Progress in Pediatric Cardiology 32 (2011) 51–54

Contents lists available at ScienceDirect

Progress in Pediatric Cardiology

j ourna l homepage: www.e lsev ie r.com/ locate /ppedcard

Transplantation and pediatric cardiomyopathies: Indications for listing and riskfactors for death while waiting

Jennifer Conway a,b,c, Anne I. Dipchand a,b,c,⁎a Labatt Family Heart Centre, Hospital for Sick Children, Toronto, Canadab University of Toronto, Canadac SickKids Transplant Centre, Hospital for Sick Children, Toronto, Canada

⁎ Corresponding author at: Labatt Family Heart Cent555 University Avenue, Toronto, Ontario, Canada, M5Gfax: +1 416 813 7547.

E-mail addresses: jennifer.conway@sickkids.ca (J. Coanne.dipchand@sickkids.ca (A.I. Dipchand).

1058-9813/$ – see front matter © 2011 Elsevier Irelanddoi:10.1016/j.ppedcard.2011.06.010

a b s t r a c t

a r t i c l e i n f o

Keywords:CardiomyopathyHeart transplantListingPediatricWaitlist mortality

Cardiomyopathies are the primary indication for transplantation in childrenover one year of age. Transplantationoffers excellent short and intermediate term survival. However, there continues to be a number of patients whodie awaiting transplantation due to the ongoing challenges with donor organ availability. This chapter willexplore general indications for transplantation in children with cardiomyopathies, the waitlist mortality in thispatient population and risk factors for delisting or death while waiting.

re, Hospital for Sick Children,1X8. Tel.: +1 416 813 8641;

nway),

Ltd. All rights reserved.

© 2011 Elsevier Ireland Ltd. All rights reserved.

1. Introduction

Todate there remains a number of controversies regarding the timingof listing for children with cardiomyopathies and whether there aremodifiable risk factors in the waiting period that may improvepretransplant survival. The following review will look at indications fortransplantation in this patient population aswell as describe in detail theissues that impact waitlist mortality in children with cardiomyopathies.

2. Text

The incidence of cardiomyopathies as reportedby theNorthAmericanPediatric Cardiomyopathy Registry (PCMR) and the National AustralianChildhood Cardiomyopathy Study ranges from 1.13/100,000 to1.24/100,000 respectively [1,2]. Cardiac transplantation plays an impor-tant role in the management of these patients due to the overall poorprognosis, with 40–45% of affected children having died or undergonecardiac transplantation within five years of their diagnosis [3,2,4].

The American Heart Association has recently redefined cardiomy-opathies as ‘a heterogeneous group of diseases of the myocardiumassociated with mechanical and/or electrical dysfunction that usually(but not invariably) exhibit inappropriate ventricular hypertrophy ordilatation, and are due to a variety of causes that frequently aregenetic’ [5]. The American Heart Association further went on tobroadly classify cardiomyopathies into two categories: primary and

secondary [5]. The primary cardiomyopathy group was subdividedinto genetic causes, mixed (genetic and non-genetic) and acquired.While this new system may provide a more detailed, up to date andrelevant classification system; for the purpose of this paper we willfocus on the traditional categories of dilated (DCM), restrictive (RCM)and hypertrophic HCM) cardiomyopathy.

These conditions, although relatively rare, represent the mostcommon diagnosis in children over one year of age undergoingtransplantation [6]. In children less than one year of age, congenitalheart disease continues to make up the largest fraction of patients;however, the proportion with cardiomyopathies is increasing [6]. Notonly are cardiomyopathies a primary reason for transplantation, theyalso account for a substantial number of patients who are listed fortransplantation. According to the Pediatric Heart Transplant StudyGroup, the diagnosis of cardiomyopathy accounted for 42% of patientslisted for transplantation [7]. This was also reflected in the USScientific Registry of Transplant Recipients (SRTR) with 44% of thepatients listed having either a cardiomyopathy or myocarditis [8].

3. Indications for transplantation

In general, pediatric heart transplantation becomes a reasonabletreatment option when it is felt that the child's quality of life and long-termsurvivalwouldbenefit.While this principle seems straightforward,the exact timing of listing still remains controversial as there are nouniversally accepted listing criteria for childrenwith cardiomyopathies.This is related to the various cardiomyopathies, their associatedphysiology and natural history, the underlying mechanism of failure(systolic or diastolic), the distinct center-specific practices and thediverse age spectrum of these children.

52 J. Conway, A.I. Dipchand / Progress in Pediatric Cardiology 32 (2011) 51–54

Recent consensus guidelines, based predominantly on expertopinion, have suggested situations where children with cardiomyopa-thies would most likely benefit from transplantation [9,10]. Thesecriteria can be broadly defined as life saving or life enhancing therapiesfor heart failure and include:

a) Symptomatic ventricular dysfunction requiring intensive therapyincluding: inotropic, mechanical circulatory or ventilatory support.

b) Symptomatic ventricular dysfunction despite appropriate medicalmanagement associated with severe limitations in exercise,activities or growth failure.

c) Heart failure associated with life threatening arrhythmias unre-sponsive to medical or device therapy.

d) Patients with restrictive cardiomyopathy and reactive pulmonaryhypertension.

e) Heart failure associated with an increased risk of developing fixedpulmonary hypertension that would preclude a future transplant.

While these are some general guiding principles, there is a lack ofappropriately designed studies in the pediatric population to identifyfactors that indicate when the benefits of transplantation outweigh therisks of transplantation and the ongoing risk of morbidity andmortalityrelated to the underlying cardiomyopathy. Further complicating thesituation is the fact that there are no specific objective measurementsfrom echocardiography,MRI, exercise testing or other functional testingthat can guide the timing of listing. While the American HeartAssociation suggests that an indication for transplantation is a peakmaximum oxygen consumption of b50% predicted for age and sex onexercise testing, this is largely based on adult criteria and has not beenadequately evaluated in the pediatric population [11–13].

4. Contraindications

A thorough assessment of a potential transplant candidate isessential prior to listing. This allows for reversible factors to beidentified and aides in the identification of factors that maycomplicate or exclude transplantation. As knowledge about trans-plantation has evolved, the list of contraindications has beenmodifiedand many factors no longer preclude transplantation. For patientswith cardiomyopathies, issues such as reversible pulmonary hyper-tension, non-cardiac congenital abnormalities, non-progressive orslowly progressive systemic diseases (genetic or isolated metaboliccardiomyopathies), no longer are a barrier to transplantation.[10,14,15]. For patients with cardiomyopathies the following stillexist as potential contraindications to transplantation [10,14,15]:

(1) Severe and irreversible end organ damage or multisystemorgan failure,

(2) Severe or progressive non-cardiac disease, such as a chromo-somal, neurologic, or syndromic condition, which is associatedwith limited survival (e.g. Duchenne muscular dystrophy,systemic mitochondrial disorder, or an untreatable and multi-system metabolic disorder with limited survival)

(3) Severe irreversible pulmonary hypertension(4) Psychological issues: smoking, drug/alcohol abuse, unsta-

ble or chronic psychiatric conditions, and life threateningnoncompliance

(5) Others: coexisting malignancy; morbid obesity; diabetesmellitus with end organ damage; hypercoagulable states.

5. Waitlist mortality and risk factors

Once the decision has been made to list a patient with acardiomyopathy for transplantation, one of four possible outcomescan be expected. These include death while waiting, transplantation,delisting due to clinical deterioration or delisting due to clinicalimprovement. Outcomes after transplantation are continuing to

improve as reflected in the recent report from the International Societyof Heart and Lung Transplantation [6]. The median survival wasreported as 18.3 years for patients who received a transplant duringinfancy and 11.3 years for those transplanted as an adolescent [6]. Forthose children who survive beyond the first year of transplant, themedian survival is now 21.4 years for infants, 19.3 years for thosetransplanted between 1 and 10 years and 15.2 years for those N10 yearsof age at the time of transplantation [6]. At 10-years post-transplant 66%of infants, 62% for children between 1 and 10 years of age and 51% foradolescents are still alive [6]. Although the ultimate goal of listing is toundergo successful transplantation, deathsoccurring during thewaitingperiod continue to be a significant problem contributing to the overallmortality in this patient population. Death on thewaitlist for all patientslisted has been reported to range from 10 to 30% [16–19]. In a recentcontemporary analysis of the US SRTR, between 1999 and 2006, theoverall waitlist mortality was 17% and for thosewith cardiomyopathy itwas approximately 10.3% [8]. Overall waitlist mortality was associatedwith the need for ECMO, use of ventilatory support, need for dialysis,UNOS status 1A, nonwhite race and an underlying diagnosis ofcongenital heart disease, but not cardiomyopathy [8]. The level ofhemodynamic support significantly affected the waitlist mortality,especially for those listed as status 1A. For patients with the diagnosis ofcardiomyopathy, listed as status 1A and requiring ECMO support, thewaitlist mortality between 60 days and 6 months remained steady at21.4%. These numberswere slightly higher than those status 1A patientswith cardiomyopathies requiring mechanical ventilation as the 60-daywaitlist mortality was 17%. These trends were similar for both the 90-day and 6-month waitlist mortalities. The best waitlist survival forcardiomyopathy patients was in those 1A patients who did not requireeither ECMO ormechanical ventilation (60-daywaitlist mortality 6.3%).

While this study was not designed specifically to look at patientswith cardiomyopathies, the overall waitlist mortality is similar to arecent report from the Pediatric Heart Transplant Study Group [7].This was a multi-institutional review of 3147 patients listed fortransplantation between 1993 and 2006. Forty-two percent of thepatients listed had cardiomyopathy and were found to have a 1 yearwaitlist mortality of 17%. This was significantly better than the non-cardiomyopathy group where 32% of the children died while waitingwithin the first year of listing. These findings did differ from a previoussingle center study that reported patients with cardiomyopathy hadsimilar waitlist mortality of 12% to those with congenital heart disease[20]. However, what this study did identify was patients withcardiomyopathy were at a slightly higher risk of developingcomplications such as arrhythmias and thromboembolic events [20].

Of the patients with cardiomyopathy in the PHTS series, 83% wereclassified as dilated, 11% as restrictive and 6% as hypertrophic [7]. Atthe time of listing 72% were status 1, 60% were on inotropes, 26%wereventilated and 14% requiredmechanical circulatory support (ECMO orVAD) [7]. Patients with dilated cardiomyopathy were more likely tobe status 1 and on inotropes compared with those with HCM or RCM.Patients with RCM appeared to be less ill at the time of listing as fewerof these patients required invasive support. Despite the differences inillness severity as reflected by the cardiorespiratory support required,there was no significant difference in the waitlist mortality betweenthe different cardiomyopathy subtypes [7]. Risk factors for deathwhile waiting included black race, need for ventilation or ECMO atlisting and younger age at listing. The most common causes of deathwhile waiting included heart failure, cerebrovascular accidents andsudden cardiac death [7].

6. Dilated cardiomyopathies

Dilated cardiomyopathy is the most common form of cardiomyop-athy in the pediatric population, accounting for more than 50% of thecases in both the Australian (58%) and North American (51%) registries[2,1]. The annual incidence of DCM from the PCMR was 0.57/100,000,

53J. Conway, A.I. Dipchand / Progress in Pediatric Cardiology 32 (2011) 51–54

with infants having the highest proportion of cases. Outcomes at 5 yearshave previously been thought to be poor with survival rates varyingbetween 40 and 60% [4,21–23]. However, it is recognized that not allpatients deteriorate and that a proportion of patients will have somerecoverywith time [22,24]. At themoment there are no identifiable riskfactors that can predict which patients may recover and thereforetransplantation remains an important treatment option. This isespecially true since there is evidence to show that transplantation isable to modify the natural history of the disease [24].

Listing children for transplantation with DCM is possible followingan appropriate transplant assessment to rule out reversible causes oridentify factors that may preclude transplant as a treatment option.Specific issues that may arise in the context of a diagnosis of dilatedcardiomyopathy may include a chromosomal, neurological or meta-bolic condition with severe or progressive non-cardiac complicationsassociated with a limited survival, and therefore would be acontraindication to transplantation. Listing for transplantation shouldbe considered as part of the ongoing treatment plan with the need fortransplantation to be reevaluated after listing on a regular basis. Ingeneral, patients with DCM may be listed if they have require multiplehospital admissions; are unable to wean from ventilatory, mechanicalor inotropic support; or have ongoing symptoms despite optimaloutpatient medical management.

While transplantation improves overall survival in patients withDCM, there continues to be an ongoing risk of dying will on thewaitlist. The PHTS recently reported on the outcomes of thosepatients with DCM listed for transplant [25]. In this study there were1098 patients with DCMwith 81% being idiopathic. A majority of thepatients were status 1, on inotropes with a smaller proportionrequiring ventilation or mechanical support. Waitlist mortality was11% at 2 years after listing and overall survival (including trans-plantation) at 10 years post-listing was 75% [25]. The majority of thedeaths occurred within the first 6 months after listing and theprimary reason for death while waiting was secondary to heartfailure (45%). The risk of dying while waiting has significantlyimproved in the current era decreasing from 16% (1993–1997) to 7%(2003–2006). In this group of patients death while waiting wassignificantly associated with the need for ventilation, ECMO or thepresence of arrhythmias. The use of a ventricular assist device wasnot a risk factor for dying while waiting. Therefore, with theadvances in medical management and the care in the current era,patients with dilated cardiomyopathy have a significant chance ofundergoing transplantation as a therapeutic strategy. The role ofventricular assist devices, particularly evolving technologies tar-geted at the pediatric population, remains to be determinedspecifically with regards to timing of insertion vis a vis changingthe profile of risk factors for waitlist mortality.

7. Restrictive cardiomyopathy

Restrictive cardiomyopathy is the least common form ofcardiomyopathy, compromising 2.5–3% of the cardiomyopathies inchildhood [2,1]. Previous reports have suggested that the long-termoutcomes are poor with survival being approximately 50% at 2 yearsafter diagnosis [26–28]. Medical management for restrictive cardio-myopathy is primarily aimed at symptoms, with no therapiesidentified to improve outcomes. Transplantation remains the onlydefinitive therapy significantly altering the natural history [6]. Thetiming of listing remains controversial and is complicated by the factthat some patients survive for many years while others developprogressive pulmonary vascular disease, systolic dysfunction,ischemia, arrhythmias or die suddenly. Currently, no risk factorshave been identified that help predict an individual patient'soutcome [29,30,31]. What is clear is that listing should occur beforeirreversible changes develop in the pulmonary vasculature that maypreclude transplantation. Weller et al., reported on their experience

with RCM and noted that 40% of their patients were not eligible fortransplant due to irreversible pulmonary hypertension [26].

Despite RCM being rare, this diagnosis was the second mostcommon reason for a child with cardiomyopathy to be listed in theseries from PHTS [7]. Of the 145 children with RCM, the mean age atlisting was 8.1±0.4 years and a majority were boys (73%) [32]. Withrespect to listing strategy, more than half of the patients were listed asUNOS status 2 suggesting that they were waiting at home [32]. Therewas a smaller proportion of patients requiring ventilation (10%) ormechanical circulatory support (5%) at the time of listing incomparison to those with DCM. Overall survival at 10 years was 63%and 10% of these children died while waiting. Deaths while waitingoccurred due to central nervous system events, a sudden event or, lessfrequently, heart failure. As with the patients with DCM, most of thedeaths on the waitlist occurred in the first 6 months. Those patientslisted as status 1 had a significantly higher risk of dying while waiting(5% vs. 18%). The only risk factors identified for waitlist mortality inmultivariate analysis were younger age at listing (RR 1.5, p=0.002)and the use of mechanical circulatory support (RR 11.7, pb0.001).Those patients listed at less than 1 year of age were significantly morelikely to die waiting in comparison to the older children (43% vs. 6.8%)[32]. Despite this knowledge, pediatric heart function and transplantphysicians remain divided as to the best management algorithm—

medical vs. transplantation—for the newly diagnosed patient withRCM, particularly those who are not symptomatic. Further along thespectrum of symptomatology and management challenges, remainsthe well recognized disadvantaged RCM patient within the currentUNOS listing algorithm. Thus on both ends of the severity of thisdisease, there remain many unanswered questions and yet to bedefined consensus management algorithms.

8. Hypertrophic cardiomyopathy

Hypertrophic cardiomyopathy is the second most commonchildhood cardiomyopathy with a reported incidence between0.32 and 0.47/100,000 children from the Australian registry andPCMR [1,2]. However, patients with HCM are less likely to be listedfor transplantation [7,33]. Of the patients with cardiomyopathylisted in the PHTS, only 6% had a diagnosis of hypertrophiccardiomyopathy [7,33]. Listing for transplantation in patients withHCM may occur in the setting of severe outflow tract obstructiondespite optimal medical or surgical management, malignantarrhythmias unresponsive to therapy or progression to significantsystolic dysfunction. It is essential for these patients to undergo athorough evaluation, especially those under the age of one to ruleout any associated conditions. Both inborn errors of metabolism andsyndromes have been reported in almost 30% of children whopresent before the age of one [34].

The information reported from the PHTS gives some insight intothose children who are listed for transplantation with HCM. Themeanage of listing was 7.6 years (±0.8 years), they were predominantlymale (61%) and the majority were UNOS status 1 (59%) [33]. Of thepatients with HCM listed for transplant, 30% required inotropes, 27%mechanical ventilation and 8% were on ECMO. Similar to the othercardiomyopathies, the waitlist mortality was 14%. The majority of thedeaths were due to congestive heart failure or cardiogenic shock(64%). Survival after listing was significantly affected by age with33.3% of those under 1 year dying on the waitlist compared to nodeaths in children greater than 10 years of age. In fact, age was theonly factor identified by multivariable analysis to impact waitlistsurvival. These findings mirror previous reports that have shown pooroutcomes in patients diagnosed with HCM before the age of 1 year[34]. HCM as a diagnosis presents different challenges than DCM andRCM. Very good outcomes beyond 1 year of age raise the question ofwhether there is a role for transplantation, even for the most severephenotype, in the current era of medical and device management. On

54 J. Conway, A.I. Dipchand / Progress in Pediatric Cardiology 32 (2011) 51–54

the opposite end of the spectrum, further study is needed intodiagnostic and management algorithms for the infant less than 1 yearwith HCM, especially given the poor post-listing and post-transplantoutcomes in this era of significant donor organ shortages andexcellent outcomes in other infant patient populations.

9. Summary

Listing a child for transplantation with a cardiomyopathycontinues to be a controversial subject with no clear guidelines fortiming. The risks of the transplant must be weighed against theongoing risks of the current management and the expected quality oflife either with or without transplantation. While it is clear thatfollowing listing, children with cardiomyopathies tend to have lowerwaitlist mortality, there are still some higher risks groups that maybenefit from earlier listing or a modification of the current listingstrategies. Conversely, there may be patients that should not be listedfor transplantation given excessively high waitlist mortalities and lowpost-transplant survival. Therefore patients with cardiomyopathiesshould be referred relatively early for evaluation by a heart functionand transplantation service in order to optimize their managementincluding the appropriate timing for transplant assessment.

References

[1] Nugent. 030424 the epidemiology of childhood cardiomyopathy in Australia; Apr10 2003. p. 1–8.

[2] Lipshultz SE, Sleeper LA, Towbin JA, et al. The incidence of pediatric cardiomyopathyin two regions of the United States. N Engl J Med Apr 24 2003;348(17):1647–55.

[3] Towbin JA, Lowe AM, Colan SD, et al. Incidence, causes, and outcomes of dilatedcardiomyopathy in children. JAMA Oct 18 2006;296(15):1867–76.

[4] Daubeney PEF, Nugent AW, Chondros P, et al. Clinical features and outcomes ofchildhood dilated cardiomyopathy: results from a national population-based study.Circulation Dec 12 2006;114(24):2671–8.

[5] Maron BJ. Contemporary definitions and classification of the cardiomyopathies: anAmerican Heart Association Scientific Statement from the Council on ClinicalCardiology, Heart Failure and Transplantation Committee; Quality of Care andOutcomes Research and Functional Genomics and Translational Biology Interdisci-plinary Working Groups; and Council on Epidemiology and Prevention. Circulation2006;113(14):1807–16.

[6] Kirk R, Edwards LB, Kucheryavaya AY, et al. The Registry of the International Societyfor Heart and Lung Transplantation: thirteenth official pediatric heart transplanta-tion report—2010. J Heart Lung Transplant Oct 2010;29(10):1119–28.

[7] Dipchand AI, Naftel DC, Feingold B, et al. Outcomes of children withcardiomyopathy listed for transplant: a multi-institutional study. HEALUN Dec6 2009;28(12):1312–21.

[8] Almond CSD, Thiagarajan RR, Piercey GE, et al. Waiting list mortality amongchildren listed for heart transplantation in the United States. Circulation Feb 102009;119(5):717–27.

[9] Canter CE, Shaddy RE, Bernstein D, et al. Indications for heart transplantation inpediatric heart disease: a scientific statement from the American Heart AssociationCouncil on Cardiovascular Disease in the Young; the Councils on Clinical Cardiology,Cardiovascular Nursing, and Cardiovascular Surgery and Anesthesia; and the Qualityof Care and Outcomes Research Interdisciplinary Working Group. Circulation Feb 62007;115(5):658–76.

[10] Dipchand A, Cecere R, Delgado D, et al. Canadian Consensus on cardiactransplantation in pediatric and adult congenital heart disease patients 2004:executive summary. Can J Cardiol Nov 2005;21(13):1145–7.

[11] Mancini DM, Eisen H, Kussmaul W, Mull R, Edmunds Jr LH, Wilson JR. Value of peakexercise oxygen consumption for optimal timing of cardiac transplantation inambulatory patients with heart failure. Circulation Mar 1991;83(3):778–86.

[12] Miller LW. Listing criteria for cardiac transplantation: results of an American Societyof Transplant Physicians–National Institutes of Health conference. TransplantationOct 15 1998;66(7):947–51.

[13] Mehra MR, Kobashigawa J, Starling R, et al. Listing criteria for hearttransplantation: International Society for Heart and Lung Transplantationguidelines for the care of cardiac transplant candidates—2006. J Heart LungTransplant Sep 2006;25(9):1024–42.

[14] Gajarski RJ, Benett Pearce F. Recipient evaluation: medical and psychologicalmorbidities. In: Canter CE, Kirklin JK, editors. ISHLT Monograph Series: pediatricheart transplantation. Elsevier: Philadephia; 2007.

[15] Canter CE. Preoperative assessment and management of pediatric hearttransplantation. Prog Pediatr Cardiol Jun 1 2000;11(2):91–7.

[16] McGiffin DC, Naftel DC, Kirklin JK, et al. Predicting outcome after listing for hearttransplantation in children: comparison of Kaplan–Meier and parametriccompeting risk analysis. Pediatric Heart Transplant Study Group. J Heart LungTransplant Jul 1997;16(7):713–22.

[17] Chen JM, Weinberg AD, Rose EA, et al. Multivariate analysis of factors affectingwaiting time to heart transplantation. Ann Thorac Surg Feb 1996;61(2):570–5.

[18] Morrow WR, Naftel D, Chinnock R, et al. Outcome of listing for hearttransplantation in infants younger than six months: predictors of death andinterval to transplantation. The Pediatric Heart Transplantation Study Group. JHeart Lung Transplant Dec 1997;16(12):1255–66.

[19] Pollock-BarZiv SM, McCrindle BW, West LJ, Manlhiot C, VanderVliet M,Dipchand AI. Competing outcomes after neonatal and infant wait-listing forheart transplantation. J Heart Lung Transplant Oct 2007;26(10):980–5.

[20] Rosenthal DN, Dubin AM, Chin C, Falco D, Gamberg P, Bernstein D. Outcomewhile awaiting heart transplantation in children: a comparison of congenitalheart disease and cardiomyopathy. HEALUN Aug 1 2000;19(8):751–5.

[21] Akagi T, Benson LN, Lightfoot NE, Chin K, Wilson G, Freedom RM. Natural historyof dilated cardiomyopathy in children. Am Heart J May 1 1991;121(5):1502–6.

[22] Arola A, Tuominen J, Ruuskanen O, Jokinen E. Idiopathic dilated cardiomyopathy inchildren: prognostic indicators and outcome. Pediatrics Mar 1 1998;101(3):369–76.

[23] Burch M, Siddiqi SA, Celermajer DS, Scott C, Bull C, Deanfield JE. Dilatedcardiomyopathy in children: determinants of outcome. Br Heart J Sep 1994;72(3):246–50.

[24] Tsirka AE, Trinkaus K, Chen SC, et al. Improved outcomes of pediatric dilatedcardiomyopathy with utilization of heart transplantation. J Am Coll Cardiol Jul21 2004;44(2):391–7.

[25] Kirk R, Naftel D, Hoffman TM, et al. Outcome of pediatric patients with dilatedcardiomyopathy listed for transplant: a multi-institutional study. HEALUN Jan 72010;28(12):1322–8.

[26] Weller RJ, Weintraub R, Addonizio LJ, Chrisant MR, Gersony WM, Hsu DT.Outcome of idiopathic restrictive cardiomyopathy in children. Am J Cardiol Sep1 2002;90(5):501–6.

[27] Cetta F, O'Leary PW, Seward JB, Driscoll DJ. Idiopathic restrictive cardiomyop-athy in childhood: diagnostic features and clinical course. Mayo Clin Proc Jul1995;70(7):634–40.

[28] Lewis AB. Clinical profile and outcome of restrictive cardiomyopathy inchildren. Am Heart J Jun 1992;123(6):1589–93.

[29] Russo LM, Webber SA. Idiopathic restrictive cardiomyopathy in children. HeartSep 2005;91(9):1199–202.

[30] Rivenes SM, Kearney DL, Smith EO, Towbin JA, Denfield SW. Sudden death andcardiovascular collapse in children with restrictive cardiomyopathy. CirculationAug 22 2000;102(8):876–82.

[31] Zangwill S, Hamilton R. Restrictive cardiomyopathy. Pacing Clin ElectrophysiolJul 2009;32(Suppl 2):S41–3.

[32] Zangwill SD, Naftel D, L'Ecuyer T, et al. Outcomes of children with restrictivecardiomyopathy listed for heart transplant: a multi-institutional study. J HeartLung Transplant Dec 2009;28(12):1335–40.

[33] Gajarski R, Naftel DC, Pahl E, et al. Outcomes of pediatric patients withhypertrophic cardiomyopathy listed for transplant. HEALUN Dec 6 2009;28(12):1329–34.

[34] Colan SD, Lipshultz SE, Lowe AM, et al. Epidemiology and cause-specificoutcome of hypertrophic cardiomyopathy in children: findings from thePediatric Cardiomyopathy Registry. Circulation Feb 13 2007;115(6):773–81.