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13 Cardiac Allograft Hypertrophy Is Associated with Impaired Exercise Tolerance after Heart Transplantation
S12
The Journal of Heart and Lung Transplantation, Vol 30, No 4S, April 2011
pts with DES in both CAV2 (57% vs 83%, p⫽0.14) and CAV3 (30% vs 50%, p⫽0.57) categories. Table 1
CAV despite statin therapy. Risk-benefit ratio for the use of SRL in these patients needs to be reviewed. 13
N Subsequent 5-Year Actuarial Survival Subsequent 5-Year Actuarial Freedom from NF-MACE
CAV2
CAV2 Control
CAV3
CAV3 Control
25 76%
25 64%
38 45%
38 61%
88%
92%
88%
97%
N Subsequent 5-Year Actuarial Survival Subsequent 5-Year Actuarial Freedom from NF-MACE
BMS
DES
BMS
DES
7 57%
18 83%
10 50%
28 30%
86%
89%
90%
86%
P⫽NS in all groups.
Conclusions: For same disease severity (CAV2 or CAV3) PCI has similar outcome to patients who did not have PCI. PCI may not be necessary for all CAV lesions. A randomized clinical trial to assess PCI vs medical therapy is indicated. 12 Hyperlipidemia from Sirolimus: Adverse Impact on Development of Cardiac Allograft Vasculopathy J. Patel, M. Kittleson, M. Kawano, Z. Goldstein, M. Rafiei, A. Moradzadeh, B. Azarbal, L. Czer, R. Kass, J. Kobashigawa. CedarsSinai Heart Institute, Los Angeles, CA. Purpose: Sirolimus (SRL) has been shown to decrease the incidence of rejection and cardiac allograft vasculopathy (CAV). Yet SRL also causes dyslipidemia, primarily hypertriglyceridemia and an increase in LDL cholesterol. The purpose of the current study was to determine if SRL-treated patients with dyslipidemia have worse outcomes after transplant. Methods and Materials: We evaluated 271 patients transplanted 1994 to 2010, on SRL for renal sparing protocol, malignancy, rejection, CAV, or cytomegalovirus infection. Patients were divided into groups: low (⬍200 mg/dl) vs high (⬎200 mg/dl) total cholesterol, and low (⬍150 mg/dl) vs high (⬎150 mg/dl) triglycerides. Outcomes assessed: subsequent 5-year survival, subsequent freedom from CAV (stenosis ⬎ 30%), and subsequent freedom from non-fatal major adverse cardiac events (NF-MACE: myocardial infarction, heart failure, stenting, defibrillator, stroke, and new peripheral vascular disease). Results: The indications for SRL use were similar among groups. Subsequent 5-year freedom from CAV was significantly lower in the high cholesterol group (53% vs. 74%, p⫽0.002), but there was no difference in subsequent 5-year survival or freedom from NF-MACE. The low and high triglyceride groups had comparable subsequent 5-year survival, freedom from CAV, and freedom from NF-MACE (table). 80% of patients in all groups were treated with statins and/or fibric acid derivatives. Low Cholesterol (⬍200 mg/dl)
High Cholesterol (⬎200 mg/dl)
Low Triglycerides (⬍150 mg/dl)
High Triglycerides (⬎150 mg/dl)
N
197
74
122
147
Mean Levels
153 ⫾ 28
233 ⫾ 40
95 ⫾ 30
262 ⫾ 194
Subsequent 5-Year Actuarial Survival
68%
74%
70%
71%
Subsequent Freedom from CAV
74%*
57%
73%
67%
Subsequent Freedom from NF-MACE
90%
85%
90%
88%
*p⫽0.007, compared to High
Conclusions: Hypercholesterolemia in SRL-treated heart transplant patients appears to be associated with greater subsequent development of
Cardiac Allograft Hypertrophy Is Associated with Impaired Exercise Tolerance after Heart Transplantation E. Raichlin,2 M.A. Al-Omari,1 S.S. Kushwaha,1 B.S. Eswards,1 A.L. Clavel,1 R.J. Rodeheffer,1 R.P. Frantz,1 R.C. Daly,1 S. Park,1 T.G. Allison,1 N.L. Pereira.1 1Cardiovascular Diseases, Mayo Clinic, Rochester, MN; 2Department of Cardiology, University of Nebraska Medical Center, Omaha, NE. Purpose: Exercise performance, an important aspect of quality of life, remains limited after heart transplantation (HTx). This prospective crosssectional study examined the effect of early changes of cardiac allograft geometry on post-HTx functional capacity. Methods and Materials: Based on echocardiographic determination of left ventricle mass and relative wall thickness at 1 year after HTx, the total cohort of 117 HTx recipients was divided into 3 groups: (1) NG – normal geometry (2) CR – concentric remodeling and (3) CH – concentric hypertrophy. Cardiopulmonary exercise test was performed 5.03⫾3.08 years after HTx. Results: At 1 year after HTx 34 (30%) patients had CH, 64 (55%) had CR and 18 (15%) demonstrated NG. There was no difference in demographic and clinical characteristics between the groups. LV geometry pattern at 1 year after HTx correlated strongly with LV geometry pattern at echocardiographic study performed prior to CPET (r ⫽ 0.72, p ⫽ 0.001). Heart rate, blood pressure and exercise duration (mean 6.88 ⫾ 2.20 min) did not differ between the groups. The maximum achieved metabolic equivalents and peak VO2 was lower and VE/VCO2 was higher in patients presented with CH pattern at 1 year after HTx as compared to NG. After multivariate analysis decreased exercise capacity in metabolic equivalents associated with increased BMI and worse kidney function; reduced peak VO2 associated with 1-year CH pattern (p⫽0.018), older recipients’ and donors’ age, higher BMI and lower E/E’; elevated VE/VCO2 associated with 1-year CH geometric pattern (p⫽0.01), higher heart rate, lower E’ and higher pulmonary artery systolic pressure. Conclusions: Early cardiac allograft remodeling and the presence of CH at one year after transplantation is associated with decreased exercise tolerance, decreased peak oxygen uptake and increase ventilatory response of the HTx recipients. Identifying of this potentially reversible mechanism of the decline in exercise capacity after cardiac transplantation could have important clinical implications. 14 Heart-Lung Transplantation May Confer Protection from Developing Transplant Coronary Artery Disease: An Analysis of the United Organ Network Sharing Database V.K. Topkara,1 M. Yeung,1 P.-H. Huang,1 A.M. Hadi,1 S.M. Joseph,1 J.D. Schilling,1 S.C. Sylvestry,2 N. Moazami,3 I.-W. Wang,2 G.A. Ewald.1 1 Cardiology, Washington University School of Medicine, St. Louis, MO; 2 Cardiothoracic Surgery, Washington University School of Medicine, St. Louis, MO; 3Cardiothoracic Surgery, Minneapolis Heart Institute, Minneapolis, MN. Purpose: Previous studies suggested a protective effect of one organ on another in combined organ allografts with reduced rejection rates. Whether a similar protection is present for the development of transplant coronary artery disease (TCAD) after heart transplantation remains unknown. Given that immunological risk factors have been implicated in pathogenesis of TCAD, we hypothesized that simultaneous organ transplantation reduces the incidence of TCAD. Methods and Materials: UNOS provided de-identified patient-level data. Analysis included 28,847 adults receiving heart-only, 505 receiving heartlung transplants, 502 heart-liver transplants, and 60 heart-kidney transplants between 04/94 and 12/08. Kaplan-Meier analysis was used to determine freedom from TCAD. Results: Freedom from TCAD at 1, 5, and 10 years was 97.5%, 71.4%, and 45.9% in heart-only transplants; 99.1%, 86.6%, and 70.9% in heartlung transplants; 98.3%, 76.4%, and 50.5% in heart-kidney transplants; and
The Journal of Heart and Lung Transplantation, Vol 30, No 4S, April 2011
pts with DES in both CAV2 (57% vs 83%, p⫽0.14) and CAV3 (30% vs 50%, p⫽0.57) categories. Table 1
CAV despite statin therapy. Risk-benefit ratio for the use of SRL in these patients needs to be reviewed. 13
N Subsequent 5-Year Actuarial Survival Subsequent 5-Year Actuarial Freedom from NF-MACE
CAV2
CAV2 Control
CAV3
CAV3 Control
25 76%
25 64%
38 45%
38 61%
88%
92%
88%
97%
N Subsequent 5-Year Actuarial Survival Subsequent 5-Year Actuarial Freedom from NF-MACE
BMS
DES
BMS
DES
7 57%
18 83%
10 50%
28 30%
86%
89%
90%
86%
P⫽NS in all groups.
Conclusions: For same disease severity (CAV2 or CAV3) PCI has similar outcome to patients who did not have PCI. PCI may not be necessary for all CAV lesions. A randomized clinical trial to assess PCI vs medical therapy is indicated. 12 Hyperlipidemia from Sirolimus: Adverse Impact on Development of Cardiac Allograft Vasculopathy J. Patel, M. Kittleson, M. Kawano, Z. Goldstein, M. Rafiei, A. Moradzadeh, B. Azarbal, L. Czer, R. Kass, J. Kobashigawa. CedarsSinai Heart Institute, Los Angeles, CA. Purpose: Sirolimus (SRL) has been shown to decrease the incidence of rejection and cardiac allograft vasculopathy (CAV). Yet SRL also causes dyslipidemia, primarily hypertriglyceridemia and an increase in LDL cholesterol. The purpose of the current study was to determine if SRL-treated patients with dyslipidemia have worse outcomes after transplant. Methods and Materials: We evaluated 271 patients transplanted 1994 to 2010, on SRL for renal sparing protocol, malignancy, rejection, CAV, or cytomegalovirus infection. Patients were divided into groups: low (⬍200 mg/dl) vs high (⬎200 mg/dl) total cholesterol, and low (⬍150 mg/dl) vs high (⬎150 mg/dl) triglycerides. Outcomes assessed: subsequent 5-year survival, subsequent freedom from CAV (stenosis ⬎ 30%), and subsequent freedom from non-fatal major adverse cardiac events (NF-MACE: myocardial infarction, heart failure, stenting, defibrillator, stroke, and new peripheral vascular disease). Results: The indications for SRL use were similar among groups. Subsequent 5-year freedom from CAV was significantly lower in the high cholesterol group (53% vs. 74%, p⫽0.002), but there was no difference in subsequent 5-year survival or freedom from NF-MACE. The low and high triglyceride groups had comparable subsequent 5-year survival, freedom from CAV, and freedom from NF-MACE (table). 80% of patients in all groups were treated with statins and/or fibric acid derivatives. Low Cholesterol (⬍200 mg/dl)
High Cholesterol (⬎200 mg/dl)
Low Triglycerides (⬍150 mg/dl)
High Triglycerides (⬎150 mg/dl)
N
197
74
122
147
Mean Levels
153 ⫾ 28
233 ⫾ 40
95 ⫾ 30
262 ⫾ 194
Subsequent 5-Year Actuarial Survival
68%
74%
70%
71%
Subsequent Freedom from CAV
74%*
57%
73%
67%
Subsequent Freedom from NF-MACE
90%
85%
90%
88%
*p⫽0.007, compared to High
Conclusions: Hypercholesterolemia in SRL-treated heart transplant patients appears to be associated with greater subsequent development of
Cardiac Allograft Hypertrophy Is Associated with Impaired Exercise Tolerance after Heart Transplantation E. Raichlin,2 M.A. Al-Omari,1 S.S. Kushwaha,1 B.S. Eswards,1 A.L. Clavel,1 R.J. Rodeheffer,1 R.P. Frantz,1 R.C. Daly,1 S. Park,1 T.G. Allison,1 N.L. Pereira.1 1Cardiovascular Diseases, Mayo Clinic, Rochester, MN; 2Department of Cardiology, University of Nebraska Medical Center, Omaha, NE. Purpose: Exercise performance, an important aspect of quality of life, remains limited after heart transplantation (HTx). This prospective crosssectional study examined the effect of early changes of cardiac allograft geometry on post-HTx functional capacity. Methods and Materials: Based on echocardiographic determination of left ventricle mass and relative wall thickness at 1 year after HTx, the total cohort of 117 HTx recipients was divided into 3 groups: (1) NG – normal geometry (2) CR – concentric remodeling and (3) CH – concentric hypertrophy. Cardiopulmonary exercise test was performed 5.03⫾3.08 years after HTx. Results: At 1 year after HTx 34 (30%) patients had CH, 64 (55%) had CR and 18 (15%) demonstrated NG. There was no difference in demographic and clinical characteristics between the groups. LV geometry pattern at 1 year after HTx correlated strongly with LV geometry pattern at echocardiographic study performed prior to CPET (r ⫽ 0.72, p ⫽ 0.001). Heart rate, blood pressure and exercise duration (mean 6.88 ⫾ 2.20 min) did not differ between the groups. The maximum achieved metabolic equivalents and peak VO2 was lower and VE/VCO2 was higher in patients presented with CH pattern at 1 year after HTx as compared to NG. After multivariate analysis decreased exercise capacity in metabolic equivalents associated with increased BMI and worse kidney function; reduced peak VO2 associated with 1-year CH pattern (p⫽0.018), older recipients’ and donors’ age, higher BMI and lower E/E’; elevated VE/VCO2 associated with 1-year CH geometric pattern (p⫽0.01), higher heart rate, lower E’ and higher pulmonary artery systolic pressure. Conclusions: Early cardiac allograft remodeling and the presence of CH at one year after transplantation is associated with decreased exercise tolerance, decreased peak oxygen uptake and increase ventilatory response of the HTx recipients. Identifying of this potentially reversible mechanism of the decline in exercise capacity after cardiac transplantation could have important clinical implications. 14 Heart-Lung Transplantation May Confer Protection from Developing Transplant Coronary Artery Disease: An Analysis of the United Organ Network Sharing Database V.K. Topkara,1 M. Yeung,1 P.-H. Huang,1 A.M. Hadi,1 S.M. Joseph,1 J.D. Schilling,1 S.C. Sylvestry,2 N. Moazami,3 I.-W. Wang,2 G.A. Ewald.1 1 Cardiology, Washington University School of Medicine, St. Louis, MO; 2 Cardiothoracic Surgery, Washington University School of Medicine, St. Louis, MO; 3Cardiothoracic Surgery, Minneapolis Heart Institute, Minneapolis, MN. Purpose: Previous studies suggested a protective effect of one organ on another in combined organ allografts with reduced rejection rates. Whether a similar protection is present for the development of transplant coronary artery disease (TCAD) after heart transplantation remains unknown. Given that immunological risk factors have been implicated in pathogenesis of TCAD, we hypothesized that simultaneous organ transplantation reduces the incidence of TCAD. Methods and Materials: UNOS provided de-identified patient-level data. Analysis included 28,847 adults receiving heart-only, 505 receiving heartlung transplants, 502 heart-liver transplants, and 60 heart-kidney transplants between 04/94 and 12/08. Kaplan-Meier analysis was used to determine freedom from TCAD. Results: Freedom from TCAD at 1, 5, and 10 years was 97.5%, 71.4%, and 45.9% in heart-only transplants; 99.1%, 86.6%, and 70.9% in heartlung transplants; 98.3%, 76.4%, and 50.5% in heart-kidney transplants; and