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69 Intracoronary Autologous Peripheral Stem Cell Therapy: A Promising Treatment for Heart Failure in Pediatric Dilated Cardiomyopathy
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The Journal of Heart and Lung Transplantation, Vol 30, No 4S, April 2011
Purpose: Transplantation of healthy regenerative cardiomyocytes into the injured heart is effective option to improve cardiac function. The optimal transplantation of cardiomyocytes must be developed. The aim of this study is to fabricate scaffold-free 3-Dimensional pulsatile cardiac tissue by nobel tissue engineering technology. Methods and Materials: Approximately two thousands of mouse embryonic stem cells (ESc) derived cardiomyocyte were formed into spheroids. To construct 3-dimensional cardiac tissue, a large number of spheroids are fused via our nobel technology, named bio-rapid prototyping system (BRP). This technolog is based on the original characteristic of cells to form spheroid cell aggregates. The constructs were produced semi-automatically by stabbing spheroids with numerous needles. Finally, we succeeded in fabricating scaffold-free contractile cardiac tissue 3⫻1⫻1mm in diameter. Electrophysiological and histological analysis are performed to evaluate the function of the constructs. Results: Electrophysiological studies revealed that electrical spikes detected on the construct. Immunofluorescent images with anti-connexin43 antibody demonstrated that gap junctions also established within the construct within 24 hours. This constructs continued pulsation for two weeks in vitro.
forming growth factor-beta, Smad2, and reversion-inducing cysteine-rich protein with Kazal morifs.
Conclusions: MS implantation decreased cardiac fibrosis by suppressing the pro-fibrotic gene expression, and attenuated the impairment of diastolic function and the late remodeling after LVR. 68 Liver Dysfunction Predicts Adverse Long-Term Outcome after Stem Cell Transplantation in Dilated Cardiomyopathy B. Vrtovec,1 G. Poglajen,1 D. Domanovic,2 M. Sever,1 L. Lezaic,1 M. Sebestjen,1 V. Androcec,1 F. Haddad,3 G. Torre-Amione.4 1Advanced Hear Failure and Transplantation Programme, UMC Ljubljana, Ljubljana, Slovenia; 2National Blood Transfusion Center, Ljubljana, Slovenia; 3Cardiovascular Medicine, Stanford University School of Medicine, Palo Alto; 4DeBakey Heart Center, Houston, TX.
Conclusions: These results demonstrate that electrically communicative pulsatile 3-D cardiac constructs were achieved in vitro by fusing cardiomyocytes spheroids. We concluded that cardiac tissue engineering based on this technology may prove useful for heart model fabrication and cardiovascular tissue repair. 67 Myoblast Sheet Implantation Can Prevent the Impairment of Cardiac Diastolic Function after Left Ventricular Restoration by Modulating the Extracellular Matrix Gene Expression S. Saito, T. Sakaguchi, S. Miyagawa, H. Nishi, Y. Yoshikawa, S. Fukushima, T. Ueno, T. Kuratani, A. Saito, Y. Sawa. Cardiovascular Surgery, Osaka University Graduate School of Medicine, Suita, Osaka, Japan. Purpose: This study aims to evaluate the effects of combined surgery of myoblast sheets (MS) implantation and left ventricular restoration (LVR). Methods and Materials: Myoblasts were isolated from skeletal muscle of 3-week-old Lewis rats. They were incubated and made into MS using temperature-responsive culture dishes. Rat myocardial infarction model was established 2 weeks after left anterior descending artery ligation. They were divided into 3 groups: sham operation (n⫽15; Group Sham), LVR by plicating the infracted area (n⫽15; Group LVR) and MS implantation with LVR (n⫽15; Group MS⫹LVR). Results: Echocardiographic study revealed significant LV re-dilatation and decrease of ejection fraction 4 weeks after LVR in Group LVR. MS implantation combined with LVR prevented those later deteriorations of LV function in Group MS⫹LVR. Four weeks after the operation, a hemodynamic assessment using a pressure-volume loop showed significantly preserved diastolic function in Group MS⫹LVR; end-diastolic pressure (LVR vs. LVR⫹MS: 9.0 ⫾ 6.6 vs. 2.0 ⫾ 1.0 mmHg, p ⬍ 0.05), end-diastolic pressure-volume relationship (LVR vs. LVR⫹MS 42 ⫾ 23 vs. 13 ⫾ 6). Histological examination revealed cellular hypertrophy and LV fibrosis were significantly less and vascular density was significantly higher in group MS⫹LVR than in the other 2 groups. RT-PCR demonstrated significantly suppressed expression of trans-
Purpose: Although stem cell therapy has been shown to be beneficial in advanced chronic heart failure, patient selection criteria remain undefined. We sought to identify parameters predicting response to stem cell therapy in patients with dilated cardiomyopathy. Methods and Materials: In a prospective study we enrolled 55 patients with dilated cardiomyopathy. In all patients, peripheral blood stem cells were mobilised by daily subcutaneous injections of filgrastim; CD34⫹ cells were collected via apheresis and labelled with technetium. Patients underwent myocardial perfusion scintigraphy for myocardial viability assessment and the collected CD34⫹ cells were injected intracoronary in the artery supplying the segments of reduced tracer accumulation. Patients were followed for 4 years for combined end-point of cardiac death or heart transplantation. Results: During follow-up 8 (14%) patients died and 7 (13%) underwent heart transplantation. At baseline, the survivors did not differ from the remaining cohort in age (54⫾6 years vs. 53⫾9 years; P⫽0.70), left ventricular ejection fraction (25⫾7% vs. 22⫾7%; P⫽0.20), left ventricular end-diastolic dimension (6.9⫾1.0 cm vs. 7.0⫾0.9 cm; P⫽0.88), creatinine (94⫾20 mol/l vs. 98⫾36 mol/l; P⫽0.38), NT-proBNP levels (2353⫾2802 pg/ml vs. 2974⫾2721 pg/ml; P⫽0.49) or 6-minute walk test distance (360⫾111 m vs. 358⫾99 m; P⫽0.95). However, liver function was significantly better in survivors than in patients who either expired or underwent heart transplantation (bilirubine: 17.5⫾9.1 mol/l vs. 26.3⫾14.5 mol/l; P⫽0.01, GGT:1.1⫾ 0.9 U/l vs.1.8 ⫾ 0.5 U/l; P⫽0.04). The number of mobilized CD34 cells was significantly lower in patients with liver dysfunction (36 ⫾16 x 109) than in the remaining cohort (53⫾27 x 109; P⫽0.03). Liver dysfunction was the only independent predictor of 4-year outcome on multivariate analysis (P⫽0.04). Conclusions: Liver dysfunction in associated with poor stem cell mobilization and adverse long-term outcome after intracoronary stem cell transplantation in patients with dilated cardiomyopathy. 69 Intracoronary Autologous Peripheral Stem Cell Therapy: A Promising Treatment for Heart Failure in Pediatric Dilated Cardiomyopathy J.J. Menendez,1 J. Rivas,2 L. Guereta,2 F. Gutierrez-Larraya,2 R. Arrieta,3 M. Romero,5 J. Alves,4 R. Alvarez-Doforno,7 A. González.6 1 Pediatric Intensive Care Unit, Hospital Universitario La Paz, Madrid, Spain; 2Pediatric Cardiology, Hospital Universitario La Paz, Madrid, Spain; 3Haematology, Cell Therapy and Bone Marrow Unit, Hospital Universitario La Paz, Madrid, Spain; 4Pathology, Hospital Universitario
Abstracts
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La Paz, Madrid, Spain; 5Microbiology, Hospital Universitario La Paz, Madrid, Spain; 6Pediatric Cardiac Surgery, Hospital Universitario La Paz, Madrid, Spain; 7Immunology, Hospital Universitario La Paz, Madrid, Spain. Purpose: Nearly one-third of children diagnosed with dilated cardiomyopathy (DCM) receive a transplant or die within the first year after diagnosis. Limited long-term outcome of heart transplantation and scarcity of young donors justify every effort to improve medical therapy and to find alternative therapeutic approaches. There is increasing evidence that cardiac stem cell transplantation induce sustained improvement in cardiac function in patients with heart failure. We describe the compassionate use of intracoronary autologous peripheral stem cell therapy in two young infants diagnosed with DCM and severe heart failure. Methods and Materials: Descriptive study that analyzes the evolution of two pediatric patients diagnosed with DCM and severe heart failure, and who were treated with intracoronary infusion of autologous stem cells. Patient 1 is a 3-month male infant weighing 4 Kg. Patient 2 is a 4-month male infant weighing 5 Kg. Results: At the time of admission, both patients were in poor clinical status (NYHA IV), had high levels of NT-ProBNP and severe LV dilation and systolic dysfunction (EF⬍30%). Both were mechanically ventilated and needed IV inotropes. Endomyocardial biopsy ruled out myocarditis. In each case, after treatment with G-CSF for 4 days, autologous stem cells were recovered from peripheral blood, implanting them via the coronary arteries afterwards. As soon as one week after the procedure, echocardiography showed a remarkable improvement in LV dilation. One month later a significant gain in their EF (⬎40%) was also detected and this was maintained over time. The long-term outcome was favorable. Although first patient has shown LV dilation 17 weeks after the procedure, he is still in functional class I and has adequate weight gain. Conclusions: Although currently heart transplantation is the only established treatment for DCM, stem cell therapy could be an option to improve clinical status, and serve as a bridge to decision, to transplantation or, more importantly, to recovery for these very sick children. 70 The HeartMate II Risk Score: Predicting Survival in Candidates for Left Ventricular Assist Device Support J. Cowger,1 K. Sundareswaran,2 J.G. Rogers,3 S.J. Park,4 F.D. Pagani,1 G. Bhat,5 B. Jaski,6 D.J. Farrar,7 M.S. Slaughter.2 1University of Michigan Health System, Ann Arbor, MI; 2Thoratec Corporation, Pleasanton, CA; 3Duke University Medical Center, Durham, NC; 4Mayo Clinic, Rochester, MN; 5Advocate Christ Medical Center, Oaklawn, IL; 6 Sharp Memorial Hospital, San Diego, CA; 7University of Louisville, Louisville, KY. Purpose: To derive and validate a survival model for HeartMate II (HMII) LVAD candidates. Methods and Materials: HMII patients enrolled into the Thoratec bridge to transplantation and destination therapy (DT) trials were randomly divided into derivation (DC, n⫽583) and validation cohorts (VC, n⫽539). Potential preoperative clinical, laboratory, and hemodynamic predictors of survival from the DC were analyzed using Cox proportional hazards. A HMII Risk Score (HMRS) was determined for DC and VC patients using Cox model multivariable predictors, adjusting for implant era. Patients were divided into low, medium, and high risk groups based on their HMRS. The area under the receiver operative curve (AUC) for survival by HMRS was calculated. Results: The mean (⫾SD) age of the DC was 59⫾13 years and DT was the intended use in 338 (58%). Multivariable preoperative mortality predictors (hazard ratio [95% CI]) included age (1.3 [1.1,1.5] per 10 years]), albumin (0.71 [0.55,0.91] per mg/dL), serum creatinine (1.4 [1.1,1.7] per mg/dL), INR (1.9 [1.3,2.7]), implant after May 2007 (0.67 [0.49,0.90]), and implant center experience (0.52 [0.36,0.75] for ⱖ15 implants) (model AUC⫽0.70, p⬍0.001). The table and figure show cohort survivals. The only preoperative predictors of long term survival, conditioned on 90 day survival, were age and implant center experience. DT indication was not a multivariable predictor of survival after LVAD.
Table 1
Survival by HMRS
Survival by HMRS DC Survival (%)
VC Survival (%)
HMRS Group
90 day
2 year
90 day
2 year
Low Medium High
96 ⫾ 2 90 ⫾ 2 74 ⫾ 3
84 ⫾ 4 66 ⫾ 4 47 ⫾ 4
96 ⫾ 2 88 ⫾ 2 78 ⫾ 3
72 ⫾ 5 65 ⫾ 4 51 ⫾ 4
Conclusions: The HMRS may be useful for operative and long term mortality risk stratification in HMII candidates. 71 Application of the Destination Therapy Risk Score to HeartMate II Clinical Trial Data J.J. Teuteberg,1 G. Ewald,2 R. Adamson,3 K. Lietz,4 L. Miller,5 A. Tatooles,6 R.L. Kormos,7 K. Sundareswaran,8 D. Farrar,8 J. Rogers.9 1 Cardiovascular Institute, University of Pittsburgh, Pittsburgh, PA; 2 Cardiology, Washington University, St. Louis, Mo; 3Cardiovascular Surgery, Sharp Memorial, San Diego, CA; 4Cardiology, Yale University, New Haven, Ct; 5Cardiovascular Medicine, University of South Florida, Tampa, Fl; 6Cardiovascular Surgery, Advocate Christ Medical Center, Oak Lawn, IL; 7Heart, Lung, Esophageal Surgery Institute, University of Pittsburgh, Pittsburgh, PA; 8Thoratec Corporation, Pleasanton, CA; 9 Cardiology, Duke University, Durham, NC. Purpose: The Destination Therapy Risk Score (DTRS) was developed to preoperatively predict the risk of 90 day in-hospital mortality with pulsatile flow LVADs as DT from 2002-2005 (Lietz et al Circulation 2007;116:497). Mortality by risk category was 6% (low), 14% (medium), 74% (high). However the clinical utility of the DTRS in the contemporary LVAD patient is unclear. Methods and Materials: The DTRS was determined in 1124 patients with the HeartMate II continuous flow LVAD in the BTT (n⫽486) and DT (n⫽638) clinical trials, and 114 DT patients randomized to receive the pulsatile HeartMate XVE. Patients were divided into the same risk groups based upon DTRS: low (0-8), medium (9-16), and high (⬎16). Results: The median age was 55 (BTT), 67 (DT), 63 (DTXVE), etiology was ischemic in 44% (BTT), 60%(DT), 67%(DTXVE). The risk of 90 day inhospital mortality increased with each risk category for all groups of patients, but was only statistically significant for the high risk HMII patients in the BTT⫹DT and DT populations, compared to the low risk groups. These high risk groups had more than a twofold increased risk of mortality compared to the low risk group. In the XVE group, the 90 day in-hospital mortality was similar to the initial DTRS cohort with the exception of a much lower mortality in the highest risk group. Goodness of fit for 90 day in-hospital mortality yielded modest c-statistics of 0.54 to 0.59 for the groups.
Conclusions: Patients with the lowest DTRS have the lowest in-hospital mortality with both devices. However, due to improvements in outcomes
The Journal of Heart and Lung Transplantation, Vol 30, No 4S, April 2011
Purpose: Transplantation of healthy regenerative cardiomyocytes into the injured heart is effective option to improve cardiac function. The optimal transplantation of cardiomyocytes must be developed. The aim of this study is to fabricate scaffold-free 3-Dimensional pulsatile cardiac tissue by nobel tissue engineering technology. Methods and Materials: Approximately two thousands of mouse embryonic stem cells (ESc) derived cardiomyocyte were formed into spheroids. To construct 3-dimensional cardiac tissue, a large number of spheroids are fused via our nobel technology, named bio-rapid prototyping system (BRP). This technolog is based on the original characteristic of cells to form spheroid cell aggregates. The constructs were produced semi-automatically by stabbing spheroids with numerous needles. Finally, we succeeded in fabricating scaffold-free contractile cardiac tissue 3⫻1⫻1mm in diameter. Electrophysiological and histological analysis are performed to evaluate the function of the constructs. Results: Electrophysiological studies revealed that electrical spikes detected on the construct. Immunofluorescent images with anti-connexin43 antibody demonstrated that gap junctions also established within the construct within 24 hours. This constructs continued pulsation for two weeks in vitro.
forming growth factor-beta, Smad2, and reversion-inducing cysteine-rich protein with Kazal morifs.
Conclusions: MS implantation decreased cardiac fibrosis by suppressing the pro-fibrotic gene expression, and attenuated the impairment of diastolic function and the late remodeling after LVR. 68 Liver Dysfunction Predicts Adverse Long-Term Outcome after Stem Cell Transplantation in Dilated Cardiomyopathy B. Vrtovec,1 G. Poglajen,1 D. Domanovic,2 M. Sever,1 L. Lezaic,1 M. Sebestjen,1 V. Androcec,1 F. Haddad,3 G. Torre-Amione.4 1Advanced Hear Failure and Transplantation Programme, UMC Ljubljana, Ljubljana, Slovenia; 2National Blood Transfusion Center, Ljubljana, Slovenia; 3Cardiovascular Medicine, Stanford University School of Medicine, Palo Alto; 4DeBakey Heart Center, Houston, TX.
Conclusions: These results demonstrate that electrically communicative pulsatile 3-D cardiac constructs were achieved in vitro by fusing cardiomyocytes spheroids. We concluded that cardiac tissue engineering based on this technology may prove useful for heart model fabrication and cardiovascular tissue repair. 67 Myoblast Sheet Implantation Can Prevent the Impairment of Cardiac Diastolic Function after Left Ventricular Restoration by Modulating the Extracellular Matrix Gene Expression S. Saito, T. Sakaguchi, S. Miyagawa, H. Nishi, Y. Yoshikawa, S. Fukushima, T. Ueno, T. Kuratani, A. Saito, Y. Sawa. Cardiovascular Surgery, Osaka University Graduate School of Medicine, Suita, Osaka, Japan. Purpose: This study aims to evaluate the effects of combined surgery of myoblast sheets (MS) implantation and left ventricular restoration (LVR). Methods and Materials: Myoblasts were isolated from skeletal muscle of 3-week-old Lewis rats. They were incubated and made into MS using temperature-responsive culture dishes. Rat myocardial infarction model was established 2 weeks after left anterior descending artery ligation. They were divided into 3 groups: sham operation (n⫽15; Group Sham), LVR by plicating the infracted area (n⫽15; Group LVR) and MS implantation with LVR (n⫽15; Group MS⫹LVR). Results: Echocardiographic study revealed significant LV re-dilatation and decrease of ejection fraction 4 weeks after LVR in Group LVR. MS implantation combined with LVR prevented those later deteriorations of LV function in Group MS⫹LVR. Four weeks after the operation, a hemodynamic assessment using a pressure-volume loop showed significantly preserved diastolic function in Group MS⫹LVR; end-diastolic pressure (LVR vs. LVR⫹MS: 9.0 ⫾ 6.6 vs. 2.0 ⫾ 1.0 mmHg, p ⬍ 0.05), end-diastolic pressure-volume relationship (LVR vs. LVR⫹MS 42 ⫾ 23 vs. 13 ⫾ 6). Histological examination revealed cellular hypertrophy and LV fibrosis were significantly less and vascular density was significantly higher in group MS⫹LVR than in the other 2 groups. RT-PCR demonstrated significantly suppressed expression of trans-
Purpose: Although stem cell therapy has been shown to be beneficial in advanced chronic heart failure, patient selection criteria remain undefined. We sought to identify parameters predicting response to stem cell therapy in patients with dilated cardiomyopathy. Methods and Materials: In a prospective study we enrolled 55 patients with dilated cardiomyopathy. In all patients, peripheral blood stem cells were mobilised by daily subcutaneous injections of filgrastim; CD34⫹ cells were collected via apheresis and labelled with technetium. Patients underwent myocardial perfusion scintigraphy for myocardial viability assessment and the collected CD34⫹ cells were injected intracoronary in the artery supplying the segments of reduced tracer accumulation. Patients were followed for 4 years for combined end-point of cardiac death or heart transplantation. Results: During follow-up 8 (14%) patients died and 7 (13%) underwent heart transplantation. At baseline, the survivors did not differ from the remaining cohort in age (54⫾6 years vs. 53⫾9 years; P⫽0.70), left ventricular ejection fraction (25⫾7% vs. 22⫾7%; P⫽0.20), left ventricular end-diastolic dimension (6.9⫾1.0 cm vs. 7.0⫾0.9 cm; P⫽0.88), creatinine (94⫾20 mol/l vs. 98⫾36 mol/l; P⫽0.38), NT-proBNP levels (2353⫾2802 pg/ml vs. 2974⫾2721 pg/ml; P⫽0.49) or 6-minute walk test distance (360⫾111 m vs. 358⫾99 m; P⫽0.95). However, liver function was significantly better in survivors than in patients who either expired or underwent heart transplantation (bilirubine: 17.5⫾9.1 mol/l vs. 26.3⫾14.5 mol/l; P⫽0.01, GGT:1.1⫾ 0.9 U/l vs.1.8 ⫾ 0.5 U/l; P⫽0.04). The number of mobilized CD34 cells was significantly lower in patients with liver dysfunction (36 ⫾16 x 109) than in the remaining cohort (53⫾27 x 109; P⫽0.03). Liver dysfunction was the only independent predictor of 4-year outcome on multivariate analysis (P⫽0.04). Conclusions: Liver dysfunction in associated with poor stem cell mobilization and adverse long-term outcome after intracoronary stem cell transplantation in patients with dilated cardiomyopathy. 69 Intracoronary Autologous Peripheral Stem Cell Therapy: A Promising Treatment for Heart Failure in Pediatric Dilated Cardiomyopathy J.J. Menendez,1 J. Rivas,2 L. Guereta,2 F. Gutierrez-Larraya,2 R. Arrieta,3 M. Romero,5 J. Alves,4 R. Alvarez-Doforno,7 A. González.6 1 Pediatric Intensive Care Unit, Hospital Universitario La Paz, Madrid, Spain; 2Pediatric Cardiology, Hospital Universitario La Paz, Madrid, Spain; 3Haematology, Cell Therapy and Bone Marrow Unit, Hospital Universitario La Paz, Madrid, Spain; 4Pathology, Hospital Universitario
Abstracts
S31
La Paz, Madrid, Spain; 5Microbiology, Hospital Universitario La Paz, Madrid, Spain; 6Pediatric Cardiac Surgery, Hospital Universitario La Paz, Madrid, Spain; 7Immunology, Hospital Universitario La Paz, Madrid, Spain. Purpose: Nearly one-third of children diagnosed with dilated cardiomyopathy (DCM) receive a transplant or die within the first year after diagnosis. Limited long-term outcome of heart transplantation and scarcity of young donors justify every effort to improve medical therapy and to find alternative therapeutic approaches. There is increasing evidence that cardiac stem cell transplantation induce sustained improvement in cardiac function in patients with heart failure. We describe the compassionate use of intracoronary autologous peripheral stem cell therapy in two young infants diagnosed with DCM and severe heart failure. Methods and Materials: Descriptive study that analyzes the evolution of two pediatric patients diagnosed with DCM and severe heart failure, and who were treated with intracoronary infusion of autologous stem cells. Patient 1 is a 3-month male infant weighing 4 Kg. Patient 2 is a 4-month male infant weighing 5 Kg. Results: At the time of admission, both patients were in poor clinical status (NYHA IV), had high levels of NT-ProBNP and severe LV dilation and systolic dysfunction (EF⬍30%). Both were mechanically ventilated and needed IV inotropes. Endomyocardial biopsy ruled out myocarditis. In each case, after treatment with G-CSF for 4 days, autologous stem cells were recovered from peripheral blood, implanting them via the coronary arteries afterwards. As soon as one week after the procedure, echocardiography showed a remarkable improvement in LV dilation. One month later a significant gain in their EF (⬎40%) was also detected and this was maintained over time. The long-term outcome was favorable. Although first patient has shown LV dilation 17 weeks after the procedure, he is still in functional class I and has adequate weight gain. Conclusions: Although currently heart transplantation is the only established treatment for DCM, stem cell therapy could be an option to improve clinical status, and serve as a bridge to decision, to transplantation or, more importantly, to recovery for these very sick children. 70 The HeartMate II Risk Score: Predicting Survival in Candidates for Left Ventricular Assist Device Support J. Cowger,1 K. Sundareswaran,2 J.G. Rogers,3 S.J. Park,4 F.D. Pagani,1 G. Bhat,5 B. Jaski,6 D.J. Farrar,7 M.S. Slaughter.2 1University of Michigan Health System, Ann Arbor, MI; 2Thoratec Corporation, Pleasanton, CA; 3Duke University Medical Center, Durham, NC; 4Mayo Clinic, Rochester, MN; 5Advocate Christ Medical Center, Oaklawn, IL; 6 Sharp Memorial Hospital, San Diego, CA; 7University of Louisville, Louisville, KY. Purpose: To derive and validate a survival model for HeartMate II (HMII) LVAD candidates. Methods and Materials: HMII patients enrolled into the Thoratec bridge to transplantation and destination therapy (DT) trials were randomly divided into derivation (DC, n⫽583) and validation cohorts (VC, n⫽539). Potential preoperative clinical, laboratory, and hemodynamic predictors of survival from the DC were analyzed using Cox proportional hazards. A HMII Risk Score (HMRS) was determined for DC and VC patients using Cox model multivariable predictors, adjusting for implant era. Patients were divided into low, medium, and high risk groups based on their HMRS. The area under the receiver operative curve (AUC) for survival by HMRS was calculated. Results: The mean (⫾SD) age of the DC was 59⫾13 years and DT was the intended use in 338 (58%). Multivariable preoperative mortality predictors (hazard ratio [95% CI]) included age (1.3 [1.1,1.5] per 10 years]), albumin (0.71 [0.55,0.91] per mg/dL), serum creatinine (1.4 [1.1,1.7] per mg/dL), INR (1.9 [1.3,2.7]), implant after May 2007 (0.67 [0.49,0.90]), and implant center experience (0.52 [0.36,0.75] for ⱖ15 implants) (model AUC⫽0.70, p⬍0.001). The table and figure show cohort survivals. The only preoperative predictors of long term survival, conditioned on 90 day survival, were age and implant center experience. DT indication was not a multivariable predictor of survival after LVAD.
Table 1
Survival by HMRS
Survival by HMRS DC Survival (%)
VC Survival (%)
HMRS Group
90 day
2 year
90 day
2 year
Low Medium High
96 ⫾ 2 90 ⫾ 2 74 ⫾ 3
84 ⫾ 4 66 ⫾ 4 47 ⫾ 4
96 ⫾ 2 88 ⫾ 2 78 ⫾ 3
72 ⫾ 5 65 ⫾ 4 51 ⫾ 4
Conclusions: The HMRS may be useful for operative and long term mortality risk stratification in HMII candidates. 71 Application of the Destination Therapy Risk Score to HeartMate II Clinical Trial Data J.J. Teuteberg,1 G. Ewald,2 R. Adamson,3 K. Lietz,4 L. Miller,5 A. Tatooles,6 R.L. Kormos,7 K. Sundareswaran,8 D. Farrar,8 J. Rogers.9 1 Cardiovascular Institute, University of Pittsburgh, Pittsburgh, PA; 2 Cardiology, Washington University, St. Louis, Mo; 3Cardiovascular Surgery, Sharp Memorial, San Diego, CA; 4Cardiology, Yale University, New Haven, Ct; 5Cardiovascular Medicine, University of South Florida, Tampa, Fl; 6Cardiovascular Surgery, Advocate Christ Medical Center, Oak Lawn, IL; 7Heart, Lung, Esophageal Surgery Institute, University of Pittsburgh, Pittsburgh, PA; 8Thoratec Corporation, Pleasanton, CA; 9 Cardiology, Duke University, Durham, NC. Purpose: The Destination Therapy Risk Score (DTRS) was developed to preoperatively predict the risk of 90 day in-hospital mortality with pulsatile flow LVADs as DT from 2002-2005 (Lietz et al Circulation 2007;116:497). Mortality by risk category was 6% (low), 14% (medium), 74% (high). However the clinical utility of the DTRS in the contemporary LVAD patient is unclear. Methods and Materials: The DTRS was determined in 1124 patients with the HeartMate II continuous flow LVAD in the BTT (n⫽486) and DT (n⫽638) clinical trials, and 114 DT patients randomized to receive the pulsatile HeartMate XVE. Patients were divided into the same risk groups based upon DTRS: low (0-8), medium (9-16), and high (⬎16). Results: The median age was 55 (BTT), 67 (DT), 63 (DTXVE), etiology was ischemic in 44% (BTT), 60%(DT), 67%(DTXVE). The risk of 90 day inhospital mortality increased with each risk category for all groups of patients, but was only statistically significant for the high risk HMII patients in the BTT⫹DT and DT populations, compared to the low risk groups. These high risk groups had more than a twofold increased risk of mortality compared to the low risk group. In the XVE group, the 90 day in-hospital mortality was similar to the initial DTRS cohort with the exception of a much lower mortality in the highest risk group. Goodness of fit for 90 day in-hospital mortality yielded modest c-statistics of 0.54 to 0.59 for the groups.
Conclusions: Patients with the lowest DTRS have the lowest in-hospital mortality with both devices. However, due to improvements in outcomes