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Prophylactic Ventricular Wrapping Does Not Impair Diastolic Function
S130
Journal of Cardiac Failure Vol. 11 No. 6 Suppl. 2005
Surgery, Transplantation, Devices 145
147
Early Post Infarction Ventricular Restraint Improves Borderzone Dynamics during Remodeling James J. Pilla1,2, Aaron S. Blom1, Joseph H. Gorman III1, Daniel J. Brockman1, John Affuso1, Landi M. Parish1, Hiroaki Sakamoto1, Michael A. Acker1, Robert C. Gorman1; 1 Surgery, University of Pennsylvania, School of Medicine, Philadelphia, PA; 2 Radiology, University of Pennsylvania, School of Medicine, Philadelphia, PA
Chronic Benefit after Cardiac Resynchronization Therapy Is Associated with Acute Improvement in Diastolic Function in Patients with Moderate Acute Improvement in Systolic Function Rodney W. Salo, Ding Jiang, Yu Yinghong, Angelo Auricchio; Basic Research Department, Guidant Corporation, St. Paul, MN; Applied Research Department, Guidant Corporation, St. Paul, MN; Department of Medicine, University of Magdeburg, Magdeburg, Germany
Background: Early infarct expansion impairs function of the normally perfused borderzone myocardium (BZM), initiates adverse remodeling, and portends a poor long-term outcome. Early ventricular restraint has been demonstrated to improve global remodeling but its effect on BZM function has not been assessed. Using an ovine model of infarct induced remodeling and MRI, we tested the hypothesis that ventricular restraint early after MI preserves BZM function and reduces remodeling. Methods: Six sheep had a large anterior infarction after ligation of all diagonal branches of the LAD. One week after infarction 3 sheep had placement of a CorCap쑓 Cardiac Support Device (CSD) to restrain infarct expansion. Global remodeling and borderzone wall thickening were assessed using MRI before and 8 weeks after infarction. Results: Global remodeling was greatly improved in the CSD compared to control [figure1, ED; end-diastole, ES; end-systole, EIVC; end-isovolumic contraction]. BZM systolic wall thickening was similar in both groups at baseline (13.5 ⫾ 2.0%, control; 12.8 ⫾ 2.0%, CSD, P ⫽ NS). After 8 weeks of infarction induced remodeling systolic wall thickening decreased significantly to 4.9 ⫾ 0.7%, in the control group, p ⫽ 0.03. Systolic wall thickening was, however preserved in the CSD group at 8 weeks: 11.0 ⫾ 1.6%, p ⫽ NS. In the control group all thickening occurred during isovolemic contraction (IVC). No further thickening occurred during ejection. The CSD improved late systolic wall thickening over control. Conclusion: Ventricular restraint early after MI improves contractile function of the BZM as well as global indices of ventricular remodeling. The dynamics of BZM wall thickening are profoundly impaired by the remodeling process. The CSD improves but does not normalize BZM wall thickening dynamics.
Cardiac Resynchronization Therapy (CRT) has been shown to acutely improve systolic function in failing hearts by correcting intraventricular dyssynchrony during contraction. Intraventricular dyssynchrony can also impact ventricular relaxation resulting in diastolic dysfunction. Thus, CRT may improve diastolic function and this may contribute to chronic benefit, especially in patients (pts) who show moderate acute improvement in systolic function. Methods: 102 pts (NYHA class II-III, EF ⬍ 40% and QRS width ⬎120 ms) enrolled in the PATH CHF II trial were studied. Each pt underwent acute CRT testing at the lateral wall of the left ventricle (LV) at five AV delays. Maximum LV dP/dt, aortic pulse pressure (PP), and LV end-diastolic pressure (LVEDP) were monitored with a Millar microtip catheter. Pts then received chronic CRT at the tested site using the AV delay that gave the greatest acute increase in maximum LV dP/dt and PP. Patients with an acute increase in PP ⬍ 15 mmHg and maximum LV dP/dt ⬍ 20 mmHg/ sec were considered to have, at most, moderate systolic improvement. Before implant and after one year, pts underwent exercise testing to determine peak oxygen consumption (peak VO2). Chronic benefit was defined as an increase in peak VO2 after one year of therapy. Results: As shown in the accompanying plot of the chronic change in Peak VO2 vs. acute change in LVEDP in pts with acute increase in PP ⬍ 15 mmHg and in LV dP/dt ⬍ 20 mmHg/sec (41% of pts), there was little or no chronic benefit unless coupled with an acute decrease in LVEDP. Acute change in LV dP/dt predicted the correct chronic response in 53% of these pts while LVEDP predicted correctly in 68% of pts. Conclusions: In pts with moderate acute improvement in systolic function, a concomitant improvement in diastolic function, indicated by an acute decrease in LVEDP, is necessary for chronic CRT benefit. Therefore, the impact of CRT on diastolic function should be considered during CRT optimization.
146 Prophylactic Ventricular Wrapping Does Not Impair Diastolic Function Landi M. Parish1, Ahmad Zeeshan1, Benjamin M. Jackson1, Theodore Plappert2, Martin G. St. John-Sutton2, Joseph H. Gorman III1, Robert C. Gorman1; 1Harrison Department of Surgical Research, University of Pennsylvania School of Medicine, Philadelphia, PA; 2Department of Medicine, University of Pennsylvania School of Medicine, Philadelphia, PA Introduction: Ventricular wrapping has been shown to reduce adverse remodeling in ovine models of ischemic heart failure. It is unknown whether ventricular wrapping adversely affects diastolic function. We used two ovine models of heart failure to evaluate the effect of ventricular wrapping on diastolic function. Methods: Sheep assigned to the treatment group had a left ventricular wrap placed prior to either an anteroapical (N ⫽ 6) or posterobasal (N ⫽ 10) infarct, while control sheep received infarct only (anteroapical N ⫽ 7, posterobasal N ⫽ 5). Continuous LV pressure was measured with a high fidelity pressure transducer (Millar Instruments). Sheep were followed for 8 weeks. The time constant of LV pressure decline (tau), LVEDP, and maximum negative dLVP/dT were calculated. Results: No measure of diastolic function was significantly different at any timepoint in either model (Table; posterobasal infarct data not shown). Conclusion: Ventricular wrapping reduces adverse remodeling after myocardial infarction without significantly reducing diastolic function. Diastolic Function in Apical Infarct: Wrap vs. Control
Tau (1/s)
LVEDP (mmHg) Max Negative dLVP/dt (mmHg/s)
Control Wrap p Control Wrap p Control Wrap p
Baseline
Post Ischemia
2 Weeks
5 Weeks
8 Weeks
0.023 ⫾ 0.003 0.020 ⫾ 0.003 0.505 5.00 ⫾ 2.30 1.98 ⫾ 3.18 0.448 ⫺1629 ⫾ 82 ⫺1551 ⫾ 110 0.578
0.030 ⫾ 0.003 0.027 ⫾ 0.002 0.358 15.13 ⫾ 3.08 13.97 ⫾ 2.52 0.776 ⫺1383 ⫾ 117 ⫺1476 ⫾ 78 0.509
0.019 ⫾ 0.001 0.020 ⫾ 0.003 0.808 2.37 ⫾ 2.25 0.56 ⫾ 2.16 0.573 ⫺1582 ⫾ 150 ⫺1480 ⫾ 122 0.606
0.022 ⫾ 0.002 0.022 ⫾ 0.005 0.874 4.22 ⫾ 2.70 ⫺0.94 ⫾ 2.21 0.169 ⫺1577 ⫾ 143 ⫺1479 ⫾ 135 0.630
0.020 ⫾ 0.003 0.018 ⫾ 0.003 0.563 1.95 ⫾ 3.65 0.76 ⫾ 3.25 0.816 ⫺1566 ⫾ 129 ⫺1603 ⫾ 64 0.809
P-values are by Student’s t-test.
148 Peritransplant Ischemic Injury Triggers Mobilization of Stem Cells to Allograft Following Heart Transplantation Mohamad H. Yamani1, Daniel J. Cook2, Norman B. Ratliff3, E. Murat Tuzcu1, Yang Yu1, Robert Hobbs1, Gustavo Rincon1, Corinne Bott-Silverman1, James B. Young1, Nicholas Smedira4, Randall C. Starling1; 1Cardiovascular Medicine, Cleveland Clinic Foundation; 2Allogen Laboratory; 3Anatomic Pathology; 4Cardiothoracic Surgery, Cleveland Clinic Foundation, Cleveland, OH Myocardial ischemia has been shown to trigger mobilization of stem cells to the heart in animal experiments. Objectives: We evaluated chimerism and stromal cell-derived factor-1 (SDF-1) expression in response to peri-transplant ischemic injury following human heart transplantation. Methods: Between January 1998 and April 2002, a total of 114 male recipients received hearts from female donors. Of these 114 recipients, 26 had evidence of ischemic injury on their initial heart biopsies (Ischemia group). These were compared to the remaining 88 patients (Control group). Heart biopsy specimens obtained initially at one week and at one year post transplant, were evaluated from 20 matched patients of each group for the presence of Y chromosome containing nuclei. SDF-1 mRNA and protein expressions were also evaluated on initial heart biopsy specimens. Results: At one week, Y chromosome containing nuclei were significantly increased in the Ischemia group (0.68% vs 0.04%, P ⬍ 0.0001) compared to Control. These were positive for c-kit suggesting stem cell in origin. A significant 3.3 fold increased mRNA expression (P ⫽ 0.001) and 2.8 fold increased protein expression (P ⫽ 0.01) of SDF-1 was noted in the Ischemia group. At one year, Y chromosome was detected in 0.29% of cardiomyocyte nuclei in the ischemia group but none in Control. At one year, 3 patients in the ischemic group, but none in control, had evidence of graft dysfunction (P ⫽ 0.01). The left ventricular ejection fractions were 35%, 40%, and 45%, respectively. The freedom from vasculopathy was 41% in the ischemic group compared to 95% in the Control group at 5 years (P ⬍ 0.001). Further, the ischemic group experienced worse 4-year survival, 64% versus 85% (P ⫽ 0.047). Conclusions: This is the first report to describe upregulation of SDF-1 in human heart transplantation in response to ischemic injury. Peritransplant ischemic injury is associated with worse vasculopathy and poorer survival.
Journal of Cardiac Failure Vol. 11 No. 6 Suppl. 2005
Surgery, Transplantation, Devices 145
147
Early Post Infarction Ventricular Restraint Improves Borderzone Dynamics during Remodeling James J. Pilla1,2, Aaron S. Blom1, Joseph H. Gorman III1, Daniel J. Brockman1, John Affuso1, Landi M. Parish1, Hiroaki Sakamoto1, Michael A. Acker1, Robert C. Gorman1; 1 Surgery, University of Pennsylvania, School of Medicine, Philadelphia, PA; 2 Radiology, University of Pennsylvania, School of Medicine, Philadelphia, PA
Chronic Benefit after Cardiac Resynchronization Therapy Is Associated with Acute Improvement in Diastolic Function in Patients with Moderate Acute Improvement in Systolic Function Rodney W. Salo, Ding Jiang, Yu Yinghong, Angelo Auricchio; Basic Research Department, Guidant Corporation, St. Paul, MN; Applied Research Department, Guidant Corporation, St. Paul, MN; Department of Medicine, University of Magdeburg, Magdeburg, Germany
Background: Early infarct expansion impairs function of the normally perfused borderzone myocardium (BZM), initiates adverse remodeling, and portends a poor long-term outcome. Early ventricular restraint has been demonstrated to improve global remodeling but its effect on BZM function has not been assessed. Using an ovine model of infarct induced remodeling and MRI, we tested the hypothesis that ventricular restraint early after MI preserves BZM function and reduces remodeling. Methods: Six sheep had a large anterior infarction after ligation of all diagonal branches of the LAD. One week after infarction 3 sheep had placement of a CorCap쑓 Cardiac Support Device (CSD) to restrain infarct expansion. Global remodeling and borderzone wall thickening were assessed using MRI before and 8 weeks after infarction. Results: Global remodeling was greatly improved in the CSD compared to control [figure1, ED; end-diastole, ES; end-systole, EIVC; end-isovolumic contraction]. BZM systolic wall thickening was similar in both groups at baseline (13.5 ⫾ 2.0%, control; 12.8 ⫾ 2.0%, CSD, P ⫽ NS). After 8 weeks of infarction induced remodeling systolic wall thickening decreased significantly to 4.9 ⫾ 0.7%, in the control group, p ⫽ 0.03. Systolic wall thickening was, however preserved in the CSD group at 8 weeks: 11.0 ⫾ 1.6%, p ⫽ NS. In the control group all thickening occurred during isovolemic contraction (IVC). No further thickening occurred during ejection. The CSD improved late systolic wall thickening over control. Conclusion: Ventricular restraint early after MI improves contractile function of the BZM as well as global indices of ventricular remodeling. The dynamics of BZM wall thickening are profoundly impaired by the remodeling process. The CSD improves but does not normalize BZM wall thickening dynamics.
Cardiac Resynchronization Therapy (CRT) has been shown to acutely improve systolic function in failing hearts by correcting intraventricular dyssynchrony during contraction. Intraventricular dyssynchrony can also impact ventricular relaxation resulting in diastolic dysfunction. Thus, CRT may improve diastolic function and this may contribute to chronic benefit, especially in patients (pts) who show moderate acute improvement in systolic function. Methods: 102 pts (NYHA class II-III, EF ⬍ 40% and QRS width ⬎120 ms) enrolled in the PATH CHF II trial were studied. Each pt underwent acute CRT testing at the lateral wall of the left ventricle (LV) at five AV delays. Maximum LV dP/dt, aortic pulse pressure (PP), and LV end-diastolic pressure (LVEDP) were monitored with a Millar microtip catheter. Pts then received chronic CRT at the tested site using the AV delay that gave the greatest acute increase in maximum LV dP/dt and PP. Patients with an acute increase in PP ⬍ 15 mmHg and maximum LV dP/dt ⬍ 20 mmHg/ sec were considered to have, at most, moderate systolic improvement. Before implant and after one year, pts underwent exercise testing to determine peak oxygen consumption (peak VO2). Chronic benefit was defined as an increase in peak VO2 after one year of therapy. Results: As shown in the accompanying plot of the chronic change in Peak VO2 vs. acute change in LVEDP in pts with acute increase in PP ⬍ 15 mmHg and in LV dP/dt ⬍ 20 mmHg/sec (41% of pts), there was little or no chronic benefit unless coupled with an acute decrease in LVEDP. Acute change in LV dP/dt predicted the correct chronic response in 53% of these pts while LVEDP predicted correctly in 68% of pts. Conclusions: In pts with moderate acute improvement in systolic function, a concomitant improvement in diastolic function, indicated by an acute decrease in LVEDP, is necessary for chronic CRT benefit. Therefore, the impact of CRT on diastolic function should be considered during CRT optimization.
146 Prophylactic Ventricular Wrapping Does Not Impair Diastolic Function Landi M. Parish1, Ahmad Zeeshan1, Benjamin M. Jackson1, Theodore Plappert2, Martin G. St. John-Sutton2, Joseph H. Gorman III1, Robert C. Gorman1; 1Harrison Department of Surgical Research, University of Pennsylvania School of Medicine, Philadelphia, PA; 2Department of Medicine, University of Pennsylvania School of Medicine, Philadelphia, PA Introduction: Ventricular wrapping has been shown to reduce adverse remodeling in ovine models of ischemic heart failure. It is unknown whether ventricular wrapping adversely affects diastolic function. We used two ovine models of heart failure to evaluate the effect of ventricular wrapping on diastolic function. Methods: Sheep assigned to the treatment group had a left ventricular wrap placed prior to either an anteroapical (N ⫽ 6) or posterobasal (N ⫽ 10) infarct, while control sheep received infarct only (anteroapical N ⫽ 7, posterobasal N ⫽ 5). Continuous LV pressure was measured with a high fidelity pressure transducer (Millar Instruments). Sheep were followed for 8 weeks. The time constant of LV pressure decline (tau), LVEDP, and maximum negative dLVP/dT were calculated. Results: No measure of diastolic function was significantly different at any timepoint in either model (Table; posterobasal infarct data not shown). Conclusion: Ventricular wrapping reduces adverse remodeling after myocardial infarction without significantly reducing diastolic function. Diastolic Function in Apical Infarct: Wrap vs. Control
Tau (1/s)
LVEDP (mmHg) Max Negative dLVP/dt (mmHg/s)
Control Wrap p Control Wrap p Control Wrap p
Baseline
Post Ischemia
2 Weeks
5 Weeks
8 Weeks
0.023 ⫾ 0.003 0.020 ⫾ 0.003 0.505 5.00 ⫾ 2.30 1.98 ⫾ 3.18 0.448 ⫺1629 ⫾ 82 ⫺1551 ⫾ 110 0.578
0.030 ⫾ 0.003 0.027 ⫾ 0.002 0.358 15.13 ⫾ 3.08 13.97 ⫾ 2.52 0.776 ⫺1383 ⫾ 117 ⫺1476 ⫾ 78 0.509
0.019 ⫾ 0.001 0.020 ⫾ 0.003 0.808 2.37 ⫾ 2.25 0.56 ⫾ 2.16 0.573 ⫺1582 ⫾ 150 ⫺1480 ⫾ 122 0.606
0.022 ⫾ 0.002 0.022 ⫾ 0.005 0.874 4.22 ⫾ 2.70 ⫺0.94 ⫾ 2.21 0.169 ⫺1577 ⫾ 143 ⫺1479 ⫾ 135 0.630
0.020 ⫾ 0.003 0.018 ⫾ 0.003 0.563 1.95 ⫾ 3.65 0.76 ⫾ 3.25 0.816 ⫺1566 ⫾ 129 ⫺1603 ⫾ 64 0.809
P-values are by Student’s t-test.
148 Peritransplant Ischemic Injury Triggers Mobilization of Stem Cells to Allograft Following Heart Transplantation Mohamad H. Yamani1, Daniel J. Cook2, Norman B. Ratliff3, E. Murat Tuzcu1, Yang Yu1, Robert Hobbs1, Gustavo Rincon1, Corinne Bott-Silverman1, James B. Young1, Nicholas Smedira4, Randall C. Starling1; 1Cardiovascular Medicine, Cleveland Clinic Foundation; 2Allogen Laboratory; 3Anatomic Pathology; 4Cardiothoracic Surgery, Cleveland Clinic Foundation, Cleveland, OH Myocardial ischemia has been shown to trigger mobilization of stem cells to the heart in animal experiments. Objectives: We evaluated chimerism and stromal cell-derived factor-1 (SDF-1) expression in response to peri-transplant ischemic injury following human heart transplantation. Methods: Between January 1998 and April 2002, a total of 114 male recipients received hearts from female donors. Of these 114 recipients, 26 had evidence of ischemic injury on their initial heart biopsies (Ischemia group). These were compared to the remaining 88 patients (Control group). Heart biopsy specimens obtained initially at one week and at one year post transplant, were evaluated from 20 matched patients of each group for the presence of Y chromosome containing nuclei. SDF-1 mRNA and protein expressions were also evaluated on initial heart biopsy specimens. Results: At one week, Y chromosome containing nuclei were significantly increased in the Ischemia group (0.68% vs 0.04%, P ⬍ 0.0001) compared to Control. These were positive for c-kit suggesting stem cell in origin. A significant 3.3 fold increased mRNA expression (P ⫽ 0.001) and 2.8 fold increased protein expression (P ⫽ 0.01) of SDF-1 was noted in the Ischemia group. At one year, Y chromosome was detected in 0.29% of cardiomyocyte nuclei in the ischemia group but none in Control. At one year, 3 patients in the ischemic group, but none in control, had evidence of graft dysfunction (P ⫽ 0.01). The left ventricular ejection fractions were 35%, 40%, and 45%, respectively. The freedom from vasculopathy was 41% in the ischemic group compared to 95% in the Control group at 5 years (P ⬍ 0.001). Further, the ischemic group experienced worse 4-year survival, 64% versus 85% (P ⫽ 0.047). Conclusions: This is the first report to describe upregulation of SDF-1 in human heart transplantation in response to ischemic injury. Peritransplant ischemic injury is associated with worse vasculopathy and poorer survival.