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Journal of the American College of Cardiology Vol. 36, No. 7, 2000 © 2000 by the American College of Cardiology ISSN 0735-1097/00/$20.00 Published by Elsevier Science Inc. PII S0735-1097(00)01036-6 Acute and Short-Term Effects of Partial Left in Assessment by Pressure-Volume Loops Jan J. Schreuder, MD, PHD,†§ Paul Steendijk, PHD,࿣ Frederik H. van der Veen, PHD,‡ Ottavio Alfieri, MD,† Theo van der Nagel, MS,§ Roberto Lorusso, MD, PHD,§ Jan-Melle van Dantzig, MD, PHD,‡ Kees B. Prenger, MD,§ Jan Baan, PHD,࿣ Hein J. J. Wellens, MD, PHD,‡ Randas J. V. Batista, MD* Campina Grande do Sul, Brazil; Milan, Italy; Maastricht and Leiden, The Netherlands

OBJECTIVES The aim of this study was to evaluate the short-term effects of partial left ventriculectomy (PLV) on left ventricular (LV) pressure-volume (P-V) loops, wall stress, and the synchrony of LV segmental volume motions in patients with dilated cardiomyopathy. BACKGROUND Surgical LV volume reduction is under investigation as an alternative for, or bridge to, transplantation for patients with end-stage dilated cardiomyopathy. METHODS We measured P-V loops in eight patients with dilated cardiomyopathy before, during and two to five days after PLV. The conductance catheter technique was used to measure LV volume instantaneously. RESULTS The PLV reduced end-diastolic volume (EDV) acutely from 141 Ϯ 27 to 68 Ϯ 16 ml/m2 (p Ͻ 0.001) and to 65 Ϯ 6 ml/m2 (p Ͻ 0.001) at two to five days postoperation (post-op). Cardiac index (CI) increased from 1.5 Ϯ 0.5 to 2.6 Ϯ 0.6 l/min/m2 (p Ͻ 0.002) and was 1.8 Ϯ 0.3 l/min/m2 (NS) at two to five days post-op. The LV ejection fraction (EF) increased from 15 Ϯ 8% to 35 Ϯ 6% (p Ͻ 0.001) and to 26 Ϯ 3% (p Ͻ 0.003) at two to five days post-op. Tau decreased from 54 Ϯ 8to38Ϯ 6ms(pϽ 0.05) and was 38 Ϯ 5 ms (NS) at two to five days post-op. Peak wall stress decreased from 254 Ϯ 85 to 157 Ϯ 49 mm Hg (p Ͻ 0.001) and to 184 Ϯ 40 mm Hg (p Ͻ 0.003) two to five days post-op. The synchrony of LV segmental volume changes increased from 68 Ϯ 6% before PLV to 80 Ϯ 7% after surgery (p Ͻ 0.01) and was 73 Ϯ 4% (NS) at two to five days post-op. The LV synchrony index and CI showed a significant (p Ͻ 0.0001) correlation. CONCLUSIONS The acute decrease in LV volume in heart-failure patients following PLV resulted at short-term in unchanged SV, increases in LVEF, and decreases in peak wall stress. The increase in LV synchrony with PLV suggests that the transition to a more uniform LV contraction and relaxation pattern might be a rationale of the working mechanism of PLV. (J Am Coll Cardiol 2000;36:2104–14) © 2000 by the American College of Cardiology

Batista et al. (1) introduced surgical reconstruction of the dure. The procedure aims to restore the normal relationship heart by partial left ventriculectomy (PLV) as a treatment between ventricular mass and dimension to normalize wall for end-stage heart failure in patients with dilated cardio- stress throughout the cardiac cycle. From a multiple com- myopathy. Often, PLV is combined with mitral valve and partment elastance model study, in which the effects of PLV tricuspid valve reconstruction (1–5). The procedure has were simulated, it was concluded that PLV leads to a reduction in wall stress (WS) for any level of LV pressure See page 2115 (6). This implies an improvement of the efficiency by which WS is transferred to intraventricular pressure. been performed in patients with dilated cardiomyopathy, In patients with dilated cardiomyopathy, impairment of with or without known etiology, and who are grouped in cardiac performance is generally associated with impaired New York Heart Association (NYHA) functional classes III LV relaxation and diastolic and systolic wall motion abnor- and IV. Initial reports (2–5) indicated improved left ven- malities (7–9). Nonuniformity in wall motion reduces the tricular (LV) ejection fraction (EF), and decreased LV mechanical efficiency of ventricular ejection and contributes end-diastolic pressure (EDP) following the surgical proce- to regional diastolic abnormalities (10). In a previous study we observed marked LV nonuniformity in patients with dilated cardiomyopathy before undergoing . From the *Hospital Angelina Caron, Campina Grande do Sul, Brazil; †Depart- Six months after cardiomyoplasty, WS was decreased by the ment of , San Raffaele Hospital, Milan, Italy; ‡Department of Cardiology and the §Cardiovascular Research Institute Maastricht, Maastricht, The wrapped latissimus dorsi muscle and the decreased Netherlands; and the ࿣Department of Cardiology, Leiden University Medical Center, LVEDV, whereas LV nonuniformity was markedly de- Leiden, The Netherlands. This study was funded by the Cardiovascular Research creased (7). Because PLV should lead to a decrease in WS, Institute, University of Maastricht, Maastricht, The Netherlands. Manuscript received April 7, 1999; revised manuscript received April 27, 2000, PLV should also improve the mechanical efficiency of LV accepted September 19, 2000. ejection by reducing LV nonuniformity. JACC Vol. 36, No. 7, 2000 Schreuder et al. 2105 December 2000:2104–14 P-V Loops in Partial Left Ventriculectomy

Before surgery as well as up to five days after the operation, Abbreviations and Acronyms the patients were catheterized. All operations were per- CI ϭ cardiac index formed by R.J.V.B. The study was approved by the medical EDP ϭ end-diastolic pressure ethics committee of the hospital. Informed patient consent ϭ EDV end-diastolic volume was obtained for insertion of the catheters and the measure- EF ϭ ejection fraction ESV ϭ end-systolic volume ments. ESP ϭ end-systolic pressure Surgical procedure. The surgical technique has been de- LV ϭ left /ventricular scribed previously by Batista et al. (1). After inducing PLV ϭ partial left ventriculectomy anesthesia, a midline sternotomy was performed. Bypass ϭ SNP sodium nitroprusside was routinely instituted, using double venous cannulas. All SV ϭ stroke volume WS ϭ wall stress procedures with exception of the autotransplantation (Table 1) were performed on a beating heart. In seven patients a tricuspid valvuloplasty was done by a modified De Vega The conductance catheter was used to study LV nonuni- plasty. Subsequently, in all cases the posterolateral wall was formity by measuring regional synchrony of contraction and excised, starting near the apex of the heart. The incision was relaxation. With this technique, the volume changes occur- performed down to the crux of the heart, excising the obtuse ring in five LV segments, perpendicular to the long heart marginal coronary artery, and in between the papillary axis, can be measured throughout the cardiac cycle (11). By muscles to preserve the mitral valve. The mitral valve was comparing changes in LV segmental volumes with total LV reconstructed using the Alfieri repair technique, approxi- volume changes, the LV synchrony, representing mechani- mating the mid-portion of the free edge of the anterior and cal efficiency, can be calculated throughout the cardiac cycle. posterior leaflets with a single suture (12). The ventriculot- To evaluate the acute hemodynamic effects of PLV in omy was closed with absorbable sutures. patients with dilated cardiomyopathy, we measured LV Anesthesia. All patients received 0.05 mg/kg of lorazepam pressure-volume (P-V) loops and LV synchrony before, as oral premedication 2 h before surgery. Anesthesia was during, and up to five days after the operation. induced with hypnomidate (0.25 mg/kg) and maintained by ethrane (0.2% to 0.5%) and fentanyl (3␮g/kg/h). For muscle METHODS relaxation, 0.1 mg/kg of pancuronium bromide was given. The patients were ventilated with an oxygen/air mixture ϭ Patients. Eight consecutive patients, 45 to 60 years old, (FiO2 0.5) at a ventilatory rate of 12/min and ventilatory scheduled to undergo PLV were studied preoperatively, volume was adjusted to maintain arterial CO2 tension during the procedure, and up to five days postoperatively. between 32 and 42 mm Hg. Sodium-nitroprusside (SNP), All patients had dilated cardiomyopathy, either idiopathic isoprenaline and adrenaline were used during surgery before or related to postischemic damage, or (Table and after bypass as needed to maintain systolic blood 1). At the time of the PLV procedure, seven patients were pressure between 80 to 100 mm Hg and heart rate between in NYHA functional class IV, and one in class III (patient 90 to 120 beats/min. 8). All patients were receiving chronic treatment with Instrumentation. Patients were sedated and heparinized diuretics, digoxin, and angiotensin-converting enzyme before catheterization. A Swan-Ganz thermodilution cath- (ACE) inhibitors at the time of PLV. The patients studied eter was placed via a subclavian vein into the pulmonary were operated on in the Hospital Angelina Caron, Brazil. artery. A dual-micromanometer transducer conductance

Table 1. Patient Characteristics Age; CI Associated Area Mass Rhythm Pts Gender Origin l/min/m2 Surgery exc cm2 exc g Pre–Post 1 59; F Idiopathic TR, MR, RAR 42 48 SR-SR 2 58; M Idiopathic 1.6 TR, MR 42 69 SR-SR 3 47; M Ischemic 1.35 TR, MR, Th, 73 92 SR-SR CABG 1X 4 52; M Idiopathic 1.05 TR, MR, RAR, 39 86 AF-AF LAR, AT 5 60; M Ischemic 1.07 TR, MR, 33 66 AF-SR CABG 2X 6 45; M Chagas 1.54 TR, MR, RAR, 43 70 AF-SR RVR 7 57; M Idiopathic 1.4 TR, MR, AVR 74 83 AF-SR 8 50; M Idiopathic 2.44 26 46 SR-SR

AF ϭ atrial fibrillation; AT ϭ autotransplant; AVR ϭ aortic valve reconstruction; CABG ϭ coronary artery bypass grafting; CI ϭ cardiac index; LAR ϭ left atrial reconstruction; MR ϭ ; RAR ϭ right atrial reconstruction; RVR ϭ right ventricular reduction; SR ϭ sinus rhythm; Th ϭ thrombectomy; TR ϭ tricuspid valve repair. 2106 Schreuder et al. JACC Vol. 36, No. 7, 2000 P-V Loops in Partial Left Ventriculectomy December 2000:2104–14 catheter (F7, Sentron, CD Leycom, Zoetermeer, The the simultaneous change of the total volume signal. The LV Netherlands) was inserted via the femoral artery into the LV segmental synchrony along the long heart axis was quanti- for measurement of aortic and LV pressures and LV fied by calculating the percentage of time over the cardiac volume. The feasibility of the conductance catheter method cycle that a segmental signal was synchronous with the total during cardiac surgery has been shown in a previous study volume signal. Thus, a segmental synchrony of 80% means (13). The correct position of the conductance catheter was that the segmental conductance signal was in phase (i.e., verified by fluoroscopy and by inspection of the segmental showing changes in the same direction) with the total conductance signals. The conductance catheter was con- volume signal during 80% of the full cardiac cycle. Conse- nected to a Leycom Sigma-5DF signal conditioner- quently, during the remaining 20% of time this segmental processor (CD Leycom, Zoetermeer, The Netherlands) to signal would show volume changes in the opposite direction measure instantaneous LV and segmental volumes of the total volume signal. An overall LV synchrony index (7,11,13,14). The dual-field excitation mode, which has (Sync) was obtained by determining the synchrony for all been shown to improve the accuracy of the method, was individual segments, and calculating their mean value. used in all patients (15). Time-varying wall stress. Obtaining ventricular pressure The conductance catheter measures the instantaneous P(t) and volume V(t) simultaneously enabled us to calculate volumes of five ventricular segments delineated by selected time-varying wall stress, WS(t). Arts et al. (17) have shown catheter electrodes. It has been shown previously that the that WS is fairly uniform throughout the ventricular wall time-varying segmental conductance reflects time-varying and is relatively independent of the geometry of the ventri- segmental LV volume as obtained by cine computed tomo- cle and can be calculated as graphy (CT) in canine (16). Total volume is calcu- ͑ ͒ ϭ ͑ ͒⅐͑ ϩ ⅐ ͑ ͒ ͒ lated as the sum of the segmental volumes. Occasionally, the WS t P t 1 3 V t /Vwall . segment near the base of the heart was in the and Preoperative (pre-op) wall volume (Vwall) was calculated therefore not included in the calculations. as the volume of a spherical shell with a thickness equal to The conductance catheter not only continuously mea- the thickness of the excised segment and an internal sures the relative amount of blood in the LV but also the diameter as estimated from pre-op end-diastolic volume conductance of the myocardium and other surrounding (EDV). Postoperative (post-op) Vwall was calculated by tissues, the parallel conductance. This parallel conductance subtracting the volume of the excised segment from the offset term (Vc) for the LV was estimated by injection of 7.5 pre-op wall volume. Peak WS is the maximum of the WS(t) ml hypertonic saline (6%) into the (11). curve. The Vc estimation was performed by the dedicated software Data acquisition and analysis. Electrocardiogram ECG package CONDUCT-PC (CD Leycom, Zoetermeer, The (extremity leads), aortic pressure (PaO), LV pressure and Netherlands). The implemented algorithm finds the best Vc LV volume signals were digitized at a sampling rate of values, thus avoiding an operator-dependent bias. At each 200 Hz and stored on hard disc for subsequent analysis. The stage of the procedure the parallel conductance measure- dedicated data-acquisition and data-analysis software pack- ments were performed in duplicate. To get absolute volumes age CONDUCT-PC was applied for conductance-catheter with the conductance catheter technique, the effective con- related data analysis. In addition to the volumetric variables, ductance SV must be matched with a gold standard SV pressures, and the peak first derivatives, the following measurement technique. Therefore, cardiac output (CO) variables were calculated: tau, the time constant of LV was determined at each stage of the procedure by perform- pressure relaxation, which was defined as the time required ing five thermodilution measurements, using a cardiac from the LV pressure at peak negative dP/dt to be reduced output computer (COM-2, Baxter), and using injections of by half (18); peak ejection rate and peak filling rate, 10 ml ice-cold glucose 5%. Consequently, absolute LV calculated as maximal ϪdV/dt and maximal dV/dt, respec- volumes were calculated by matching effective conductance tively. Effective LV ejection fraction (EF) was calculated SV with simultaneously measured thermodilution SV, and from the thermodilution derived stroke volume (SV) and by subtracting parallel conductance correction volume from the LVEDV measured by the conductance catheter. total conductance volume. Both methods are indicator- Measurement protocol. Hemodynamic measurements dilution methods and therefore largely independent of were obtained at five stages: before anesthetic induction anticipated geometric changes, as will be caused by the (pre-surgery); immediately preceding cardiopulmonary by- PLV. pass (pre-bypass); 15 min after cardiopulmonary bypass Ventricular synchrony. Regional contraction patterns were (post-bypass); after sternal closure (post-surgery); and dur- studied by recording the segmental conductance signals ing recatheterization at two to five days after the operation individually, making assessment of regional synchrony of (re-cath). Because the surgery and large changes in both contraction and relaxation possible. The volume segments pre- and afterload may affect catheter position and parallel are located perpendicular to the long heart axis. A segmental conductance, we performed the following measurements to volume signal was defined as synchronous whenever the calibrate the conductance catheter. At each stage of the change in this segmental signal was in the same direction as procedure we determined parallel conductance in duplicate, JACC Vol. 36, No. 7, 2000 Schreuder et al. 2107 December 2000:2104–14 P-V Loops in Partial Left Ventriculectomy

Figure 1. P-V loops of Patient 2 during all stages of the PLV procedure. The P-V loops are shifted to the left after the PLV. At the first re-cath after two days, EDP and EDV were increased compared to post-surgery, whereas five days after PLV, both EDP and EDV were lowest.

blood resistivity and CO by thermodilution (5 injections). RESULTS Steady-state P-V loops were acquired during at least 15 s, Clinical and operative data are presented in Table 1. Mean achieved by breath-holding when the patients were awake excised endocardial area was 46 Ϯ 18 cm2; mean excised and by ventilatory stop when the patients were anesthetized. cardiac mass was 70 Ϯ 17 g. Statistical analysis. Statistical analysis of all hemodynamic Missing data for Patients 1 and 3 in the pre-surgery series measured variables was performed by repeated-measures is due to failure to insert the conductance catheters before analysis of variance (ANOVA), using the following multiple induction. No re-cath data are available for Patient 7, who linear regression model: died on the third postoperative day due to an arrhythmia. ϭ 0 ϩ ¥ C ⅐ ϩ¥ P ⅐ Also, in two other patients no data on re-cath are available; Y a a i Ci a i Pi in Patient 1 this was due to failure to insert the conductance catheter in the LV, whereas Patient 6 was still dependent on (19). The dependent Y represents the various hemodynamic intensive care treatment at the time of the scheduled variables (heart rate, cardiac index, etc.), the dummy vari- re-cath. ables C code the conditions (pre-surgery, pre-bypass, post- i Low doses (Ͻ0.5 ␮g/kg/min) of SNP were used pre- and bypass, post-surgery and re-cath), and the dummy variables post-bypass in Patients 1, 2, 3, 7, and 8, whereas Patients 4 P code the individual patients. For the set of patient i and 6 received similar doses only at post-bypass. Low doses variables we used effects coding; for the conditions we used of isoprenaline or adrenaline were used post-bypass in reference cell coding, with the pre-surgery condition as 0 Patients 2, 5, and 7; these infusions were stopped 5 min control group. Using this coding, the intercept a yields the before the measurements were performed. During pre- mean value of the dependent in the pre-surgery condition, surgery and re-cath measurements, none of these drugs were C and the coefficients a i give the difference between the administered. corresponding condition (pre-bypass, post-bypass, etc.) and In Figure 1, the P-V loops of Patient 2 at all operative C the pre-surgery value. The p values of the coefficients a i stages, and one extra re-cath at two days after PLV, are indicate the significance of these differences. The dummy shown. In Figure 2, the left ventricular P-V loops of all variables Ai account for between-subject differences, allow- eight patients before and after the PLV are given. Preop- ing all patients to have a different mean value. The standard eratively, the P-V loops are heterogeneous; the P-V loops of P deviation (SD) of the group of patient coefficients, a i,isa Patients 6 and 7 show characteristics of aortic regurgitation, measure of between-subject variability. Statistical analysis while signs of mitral regurgitation are present in Patient 5. was performed using commercial software (Microsoft Excel Postoperatively, the P-V loops are more homogeneous. An 97, Microsoft Corp.). Statistical significance was defined as obvious shift toward lower LV volumes after PLV is present p Ͻ 0.05. in all patients, indicating substantial surgical reversed re- 2108 Schreuder et al. JACC Vol. 36, No. 7, 2000 P-V Loops in Partial Left Ventriculectomy December 2000:2104–14

Figure 2. P-V loops of all eight patients before PLV (thick lines), after PLV (fine lines), and at re-cath two to five days after PLV (dotted lines). modeling. No clear signs of aortic and mitral regurgitation The LVEF increased after PLV in all patients from 15 Ϯ are present in the P-V loops after surgery. 8% at pre-bypass to 35 Ϯ 6% at post-surgery (p Ͻ 0.001) Table 2 provides data on all eight patients measured at all and remained increased at 26 Ϯ 3% during the re-cath (p Ͻ stages pre-surgery, pre-bypass, post-bypass, post-surgery, 0.003) compared to the pre-PLV series. The LVEDV and at re-cath two to five days after PLV. All P-V data were decreased from 141 Ϯ 27 at pre-bypass to 68 Ϯ 16 ml/m2 measured during 15-s sampling periods, and the values of all (p Ͻ 0.001) at post-surgery and to 65 Ϯ 6 ml/m2 (p Ͻ beats were averaged. No significant changes in heart rate 0.001) at re-cath. The LV end-systolic volume (ESV) (HR), SV, LV EDP, peak ϩdP/dt, peak ϪdP/dt, LV peak decreased from 109 Ϯ 23 at pre-surgery to 37 Ϯ 11 ml/m2 ejection rate, and LV peak filling rate were observed (p Ͻ 0.001) at post-surgery and to 38 Ϯ 5 ml/m2 (p Ͻ between these stages. Cardiac index (CI) increased from 0.001) at re-cath. Tau decreased from 54 Ϯ 8to38Ϯ 6ms pre-surgery 1.5 Ϯ 0.5 to 2.6 Ϯ 0.6 l/min/m2 (p Ͻ 0.002) at (p Ͻ 0.03) when comparing the pre-bypass and the post- post-surgery, and was 1.8 Ϯ 0.3 l/min/m2 (NS) at re-cath. surgery values. Peak WS decreased from a pre-surgery Table 2. Hemodynamic Variables at all Stages of the PLV Procedure 2000 7, 2000:2104–14 No. December 36, Vol. JACC HR CI SV EF EDV ESV EDP ESP ؉dP/dt ؊dP/dt TAU PER PFR PWS Sync Condition Patient (bpm) (l/min/m2) (ml) (%) (ml/m2) (ml/m2) (mm Hg) (mm Hg) (mm Hg/s) (mm Hg/s) (ms) (ml/s) (ml/s) (mm Hg) (%) Presurgery 1 2 51 1.60 56 23 135 92 14 95 565 Ϫ496 53 596 541 66 3 4 107 1.05 16 7 142 103 21 92 771 Ϫ640 44 784 708 189 67 5 161 1.07 15 6 105 92 20 96 847 Ϫ832 41 371 512 230 68 6 79 1.54 34 14 139 84 25 89 605 Ϫ650 58 1027 860 235 72 7 107 1.40 21 26 86 641 Ϫ545 59 8 131 2.44 37 16 117 75 10 166 2014 Ϫ1743 35 731 725 388 76 Mean 106 1.52 30 13 127 89 19 104 907 Ϫ818 48 702 669 261 70 ϮSD 38 0.51 16 7 16 10 6 30 553 468 10 242 143 87 4 Pre-bypass 1 89 3.46 56 23 168 113 23 117 946 Ϫ816 50 610 650 401 80 2 73 2.25 55 24 129 97 20 114 801 Ϫ634 56 553 613 295 67 3 117 1.35 17 7 171 149 35 80 676 Ϫ532 60 250 343 286 66 4 119 2.16 29 17 106 83 8 62 534 Ϫ442 49 441 526 158 67 5 112 1.12 23 10 105 92 14 60 379 Ϫ448 51 495 492 138 70 6 79 2.63 58 24 154 95 14 94 775 Ϫ661 59 1099 831 201 69 7 100 1.34 21 8 167 135 21 79 536 Ϫ468 63 574 912 272 58 8 134 1.34 19 8 129 105 13 98 1419 Ϫ967 40 728 968 282 68 Mean 103 1.96 35 15 141 109 18 88 758 Ϫ621 54 594 667 254 68 ϮSD 21 0.82 18 8 27 23 8 22 322 190 8 247 219 85 6 p-value 0.1 Post-bypass 1 131 2.62 29 25 83 59 37 64 375 Ϫ438 285 164 76 2 88 2.57 53 39 75 44 20 79 669 Ϫ629 50 317 450 195 77 3 142 2.38 25 34 49 28 28 72 859 Ϫ548 300 498 148 77 4 5 102 3.14 71 48 65 31 25 68 895 Ϫ711 39 533 675 139 89 6 123 3.50 50 45 65 33 21 78 852 Ϫ745 41 805 133 84 - op nPrilLf Ventriculectomy Left Partial in Loops P-V 7 8 124 3.05 48 30 81 55 33 87 1046 Ϫ726 55 469 548 217 76 Mean 118 2.88 46 37 70 42 27 75 783 Ϫ633 46 451 543 166 80 ϮSD 20 0.42 17 9 13 13 7 8 233 120 8 200 97 33 6 p-value Ͻ 0.002 0.1 Ͻ 0.001 Ͻ 0.001 Ͻ 0.001 Ͻ 0.004 Ͻ 0.001 Ͻ 0.02 Post-surgery 1 97 3.11 46 33 98 57 18 59 630 Ϫ604 34 436 616 219 76 2 93 2.34 45 38 67 36 13 65 759 Ϫ658 40 369 471 140 75 3 126 2.63 30 41 51 27 27 72 964 Ϫ690 40 341 431 137 74 4 105 1.75 27 31 55 21 9 46 501 Ϫ403 46 654 385 77 70 5 109 3.58 76 43 76 37 25 81 915 Ϫ736 40 636 820 153 90 Schreuder 6 123 2.90 41 36 65 43 16 69 692 Ϫ643 44 658 127 86 7 111 2.19 32 25 79 37 11 83 1095 Ϫ819 32 434 635 177 88 8 130 2.50 37 34 57 35 14 94 1569 Ϫ983 30 394 375 224 81 Mean 112 2.63 42 35 68 37 17 71 891 Ϫ692 38 490 533 157 80 al. et ϮSD 14 0.57 15 6 16 11 7 15 335 168 6 136 164 49 7 p-value Ͻ 0.002 0.1 Ͻ 0.001 Ͻ 0.001 Ͻ 0.001 Ͻ 0.002 Ͻ 0.03 Ͻ 0.001 Ͻ 0.007

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254 Ϯ 85 to 157 Ϯ 49 mm Hg (p Ͻ 0.001) at post-surgery 4 Ϯ Ͻ (%)

Sync and to 184 40 mm Hg (p 0.003) at re-cath two to five

peak filling days post-op. ϭ The LV synchrony index (Table 2) increased from 68 Ϯ 6% at pre-bypass to 80 Ϯ 7% (p Ͻ 0.01) at post-surgery and 0.003

PWS Ϯ Ͻ to 73 4% (NS) at re-cath. Five segmental volumes were (mm Hg) included at pre-bypass in all patients, with exception of Patient 2, in which four segments were included. Four PFR (ml/s) segments were included in all patients at post-bypass, except peak ejection rate; PFR

ϭ Patient 2, in which three segments were included.

515 464 153 71 Results of the calculated WS throughout one cardiac PER (ml/s) cycle of all patients are presented in Figure 3. The same cardiac cycles are presented as those used for the P-V loops 0.09 (ms) TAU

heart rate; PER in Figure 2. In all patients, systolic WS was decreased after

ϭ the procedure. Immediately after PLV a decreased WS throughout the cardiac cycle was observed in all patients

285 5 196 199with 40 the exception of Patient 1, where higher values during Ϫ 927 43 804 771 161 72 Ϫ 910Ϫ 697 40 415 390 167 76 Ϫ 1466Ϫ 1010 33 38 475 496 716 533 251 184 78 73 Ϫ 1048 35 270 326 187 69 ؊ dP/dt the diastolic filling phase were measured. In three out of five (mm Hg/s) patients (Patients 2,3,5) a decreased WS throughout the cardiac cycle during the re-cath at two to five days after PLV

end-systolic volume; HR was measured. In Patient 4, end-diastolic WS was increased ϭ ؉ dP/dt compared to pre-surgery, and in Patient 8 the WS was (mm Hg/s) increased during the diastolic filling phase.

ESP DISCUSSION (mm Hg) This study shows the acute and short-term effects of PLV end-systolic pressure; ESV 7 19 406 combined with various other cardiac reconstructions. The ϭ EDP LV volumes were reduced as anticipated with a concomitant (mm Hg) increase in LVEF, together with unchanged CI, SV, and ) 2 LV EDP. Peak WS decreased in all patients after PLV. The 0.001

ESV occurrence of systolic and diastolic paradoxical and asyn- (ml/m Ͻ chronous segmental LV volume motions decreased after

) PLV. ejection fraction; ESP 2

ϭ Hemodynamics. The pronounced acute average decrease 0.001 EDV Ͻ (ml/m in LVEDV by 52% immediately post-PLV, as measured with the conductance catheter technique, concurrently with an average mass reduction of 70 g, are comparable with 0.003 EF (%) results as measured with transesophageal

Ͻ by McCarthy et al. (3), Gorcsan et al. (4), and Popovic et al. end-diastolic volume; EF

LV synchrony index. (5). Differences in decreases in EDV for a certain amount of SV ϭ (ml) ϭ mass resection in different studies might be attributed to

) differences in wall thickness; therefore, to really compare 2 effects of mass resection on EDV, the excised endocardial

CI area should be known.

(l/min/m The increases in effective LVEF from 15% to 35% were

stroke volume; Sync similar to the intraoperative results of McCarthy et al. (3), ϭ from 16% to 33%. The two-week post-PLV LVEF results HR (bpm) end-diastolic pressure; EDV of Bocchi et al. (2), from 17% pre-PLV to 26% (n ϭ 24) are ϭ also similar to the one-week post-PLV mean values of 56 7 1048 1.56 118 34 2.16 23 35 30 67 72 41 42 23 28 91 129 958 1870 34 121 91 1.85 1.52 23 26 26 23 59 71 40 39 25 23 84 95 1383 927 2 103 1.78 31 30 58McCarthy 30 11 et al. (3) 86 of 23% 984 and with our two to five-day p-value MeanϮ SD 107 12 1.77 0.26 30 26 5post-PLV 3 65 value 6 38of 26%. 5 22 97 1224 peak wall stress; SV (continued)

ϭ The observed acute decreases in LVEDV and ESV and increases in LVEF after PLV are comparable with long- cardiac index; EDP

ϭ term hemodynamic effects of cardiomyoplasty in patients Condition Patient Re-cath 1 Table 2. CI rate; PWS with dilated cardiomyopathy. In a clinical study, we ob- JACC Vol. 36, No. 7, 2000 Schreuder et al. 2111 December 2000:2104–14 P-V Loops in Partial Left Ventriculectomy

Figure 3. Time-varying wall stress tracings throughout one cardiac cycle of all eight patients before PLV (thick lines), after PLV (fine lines) and at re-cath two to five days after PLV (dotted lines). served an increased LVEF from 27% to 40%, a decrease of Cardiac index (CI) did not change significantly when 26% in LVEDV as well as decreases in LVEDP at six comparing pre-PLV to re-cath values, which accords with months after cardiomyoplasty. At 12 months after cardio- the study of McCarthy et al. (3). However, comparing myoplasty, LVEDV was decreased by 40% (7). pre-surgery data with end-of-surgery data of the present A striking observation of the present and other PLV study revealed an increased CI. Moreover, in the four studies (2,3,5) is the unchanged SV after the procedure in low-output-state patients, who were re-catheterized (Pa- these patients. Reducing LV dimensions in normal hearts tients 2 through 5), this increase was maintained. These by about 50% should also reduce SV considerably. There- findings are similar to Bocchi et al. (2) and Popovic et al. fore, these dilated hearts apparently possess a property that (5), who also found increases in CI. Also, peak ϩdP/dt was preserves the SV when the volume has been reduced by the increased in the four low-output patients at re-cath, which PLV. This property is probably related to afterload decrease, indicates an increased contractile state because LV end- similar to the effects by which nitroprusside administration systolic pressure (ESP) was similar, and the LVEDV was in congestive heart failure patients may increase SV (20,21). decreased compared to the pre-PLV state. Additionally, 2112 Schreuder et al. JACC Vol. 36, No. 7, 2000 P-V Loops in Partial Left Ventriculectomy December 2000:2104–14

Figure 4. Tracings of LV volume segments of Patients 2 and 3 before and after PLV and at re-cath five days after PLV. Vlv ϭ total LV volume in time during four consecutive heart beats. Dotted lines ϭ start of the ejection phase. The pre-PLV segmental synchrony values of Patient 2 were 64%, 62%, 63% and 80% for, respectively, segments 1 through 4 yielding a synchrony index (Sync) of 68%, whereas at re-cath the segmental values were 75%, 77%, 71% and 80% yielding a Sync of 76%. these patients showed the lowest LV synchrony indices although in the two Patients (Patients 2 and 3) who were before PLV (Table 2), which were increased after PLV. recatherized on their fifth post-op day a decrease in EDP In congestive heart failure patients, the relaxation indices was measured (Fig. 1). From the PLV model study of peak ϪdP/dt and Tau are generally decreased and pro- Dickstein et al. (6) it can be predicted that LVEDP rises longed, respectively (8,9). In the present patient group these after PLV, with a positive correlation to the excised LV variables were grossly abnormal, with the exception of mass. This was confirmed by the intraoperative results of Patient 8. During re-cath, peak ϪdP/dt was more negative Gorcsan et al. (4), which showed increased regional end- in the four patients with the preoperatively low-output, and diastolic stiffness. However, McCarthy et al. (3) observed Tau was improved significantly, when comparing pre- postoperative (one week) decreases in left atrial pressures, bypass with post-surgery values, indicating a relaxation and Popovic et al. (5) reported a significant decrease in improvement of the compromised early diastolic phase. LVEDP two weeks after surgery. This might imply that The LVEDP did not change significantly due to PLV, during the first days after the operation, LVEDP is in- JACC Vol. 36, No. 7, 2000 Schreuder et al. 2113 December 2000:2104–14 P-V Loops in Partial Left Ventriculectomy creased, possibly due to edema around the suture-line, which might temporarily decrease ventricular distensibility. Wall stress. Ventricular wall stress is related directly to cavity volume and inversely to wall thickness. Hayashida et al. (22) demonstrated in patients with dilated cardiomyop- athy a markedly elevated WS throughout the cardiac cycle. The reduction in EDV and ESV by PLV will decrease WS, which, however, will be partly offset by the reduction in wall volume. Arts et al. (17) demonstrated that the ratio of myocardial fiber stress to LV pressure depends mainly on the ratio of cavity volume to wall volume, and is quite independent of geometry. Dickstein et al. (6) predicted in their model study, using the same WS equation, a reduction in peak WS for each reduction in mass of up to 75 g. From Figure 5. Linear regression diagram between CI (cardiac index) and Sync the present clinical data we confirm the decrease in peak (LV synchrony index) of all patients at all stages of the procedure. n ϭ 32, stress after PLV, which induces a decrease in cardiac R2 ϭ 0.54, p Ͻ 0.0001. All data points fall within 95% prediction limits afterload stress. Popovic et al. (5) observed significant (dotted lines). The highly significant correlation indicates the synchrony index as an important determinant of CI in this patient group. decreases in LV circumferential end-systolic and end- diastolic stresses two weeks after PLV. as well as to the decrease in LVEDV (7). Analogously, the The calculated WS is an estimation of the stress averaged acute synchronizing effects of PLV and associated proce- over the total LV wall, neglecting regional differences. In dures might be primarily ascribed to the marked acute this patient group we observed before PLV a marked decrease in LVEDV, and therefore to the PLV itself. asynchrony between LV segmental volume changes The aspect of segmental volume asynchrony reveals the throughout the cardiac cycle. This is an indication for ineffective mechanical cardiac work in these severe heart marked regional differences in WS at any moment in the failure patients. Segmental synchrony, during both contrac- cardiac cycle. Therefore, ventricular efficiency and maxi- mum work output might be compromised by asynchrony tion and relaxation, is a major determinant of efficient and regional stress differences. The LV nonuniformity mechanical cardiac performance (10). Figure 5 shows a might have led to an undetermined inaccuracy in the linear regression diagram between CI and the LV synchrony estimation of WS using the formula of Arts et al. (17), index from all measured values throughout the procedure in which assumes homogeneously distributed fiber stress and this study. This highly significant correlation clearly dem- strain. In case of asynchrony the actual regional peak wall onstrates the importance of a uniform contracting and stress is likely to be higher. Therefore, the calculated relaxing ventricle for efficient cardiac performance. The reduction in WS induced by PLV probably underestimates occurrence of marked nonuniformity in LV contraction and the actual reduction. relaxation in congestive heart failure patients and the Wall motion asynchrony. Figure 4 shows the segmental synchronizing effects of sodium-nitroprusside, nitroglycerin, conductance signals of two patients before and after PLV. cardiomyoplasty and PLV indicate a reversible state in the Prior to PLV, marked paradoxical movements throughout patients studied, which is caused by decreases in afterload the cardiac cycle of the ventricular volume segments can be stress and WS. observed, indicating diastolic and systolic wall motion asyn- Study limitations. The specific effects of PLV are difficult chrony, which were converted into more synchronous seg- to identify because of associated surgical procedures: coro- mental volume signals after PLV. This is consistent with nary artery bypass graft surgery, and mitral, tricuspid, and previous studies showing highly asynchronous regional wall aortic valve reconstruction. Only in Patient 8 was an isolated motions in patients with dilated cardiomyopathy (7,22). PLV procedure performed. In this NYHA functional class Nonuniformity reduces the mechanical efficiency of ventric- III patient, the PLV procedure induced short-term adverse ular ejection by inducing a premature onset and a decreased effects concerning CI, peak ϩdP/dt, peak ϪdP/dt and rate of LV pressure decline (10). Wall motion asynchrony is LVEDP when the pre-surgery and the two-day post-op a major determinant of impaired LV filling in patients with data are compared. Although most patients had additional healed myocardial infarction (23). Nonuniformity can be procedures, some major effects such as acute LV volume decreased by nitroprusside through afterload reduction (8). decrease, an increase in uniformity of contraction and In a previous study in patients with dilated cardiomyop- relaxation, and a decrease in WS can be primarily attributed athy we demonstrated that both nitroglycerin and cardio- to PLV. myoplasty improved segmental synchrony, probably by re- Considerable parts of the measurements were performed ducing myocardial afterload stress (7). The synchronizing in patients under anesthesia. Also, during the operation effects of cardiomyoplasty might be attributed to the active inotropic and vasodilatory therapy was given. However, latissimus dorsi muscle stimulation synchronizing effect (24) during the pre-surgery and the re-cath measurements, 2114 Schreuder et al. JACC Vol. 36, No. 7, 2000 P-V Loops in Partial Left Ventriculectomy December 2000:2104–14 patients did not receive drug treatment other than digoxin, 3. McCarthy PM, Starling RC, Wong J, et al. Early results with partial ACE inhibitors, and diuretics. left ventriculectomy. J Thorac Cardiovasc Surg 1997;114:755–65. 4. Gorcsan J, Feldman AM, Kormos RL, Mandorino WA, Demetris J, Another important limitation is the absence of clinical Batista RJV. Heterogeneous immediate effects of partial left ventricu- follow-up and long-term hemodynamic measurements. lectomy on cardiac performance. Circulation 1998;97:839–42. Thus, our study does not address the question of the 5. Popovic Z, Miric M, Gradinac S, et al. Effects of partial left ventriculectomy on left ventricular performance in patients with long-term value of the PLV operation. nonischemic dilated cardiomyopathy. J Am Coll Cardiol 1998;32: Conclusions. 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