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430: Clinical outcomes after cardiac transplantation in muscular dystrophy patients
The Journal of Heart and Lung Transplantation Volume 26, Number 2S
429 B-TYPE NATRIURETIC PEPTIDE IS A SENSITIVE SCREENING TOOL FOR ACUTE REJECTION IN PEDIATRIC HEART TRANSPLANT PATIENTS J.W. Rossano,1 S.W. Denfield,1 J.J. Kim,1 J.L. Jefferies,1 J.F. Price,1 J.A. Decker,1 S.K. Clunie,1 J.A. Towbin,1 W.J. Dreyer,1 1Cardiology, Texas Children’s Hospital and Baylor College of Medicine, Houston, TX Purpose: The utility of B-type natriuretic peptide (BNP) in detecting acute rejection (AR) is unclear. The purpose of our study was to evaluate BNP as a screening test for AR in a large cohort of pediatric heart transplant patients. Methods and Materials: All endomyocardial biopsies (EMB) with concurrent BNP levels from patients transplanted between 1989 and 2005 at our institution were reviewed. Characteristics of BNP in detecting AR, defined as a biopsy score ⱖ ISHLT 3A or humoral rejection, were assessed. Results: 85 patients underwent 444 EMB. The median age at transplant was 4.9 yrs (Interquartile range [IQR] 2.0 -11.4), and the median age at EMB was 10.6 yrs (IQR 3.5-15.0). There were 50 episodes of AR, 26 (52%) occurring ⬍ 1yr post-transplant. BNP levels were higher in patients with AR, median 346 pg/ml (IQR 123-928), versus those without AR, median 70 pg/ml (IQR 39-144) (p⬍0.001). Receiver operating characteristic (ROC) curve for BNP demonstrated the mean area under the curve (AUC) of 0.80 (95%CI 0.73-0.87) (p⬍0.001). Using a cutoff BNP level of 100 pg/ml corresponds to a sensitivity for detecting AR of 0.82 (95%CI 0.68-0.91), specificity of 0.65 (95%CI 0.60-0.69), PPV of 0.23 (95%CI 0.17-0.30), and NPV of 0.97 (95%CI 0.93-0.98). At ⬎ 1 yr post-transplant, BNP values were higher in patients with AR, median 603 pg/ml (IQR 129-1311), versus those without AR, median 72 pg/ml (IQR 42-134 pg/dl) (p⬍0.001). ROC curve in patients ⬎ 1 yr post-transplant for BNP demonstrated the mean AUC of 0.87 (95%CI 0.80-0.94) (p⬍0.001), and using a cutoff BNP level of 100 pg/ml corresponds to a sensitivity for detecting AR of 0.96 (95%CI 0.77-0.99), specificity of 0.64 (95%CI 0.57-0.70), PPV of 0.23 (95%CI 0.16-0.33), and NPV of 0.992 (95%CI 0.952-0.999). Conclusions: BNP levels have a high sensitivity and NPV in evaluating AR in pediatric heart transplant patients. In patients ⬎ 1 yr posttransplant, a BNP level of ⬍ 100 pg/ml correlates to a ⬍ 1% chance of AR and may obviate the need for routine EMB. Dr. Rossano is a cardiology fellow and his salary is partially supported by Scios; Scios.
430 CLINICAL OUTCOMES AFTER CARDIAC TRANSPLANTATION IN MUSCULAR DYSTROPHY PATIENTS R.S. Wu,1 R.N. Brown,2 C.W. Yancy,1 J.W. Wald,3 P. Kaiser,1 N.M. Kirklin,2 D.J. Garry,1,4,5 P.P.A. Mammen,1,5 1Department of Internal Medicine, UT Southwestern Medical Center, Dallas, TX; 2 Cardiac Transplant Research Database, University of Alabama at Birmingham, Birmingham, AL; 3Department of Internal Medicine, Temple University, Philadelphia, PA; 4Department of Molecular Biology, UT Southwestern Medical Center, Dallas, TX; 5Donald W. Reynolds Cardiovascular Clinical Research Center, UT Southwestern Medical Center, Dallas, TX Purpose: The muscular dystrophies (MD) represent an array of neuromuscular disorders and a majority of MD patients acquire a dilated cardiomyopathy resulting in advanced heart failure and premature
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death. The only definitive therapy for advanced heart failure is orthotopic heart transplantation. However, there has been a reluctance to transplant patients with muscular dystrophy due to the systemic nature of their underlying disease. Therefore, we undertook a study to investigate the clinical outcomes of cardiac transplantation in muscular dystrophy patients. Methods and Materials: We utilized the Cardiac Transplant Research Database (CTRD), a registry of 29 US Transplant Centers, to obtain our sample population and perform our study. Between 1990 and 2005 orthotopic heart transplantation was undertaken in 29 patients with MD and 275 non-MD patients with non-ischemic cardiomyopathy who were matched according to age, body mass index, gender, and race. Results: The mean age at the time of transplantation was 37 in both groups. The majority of patients were white males and 52% of MD patients had Becker’s MD. Outcome data revealed that survival (1yr: 89% in MD pts and 91% in non-MD pts; 5 yr: 83% in MD pts and 78% in non-MD pts, p⫽0.5), rate of cumulative rejections (1yr: 1.1 in MD pts and 1.1 in non-MD pts; 5 yr: 1.3 in MD pts and 1.7 in non-MD pts, p⫽0.4), and rate of cumulative infections (1yr: 0.6 in MD pts and 0.6 in non-MD pts; 5 yr: 0.9 in MD pts and 0.8 in non-MD pts, p⫽0.5) was similar between the two groups. This analysis represents the largest study evaluating the outcome of MD patients who have undergone cardiac transplantation. Conclusions: Based on this analysis, we conclude that the clinical outcomes following cardiac transplantation in muscular dystrophy patients are similar to age-matched patients with non-ischemic cardiomyopathy. Therefore, we propose that the diagnosis of muscular dystrophy should not be the sole limiting factor excluding patients with advanced heart failure for consideration of a cardiac transplantation. 431 HEART TRANSPLANTATION FOR AL AMYLOIDOSIS C.G.A. McGregor,1 B.S. Edwards,1 R.J. Rodeheffer,1 R.P. Frantz,1 S.S. Kushwaha,1 A.L. Clavell,1 J.A. Dearani,1 T.M. Sundt,1 R.C. Daly,1 1 Mayo Clinic-Rochester William J von Liebig Transplant Center, Mayo Clinic, Rochester, MN Purpose: We report on 140 patients with AL amyloidosis referred for heart transplantation. Methods and Materials: Forty-three patients were accepted for heart transplantation. Twenty-three patients have been transplanted. Results: Eleven patients are currently alive at 1, 2, 14, 14, 27, 34, 85, 90, 103, 106 and 153 mo. after transplant. Twelve patients have died. Two patients developed nephrotic syndrome. These two patients underwent kidney transplant 24 and 54 mo. after heart transplant and remained alive and well for 40 and 114 mo. after kidney transplant. Eleven patients had stem cell transplants and six are currently alive at 11, 23, 29, 73, 84 and 95 mo. In these 6 patients mean 24-hr urine protein is 1297 mg (range 61-2852). One and five-year survival after transplantation is 85.7⫾7.6% and 62.9⫾11.3%, respectively, compared with 93.3⫾1.5% and 84.1⫾2.4% respectively in the nonamyloid population transplanted here (p⫽⬍0.0025). Conclusions: In this series, heart transplantation achieved improved longevity and quality of life in at least the intermediate time frame. Outcomes are significantly less than the non-amyloid heart transplant population. Aggressive treatment of systemic amyloidosis after heart transplantation, including peripheral stem cell transplant, is indicated. Selection criteria remain uncertain and evolving. We believe heart transplantation should continue to be offered to highly selected patients with end-stage cardiac amyloid disease in centers with extensive experience in the management of amyloidosis.
429 B-TYPE NATRIURETIC PEPTIDE IS A SENSITIVE SCREENING TOOL FOR ACUTE REJECTION IN PEDIATRIC HEART TRANSPLANT PATIENTS J.W. Rossano,1 S.W. Denfield,1 J.J. Kim,1 J.L. Jefferies,1 J.F. Price,1 J.A. Decker,1 S.K. Clunie,1 J.A. Towbin,1 W.J. Dreyer,1 1Cardiology, Texas Children’s Hospital and Baylor College of Medicine, Houston, TX Purpose: The utility of B-type natriuretic peptide (BNP) in detecting acute rejection (AR) is unclear. The purpose of our study was to evaluate BNP as a screening test for AR in a large cohort of pediatric heart transplant patients. Methods and Materials: All endomyocardial biopsies (EMB) with concurrent BNP levels from patients transplanted between 1989 and 2005 at our institution were reviewed. Characteristics of BNP in detecting AR, defined as a biopsy score ⱖ ISHLT 3A or humoral rejection, were assessed. Results: 85 patients underwent 444 EMB. The median age at transplant was 4.9 yrs (Interquartile range [IQR] 2.0 -11.4), and the median age at EMB was 10.6 yrs (IQR 3.5-15.0). There were 50 episodes of AR, 26 (52%) occurring ⬍ 1yr post-transplant. BNP levels were higher in patients with AR, median 346 pg/ml (IQR 123-928), versus those without AR, median 70 pg/ml (IQR 39-144) (p⬍0.001). Receiver operating characteristic (ROC) curve for BNP demonstrated the mean area under the curve (AUC) of 0.80 (95%CI 0.73-0.87) (p⬍0.001). Using a cutoff BNP level of 100 pg/ml corresponds to a sensitivity for detecting AR of 0.82 (95%CI 0.68-0.91), specificity of 0.65 (95%CI 0.60-0.69), PPV of 0.23 (95%CI 0.17-0.30), and NPV of 0.97 (95%CI 0.93-0.98). At ⬎ 1 yr post-transplant, BNP values were higher in patients with AR, median 603 pg/ml (IQR 129-1311), versus those without AR, median 72 pg/ml (IQR 42-134 pg/dl) (p⬍0.001). ROC curve in patients ⬎ 1 yr post-transplant for BNP demonstrated the mean AUC of 0.87 (95%CI 0.80-0.94) (p⬍0.001), and using a cutoff BNP level of 100 pg/ml corresponds to a sensitivity for detecting AR of 0.96 (95%CI 0.77-0.99), specificity of 0.64 (95%CI 0.57-0.70), PPV of 0.23 (95%CI 0.16-0.33), and NPV of 0.992 (95%CI 0.952-0.999). Conclusions: BNP levels have a high sensitivity and NPV in evaluating AR in pediatric heart transplant patients. In patients ⬎ 1 yr posttransplant, a BNP level of ⬍ 100 pg/ml correlates to a ⬍ 1% chance of AR and may obviate the need for routine EMB. Dr. Rossano is a cardiology fellow and his salary is partially supported by Scios; Scios.
430 CLINICAL OUTCOMES AFTER CARDIAC TRANSPLANTATION IN MUSCULAR DYSTROPHY PATIENTS R.S. Wu,1 R.N. Brown,2 C.W. Yancy,1 J.W. Wald,3 P. Kaiser,1 N.M. Kirklin,2 D.J. Garry,1,4,5 P.P.A. Mammen,1,5 1Department of Internal Medicine, UT Southwestern Medical Center, Dallas, TX; 2 Cardiac Transplant Research Database, University of Alabama at Birmingham, Birmingham, AL; 3Department of Internal Medicine, Temple University, Philadelphia, PA; 4Department of Molecular Biology, UT Southwestern Medical Center, Dallas, TX; 5Donald W. Reynolds Cardiovascular Clinical Research Center, UT Southwestern Medical Center, Dallas, TX Purpose: The muscular dystrophies (MD) represent an array of neuromuscular disorders and a majority of MD patients acquire a dilated cardiomyopathy resulting in advanced heart failure and premature
Abstracts
S215
death. The only definitive therapy for advanced heart failure is orthotopic heart transplantation. However, there has been a reluctance to transplant patients with muscular dystrophy due to the systemic nature of their underlying disease. Therefore, we undertook a study to investigate the clinical outcomes of cardiac transplantation in muscular dystrophy patients. Methods and Materials: We utilized the Cardiac Transplant Research Database (CTRD), a registry of 29 US Transplant Centers, to obtain our sample population and perform our study. Between 1990 and 2005 orthotopic heart transplantation was undertaken in 29 patients with MD and 275 non-MD patients with non-ischemic cardiomyopathy who were matched according to age, body mass index, gender, and race. Results: The mean age at the time of transplantation was 37 in both groups. The majority of patients were white males and 52% of MD patients had Becker’s MD. Outcome data revealed that survival (1yr: 89% in MD pts and 91% in non-MD pts; 5 yr: 83% in MD pts and 78% in non-MD pts, p⫽0.5), rate of cumulative rejections (1yr: 1.1 in MD pts and 1.1 in non-MD pts; 5 yr: 1.3 in MD pts and 1.7 in non-MD pts, p⫽0.4), and rate of cumulative infections (1yr: 0.6 in MD pts and 0.6 in non-MD pts; 5 yr: 0.9 in MD pts and 0.8 in non-MD pts, p⫽0.5) was similar between the two groups. This analysis represents the largest study evaluating the outcome of MD patients who have undergone cardiac transplantation. Conclusions: Based on this analysis, we conclude that the clinical outcomes following cardiac transplantation in muscular dystrophy patients are similar to age-matched patients with non-ischemic cardiomyopathy. Therefore, we propose that the diagnosis of muscular dystrophy should not be the sole limiting factor excluding patients with advanced heart failure for consideration of a cardiac transplantation. 431 HEART TRANSPLANTATION FOR AL AMYLOIDOSIS C.G.A. McGregor,1 B.S. Edwards,1 R.J. Rodeheffer,1 R.P. Frantz,1 S.S. Kushwaha,1 A.L. Clavell,1 J.A. Dearani,1 T.M. Sundt,1 R.C. Daly,1 1 Mayo Clinic-Rochester William J von Liebig Transplant Center, Mayo Clinic, Rochester, MN Purpose: We report on 140 patients with AL amyloidosis referred for heart transplantation. Methods and Materials: Forty-three patients were accepted for heart transplantation. Twenty-three patients have been transplanted. Results: Eleven patients are currently alive at 1, 2, 14, 14, 27, 34, 85, 90, 103, 106 and 153 mo. after transplant. Twelve patients have died. Two patients developed nephrotic syndrome. These two patients underwent kidney transplant 24 and 54 mo. after heart transplant and remained alive and well for 40 and 114 mo. after kidney transplant. Eleven patients had stem cell transplants and six are currently alive at 11, 23, 29, 73, 84 and 95 mo. In these 6 patients mean 24-hr urine protein is 1297 mg (range 61-2852). One and five-year survival after transplantation is 85.7⫾7.6% and 62.9⫾11.3%, respectively, compared with 93.3⫾1.5% and 84.1⫾2.4% respectively in the nonamyloid population transplanted here (p⫽⬍0.0025). Conclusions: In this series, heart transplantation achieved improved longevity and quality of life in at least the intermediate time frame. Outcomes are significantly less than the non-amyloid heart transplant population. Aggressive treatment of systemic amyloidosis after heart transplantation, including peripheral stem cell transplant, is indicated. Selection criteria remain uncertain and evolving. We believe heart transplantation should continue to be offered to highly selected patients with end-stage cardiac amyloid disease in centers with extensive experience in the management of amyloidosis.