Outcomes of adults with restrictive cardiomyopathy after heart transplantation

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1 Outcomes of adults with restrictive cardiomyopathy after heart transplantation Eugene C. DePasquale, MD, a Khurram Nasir, MD, MPH, b and Daniel L. Jacoby, MD b From the a Division of Cardiology, David Geffen School of Medicine, University of California, Los Angeles; and b Section of Cardiovascular Medicine, Yale University School of Medicine, New Haven, Connecticut. KEYWORDS: amyloid; chemotherapy-induced cardiomyopathy; heart transplantation; outcomes; radiation-induced cardiomyopathy; restrictive cardiomyopathy BACKGROUND: Restrictive cardiomyopathy (RCM) represents a spectrum of disorders with a common physiology but divergent etiologies. RCM commonly leads to progressive heart failure and the need for heart transplantation (HTx). Pediatric RCM is a more homogeneous disorder with post-htx outcomes comparable to those for non-rcm patients. However, post-htx outcomes in adult RCM patients have not been studied to date. METHODS: Demographic, clinical and survival outcomes of 38,190 adult HTx-only recipients from 1987 to 2010 were acquired from the registry of the United Network of Organ Sharing. The study population included 544 RCM patients (1.4%) and 37,646 non-rcm patients (98.6%). RCM diagnoses included idiopathic (n ¼ 227, 42%), amyloid (n ¼ 142, 26%), sarcoid (n ¼ 81, 15%), radiation/ chemotherapy (XRT) (n ¼ 35, 6%) and other (n ¼ 59, 11%). RESULTS: Follow-up began at the time of HTx (74 64 months). During the follow-up period, 224 (41%) patients in the RCM group died, whereas 18,791 (50%) in the non-rcm group died. Crude 1-, 5- and 10-year survival for RCM patients was 84%, 66% and 45%, and for non-rcm patients was 85%, 70% and 50%, respectively. The overall unadjusted hazard ratio of RCM vs non-rcm for all-cause mortality was 1.07 (confidence interval [CI] 0.93 to 1.22). Multivariate Cox proportional hazards regression analysis yielded a hazard ratio of 1.06 (CI 0.91 to 1.25). RCM subgroup analysis showed decreased survival at 1, 5 and 10 years in the XRT (71%, 47% and 32%) and amyloid (79%, 47% and 28%) patient groups. The unadjusted hazard ratio for the XRT and amyloid subgroups vs RCM for allcause mortality was 1.81 (p ¼ 0.002) and 1.85 (p ¼ ), respectively. CONCLUSIONS: Outcomes for RCM patients post-htx are comparable to those of non-rcm patients. However, RCM subgroup analysis suggests increased mortality for XRT and amyloid subgroups. Further analysis is warranted to understand the contributing factors. J Heart Lung Transplant 2012; 31: r 2012 International Society for Heart and Lung Transplantation. All rights reserved. Restrictive cardiomyopathy is a disorder characterized by diverse etiologies, including idiopathic, amyloidosis, sarcoidosis and radiation/chemotherapy-induced restrictive cardiomyopathies, among other entities. Overall prognosis Reprint requests: Daniel L. Jacoby, MD, Section of Cardiovascular Medicine, Yale University School of Medicine, 333 Cedar Street, Dana 3, New Haven, CT Telephone: Fax: address: daniel.jacoby@yale.edu /$ - see front matter r 2012 International Society for Heart and Lung Transplantation. All rights reserved. is poor with eventual progression to heart failure and is associated with increased mortality. 1 3 Cardiac transplantation is an end-stage therapy for this patient population; however, studies evaluating of the merits of this approach have been limited to predominantly small series or single-center experiences in adults Pediatric restrictive cardiomyopathy, a more homogeneous disorder, has been evaluated more extensively and has shown favorable outcomes. 12,13 We evaluated the clinical characteristics and outcomes of

2 1270 The Journal of Heart and Lung Transplantation, Vol 31, No 12, December 2012 RCM patients undergoing cardiac transplantation in an adult population in the USA. Methods Selection and identification of patients Transplant centers in the USA are required to report clinical and demographic data to the Organ Procurement and Transplantation Network Registry, which is operated by the United Network of Organ Sharing (UNOS). Our analysis was limited to patients in the UNOS Thoracic Registry who were Z18 years of age and who underwent heart transplantation between January 1987 and December Analysis was further limited to first-time, single-organ, heart-only transplant recipients. Patients with repeat cardiac transplants or multiple-organ transplants were excluded from the study. Baseline clinical characteristics of the study population were obtained from the UNOS Thoracic Registry. The cohort was then divided into RCM and non-rcm groups according to the Heart Transplant Recipient Registration Worksheet. The non-rcm groups consisted of 4 subgroups of patients: (1) ischemic cardiomyopathy (i.e., predominant etiology of heart failure due to coronary heart disease); (2) dilated cardiomyopathy (i.e., idiopathic, viral, post-partum or familial); (3) hypertrophic; and (4) other (i.e., congenital or valvular heart disease). RCM was further subdivided into: (1) idiopathic; (2) amyloid; (3) sarcoid; (4) radiation/chemotherapy; and (5) other. Cases were excluded if recipients were lost to follow-up (n ¼ 9,650, which consisted of 332 RCM and 9,318 non-rcm patients). Statistical analyses Patient demographic and clinical characteristics of the cohort were first compared by status of RCM, ischemic, dilated, hypertrophic or other. For continuous variables, the mean and SD were calculated, and for categorical variables, proportions or percentages were calculated. For unadjusted comparisons between groups, the Kruskal Wallis rank test was used for continuous variables, and the chi-square test was used for categorical variables. Follow-up time was censored at 12 years (144 months) for mortality analysis. Most recent follow-up was determined as the last clinic visit entered into the database and was defined as time from transplantation to death or last clinic visit. For descriptive purposes, crude cumulative mortality rates were estimated and plotted with the Kaplan Meier method and compared between groups using the log-rank test. Using Cox proportional hazards regression models, we estimated association of RCM with mortality with unadjusted and adjusted models for previously established pre- and post-transplant risk factors. Previously established pre- and post-transplant risk factors were adjusted in the Cox regression models. Pre-transplant variables included: recipient gender; recipient age; body mass index; duration on the transplant waiting list; UNOS status; serum creatinine; serum bilirubin; peak panel-reactive antibody; human leukocyte antigen mismatch; and need for life support (including pre-transplant intra-aortic balloon pump, ventricular assist device and/or ventilator). Transplantation variables included donor age and ischemic time. A backward stepwise elimination procedure was used to identify the final multivariable models, starting with a set of potential covariates known to be associated with posttransplant mortality. Variables were included when their significance level was p r Final variables included: age; gender; diabetes; race; ischemic time; dialysis; life support; duration on transplant waiting list; and HLA mismatch. Results Occurrence During the 24-year study period, 38,190 patients underwent cardiac transplantation, including 544 (1.4%) RCM patients and 37,646 non-rcm patients (ischemic cardiomyopathy, n ¼ 18,517 [48.5%]; hypertrophic cardiomyopathy, n ¼ 499 [1.3%]; dilated cardiomyopathy, n ¼ 16,127 [42.2%]; other, n ¼ 2,503 [6.6%]). RCM subgroups included: idiopathic (n ¼ 227 [41.7%]); amyloid (n ¼ 142 [26.1%]); sarcoid (n ¼ 81 [14.9%]); radiation/chemotherapy (n ¼ 35 [6.4%]); and other (n ¼ 59 [10.9%]). For the 38,190 patients included in the analysis, follow-up time for the study was (mean SD) months. Clinical and demographic profile of study group The clinical and demographic characteristics of the overall study population are shown in Table 1. Compared with non- RCM transplant patients, RCM transplant patients were younger (49 13 vs years, p ¼ ), less likely to be male (56% vs 78%, p o ) or have diabetes (9.9% vs 20.9%, p o ), and had a lower body mass index (25 5vs26 5 kg/m 2, p o ). RCM transplant patients were also more likely to have a longer ischemic time (p ¼ 0.002), higher PRA (53% vs 45%, p o ) and shorter waiting time for transplant (median 67 vs 88 days, p ¼ ). RCM transplants were less likely to be supported by a ventricular assist device (VAD) at the time of transplant (10% vs 16%, p o ). Pulmonary artery pressures (systolic, diastolic and mean) were similar in both groups. Cardiac output (p ¼ ) and transpulmonary gradient (p ¼ 0.012) were both lower in RCM patients. The characteristics of the RCM subgroups are shown in Table 2. Survival after cardiac transplantation For the 38,190 patients included in the analysis, mean SD follow-up time for the study was months. During the follow-up period, 224 RCM patients died (41%) as compared with 18,791 non-rcm patients (50%). The mean age at death was (range 18 to 80) years, occurring (range 0 to 12) years after transplantation for RCM patients. Cause of death for RCM patients was divided into non-cardiovascular (n ¼ 169, 76%) and cardiovascular (n ¼ 54, 22%) cases. RCM patients were more likely to die from non-cardiovascular causes compared with the non-rcm patients (76% vs 67%, p ¼ 0.005). Among RCM transplant patients, the most common causes of death within the first year were infection (33.7%) and multipleorgan failure (16.9%). After the first year, cardiovascular death (16.4%) and multiple-organ failure (16.3%) were the most common causes of death in this group (Table 3).

3 DePasquale et al. Restrictive Cardiomyopathy Post-HTx 1271 Table 1 Baseline Demographics and Clinical Data for RCM and Non-RCM Heart-only Transplant Recipients Recipient characteristics Overall (n ¼ 38,190) a RCM (n ¼ 544) a Non-RCM (n ¼ 37,646) a p-value Age (years) Gender: number of males (%) 29,621 (78%) 302 (56%) (78%) o Race: number of whites (%) 29,952 (78%) 438 (81%) 29,514 (78%) Diabetes mellitus 5,774 (21%) 47 (10%) 5,727 (21%) o COPD 704 (3.3%) 1 (0.3%) 703 (3.3%) History of prior cardiac surgery 4,032 (11%) 48 (9%) 3,984 (11%) BMI (kg/m 2 ) Donor age (years) Ischemic time (hours) ,431 (18%) 63 (13%) 6,368 (18%) 2 12,167 (34%) 163 (32%) 12,004 (34%) 3 11,963 (33%) 181 (36%) 11,782 (33%) Z4 5,590 (16%) 99 (20%) 5,491 (15%) Life support at transplant 20,974 (55%) 295 (54%) 20,679 (55%) IABP 2,160 (6%) 21 (4%) 2,139 (6%) VAD 6,042 (16%) 52 (10%) 5,990 (16%) o Ventilation 1,047 (3%) 10 (2%) 1,037 (3%) Days waited for transplant (median) (88) (67) (88) Serum creatinine (mg/dl) Peak VO 2 (ml/kg/min) PA systolic pressure (mm Hg) PA diastolic pressure (mm Hg) PAP (mm Hg) PCWP (mm Hg) Cardiac output (liters/min) Transpulmonary gradient (mm Hg) PVR (Woods units) UNOS Status 1 26,986 (71%) 401 (74%) 26,585 (71%) History of smoking 12,897 (34%) 121 (22%) 12,776 (34%) o Dialysis 661 (2%) 10 (2%) 651 (2%) PRA Z20% 17,081 (45%) 290 (53%) 16,791 (45%) o Amiodarone 5,267 (14%) 52 (10%) 5,215 (14%) Number listed by era o ,721 (31%) 87 (16%) 11,634 (31%) ,014 (24%) 101 (19%) 8,913 (24%) ,855 (21%) 141 (26%) 7,714 (21%) ,600 (25%) 215 (40%) 9,385 (25%) Cause of death (CV) 6,277 (33%) 54 (24%) 6,223 (33%) Data expressed as mean SD or n (%). BMI, body mass index; COPD, chronic obstructive pulmonary disease; IABP, intra-aortic balloon pump; PAP, pulmonary artery pressure; PCWP, pulmonary artery capillary wedge pressure; PRA, peak panel-reactive antibodies; PVR, pulmonary vascular resistance VAD, ventricular assist device. a Excluding unknowns. Overall, there was no significant difference between cardiovascular and non-cardiovascular death among RCM subtypes (p ¼ 0.592). Crude 1-, 5- and 10-year overall survival for RCM patients was 84%, 66% and 45%, respectively, with no significant difference in survival compared with all non- RCM patients (86%, 70% and 49%, respectively; log-rank test, p ¼ 0.36) (Figure 1). However, crude 1-, 5- and 10-year survival was worse among RCM patients compared with those transplanted for dilated (87%, 71% and 53%, respectively; log rank, p ¼ 0.025) and hypertrophic cardiomyopathy (88%, 77% and 65%, respectively; log rank, p o 0.001). There was no difference compared with patients transplanted for ischemic (85%, 69% and 50%, respectively; log rank, p ¼ 0.08) and other cardiomyopathies (83%, 69% and 53%, respectively; log rank, p ¼ 0.30) (Figure 2). The overall crude Cox proportional hazard ratio (95% confidence intervals [CIs]) of RCM vs non-rcm for allcause mortality was 1.07 (0.93 to 1.22). The adjusted Cox proportional hazard ratio for RCM vs non-rcm was 1.06 (0.91 to 1.25). RCM subgroups The crude 1-, 5- and 10-year overall transplant survival for amyloid (79%, 47% and 28%, respectively; log rank, p o 0.001) and radiation/chemotherapy (71%, 47% and 32%, respectively; log rank, p ¼ 0.015) subgroups were

4 1272 Table 2 Clinical Characteristics of RCM Subgroup Heart-only Transplant Recipients The Journal of Heart and Lung Transplantation, Vol 31, No 12, December 2012 Recipient characteristics a Idiopathic (n ¼ 227) Amyloid (n ¼ 142) Sarcoid (n ¼ 81) XRT (n ¼ 35) Other (n ¼ 59) p-value Age (years) o Gender: number of males (%) 126 (56%) 89 (63%) 48 (59%) 10 (29%) 29 (49%) Race: number of whites (%) 190 (84%) 104 (73%) 60 (74%) 31 (89%) 53 (90%) Diabetes mellitus 20 (10%) 10 (8%) 9 (12%) 5 (15%) 3 (7%) COPD 1 (1%) 0 (0%) 0 (0%) 0 (0%) 0 (0%) History of prior cardiac surgery 22 (10%) 5 (4%) 2 (3%) 13 (37%) 6 (10%) o Donor age (years) Ischemic time (hours) (12%) 13 (10%) 10 (13%) 3 (9%) 13 (23%) 2 70 (34%) 45 (33%) 22 (29%) 10 (30%) 16 (29%) 3 72 (35%) 55 (41%) 29 (39%) 8 (24%) 17 (30%) Z4 41 (20%) 22 (16%) 14 (19%) 12 (36%) 10 (18%) Life support at transplant 120 (41%) 85 (29%) 48 (16%) 19 (6%) 23 (8%) IABP 6 (3%) 8 (6%) 4 (5%) 1 (3%) 2 (3%) VAD 21 (9%) 8 (6%) 15 (19%) 4 (11%) 4 (7%) Vent 5 (2%) 2 (1%) 0 (0%) 1 (3%) 2 (3%) Days waited for transplant (37) (93) (62) (141) (median) (73) Serum creatinine (mg/dl) PA systolic pressure (mm Hg) PA diastolic pressure (mm Hg) PAP (mm Hg) PCWP (mm Hg) Cardiac output (liters/min) Transpulmonary gradient (mm Hg) PVR (Woods units) UNOS Status (75%) 109 (77%) 62 (77%) 25 (71%) 35 (59%) History of smoking 57 (25%) 30 (21%) 18 (22%) 10 (29%) 6 (10%) Dialysis 4 (2%) 1 (1%) 2 (3%) 2 (6%) 1 (2%) PRA Z20% 100 (44%) 91 (64%) 48 (59%) 22 (63%) 29 (49%) Amiodarone 18 (8%) 8 (6%) 16 (20%) 3 (9%) 7 (12%) Data expressed as mean SD or n (%). COPD indicates chronic obstructive pulmonary disease; IABP, intra-aortic balloon pump; PAP, pulmonary artery pressure; PCWP, pulmonary artery capillary wedge pressure; PRA, peak panel reactive antibody; PVR, pulmonary vascular resistance; VAD, ventricular assist device. a Excluding unknowns. worse compared with the other restrictive cardiomyopathy subgroups (overall: log rank, p o 0.001) (Figure 3). The crude Cox proportional hazard ratio (95% CIs) of amyloid vs other RCM subgroups was 1.85 (1.38 to 2.50). The crude Cox proportional hazard ratio of radiation/chemotherapy RCM vs other subgroups was 1.81 (1.12 to 2.94). Discussion RCM is a heterogeneous group of disorders in adults characterized by progressive heart failure, increased mortality and poor prognosis with limited end-stage therapies available. 2,14 Heart transplantation may represent an option Table 3 Causes of Death After Heart Transplantation Deaths r1 year post-htx (p o 0.001) Deaths 41 year post-htx (p o 0.001) Cause of death RCM [n (%)] Non-RCM [n (%)] RCM [n (%)] Non-RCM [n (%)] Graft failure 8 (9.0) 821 (14.6) 3 (2.2) 407 (3.1) Rejection 4 (4.5) 711 (12.7) 8 (6.0) 905 (6.9) Infection 30 (33.7) 1,263 (22.5) 14 (1.5) 1,250 (9.5) Cardiovascular 9 (10.1) 713 (12.7) 22 (16.4) 2,650 (20.2) Malignancy 1 (1.1) 135 (2.4) 11 (8.2) 2,137 (16.3) Multiple-organ failure 15 (16.9) 538 (9.6) 16 (11.9) 755 (5.8) Amyloid 5 (5.6) 2 (0.04) 13 (9.7) 6 (0.1) Other 17 (19.1) 1,432 (25.5) 47 (35.1) 5,020 (38.2) HTx, heart transplantation; RCM, restrictive cardiomyopathy.

5 DePasquale et al. Restrictive Cardiomyopathy Post-HTx 1273 Figure 1 Kaplan Meier curves for all-cause mortality after heart transplantation in patients with and without restrictive cardiomyopathy. for these patients; however, study to date has been limited to small series or single-center studies RCM has been studied more extensively in the pediatric population with reasonable overall survival after transplantation. 12,13 However, this disease has not been characterized in adults. Therefore, our aim was to: (1) characterize the prevalence, clinical characteristics and prognosis in a large cohort of RCM patients who underwent heart transplantation in the USA; and (2) determine the outcomes among subgroups of RCM patients. The prevalence of heart transplantation due to RCM in this large USA cohort was 1.4%. This frequency is similar to that for hypertrophic cardiomyopathy (1.3%), 15 but significantly lower than that seen in patients with dilated or ischemic cardiomyopathy (42.2% and 48.5%, respectively). The prevalence of RCM may be underestimated as the diagnosis may have been inadvertently misclassified at initial evaluation. Unfortunately, detailed clinical information or prior echocardiographic information that could potentially confirm the diagnosis is not a part of the data included on Heart Transplant Candidate Registration Forms. After heart transplantation, there was no significant difference in survival between the RCM and the entire Figure 2 Kaplan Meier curves for all-cause mortality after heart transplantation in patients with RCM, hypertrophic cardiomyopathy, ischemic cardiomyopathy, dilated cardiomyopathy and other. Figure 3 Kaplan Meier curves for all-cause mortality after heart transplantation in RCM subtypes including idiopathic, amyloidosis, sarcoidosis, radiation/chemotherapy and other. non-rcm cohort, with similar 1-, 5- and 10-year survival. However, RCM transplant patients had worse survival compared with those transplanted for hypertrophic or dilated cardiomyopathy. Although outcomes did not differ between RCM and non-rcm patients overall, the amyloid and radiation/chemotherapy RCM subgroups had significantly worse 1-, 5- and 10-year survival, with 10-year survival at 28% and 32%, respectively. Previous study data regarding outcomes in radiation/ chemotherapy groups have been limited. Uriel et al 10 demonstrated worse survival and increased malignancies in those with end-stage cardiovascular disease related to mediastinal radiation therapy (n ¼ 9 of 1886 patients). Similarly, previous findings among amyloid patients after transplantation have demonstrated adverse outcomes. 4 7 Recently, Oliveira and colleagues studied survival in a cohort of chemotherapy-induced dilated cardiomyopathy (CCMP) patients from the registry of the International Society of Heart and Lung Transplantation (ISHLT). In the ISHLT cohort, similar survival to non-ccmp patients was demonstrated despite increased risk of infection and malignancy. 16 The comparable survival is remarkable and suggests that chemotherapy-induced cardiomyopathy patients who develop dilated cardiomyopathy may have better prognosis after heart transplantation than those who develop RCM. In the UNOS cohort, survival in the radiation/chemotherapy subgroup is significantly worse compared with other RCM subgroups, as is survival among amyloid patients. Although it is difficult to ascertain from the data available why these patients fare worse, significant concern has been raised as to the safety and efficacy of heart transplantation in these patients. Overall, pulmonary hypertension was not severe, with no significant difference between RCM and non-rcm patients. These findings may reflect the strict selection criteria for heart transplantation. There is variation in pulmonary hypertension (pulmonary artery pressures, pulmonary vascular resistance and transpulmonary gradient) among RCM subgroups; however, differences were minor and statistically insignificant in both XRT and amyloid

6 1274 Table 4 The Journal of Heart and Lung Transplantation, Vol 31, No 12, December 2012 Clinical Characteristics of XRT and Amyloid Heart Transplant Recipients Compared With the RCM Cohort XRT Non-XRT Amyloid Non-amyloid Recipient characteristics a (n ¼ 35) (n ¼ 509) p-value (n ¼ 142) (n ¼ 402) p-value Age (years) Gender: number of males (%) 10 (29%) 292 (57%) (63%) 213 (53%) History of prior cardiac surgery 13 (37%) 35 (7%) o (4%) 43 (11%) Donor age (years) VAD 4 (11%) 48 (9%) (6%) 44 (11%) Days waited for transplant (median) (62) (67) (37) (83) PA systolic pressure (mm Hg) PA diastolic pressure (mm Hg) PAP (mm Hg) PCWP (mm Hg) PRA Z20% 22 (63%) 268 (53%) (64%) 199 (50%) Amiodarone 3 (9%) 49 (10%) (6%) 44 (11%) Data expressed as mean SD or n (%). PA, pulmonary artery; PAP, pulmonary artery pressure; PCWP, pulmonary wedge capillary pressure; PRA, panelreactive antibody; RCM, restrictive cardiomyopathy; VAD, ventricular assist device; XRT, radiation/chemotherapy. a Excluding unknowns. patients compared with the remainder of the RCM group. Although XRT patients were more likely to be younger, female and have prior cardiac surgery, amyloid patients were more likely to be older, male and have increased panelreactive antibodies (PRA), with shorter waiting times and older donor age (Table 4). These findings suggest differences in the etiology and natural history of the disease process, but they do not readily explain survival differences between groups. The major causes of non-cardiovascular death among the radiation/chemotherapy (multiple-organ failure, n ¼ 3 [16.7%]; respiratory failure, n ¼ 3 [16.7%]) and amyloid (amyloidosis, n ¼ 18 [26.5%]; multiple-organ failure, n ¼ 8 [11.8%]) subgroups provides further insight. In addition, radiation may damage the mediastinum, pericardium and lungs, leading to impaired lung function and increased surgical complexity. 17 Detailed clinical and echocardiographic information is not a part of the data included on the Heart Transplant Candidate Registration Forms. In addition, there have been no uniform guidelines established with regard to diagnostic criteria for cardiomyopathies. As a consequence, these limitations may have resulted in improper diagnostic categorization. Radiation/chemotherapy is listed as one diagnosis in the database and as such it is impossible to ascertain differences in survival between RCM caused by radiation vs chemotherapy. Similarly, amyloid subtypes are grouped together and cannot be analyzed separately, which limits the ability to determine outcomes among subtypes. Finally, there were patients who were lost to follow-up or those with missing data who were excluded from analysis. In conclusion, the prevalence of heart transplantation in the USA due to RCM is low (1.4%), but is comparable to that for patients transplanted for hypertrophic cardiomyopathy. Long-term survival after heart transplantation was similar for RCM patients when compared with all non-rcm patients, but was worse when compared with hypertrophic and dilated cardiomyopathies. Subgroup analysis showed that the amyloid and radiation/chemotherapy groups fared worst among RCM patients. RCM secondary to radiation/ chemotherapy has not been studied extensively among post heart transplantation patients and our results demonstrate significantly poor outcome. Prospective, multicenter studies are warranted to further evaluate RCM patients as our findings raise concerns over the safety and efficacy of transplantation in this group. Disclosure statement The authors have no conflicts of interest to disclose. The content is the responsibility of the authors alone and does not necessarily reflect the views or policies of the Department of Health and Human Services, nor does mention of trade names, commercial products or organizations imply endorsement by the U.S. Government. This work was supported in part by Health Resources and Services Administration (Contract No C). References 1. Ammash NM, Seward JB, Bailey KR, et al. Clinical profile and outcome of idiopathic restrictive cardiomyopathy. Circulation 2000;101: Kushwaha SS, Fallon JT, Fuster V. Restrictive cardiomyopathy. N Engl J Med 1997;336: Mogensen J, Arbustini E. Restrictive cardiomyopathy. Curr Opin Cardiol 2009;24: Dubrey SW, Burke MM, Hawkins PN, et al. Cardiac transplantation for amyloid heart disease: the United Kingdom experience. J Heart Lung Transplant 2004;23: Dubrey SW, Burke MM, Khaghani A, et al. Long term results of heart transplantation in patients with amyloid heart disease. Heart 2001;85: Kpodonu J, Massad MG, Caines A, et al. Outcome of heart transplantation in patients with amyloid cardiomyopathy. J Heart Lung Transplant 2005;24: Luo JM, Chou NK, Chi NH, et al. Heart transplantation in patients with amyloidosis. Transplant Proc 2010;42: Maurer MS, Raina A, Hesdorffer C, et al. Cardiac transplantation using extended-donor criteria organs for systemic amyloidosis complicated by heart failure. Transplantation 2007;83: Roig E, Almenar L, Gonzalez-Vílchez F, et al. Outcomes of heart transplantation for cardiac amyloidosis: subanalysis of the Spanish Registry for Heart Transplantation. Am J Transplant 2009;9:

7 DePasquale et al. Restrictive Cardiomyopathy Post-HTx Uriel N, Vainrib A, Jorde UP, et al. Mediastinal radiation and adverse outcomes after heart transplantation. J Heart Lung Transplant 2010;29: Zaidi AR, Zaidi A, Vaitkus PT. Outcome of heart transplantation in patients with sarcoid cardiomyopathy. J Heart Lung Transplant 2007;26: Bograd AJ, Mital S, Schwarzenberger JC, et al. Twenty-year experience with heart transplantation for infants and children with restrictive cardiomyopathy: Am J Transplant 2008;8: Zangwill SD, Naftel D, Lapos Ecuyer T, et al. Outcomes of children with restrictive cardiomyopathy listed for heart transplant: a multiinstitutional study. J Heart Lung Transplant 2009;28: Nihoyannopoulos P, Dawson D. Restrictive cardiomyopathies. Eur J Echocardiogr 2009;10:iii Maron MS, Kalsmith BM, Udelson JE, et al. Survival after cardiac transplantation in patients with hypertrophic cardiomyopathy. Circ Heart Fail 2010;3: Oliveira GH, Hardaway BW, Kucheryavaya AY, et al. Characteristics and survival of patients with chemotherapy-induced cardiomyopathy undergoing heart transplantation. J Heart Lung Transplant 2012;31: Adams MJ, Hardenbergh PH, Constine LS, et al. Radiation-associated cardiovascular disease. Crit Rev Oncol Hematol 2003;45:55-75.