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Transmural Heterogeneity of Cellular Level Power Output Is Reduced in Human Heart Failure
Abstracts S169 to host, HSC or MP are all rejected (dashed lines). Experiments are in progress to test whether increasing the MP dose will further improve outcome. Conclusion: Organ matched MP can induce tolerance in combination with autologous HSC, significantly increasing the potential clinical applicability of this approach to tolerance induction and importantly, indicating that reduced intensity preconditioning regimens should be feasible.
Purpose: Ischemic cardiomyopathy (iCMP) is a risk factor for poor survival after heart transplantation (HTx). Due to progressive organ shortage in Germany we tested whether end-stage iCMP patients might benefit from an aggressive revascularization strategy by coronary artery bypass surgery (CABG) vs. HTx. Methods: Analysis was done in 3,252 patients with iCMP who underwent CABG (n= 2,816) or HTx (n= 436) between 06/86 and 03/07. Survival was estimated by Kaplan-Meier analysis. Subgroup analysis was done with regard to ISHLT era (< 1991, 1992-2001, > 2002) and year of change in the German allocation policy (regional allocation < 2000; urgency policy ≥ 2001). Results: Overall survival at 5, 10, 15 and 20 years was similar in CABG vs. HTx patients (55% vs. 53%, 31% vs. 38%, 14% vs. 21% and 8% vs. 12%). There was a benefit of HTx vs. CABG if outcome was conditioned on 30 days (71% vs. 63%, 51% vs. 36%, 28% vs. 18% and 15% vs. 11%; p= 0.001) or 1 year (85% vs. 71%, 60% vs. 41%, 33% vs. 20% and 18% vs. 12%; p= 0.002). HTx vs. CABG was beneficial if performed between 1992 and 2001 (58% vs. 54%, 44% vs. 31%, 25% vs. 15% and 11% vs. 10%; p= 0.004) and even more beneficial if conditioned on 30-day (79% vs. 62%, 60% vs. 35%, 34% vs. 17% and 15% vs. 11%; p< 0.001) or 1-year survival (89% vs. 70%, 67% vs. 40%, 38% vs. 19% and 17% vs. 13%; p= 0.006). Regional allocation resulted in better survival rates vs. CABG only in 30-day (74% vs. 64%, 53% vs. 35%, 29% vs. 16% and 16% vs. 10%; p= 0.001) or 1-year survivors (74% vs. 64%, 53% vs. 35%, 29% vs. 16% and 16% vs. 10%; p= 0.005). Conclusion: Patients with end-stage iCMP represent a highly vulnerable cohort with poor prognosis. CABG procedure seems to be beneficial in these patients and should be considered in times of organ shortage and increasing numbers of critically ill patients when HTx is reserved for highly selected patients. 4( 49)
4( 47) The Predictive Power of Invasive Hemodynamics and MELD Scores in Ambulatory Patients With Advanced Heart Failure T.S. Kato ,1 M.S. Kim,2 C. Wu,2 M. Farr,2 D. Mancini,2 P. Schulze.2 1Heart Center, Department of Cardiothoracic Surgery, Juntendo University School of Medicine, Tokyo, Japan; 2Division of Cardiology, Department of Medicine, Columbia University Medical Center, New York, NY. Purpose: Liver abnormalities have prognostic impact on the outcome of patients with advanced heart failure (HF). We evaluated the correlation between hemodynamic data derived from right heart catheterization (RHC) and the Model of End-Stage Liver Disease (MELD) score. We analyzed the predictive power of data from RHC compared to MELD scores in ambulatory patients undergoing heart transplant (HTx) evaluation. Methods: We retrospectively analyzed a total of 156 patients undergoing RHC during HTx evaluation between 2007 and 2010. The impact of MELD and invasive hemodynamics on the outcome 3 years after the evaluation were tested. Endpoint events were defined as death/urgent HTx/ventricular assist device (VAD) requirement. Results: MELD correlated with right atrial pressure (RA, mmHg) (r= 0.27, p= 0.0013) and mean pulmonary artery pressure (mPA, mmHg) (r= 0.26, p= 0.0013) but not with pulmonary artery wedge pressure (PAWP, mmHg) or cardiac output (L/min). Although both RA and mPA alone showed an association with 3-year outcome after HTx evaluation (AUC 0.63920 and 0.61812, p= 0.0003 and 0.0152, respectively), MELD showed the highest association with 3-year outcome (ACU 0.67395, p< 0.0001). We calculated the double product of MELD and PAWP combining both markers of right and left ventricular failures (PAWP× MELD), considering the fact that there was no correlation between the two parameters . This score did not show an incremental value for predicting outcome. In a similar manner, the combination of MELD and cardiac output did not show an incremental value. Conclusion: MELD scores at the time of HTx evaluation is a useful marker for 3-year prognosis in ambulatory patients with HF. Invasive hemodynamics form RHC provide useful information for clinicians to undergo patient evaluation and to define treatment strategies. However, RHC data did not have an incremental value for predicting prognosis of patients with advanced HF. 4 ( 48) Coronary Artery Bypass Surgery or Heart Transplantation for Treatment of End-stage Ischemic Cardiomyopathy N.E. Hiemann , A. Trogisch, P. Zarubova, M. Bauer, M. Pasic, R. Hetzer. Cardiothoracic and Vascular Surgery, Deutsches Herzzentrum Berlin, Berlin, Germany.
Transmural Heterogeneity of Cellular Level Power Output Is Reduced in Human Heart Failure P. Haynes ,1 K. Nava,1 B. Lawson,1 C. Chung,1 M. Mitov,1 S. Campbell,1 A. Stromberg,2 S. Sadayappan,3 M. Bonnell,4 C. Hoopes,5 K. Campbell.1 1Physiology, University of Kentucky, Lexington, KY; 2Department of Statistics, University of Kentucky, Lexington, KY; 3Cell and Molecular Physiology, Loyola University, Chicago, IL; 4Surgery, University of Kentucky, Lexington, KY; 5University of Kentucky, Lexington, KY. Purpose: Heart failure is associated with pump dysfunction and remodeling but it is not yet known if the condition affects different transmural regions of the heart in the same way. We tested the hypotheses that tissue samples from the left ventricles of non-failing human hearts exhibit transmural heterogeneity of cellular level contractile properties, and that heart failure produces region-specific changes in contractile function. Methods: Chemically permeabilized samples were prepared from the subepicardial, mid-myocardial, and sub-endocardial regions of the left ventricle of non-failing (n= 6) and failing (n= 10) human hearts. Results: Power, an in vitro index of systolic function, was higher in nonfailing mid-myocardial samples (0.59 ± 0.06 µW mg-1) than in samples from the sub-epicardium (p= 0.021) and the sub-endocardium (p= 0.015). Nonfailing mid-myocardial samples also produced more isometric force (14.3 ± 1.33 kN m-2) than samples from the sub-epicardium (p= 0.008) and the subendocardium (p= 0.026). Heart failure reduced power (p= 0.009) and force (p= 0.042) but affected mid-myocardial samples more than sub-epicardial and sub-endocardial tissue. Fibrosis increased with heart failure (p= 0.021) and mid-myocardial tissue from failing hearts contained more collagen than the matching sub-epicardial (p< 0.001) and sub-endocardial (p= 0.043) samples. Myocardial power output was correlated with the relative content of actin, and the relative content and phosphorylation of myosin light chain-1. Conclusion: Non-failing human hearts exhibit transmural heterogeneity of contractile properties. In failing organs, region-specific fibrosis produces the greatest contractile deficits in mid-myocardial tissue. Targeting collagen deposition and sarcomeric proteins in the mid-myocardium may be particularly effective therapies for heart failure. 4( 50) Heart Failure Classification Rather Than Ejection Fraction May Be a Major Factor in Considering Patients with Hypertrophic Cardiomyopathy for Heart Transplantation K. Hryniewicz ,1 K. Anderson,1 K. Harris,1 D. Feldman,1 B. Maron.2 1Minneapolis Heart Institute, Abbott Northwestern Hospital, Minneapolis, MN; 2Minneapolis Heart Institute Foundation, Minneapolis, MN.
Purpose: Ischemic cardiomyopathy (iCMP) is a risk factor for poor survival after heart transplantation (HTx). Due to progressive organ shortage in Germany we tested whether end-stage iCMP patients might benefit from an aggressive revascularization strategy by coronary artery bypass surgery (CABG) vs. HTx. Methods: Analysis was done in 3,252 patients with iCMP who underwent CABG (n= 2,816) or HTx (n= 436) between 06/86 and 03/07. Survival was estimated by Kaplan-Meier analysis. Subgroup analysis was done with regard to ISHLT era (< 1991, 1992-2001, > 2002) and year of change in the German allocation policy (regional allocation < 2000; urgency policy ≥ 2001). Results: Overall survival at 5, 10, 15 and 20 years was similar in CABG vs. HTx patients (55% vs. 53%, 31% vs. 38%, 14% vs. 21% and 8% vs. 12%). There was a benefit of HTx vs. CABG if outcome was conditioned on 30 days (71% vs. 63%, 51% vs. 36%, 28% vs. 18% and 15% vs. 11%; p= 0.001) or 1 year (85% vs. 71%, 60% vs. 41%, 33% vs. 20% and 18% vs. 12%; p= 0.002). HTx vs. CABG was beneficial if performed between 1992 and 2001 (58% vs. 54%, 44% vs. 31%, 25% vs. 15% and 11% vs. 10%; p= 0.004) and even more beneficial if conditioned on 30-day (79% vs. 62%, 60% vs. 35%, 34% vs. 17% and 15% vs. 11%; p< 0.001) or 1-year survival (89% vs. 70%, 67% vs. 40%, 38% vs. 19% and 17% vs. 13%; p= 0.006). Regional allocation resulted in better survival rates vs. CABG only in 30-day (74% vs. 64%, 53% vs. 35%, 29% vs. 16% and 16% vs. 10%; p= 0.001) or 1-year survivors (74% vs. 64%, 53% vs. 35%, 29% vs. 16% and 16% vs. 10%; p= 0.005). Conclusion: Patients with end-stage iCMP represent a highly vulnerable cohort with poor prognosis. CABG procedure seems to be beneficial in these patients and should be considered in times of organ shortage and increasing numbers of critically ill patients when HTx is reserved for highly selected patients. 4( 49)
4( 47) The Predictive Power of Invasive Hemodynamics and MELD Scores in Ambulatory Patients With Advanced Heart Failure T.S. Kato ,1 M.S. Kim,2 C. Wu,2 M. Farr,2 D. Mancini,2 P. Schulze.2 1Heart Center, Department of Cardiothoracic Surgery, Juntendo University School of Medicine, Tokyo, Japan; 2Division of Cardiology, Department of Medicine, Columbia University Medical Center, New York, NY. Purpose: Liver abnormalities have prognostic impact on the outcome of patients with advanced heart failure (HF). We evaluated the correlation between hemodynamic data derived from right heart catheterization (RHC) and the Model of End-Stage Liver Disease (MELD) score. We analyzed the predictive power of data from RHC compared to MELD scores in ambulatory patients undergoing heart transplant (HTx) evaluation. Methods: We retrospectively analyzed a total of 156 patients undergoing RHC during HTx evaluation between 2007 and 2010. The impact of MELD and invasive hemodynamics on the outcome 3 years after the evaluation were tested. Endpoint events were defined as death/urgent HTx/ventricular assist device (VAD) requirement. Results: MELD correlated with right atrial pressure (RA, mmHg) (r= 0.27, p= 0.0013) and mean pulmonary artery pressure (mPA, mmHg) (r= 0.26, p= 0.0013) but not with pulmonary artery wedge pressure (PAWP, mmHg) or cardiac output (L/min). Although both RA and mPA alone showed an association with 3-year outcome after HTx evaluation (AUC 0.63920 and 0.61812, p= 0.0003 and 0.0152, respectively), MELD showed the highest association with 3-year outcome (ACU 0.67395, p< 0.0001). We calculated the double product of MELD and PAWP combining both markers of right and left ventricular failures (PAWP× MELD), considering the fact that there was no correlation between the two parameters . This score did not show an incremental value for predicting outcome. In a similar manner, the combination of MELD and cardiac output did not show an incremental value. Conclusion: MELD scores at the time of HTx evaluation is a useful marker for 3-year prognosis in ambulatory patients with HF. Invasive hemodynamics form RHC provide useful information for clinicians to undergo patient evaluation and to define treatment strategies. However, RHC data did not have an incremental value for predicting prognosis of patients with advanced HF. 4 ( 48) Coronary Artery Bypass Surgery or Heart Transplantation for Treatment of End-stage Ischemic Cardiomyopathy N.E. Hiemann , A. Trogisch, P. Zarubova, M. Bauer, M. Pasic, R. Hetzer. Cardiothoracic and Vascular Surgery, Deutsches Herzzentrum Berlin, Berlin, Germany.
Transmural Heterogeneity of Cellular Level Power Output Is Reduced in Human Heart Failure P. Haynes ,1 K. Nava,1 B. Lawson,1 C. Chung,1 M. Mitov,1 S. Campbell,1 A. Stromberg,2 S. Sadayappan,3 M. Bonnell,4 C. Hoopes,5 K. Campbell.1 1Physiology, University of Kentucky, Lexington, KY; 2Department of Statistics, University of Kentucky, Lexington, KY; 3Cell and Molecular Physiology, Loyola University, Chicago, IL; 4Surgery, University of Kentucky, Lexington, KY; 5University of Kentucky, Lexington, KY. Purpose: Heart failure is associated with pump dysfunction and remodeling but it is not yet known if the condition affects different transmural regions of the heart in the same way. We tested the hypotheses that tissue samples from the left ventricles of non-failing human hearts exhibit transmural heterogeneity of cellular level contractile properties, and that heart failure produces region-specific changes in contractile function. Methods: Chemically permeabilized samples were prepared from the subepicardial, mid-myocardial, and sub-endocardial regions of the left ventricle of non-failing (n= 6) and failing (n= 10) human hearts. Results: Power, an in vitro index of systolic function, was higher in nonfailing mid-myocardial samples (0.59 ± 0.06 µW mg-1) than in samples from the sub-epicardium (p= 0.021) and the sub-endocardium (p= 0.015). Nonfailing mid-myocardial samples also produced more isometric force (14.3 ± 1.33 kN m-2) than samples from the sub-epicardium (p= 0.008) and the subendocardium (p= 0.026). Heart failure reduced power (p= 0.009) and force (p= 0.042) but affected mid-myocardial samples more than sub-epicardial and sub-endocardial tissue. Fibrosis increased with heart failure (p= 0.021) and mid-myocardial tissue from failing hearts contained more collagen than the matching sub-epicardial (p< 0.001) and sub-endocardial (p= 0.043) samples. Myocardial power output was correlated with the relative content of actin, and the relative content and phosphorylation of myosin light chain-1. Conclusion: Non-failing human hearts exhibit transmural heterogeneity of contractile properties. In failing organs, region-specific fibrosis produces the greatest contractile deficits in mid-myocardial tissue. Targeting collagen deposition and sarcomeric proteins in the mid-myocardium may be particularly effective therapies for heart failure. 4( 50) Heart Failure Classification Rather Than Ejection Fraction May Be a Major Factor in Considering Patients with Hypertrophic Cardiomyopathy for Heart Transplantation K. Hryniewicz ,1 K. Anderson,1 K. Harris,1 D. Feldman,1 B. Maron.2 1Minneapolis Heart Institute, Abbott Northwestern Hospital, Minneapolis, MN; 2Minneapolis Heart Institute Foundation, Minneapolis, MN.