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Impact of the 18th Birthday on Wait-list Outcome for US Patients Listed for Heart Transplant
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The Journal of Heart and Lung Transplantation, Vol 34, No 4S, April 2015
(IQR) were used to describe the data with associated t-test and chi-square to compare groups. Results: 192 pediatric HTx pts were followed who had a LP obtained after HTx. The median age was 12.1 yr, (IQR 6.8-18.25) and an median time since heart transplant of 5 yr (IQR 1-9). For those who died the average age was 9.7 yr with the average time since heart transplant of 5.7 yr (median 5.5 yr, IQR 1.8-9.8). Figure 1 shows the year (yr) the Htxs were performed. As for the 192 patients, the average TC was 127 mg/dL (median 121, IQR 82-219), TG 130 mg/dL (median 98, IQR 67-165), HDL 40 mg/dL (median 38, IQR 31-48), LDL 62 mg/dL (median 60, IQR 46-76), and non-HDL is 87 mg/dL (median 83, IQR 67-99). There were significant differences in TC, HDL and non-HDL cholesterol between survivors and those with graft failure, shown in Figure 2. Conclusion: These findings suggest that low cholesterol levels may be a marker for poor outcome in pediatric HTx patients.
Results: A total of 711 patients met the study inclusion criteria, including 406 (56%) listed during the 24-month period prior to the 18th BD and 305 (44%) during the 24 months after the 18th BD. The groups were similar with respect to race, gender, blood type O prevalence, cardiac diagnosis, cardiac output, pulmonary capillary wedge pressure, and proportion supported with inotropes. Creatinine at listing was 0.1 mg/dL higher in the older cohort (P= 0.01) and more children in the younger cohort were supported with ECMO (P= 0.05). Overall, the median wait-time for the older cohort was 2.4x longer than the younger cohort (144 days v. 61 days, log-rank, P< 0.001) (Fig. 1). Fewer patients in the older cohort eventually received a heart transplant (64% v. 79%, P< 0.001). Wait-list mortality was higher in the older cohort (14.9% v. 7.2%, P< 0.001). Conclusion: Patients listed for HT shortly after their 18th BD have significantly longer wait-times and experience higher unadjusted mortality compared to patients listed shortly before their 18th BD. For children at high risk of waitlist mortality, birthdate may be one factor to consider in timing of transplant listing. Figure 1. Time to heart transplant expressed as a hazard function among patients listed for heart transplant +/– 24 months from their 18th birthday (N= 711).
8( 0) The Amount of Autophagy-Related Cardiomyocyte Cell Death Is Associated With the Type of Pathogenic Mutation in Genetic Dilated Cardiomyopathy Z.J. van der Klooster ,1 S. Sepehrkhouy,1 M. Harakalova,1 R. Goldschmeding,1 N. de Jonge,1 A.J. Suurmeijer,2 R.A. de Weger,1 F.W. Asselbergs,1 A. Vink.1 1Pathology, University Medical Center Utrecht, Utrecht, Netherlands; 2Pathology, University Medical Center Groningen, Groningen, Netherlands. 7( 9) Impact of the 18th Birthday on Wait-list Outcome for US Patients Listed for Heart Transplant D.M. Peng ,1 N. McDonald,1 O. Reinhartz,2 L. Barkoff,1 S.A. Hollander,1 A. Lin,1 J. Yeh,1 D.N. Rosenthal,1 C.S. Almond.1 1Department of Pediatrics, Division of Pediatric Cardiology, Stanford University/Lucile Packard Children’s Hospital Stanford, Palo Alto, CA; 2Department of Cardiothoracic Surgery, Stanford University, Palo Alto, CA. Purpose: Patients under 21 years of age listed for heart transplant (HT) after their 18th birthday (BD) purportedly wait longer to receive a donor heart compared to children listed before their 18th BD. It is unclear whether there is an actual difference in wait-times and whether any difference in wait-time is associated with lower likelihood of transplant and/or higher mortality. Methods: All patients listed for HT during a 24-month period before and 24-month period after their 18th BD between 2006-2014 were compared using OPTN data. The primary endpoint of the study was the Kaplan-Meier median wait time to receive a donor heart. Secondary endpoints were the proportion of patients who survived to transplant and mortality.
Purpose: Genetic dilated cardiomyopathy is a heterogenous group of diseases caused by mutations in various genes. Progressive cardiomyocyte loss and subsequent fibrosis is a key feature of this disease. Several types of cardiomyocyte cell death have been implicated: (macro) autophagy-related cell death, apoptosis, necroptosis and oncosis. One plausible mechanism of genetic cardiomyopathy is proteotoxicity of accumulated mutant protein aggregates. Here we investigate the association of such aggregates as a sign of autophagy-related cardiomyocyte cell death with specific pathogenic mutations in dilated cardiomyopathy. Methods: Hearts from 19 patients with a genetic dilated cardiomyopathy or a combined phenotype of dilated and arrhythmogenic cardiomyopathy were included. Donor hearts not used for transplantation were taken as controls (n= 2). A complete transversal slice was taken from each heart and divided into 8 regions. Microscopic slices from each region were immunohistochemically stained for P62, a marker for aggregated proteins destined for autophagy. A quantitative analysis was done by hotspot count to determine the number of positive cells per 750 cardiomyocytes in each region. Results: Sporadic P62 positive cells were seen in control hearts (0.5% of cardiomyocytes, range 0-2.4%). Troponin mutations (TNNT2 and TNNI3; 0.6%, range 0-2.8%, n= 2) showed hardly any increase in P62. Titin (1.2%,
The Journal of Heart and Lung Transplantation, Vol 34, No 4S, April 2015
(IQR) were used to describe the data with associated t-test and chi-square to compare groups. Results: 192 pediatric HTx pts were followed who had a LP obtained after HTx. The median age was 12.1 yr, (IQR 6.8-18.25) and an median time since heart transplant of 5 yr (IQR 1-9). For those who died the average age was 9.7 yr with the average time since heart transplant of 5.7 yr (median 5.5 yr, IQR 1.8-9.8). Figure 1 shows the year (yr) the Htxs were performed. As for the 192 patients, the average TC was 127 mg/dL (median 121, IQR 82-219), TG 130 mg/dL (median 98, IQR 67-165), HDL 40 mg/dL (median 38, IQR 31-48), LDL 62 mg/dL (median 60, IQR 46-76), and non-HDL is 87 mg/dL (median 83, IQR 67-99). There were significant differences in TC, HDL and non-HDL cholesterol between survivors and those with graft failure, shown in Figure 2. Conclusion: These findings suggest that low cholesterol levels may be a marker for poor outcome in pediatric HTx patients.
Results: A total of 711 patients met the study inclusion criteria, including 406 (56%) listed during the 24-month period prior to the 18th BD and 305 (44%) during the 24 months after the 18th BD. The groups were similar with respect to race, gender, blood type O prevalence, cardiac diagnosis, cardiac output, pulmonary capillary wedge pressure, and proportion supported with inotropes. Creatinine at listing was 0.1 mg/dL higher in the older cohort (P= 0.01) and more children in the younger cohort were supported with ECMO (P= 0.05). Overall, the median wait-time for the older cohort was 2.4x longer than the younger cohort (144 days v. 61 days, log-rank, P< 0.001) (Fig. 1). Fewer patients in the older cohort eventually received a heart transplant (64% v. 79%, P< 0.001). Wait-list mortality was higher in the older cohort (14.9% v. 7.2%, P< 0.001). Conclusion: Patients listed for HT shortly after their 18th BD have significantly longer wait-times and experience higher unadjusted mortality compared to patients listed shortly before their 18th BD. For children at high risk of waitlist mortality, birthdate may be one factor to consider in timing of transplant listing. Figure 1. Time to heart transplant expressed as a hazard function among patients listed for heart transplant +/– 24 months from their 18th birthday (N= 711).
8( 0) The Amount of Autophagy-Related Cardiomyocyte Cell Death Is Associated With the Type of Pathogenic Mutation in Genetic Dilated Cardiomyopathy Z.J. van der Klooster ,1 S. Sepehrkhouy,1 M. Harakalova,1 R. Goldschmeding,1 N. de Jonge,1 A.J. Suurmeijer,2 R.A. de Weger,1 F.W. Asselbergs,1 A. Vink.1 1Pathology, University Medical Center Utrecht, Utrecht, Netherlands; 2Pathology, University Medical Center Groningen, Groningen, Netherlands. 7( 9) Impact of the 18th Birthday on Wait-list Outcome for US Patients Listed for Heart Transplant D.M. Peng ,1 N. McDonald,1 O. Reinhartz,2 L. Barkoff,1 S.A. Hollander,1 A. Lin,1 J. Yeh,1 D.N. Rosenthal,1 C.S. Almond.1 1Department of Pediatrics, Division of Pediatric Cardiology, Stanford University/Lucile Packard Children’s Hospital Stanford, Palo Alto, CA; 2Department of Cardiothoracic Surgery, Stanford University, Palo Alto, CA. Purpose: Patients under 21 years of age listed for heart transplant (HT) after their 18th birthday (BD) purportedly wait longer to receive a donor heart compared to children listed before their 18th BD. It is unclear whether there is an actual difference in wait-times and whether any difference in wait-time is associated with lower likelihood of transplant and/or higher mortality. Methods: All patients listed for HT during a 24-month period before and 24-month period after their 18th BD between 2006-2014 were compared using OPTN data. The primary endpoint of the study was the Kaplan-Meier median wait time to receive a donor heart. Secondary endpoints were the proportion of patients who survived to transplant and mortality.
Purpose: Genetic dilated cardiomyopathy is a heterogenous group of diseases caused by mutations in various genes. Progressive cardiomyocyte loss and subsequent fibrosis is a key feature of this disease. Several types of cardiomyocyte cell death have been implicated: (macro) autophagy-related cell death, apoptosis, necroptosis and oncosis. One plausible mechanism of genetic cardiomyopathy is proteotoxicity of accumulated mutant protein aggregates. Here we investigate the association of such aggregates as a sign of autophagy-related cardiomyocyte cell death with specific pathogenic mutations in dilated cardiomyopathy. Methods: Hearts from 19 patients with a genetic dilated cardiomyopathy or a combined phenotype of dilated and arrhythmogenic cardiomyopathy were included. Donor hearts not used for transplantation were taken as controls (n= 2). A complete transversal slice was taken from each heart and divided into 8 regions. Microscopic slices from each region were immunohistochemically stained for P62, a marker for aggregated proteins destined for autophagy. A quantitative analysis was done by hotspot count to determine the number of positive cells per 750 cardiomyocytes in each region. Results: Sporadic P62 positive cells were seen in control hearts (0.5% of cardiomyocytes, range 0-2.4%). Troponin mutations (TNNT2 and TNNI3; 0.6%, range 0-2.8%, n= 2) showed hardly any increase in P62. Titin (1.2%,