. Five patients belonging to NYHA class III-IV received small steady-state dosages of inotropics (dobutamine 5u kg 1 min 1 ). The IAB catheters (Narrowflex; Arrow International, Reading, PA) were positioned under transesophageal echo control in the descending thoracic aorta at 2-cm distal to the left subclavian artery. Thermodilution catheters (Edwards Lifesciences, Inc., Irvine, CA) were inserted into the pulmonary artery and micromanometerconductance catheters (F7; CD Leycom, Zoetermeer, The Netherlands) into the LV through a pulmonary vein. The cardiac function analyzer (Leycom CFL512; CD Leycom) uses a conductance catheter to measure ventricular volumes at a dual-field excitation mode [17, 21]. The method is based on measuring time-varying electrical conductance of 5 to 7 ventricular blood segments, delineated by selected catheter electrodes. Correct positioning of the conductance catheter was verified by transesophageal echocardiography and by inspection of the segmental conductance signals. The feasibility of the conductance catheter method to measure real-time ventricular volume has been demonstrated in animal and clinical studies [14 23]. Reproducibility of conductance catheter measurements was demonstrated in patients undergoing cardiac surgery [19]. Beat-to-beat stroke volume changes were validated by pulse contour analysis [20]. Time-varying segmental conductance reflects timevarying segmental LV volume as obtained and validated by cine-angiography in canine hearts [21]. Parallel conductance was assessed by injection of 10 ml hypertonic saline (6%) into the pulmonary artery [17]. Effective conductance stroke volume (SV) was defined as difference between conductance volumes at the times of dp/dt max and dp/dt max, which largely eliminates contribution of possible regurgitant flows. Absolute LV volumes were calculated by matching effective conductance SV with simultaneously measured thermodilution SV and by subtracting parallel conductance from total conductance volume. Mechanical Ventricular Dyssynchrony Ventricular dyssynchrony assessment from segmental LV volume signals has been previously described for cine-angiography and the conductance catheter [14, 23, 24]. The conductance catheter measures volume segments located perpendicular to the long heart-axis. A volume segment was defined dyssynchronous when the volume change in that segment was in opposite direction (dyskinetic) or showed no change (akinetic) compared to total LV volume change. Segmental dyssynchrony was quantified by percent time a segment was dyssynchronous in relation to total volume change, total dyssynchrony was the average of segmental dyssynchrony in all segments [14, 23]. Systolic dyssynchrony was calculated from R-wave to dp/dt max and diastolic dyssynchrony from dp/dt max to R-wave. Data Analysis Electrocardiogram (ECG), LV pressure, aortic pressure and volume signals were digitized at a sampling rate of 250 Hz. The following variables were calculated: Tau, index of LV pressure relaxation, defined as time required from LV pressure at dp/dt max to be reduced by half [25]; peak ejection rate calculated as maximal dv/dt; Endsystolic elastance (Ees), representing a load independent index of contractile state, was determined from unassisted beats and first 8 seconds of IABP (Fig 1); Ees1 included last unassisted beat (arrow) and first 3 assisted beats; Ees2 included last unassisted beat and three latest assisted beats prior to10 seconds after IABP initiation. Values are mean standard deviation (SD) of at least four heart cycles. Comparisons between different IABP modes were assessed with a paired t-test. Statistical relations between variables were tested by least-squares linear regression. Statistical significance was assumed at p less than CARDIOVASCULAR

3 874 SCHREUDER ET AL Ann Thorac Surg LEFT VENTRICULAR PERFORMANCE AND IABP TIMING 2005;79: Fig 1. Effects of regular 1:1 IABP initiation (arrows), with IAB inflation performed near the dicrotic notch of the Pao and deflation effecting decrease in end-diastolic Pao in patient A (NYHA III, EF 14%) and patient B (NYHA III, EF 22%). IABP induced acute stroke volume increases by decreasing LV end-systolic pressure (P) and volume (V), delineating nonlinear Ees (dotted lines) followed by end-diastolic P-V decreases. Numbers 1 10 represent first 10 beats after IABP initiation. (Ees end-systolic elastance; EF ejection fraction; IABP intraaortic balloon pump; LV left ventricular; NYHA New York Heart Association; Pao mean aortic pressure; PLV left ventricular pressure; VLV left ventricular volume.) Measurement Protocol Effects of properly timed IABP (inflation at the dicrotic notch, deflation inducing end-diastolic aortic pressure decrease) were measured during 15 seconds ventilatory stop, the first 5 seconds without IABP followed by assist at a 1:1 ratio (Fig 1). All measurements were made under steady state conditions. Premature IAB inflation was set 130 to190ms before the dicrotic notch to produce an abrupt afterload increase in the second part of the ejection phase (Fig 2 [A, b]). Late IAB deflation was set 110 to180ms after the R-wave, around the start of the ejection phase, to produce a clear afterload increase in the first part of the ejection phase (Fig 2 [B, c]). Both timing errors were evaluated at a 1:4 assist ratio during a 15 seconds ventilatory stop. Results Hemodynamic Response to Conventionally Timed IABP The acute effects of proper IABP timing at a 1:1 assist ratio are illustrated by two typical examples (Fig 1). The largest decreases in LV pressure, LV end-systolic volume (ESV), LV end-diastolic volume (EDV) and concomitant increases in SV are observed within 4 assisted beats. Decreases in LVESV and LV endsystolic pressure (ESP) delineate the end-systolic P-V relationship and its slope, the Ees, representing a load independent index of contractile state. The average hemodynamic responses to 1:1 IABP are presented in Table 1. Heart rate (HR) and Tau did not change significantly. SV increased (p ) by a mean of 14% ranging from 2% to 34%. Stroke work (SW) decreased by a mean of 5% (p 0.01). LVESV, LVESP, LVEDV, and LVEDP decreased by a mean of 6% (p ), 16 mm Hg (p ), 2% (p 0.001) and 1.6 mm Hg (p 0.001), respectively. IABP decreased dp/dt max by 8% (p 0.01) and dp/dt max by 17.5% (p ). Mean aortic pressure increased by 15.5% (p ). Peak ejection rate and EF increased by 9% (p 0.03) and 3% (p 0.001, net increase), respectively. End-systolic elastance appeared to be nonlinear, the slope determined over the first 8 seconds after IABP initiation at 1:1 assist was mm Hg/mL; Ees1, determined from the first three assisted beats was significantly (p 0.01) steeper than Ees2, using the last unassisted loops and those from 4 to 8 seconds after IABP initiation (Table 1 and Fig 1).

4 Ann Thorac Surg SCHREUDER ET AL 2005;79: LEFT VENTRICULAR PERFORMANCE AND IABP TIMING 875 CARDIOVASCULAR Fig 2. Premature IAB inflation (A) applied 150 ms (arrows, b) before the dicrotic notch of the aortic pressure (Pao) generated abrupt increases in LV afterload in late ejection with impairment of LV volume (VLV) ejection in NYHA II patient (EF 33%). Late IAB deflation (B) increased end-diastolic Pao (arrows, b) and increased afterload during early ejection (c) followed by decreased afterload in late ejection increasing stroke volume in NYHA III patient (EF 24%); a, b, and c represent beats analyzed according to Tables 2 and 3. (EF ejection fraction; LV left ventricular; NYHA New York Heart Association; PLV left ventricular pressure.) Table 1. Effects of IABP at 1:1 Off On p Value HR beats/min CI L/min/m SV ml SW mm Hg ml EDV ml ESV ml EF % EDP mm Hg ESP mm Hg Pao mm Hg dp/dt max mm Hg/s dp/dt max mm Hg/s Tau ms PER ml/s SysDys % DiaDys % Ees1-2 mm Hg/mL CI cardiac index; DiaDys diastolic dyssynchrony; EDP end-diastolic pressure; EDV end-diastolic volume; Ees end-systolic elastance; EF ejection fraction; ESP end-systolic pressure; ESV end-systolic volume; HR heart rate; Pao mean aortic pressure; PER peak ejection rate; SV stroke volume; SW stroke work; SysDys systolic dyssynchrony. n 15.

5 876 SCHREUDER ET AL Ann Thorac Surg LEFT VENTRICULAR PERFORMANCE AND IABP TIMING 2005;79: Table 2. Early IAB Inflation Pre During p Values Post p Values a b a-b c a-c HR beats/min SV ml SW mm Hg ml EDV ml ESV ml EF % EDP mm Hg ESP mm Hg dp/dt max mm Hg/s dp/dt max mm Hg/s Tau ms SysDys % DiaDys % DiaDys diastolic dyssynchrony; EDP end-diastolic pressure; EDV end-diastolic volume; EF ejection fraction; ESP end-systolic pressure; ESV end-systolic volume; HR heart rate; IAB intraaortic balloon; SV stroke volume; SW stroke work; SysDys systolic dyssynchrony. n 13. Hemodynamic Response to Premature IAB Inflation The adverse effects of premature inflation are illustrated in Figure 2A. Abrupt increases in LV afterload late in LV ejection, as a result from increased aortic impedance, induced premature closure of the aortic valve and impaired LV ejection. Table 2 provides average data, before premature inflation (a), during premature IAB inflation applied at 130 to 190 ms before the dicrotic notch (b), and after IAB assist (c). LVESP, or end-systolic afterload, increased (p ) during premature IAB inflation by a mean of 14 mm Hg. SV decreased (p ) by 20%, ranging from 6% to 55%, with concomitant increase in LVESV (p ). Stroke work decreased by a mean of 25% (p 0.002). Tau increased by 44% (p ), indicating deterioration of LV relaxation. The 16% mean increase (p 0.05) in SV in the postassisted beat compared with the preassisted beat did not compensate for the 20% SV decrease of the preceding beat. Hemodynamic Response to Late IAB Deflation Figure 2B depicts an example of late deflation causing increased end-diastolic aortic pressure and aortic impedance, which increased LV afterload during early ejection (c), followed by a reduction in afterload due to IAB deflation during late ejection. Table 3 presents average data of late IAB deflation initiated 110 to 180ms after the Table 3. Late IAB Deflation Pre During Post p Values a b c a-c HR beats/min SV ml SW mm Hg ml EDV ml ESV ml EF % EDP mm Hg ESP mm Hg dp/dt max mm Hg/s dp/dt max mm Hg/s Tau ms SysDys % DiaDys % DiaDys diastolic dyssynchrony; EDP end-diastolic pressure; EDV end-diastolic volume; EF ejection fraction; ESP end-systolic pressure; ESV end-systolic volume; HR heart rate; IAB intraaortic balloon; SV stroke volume; SW stroke work; SysDys systolic dyssynchrony. n 11.

6 Ann Thorac Surg SCHREUDER ET AL 2005;79: LEFT VENTRICULAR PERFORMANCE AND IABP TIMING 877 CARDIOVASCULAR Fig 3. Five LV segmental volume tracings (s1-s5) and TVLV used for Dys analysis in patient A (Fig 1). Pronounced paradoxical segmental volume movements are located in the apex (s1-s2). The calculated Dys decreased immediately after initiation of IABP at a 1:1 ratio (arrow). (Dys dyssynchrony; IABP intraaortic balloon pump; LV left ventricular; TVLV total volume tracing.) R-wave. SV increased (p ) by a mean of 18% in the postassisted beat (c) ranging from 2 to 49% due to decreases in LVESV (p ) compared with preassisted beats (a). Peak dp/dt increased (p ) by 8% due to late IAB deflation, whereas Tau was shorter (p 0.005). SW increased by 16% (p 0.01) in contrast to conventional timed IABP. Fig 4. (A, B) Regression diagrams from IABP at 1:1 assist ratio and from (C) early/late IAB inflation/deflation at 1:4 assist ratio demonstrating: (A) percent change in SV (% SV) versus LV TDys ( TDys); (B) % SV versus Ees; and (C) % SV versus change in systolic dyssynchrony ( SysDys). Dotted lines represent 95% prediction limits. (Ees end-systolic elastance; IABP intraaortic balloon pump; LV left ventricular; SV stroke volume; TDys total dyssynchrony.) LV Performance and Mechanical Dyssynchrony Figure 3 displays segmental and total volume tracings showing a reduction in LV dyssynchrony after IABP initiation at 1:1 assist. Systolic and diastolic dyssynchrony decreased in all patients by a net mean of 2% (p 0.02 and p 0.001, Table 1) within 8 seconds of initiation IABP. Percent SV change was inversely correlated with total LV dyssynchrony change (p , Fig 4A), emphasizing its relation with LVESV and LVEDV, which codetermine alterations in SV. The percent increase in SV during IABP assist at 1:1 inversely correlated with Ees (p 0.008, Fig 4B), indicating that largest increases in SV occurred in the patients with lowest contractile state. Systolic dyssynchrony increased abruptly during premature inflation by a net mean of 1.5% (Table 2, p 0.03), although diastolic dyssynchrony and LVEDV remained unchanged. During late IAB deflation systolic and diastolic dyssynchrony did not change significantly (Table 3). The combined results of the premature inflation and late deflation data revealed a marked inverse correlation between changes in SV and systolic dyssynchrony (Fig 4C, p ).

7 878 SCHREUDER ET AL Ann Thorac Surg LEFT VENTRICULAR PERFORMANCE AND IABP TIMING 2005;79: Comment This study demonstrates acute beneficial effects of properly timed IABP at a 1:1 ratio in heart failure patients. Decreases in aortic impedance resulted in instantaneous increases in SV by LV afterload reduction with concomitant decreases in LVESV, LVEDV, and LV mechanical dyssynchrony. The decreases in LVESV and LVESP delineated the slope (Ees) of the end-systolic P-V relationship. The largest increases in SV occurred in the patients with the lowest contractile state. Premature IAB inflation acutely impaired LV ejection due to abrupt afterload increase during late ejection, increasing systolic dyssynchrony, and Tau impairing myocardial relaxation. Late IAB deflation induced a dual effect, afterload increase during early ejection and decrease in late ejection, combined these increased SV and improved LV relaxation, but at increased SW. Hemodynamics Conventionally Timed IABP Short-term effectiveness of IABP was demonstrated by Nichols and colleagues [3], using multigated cardiac blood pool imaging. Cardiac output increased by 10%, 10 minutes after initiation of IABP. Our study shows in all patients, despite the heterogeneous population, beat-tobeat SV increases due to decreases in LVESV, preceding decreases in LVEDV and LVEDP. Similar changes were observed in animals with heart failure using LV pressure-volume loops [5]. Beat-to-beat improvement of cardiac performance with IABP, as demonstrated by Cheung and coworkers [4] and confirmed in the present study, may be primarily attributed to acute decreases in aortic impedance reducing LV afterload, because cardiovascular compensatory reflexes and metabolic effects from possible increases in coronary flow can be excluded within the measurement time of 10 seconds. The decreases in LVESV and LVESP determine the end-systolic elastance (Ees) as slope of the end-systolic P-V relationship, which implies that the lower the slope the larger the decrease in LVESV. The inverse correlation between Ees and SV indicates that patients with the lowest contractile state will show the largest increases in SV with IABP (Fig 4B). The significant nonlinear convex Ees (Fig 1, Table 1) is related to low contractile state as was demonstrated by Burkhoff and associates [26] in animal studies. Decreases in wall motion abnormalities have been demonstrated 10 minutes after IABP initiation [3]. Dyssynchrony of wall motion reduces mechanical efficiency of ventricular ejection by inducing premature onset and impaired relaxation [10]. LV mechanical dyssynchrony, as demonstrated in patients with dilated cardiomyopathy and LBBB using tagged MRI, was shown to be a key predictor for multi site pacing efficacy [27]. Patients with dilated cardiomyopathy and marked LV dyssynchrony showed decreases in LV mechanical dyssynchrony by wall stress reduction following vasodilator administration, cardiomyoplasty or LV reduction surgery [13 16]. The acute decreases in both systolic and diastolic dyssynchrony with IABP point to a similar mechanism, based on decreases in impedance reducing LV afterload with concomitant decreases in LVESV and preload, improving LV mechanical efficiency. Reductions in LV total dyssynchrony showed a strong inverse correlation with increases in SV induced by IABP assist at 1:1 (Fig 4A). The largest increases in SV with IABP result from largest decreases in LVESV combined with smallest decreases in LVEDV. Therefore increases in SV with conventional IABP are causally related to decreases in LV afterload, preload, contractile state and concomitant changes in total LV mechanical dyssynchrony. Premature IAB Inflation-Late IAB Deflation The present study shows that abrupt increases in aortic impedance, and therefore in LV afterload, imposed during late ejection result in shortened ejection phases, as was demonstrated in isolated cardiac muscle experiments and in vivo animal experiments [8 11]. Premature IAB inflation performed 130 to 190 ms before the dicrotic notch resulted in increased LVESP, Tau, and decreased SV. These findings agree with the animal study by Zile and Gaasch [9] where IAB inflation was applied 80 ms before the dicrotic notch. Factors such as IAB positioning and pulse-wave velocity from IAB to LV can explain differences in timing between man and animal results and the variance observed in the current patient population. The pulse-wave velocity will also vary with changes in cardiac output or aortic compliance. IAB inflation performed in animals 20 ms before the dicrotic notch revealed no change in contraction duration while early relaxation rate increased [9]. In the present study we observed that premature IAB inflation applied less than 50 ms before the dicrotic notch did not change SV. The significant increase in systolic dyssynchrony during premature IAB inflation is analogous to increase in dyssynchronous relaxation due to altered loading conditions, as described in animal studies by Gaasch and associates [11] and Schafer and colleagues [12]. Conventional IAB deflation should produce a clear reduction in end-diastolic aortic pressure. However, Kern and coworkers [28] demonstrated in a clinical IABP study that IAB deflation might be performed later in diastole without adverse hemodynamic effects. Our study shows that incidental late IAB deflation at a 1:4 assist ratio may result in immediate increases in SV, although at increased SW. Animal experiments showed that afterload increase applied during early ejection prolongs ejection phase duration similar to a decrease in afterload applied in late ejection [8 10]. Initial afterload increase in early ejection and decrease in late ejection due to late IAB deflation may explain the relatively large mean SV increase of 18% SV in a single IABP assisted beat (Fig 2 [B, c]). Late IAB deflation induced a significantly higher SW in two ways, by increasing PLV in early ejection and by increased SV. Possible beneficial effects of late IAB deflation applied at a 1:1 ratio should be investigated in specific patient conditions. On the other hand, incidental late deflation which may occur during IABP due to arrhythmia should have no detrimental effects on cardiac performance.

8 Ann Thorac Surg SCHREUDER ET AL 2005;79: LEFT VENTRICULAR PERFORMANCE AND IABP TIMING The marked beat-to-beat SV alterations due to afterload changes applied at different times in the cardiac cycle with premature inflation or late deflation markedly correlated with systolic dyssynchrony changes (Fig 4C). Brutsaert s hypothesis that LV mechanical dyssynchrony or nonuniformity may act as a modulator of cardiac performance together with heart rate, contractile state, preload and afterload may therefore be applicable in heart failure patients [29]. In a previous study we demonstrated a direct relationship between increases in contractile state (Ees) and decreases in intraventricular dyssynchrony in patients undergoing LV restoration by the Dor procedure [16]. Limitations of the Study We analyzed acute hemodynamic effects occurring within 10 seconds after initiation of IABP in heart failure patients with open chest under general anesthesia. Longer-term analysis may show differences due to metabolic effects by possible increases in coronary flow and or resulting from compensatory cardiovascular reflexes. NYHA class III-IV patients received small constant dosages of inotropic agents which may have changed their contractile state and the magnitude of the responses to IABP. The applied LV mechanical dyssynchrony analysis is not discriminative between slow paradoxical wall motions as known from LV aneurysms or fast wall motions known from dilated cardiomyopathy or left bundle branch block [14, 16, 23, 27]. We assume that, mechanistically, both will have similar effects on LV performance. The population we studied included patients with ischemic heart disease and mitral valve dysfunction, and did not include all potential IABP indications. Conclusions Precisely timed IABP in heart failure patients is highly effective in generating beat-to-beat improvements in systolic and diastolic LV performance as demonstrated by beat-to-beat increases in SV and decreases in LV afterload, LVESV, preload and LV mechanical dyssynchrony. These beat-to-beat improvements are due to decreases in aortic impedance, were generally established within four beats after IABP initiation, because metabolic effects due to possible changes in coronary flow and cardiovascular compensatory reflexes may be excluded in this time frame. Decreases in LVESV and LVESP delineated the ESPVR and its slope, the Ees, implying that the largest SV increases occur in patients with lowest contractile state. Premature IAB inflation markedly impaired LV ejection and relaxation by afterload increase and concomitant LV mechanical dyssynchrony increase during the second part of the ejection phase, indicating that premature IAB inflation, as may occur during arrhythmia, may have detrimental effects on cardiac performance in heart failure patients. Late IAB deflation resulted in increased SV and increased SW by afterload increase during early ejection and afterload decrease in late ejection, indicating that incidental late IAB deflation will not negatively affect cardiac performance. We wish to thank Professor Attilio Maseri, MD, PhD, for his review of this manuscript. This study was funded by the Department of Cardiac Surgery, San Raffaele University Hospital (Milan, Italy) and Arrow International (Reading, PA). References Kantrowitz A, Kantrowitz A. Experimental augmentation of coronary flow by retardation of arterial pressure pulse. 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