HearttoHeart

One of the Children'sCardiomyopathyFoundation’s (CCF)top priorities is to promote and supportresearch on pediatric cardiomyopathy. As awareness of CCF’sresearch grant program hasgrown over the years, thenumber of grant applicationshas increased as well. This year we arepleased to support the promising work offour grant recipients: Bruce Gelb, MD ofMount Sinai School of Medicine, EnkhsaikhanPurevjav, MD, PhD of Baylor College ofMedicine, Monte Willis, MD, PhD of theUniversity of North Carolina Hospitals, andStephanie Ware, MD, PhD of CincinnatiChildren’s Hospital Medical Center.

Dr. Bruce Gelb is a Professor of Pediatrics andGenetics & Genomic Sciences at the MountSinai School of Medicine in New York City.He has had an interest in pediatric cardiomy-opathy since his fellowship training at BaylorCollege of Medicine. Now the Director ofHeart Transplantation and Co-Director of theCardiovascular Genetics Program at MountSinai, his research laboratory focuses on identi-fying genes responsible for heart abnormalitiesHighlights

• CCF Repository GarnersNIH Funding ......................pg. 3

• Nutrition in PediatricCardiomyopathy ............pg. 5

• Genetic Testingfor Cardiomyopathy .... pg. 6

• Family Resource Center .................................. pg. 8

• Community Awareness& Fundraising .................. pg. 10

Volume 5, Number 1 • Spring • Summer 2008

continued, page 2

CCF AWARDS2008 RESEARCH GRANTS

or dysfunction. Thus far, his research group has discovered four genes responsible for Noonan syndrome, a systemic disease that is a common cause of hypertrophic cardiomyopathy (HCM) in children. The most recently discovered gene is called RAF1 and is highly specific to HCM.

His proposed CCF study, “HypertrophicCardiomyopathy and RAS-MAP KinaseSignaling” ($49,587), will first study the effectsof introducing a mutation in the RAF1 geneinto the heart muscles of a mouse withNoonan syndrome. This mouse model isintended to replicate the human disease andpermit studies of the heart as it hypertrophies.

The second part of the study will introducemutant RAF1 genes into mouse heart musclecells in cell culture, allowing the cardiac hyper-trophy to be studied biochemically. The goal

of this study is to understand howchanges in the heart caused by the mutant gene result in HCMand to determine the direction for developing therapies to pre-vent or improve the hypertrophyrelated to Noonan syndrome.

President’s Message

From Lisa Yue,CCF Founder & President

In this issue, we will introduce to youour 2008 grant recipients - four newinvestigators dedicated to researchingdifferent areas of pediatric cardiomy-opathy. We proudly support their pilotstudies, which will hopefully break newground into understanding the geneticsbehind the disease.

We will also update you on the effortsof several past grant recipients, as theycontinue to present their findings atkey scientific sessions and to be pub-lished in prestigious medical journals.

Happily, our family involvement isgrowing with close to 650 families reg-istered from around the world. In thisnewsletter, we will salute those CCFfamilies who have hosted fundraisersand raised awareness of pediatric cardiomyopathy in their communities.

Looking ahead, the 6th Annual GolfClassic returns to the Montclair GolfClub on July 21, 2008. We welcomeback those who have supported thisevent in the past and invite new members to help raise funds for our research grant and patient support programs.

Enkhsaikhan Purevjav, MD, PhDBruce Gelb, MD

Monte Willis, MD, PhDStephanie Ware, MD, PhD

2008 RESEARCH GRANTS

Dr. Gelb hopes that the study findings will enable the search for drugs that would block the disease effect caused by this mutant gene and other HCM causinggenes unrelated to Noonan syndrome.

Dr. Enkhsaikhan Purevjav also has ties toBaylor College of Medicine in Texas. AnInstructor of Pediatrics in the Department of Pediatric Cardiology at Baylor, she alsoholds a doctorate in medical genetics and is part of the research team at the PhoebeWillingham Muzzy Pediatric MolecularCardiology Laboratory studying cardio-vascular disease.

Early in her career, Dr. Purevjav worked as a pediatric cardiologist in Mongolia whereshe managed several patients with cardio-myopathy. She lost many of them to thedisease, which has motivated her to “keepdoing research in order to find clues” to better understand the disease. As part ofher research, she has generated mousemodels that have been implanted with ahuman mutation in the nebulette gene that leads to the inherited form of dilatedcardiomyopathy (DCM).

In Dr. Purevjav’s proposed CCF study,“Effects of ACE Inhibitors and Beta-Blockers on Cardiac Function in MurineModels of Inherited Dilated Cardio-myopathy” ($45,000), she will aim to “cure these transgenic mice using the drugscaptopril (an ACE inhibitor) and carvedilol (a beta-blocker) which are broadly used for treatment of cardiomyopathy and heartfailure in humans.” She plans to administerthe captopril and carvedilol before and afterthe mice exhibit symptoms, in order toinvestigate the individual and combinedeffects of administering these two thera-peutic agents. Cardiac function will bemonitored during drug treatment, and thenthe mice hearts will undergo histological,immunochemical, ultrastructural, and protein analyses after treatment. This study will provide insight into the molecularmechanisms of the drugs’ preventative andtherapeutic effects on inherited DCM. Itwill also highlight the importance of startingdrug treatments earlier, at asymptomaticstages before heart failure occurs.

CCF’s third grant recipient is Dr. MonteWillis, an Assistant Professor in Pathology

and Laboratory Medicine as well as theAssistant Director of the Clinical Core Labat the University of North Carolina. Dr.Willis’ current research focuses on how the heart regulates energy metabolism incardiac diseases such as HCM. According to Dr. Willis,“Changes in how the heartgenerates energy occurs in patients withcardiomyopathies, but the underlying causefor this is unknown. Because these changesin energy metabolism leave the heart vulnerable to injury, it may underlie some of the morbidity and mortality in cardio-myopathies.” Dr.Willis has discovered thatthe cardiac specific protein, MuRF1 (MuscleRing Finger-1), regulates the turnover of cardiac myosin binding protein-c (cMyBP-c),a common mutated protein found in familial HCM.

Dr. Willis’ proposed CCF study, “Role ofMuRF1 in MyBP-C Turnover and Its Effectson Cardiac Energy Metabolism in FamilialHypertrophic Cardiomyopathies”($50,000) will investigate whether theMuRF1 regulation of metabolism altershearts in which the cMyBP-c mutationexists. He believes that in this situation,MuRF1 is spending all its time clearing the defective cMyBP-c proteins instead of regulating energy metabolism, making the heart more vulnerable to stress.Additionally, this shift to clearing mutantcMyBP-c makes MuRF1 unable to fulfill itsrole of regulating the heart size, leading toan enlarged heart. These findings mightexplain the cardiac hypertrophy and theenergy deficits associated with familial HCMpatients. By identifying the specific role ofthis protein in this energy deficit, Dr. Willis’research could potentially identify ways to improve cardiac energy reserves and,thus, cardiac function in patients with cardiomyopathy.

Dr. Stephanie Ware, CCF’s fourth grantrecipient, is an Assistant Professor ofPediatrics in the Divisions of HumanGenetics and Molecular Cardiovascular

HearttoHeartVOLUME 5, NUMBER 1 • SPRING • SUMMER 2008

The Heart to Heart newsletter is publishedbiannually by the Children’s CardiomyopathyFoundation (CCF), a national organizationdedicated to saving lives and improving thequality of life for children with cardiomyopathy.CCF’s mission is to accelerate the search for a cure by supporting research, educatingphysicians and patients, and increasing aware-ness and advocacy related to the needs ofaffected children and their families. CCF is apublicly supported tax-exempt organizationas described under section 501(c)(3) of theInternal Revenue Service.

Board of Directors

Lisa Yue, PresidentEddie Yu, Treasurer

Raymond Yue, SecretaryCarney HawksTami HoranBrian NoldIan Sandler

Medical Advisory Board

Wendy Chung, MD, PhDColumbia University Medical Center

Steve Colan, MDChildren’s Hospital Boston

Daphne Hsu, MD Children's Hospital at Montefiore

Steve Lipshultz, MD University of Miami Medical Center

Jeff Towbin, MDTexas Children’s Hospital

Staff

Lisa Yue, Executive DirectorPauline Pierrot, Assistant Executive Director

Stormy Hill, Patient Outreach & Support ManagerHarriet Salk, Patient Support CoordinatorFaith Armonaitis, Project Coordinator

Renee Thekkekara, Project CoordinatorChristine Chun, Data Entry Assistant

All submissions and correspondence regarding the newsletter or Foundation should be directed to:

Children’s Cardiomyopathy Foundation P.O. Box 547

Tenafly, NJ 07670Tel: 866.808.CUREFax: 201.227.7016

info@childrenscardiomyopathy.orgwww.childrenscardiomyopathy.org

The Children’s Cardiomyopathy Foundation, including allparties to or associated with Heart to Heart will not beheld responsible for any actions readers take based on theirinterpretation of articles from this newsletter. As always,readers are encouraged to discuss medical evaluations andtreatments with their own physicians.

© Copyright 2008 Children’s Cardiomyopathy Foundation.All rights reserved.

2 Heart toHeart Spring•Summer 2008

CCF Awards 2008 Research Grants continued from page 1

This year we are pleased tosupport the promising work

of four grant recipients

Spring•Summer 2008 Heart toHeart 3

Jeff Towbin, MD, a CCF

medical advisor and the Director

of the Pediatric Cardiomyopathy

Repository, recently received a

five-year, multi-million dollar grant

from the National Heart, Lung,

and Blood Institute (NHLBI) to

maintain and expand the Pediatric

Cardiomyopathy Repository.

The model for this repository was firstdeveloped with input and seed funding from CCF. The NHLBI grant will allow forblood and myocardial tissue specimens tobe obtained from children enrolled in thePediatric Cardiomyopathy Registry, aNational Institutes of Health funded patientdatabase. It will also support the correlationof clinical and scientific data, enable the identification of etiologies (genetic, viral etc.) responsible for clinical phenotypes,and encourage multi-center collaborationsamong scientists and clinicians in order tobetter understand the mechanisms involvedin the development of cardiomyopathy inchildren.

In 2005, CCF took the lead in establishingthe Pediatric Cardiomyopathy Repository.The goal was to collect DNA and tissuesamples from children with cardiomyopathyand to link the samples to a child’s clinicalinformation. Before the repository, fewresources had been designated for thestudy of children with cardiomyopathy, andunderstanding of the causes of the diseasein children was worse than that in adultdisease. Less than 25% of the patientsenrolled in the Pediatric CardiomyopathyRegistry had a defined etiology despite rigorous, standardized evaluation.

The repository provides a much-neededresource for researchers that could

potentially accelerate studies on pediatriccardiomyopathy. Researchers could use thesamples and data to better understand thegenotype - phenotype relationship, which ishow a person’s genetic makeup influenceshow they clinically present with symptomsof the disease.

To date, 225 blood and 37 tissues sampleshave been collected and stored at BaylorCollege of Medicine in Houston,TX. Toensure that researchers have equal access to the samples, the repository is monitoredby an eight-person steering committeecomprised of clinicians and researchersfrom various medical institutions.

CCF REPOSITORY GarnersNational Institutes of Health

FUNDING

Biology and Co-Director of the DiagnosticCardiomyopathy Clinic at CincinnatiChildren’s Hospital. According to Dr.Ware, significant progress has been made in identifying the genetic basis of cardio-myopathy in adults, but molecular diagnosisin children has proven more challenging.

The goal of her proposed CCF study,“Development of a Novel ResequencingChip to Diagnose Pediatric Cardio-myopathy” ($49,750), is to develop a methodology that allows for more comprehensive screening of genes thatcause this heart disease in children.More specifically, Dr. Ware will developand validate a gene chip for the diagnosisof pediatric cardiomyopathy, with particularfocus on structural cardiomyocyte-specificand metabolic etiologies. A customizedgene chip (array) encompassing 30 genescoding for structural/metabolic proteinswill be used in combination with a commercially available mitochondrial gene chip to provide the most comprehensiveinvestigation of genetic causation to date.DNA from 20 patients with known causes of cardiomyopathy will be used for validation of the customized array.The development of this gene chip is animportant step in “improving diagnosticoptions for pediatric cardiomyopathypatients.” Dr. Ware adds, “The identifica-tion of the precise cause of cardio-myopathy is important for developmentof individualized management strategies.”

In the second part of the study, Dr. Warewill focus on determining the incidenceand prevalence of these mutations in adefined group of children. DNA from 40 pediatric cardiomyopathy patients witha diagnosed mitochondrial disorder and40 pediatric patients with an unknowngenetic basis for cardiomyopathy will beanalyzed. “We will use information fromthis screening to prioritize the most frequent causes of cardiomyopathy in the pediatric population. This informationwill be useful for the future developmentof clinical genetic testing,” she concludes.

For more information about each investigator’s funded study, please visit our website at:www.childrenscardiomyopathy.org/site/grantsawarded.php

CLINICIANS & SCIENTISTS

Request for Research Applicationson Pediatric Cardiomyopathy

(Dilated, Hypertrophic, Restrictive, Left VentricularNon-Compaction, or Arrhythmogenic Right

Ventricular Cardiomyopathy)

Description of Opportunity:The Children’s Cardiomyopathy Foundation(CCF) is inviting investigator-initiated researchapplications for innovative basic, clinical, popula-tion, or translational studies relevant to the cause, diagnosis, or treatment of cardiomyopathyin children under the age of 18 years. Funding isavailable in the range of US$25,000 to US$50,000for one year of total direct costs.

Eligibility Requirements:The principal investigator must hold an MD, PhDor equivalent degree and reside in the UnitedStates or Canada. The investigator must have afaculty appointment at an accredited U.S. orCanadian institution and have the proven ability topursue independent research as evidenced byoriginal research in peer-reviewed journals.

Application Deadline:Grant guidelines and application form are availableonline at www.childrenscardiomyopathy.org/site/grants.php. The deadline for grant submissions isSeptember 5, 2008 with final award decisionsmade by January 2009.

For more information, contact Lisa Yue, CCF Executive Director at

866-808-2873, ext 901 or lyue@childrenscardiomyopathy.org

4 Heart toHeart Spring•Summer 2008

Seema Mital, MD

Seema Mital, MD, a 2004 CCF grantrecipient, published her latest researchfindings in the December 2007 issue of Human Genetics. Her molecularstudy, “RAAS Gene PolymorphismsInfluence Cardiac Remodeling inChildren with HypertrophicCardiomyopathy,” looked at differentgenetic variations, called polymor-phisms, that control the production of hormones (renin-angiotensin-aldosterone) that help to regulateblood pressure. The study investigatedhow these specific genetic variationsimpact the progression of hypertrophiccardiomyopathy (HCM) in children.Sixty-five children with HCM participatedin the study, which revealed that children with the RAAS genotype weremore likely to develop left ventricularoutflow tract obstruction. The studyalso showed that the heart gets thickermuch faster in children with more than two polymorphisms or geneticvariations, as compared to those withless than two polymorphisms.

The significance of these findings is that physicians will be able to identifywhich children with HCM are at ahigher risk of developing a severe form of the disease that requires closer monitoring. It may also help tosegment which family members withthe same disease are likely to do betteror worse depending on the number ofthese polymorphisms. In many cases, itmay be possible to adjust treatmentaccording to these polymorphisms,thus enabling physicians to better manage the disease in children in thelong term. Dr Mital’s study was thefirst to evaluate the effect of these particular genotypes on the progres-sion of HCM in children and to identifya potential genetic determinant of theobstructive phenotype.

Ju Chen, MD, PhD

In 2005, CCF awarded a research grant to Ju Chen, MD, PhD of theUniversity of California at San Diego.Dr. Chen’s study, “Role of Cypher inCardiac Muscle,” was designed tounderstand the role of the disease-causing Cypher gene by generatingmouse lines to replicate these humanmutations and then to perform preliminary characterization of the mouse models.

After one year of funding, Dr. Chensuccessfully generated two mouse lines in which long and short Cypherisoforms were deleted, and then observations were made on whichmouse models developed cardio-myopathy, at what age and life stage,the severity of it, and final outcomes.Based on those findings, Dr. Chenreceived a five-year $1.5 million grantfrom the National Heart, Lung, andBlood Institute in 2006.

In 2007, Dr. Chen and his colleaguespublished two journal articles based ontheir CCF funded research. The first,“Mouse Models for CardiomyopathyResearch,” was published in PediatricCardiology (Issue 24/2, November2007). The second article, “Zeroing in on the Role of Cypher in StriatedMuscle Function, Signaling and HumanDisease” was published in Trends inCardiovascular Medicine (November2007). A third manuscript summarizingthe final research findings will be submitted for publication in 2008.

Anne Dipchand, MD

CCF’s 2007 grant recipient AnneDipchand, MD of Toronto Hospital for Sick Children was invited to present her research findings at theInternational Society for Heart andLung Transplantation’s (ISHLT) 28thAnnual Meeting in Boston on April 9-12, 2008. The ISHLT has over 2,200members from more than 45 coun-tries, representing over ten differentdisciplines, including anesthesiologists,cardiologists, cardiac surgeons, nurses,scientists, immunologists, ethicists,perfusionists, and transplant coordinators.

Three abstracts were presented at the scientific sessions: “Outcomes of Children Listed for Transplantationfor Dilated Cardiomyopathy: A Multi-Institutional Study” (poster,April 11), “Outcomes of ChildrenListed for Transplantation forRestrictive Cardiomyopathy: A Multi-Institutional Study” (mini-oral, April 11), and “Outcomes of Children Listed for Transplantation for Hypertrophic Cardiomyopathy:A Multi-Institutional Study” (Oral,April 12). The study analyzed the different variables that may contributeto favorable or unfavorable outcomesfor children with various forms of cardiomyopathy in need of a hearttransplant. Dr. Dipchand presentedsimilar research findings at theAmerican Heart Association ScientificSession in November 2007. In thecoming months, Dr. Dipchand will finalize four manuscripts for publicationin major medical journals.

“Based on those findings (from the CCF funded study),Dr. Chen received a five-year$1.5 million grant from theNational Heart, Lung, andBlood Institute in 2006.”

UPDATES onPAST CCF GRANT RECIPIENTS

“In the coming months,Dr. Dipchand will

finalize four manuscripts for publication in major

medical journals.”

Spring•Summer 2008 Heart toHeart 5

In a CCF supported study,Tracie Miller, MD and others at the Miller School of Medicine in Miami, FLreviewed studies that examined the relationship between nutrition and thehealth of patients with cardiomyopathy.Their findings, published in Progress inPediatric Cardiology (2007 November ;24(1): 59-71), show that ancillary therapyinvolving optimal intake of micronutrients(nutrients needed in small amounts) canbe beneficial to cardiomyopathy patients.While nutritional intervention may notcure cardiomypathy, Dr. Miller and othersbelieve it has the potential to improvecardiac function and quality of life for children with all types of cardiomyopathy.

Growth failure is one of the most significant problems of children with cardiomyopathy with nearly one-third of affected children experiencing growthfailure during the course of their illness.For these children, the body spends substantial energy compensating for adysfunctional heart and devotes lessenergy to normal metabolic processes.This reduces a child’s ability to properlyabsorb and recycle important nutrients,thus affecting his/her growth. In general,children with cardiomyopathy need toreceive additional calories and nutrientsto compensate for their degree of heartfailure and to provide for normal growth.

Children with cardiomyopathy may alsorequire greater than standard intakes ofcertain micronutrients to optimize theircardiac function. In particular, antioxidantscan help prevent free radical cell damageassociated with heart failure. Eating morefruits, vegetables, and whole grains canhelp ensure patients take in enoughantioxidants, including vitamins A, C, and E.Avoiding an excess of carbohydrates andsaturated fat is generally recommended.Omega-3 fatty acids, found in such fish astuna, salmon, and trout have been shownto improve left ventricular function andcounteract harmful inflammation. Othernutritional supplements to considerinclude taurine, an amino acid that

regulates abnormal calcium levels inmyocardial energy production, and co-enzyme Q10, a natural vitamin-likesubstance that can improve mitochondriaenergy production. The mitochondriaproduces energy for all cells in the body.The above-mentioned supplements mayhelp heart tissue produce enough energyto maintain good health.

Apart from antioxidants, nutrients knownto augment myocardial energy productionin adults may help to improve cardiacfunction in affected children. Thiamine(vitamin B1) is important in carbohydratemetabolism. Up to 93% of patients withheart failure show a deficiency. Thiaminesupplementation seems to reverse someof the symptoms of congestive heart failure. L-carnitine, an amino acid deriva-tive that helps the body move fatty acidsinto the mitochondria, has also provedbeneficial. Patients given L-carnitinesupplements for a year following a heartattack had improved 3-year survival rates.Other important nutrients for heart function include vitamin D, calcium,

folate (vitamin B12), magnesium, zinc,and selenium. Patients with heart failureoften show deficiencies in one or more of the vitamins and minerals mentioned.

The researchers point out that little isunderstood regarding the role of growthand nutrition in predicting the outcome of children with cardiomyopathy. Manyscientific studies in adults with heart failureare contradictory, and there are few studies among children. Miller and others advocate that understanding therelationship among nutrition, growth, andpatient outcomes would help physiciansidentify who would benefit most fromtransplant or other types of medical treatment. Physicians may also be able torecommend early and aggressive nutritionalinterventions that would prevent or delaydeclines in heart function, keeping childrenhealthier as they await a transplant orreceive other means of treatment.

The full text of the article is available at:www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pubmed&pubmedid=18159216

Focus on New Research Publications

NUTRITION IN PEDIATRIC CARDIOMYOPATHY

PROGRESS IN PEDIATRICCARDIOLOGY:

New Cardiomyopathy Issues Released

Progress in Pediatric Cardiology has published two additional issuesfocused on pediatric cardiomyopathy. These two issues were part of a three-part series dedicated to the disease. The second issue,published in November 2007 (volume 24, issue 1), included reviewsand abstracts presented at the 2007 scientific workshop sponsoredby the Children’s Cardiomyopathy Foundation and the NationalHeart, Lung, and Blood Institute. Issue three, published in March2008 (volume 25, issue 1), included additional review articles andconsensus recommendations on future directions in pediatric cardiomyopathy research. Volume 23, issue 1-2, the first in the series, was published in September 2007. It was the first time thepublisher, Elsevier, dedicated three issues to genetics, epidemiology,and therapy for cardiomyopathy in children.

6 Heart toHeart Spring•Summer 2008

Approximately 20% of

cardiomyopathy in children

is familial, either as isolated

cardiomyopathy or associated

with neuromuscular disorders,

inborn errors of metabolism,

or malformation syndromes.

These cases of cardiomyopathy

are due to genetic variations

(mutations) in specific single

genes, many of which have been

identified. Below are commonly

asked questions about using

genetic testing to diagnose these

forms of cardiomyopathy.

• What is genetic testing?Genetic testing looks for variations (mutations) in the sequence of genesassociated with a specific inherited disease. Detection of a disease-causingmutation indicates the presence of the disease or a high risk of developing the disease.

• What are the benefits of genetic testing for cardiomyopathy?

Genetic testing can allow a definitive diagnosis of cardiomyopathy in caseswhere the clinical diagnosis is uncertain.It often is used to identify the specificcause of cardiomyopathy, helping to clarifythe prognosis and, in some cases, alertphysicians and patients to the possibility of other non-cardiac disease symptoms(e.g. bleeding disorders related to Noonansyndrome). Genetic testing can also beused to determine which family membersof a patient are at a high risk for cardiomyopathy.

• Should all children with cardiomyopathy receivegenetic testing?

Use of genetic testing should be guidedby the patient’s symptoms and the family history. It may be best to consult a pediatric geneticist as well as a pediatriccardiologist.

• If I don’t have the gene,does that mean I do not have the disease?

Unless the familial mutation is known,failure to find a disease-causing mutationdoes not “rule out” a diagnosis of cardio-myopathy. Instead, failure to detect a disease-causing mutation can mean one of three things: (1) the patient is affectedby the disease but the disease-causingmutation was not detected because it islocated in a gene that was not included inthe test, (2) the patient is affected by thedisease but the disease-causing mutation is of a type that cannot be detected bycurrent testing methods, or (3) the patientis not affected by the disease.

• What is a familial mutation and how is it identified?

All cases of cardiomyopathy in oneextended family are likely to be associatedwith the exact same mutation or the“familial mutation.” If a parent harbors a disease-causing mutation, his or her

children each have a 50% chance of inheriting this mutation. In contrast, the risk of harboring a different mutation associated with the same form of cardiomyopathy is at most 0.5%.

To identify the familial mutation, manydifferent genes have to be evaluated in a family member that has cardiomyopathy(known as the “index patient”). If that isnot possible, both parents of an affectedfamily member should be screened, sincethe affected family member, in all likeli-hood, inherited the mutation from one of his or her parents. The parent who is found to harbor a disease-associatedmutation would then become the “indexpatient” for the family.

• What are the benefits ofknowing the familial mutation?

Once the familial mutation for a family is known, genetic testing can both confirm and exclude an increased risk of cardiomyopathy in family members. Ifthe familial mutation is present, the familymember and his or her parents, siblings,and children are at an increased risk ofcardiomyopathy. They should undergoregular screening and seek treatment assoon as symptoms appear. If the familialmutation is not present, the family member and his or her descendants are at no greater risk of cardiomyopathythan the general population.

A Review of GENETIC TESTING

Mutation in MYBPC3

By Ute Geigenmuller, PhD

A Review of

Spring•Summer 2008 Heart toHeart 7

for CARDIOMYOPATHYAnother consideration is that screeningthrough standard diagnostic means,such as an echocardiogram, cannot ruleout an increased risk of cardiomyopathy.For example, a family member withoutany symptoms may still harbor the familialmutation and (1) be presymptomatic –that is symptoms of the disease may not show yet or (2) may never developsymptoms of the disease (known as “lowpenetrance” of the disease). However,this individual can still pass on the muta-tion to his or her children, who may thendevelop symptoms of the disease.

• Does every mutation found in a disease-associated genecause disease?

No. While some mutations in a disease-associated gene cause disease, othermutations in the same gene may notcause disease.

When it is not known or not certainwhether a particular mutation is associatedwith disease or not, the mutation is calleda “variant of unknown significance (VUS)”or a “possible disease variant” respectively.One way to clarify the meaning of a VUS or a possible disease variant is todetermine if all affected members of apatient's extended family harbor the VUS. If all affected family membersharbor the variant in question, it is likelyto be associated with the familial disease.If some affected family members do notharbor the variant in question, it is lesslikely to be associated with the familialdisease.

• Can genetic testing predictseverity of a cardiomyopathy?

Genetic testing typically cannot predictseverity of a particular form of cardio-myopathy. Instead, the results of genetictesting only indicate the probability or risk of disease.

• Which genetic tests for cardiomyopathy are availableand where?

Gene Tests at www.genetests.orgoffers a list of genetic tests to detect different forms of cardiomyopathy and the laboratories offering testing. At this time, Correlagen (www.correlagen.com) and Harvard Partners Lab(www.hpcgg.org) are the only two CLIA (Clinical Laboratory ImprovementAmendments) approved labs in the U.S. to offer clinical genetic testing for cardiomyopathy. Information on CLIAcan be found at www.fda.gov/cdrh/clia/.

• Can patients directly order genetic testing?

For most conditions, genetic testing can only be ordered through a physician,to guarantee that this diagnostic tool isused only when appropriate and that thetest results are considered in the contextof all other medical information for apatient, such as the results of other diagnostic tests and the personal and family medical history.

• Is genetic testing expensiveand is it covered by insurance?

The price for genetic testing is deter-mined by the number of genes tested and the size of the genes. Family testing is less expensive than testing of the indexpatient, since only a small part of onegene, where the familial variant is located,has to be screened. Insurance coveragevaries with each insurance provider. Thepolicy of diagnostic testing laboratorieswith regard to insurance also varies.

• Can genetic testing lead to discrimination by healthinsurance and life insuranceproviders?

If genetic testing is ordered by a physician,the results of any physician-ordered testsare recorded in the patient’s medical

records and will be available for the insurer to view at any time.

For health insurance, the individual cannot be discriminated against if insuredunder an employer or state-sponsoredinsurance plan. HIPAA, the HealthInsurance Portability and AccountabilityAct, prohibits discrimination in enroll-ment and in premiums charged toemployees and their dependents basedon health status-related factors. Formore information about employee protection from HIPAA, go towww.dol.gov/ebsa/newsroom/fshipaa.html.

For life insurance, discrimination mayoccur. Parents may choose to enroll theirchildren in a life insurance plan beforeobtaining genetic testing.

• Can genetic testing lead to discrimination by an employer?

While there is no federal law in place,many states have passed legislation to prevent discrimination based on geneticinformation. For more information onindividual state laws, please visit the website of the National Conference of State Legislatures at www.ncsl.org/programs/health/genetics/charts.htm.An article that explains the risks and laws related to genetic discriminationis “Genetic Discrimination” written byMark A. Hall, JD, of Wake ForestUniversity School of Medicine(www.ncbiotech.org/services_and_programs/genomics_consortium/consortium_projects_and_events/geneticdiscrimination.pdf).

Ute Geigenmuller is the Chief ScientificOfficer at Correlagen Diagnostics, aCLIA-certified genetic testing laboratory.Dr. Geigenmuller can be contacted at 866-647-0735 orugeigenmuller@correlagen.com

8 Heart toHeart Spring•Summer 2008

CCF to Sponsor HEART FAILURE

RESEARCHCONFERENCE

CCF will be one of three sponsors for an upcoming research conference entitled“The Scientific Basis of Heart Failure inthe Young” which will be held May14-16,2008 at the Stanley Hotel in Estes Park,CO. The conference is organized by Mark Payne, MD, Professor of PediatricCardiology at Indiana University School of Medicine, and co-sponsored by theAmerican Heart Association Councils on Cardiovascular Disease in the Youngand Basic Cardiovascular Sciences, andthe National Heart, Lung, and BloodInstitute.

The conference will fulfill an unmet needto bring together scientists and cliniciansto define the problems related to theunderstanding and treatment of heart failure in the young. Cardiomyopathy is a leading cause of acquired heart failure.Heart failure in children has been less well studied when compared with the rich literature and basic understanding ofheart failure in adults. As a result, therapyhas advanced more slowly for the pediatric population.

The goal of the three-day conference is to present state-of-the-art clinical andbasic research on the basis of heart failure in children and to map out futuredirections in heart failure research. In particular, new research directions andcollaborations will be encouraged and discussed. Five topics of research will becovered: basic mechanisms in pediatricheart failure, novel tools for quantifyingheart failure, clinical science of pediatricheart failure, and tools for building a pediatric heart failure research program.

Registration is ongoing for this meeting.For more information about this cardiacmedical conference, please visitwww.heart.org/presenter.jhtml?identifier=3051868#Audience.

Heart Caths for KidsA book for parents of children needingheart catheterization

This step-by-step guide covers everyaspect of a child's cardiac catheterization(heart cath) procedure. It explains thetypes and purpose of catheterization,how they are done, who will care foryour child during his/her heart cath, whatto expect before, during, and after theprocedure, and how to help your childthrough this procedure. The bookletprovides areas for personalization,checklists, and an appendix of terms.

Your Child Has a PacemakerA book for parents of children with a pacemaker or defibrillator

This booklet is for the family of a child who needs a pacemaker or animplantable cardioverter defibrillator(ICD). It covers topics such as why apacemaker is needed, how it works,the different types, how it is put in, yourchild’s health care team, what to expectbefore, during, and after surgery, how itwill affect your child’s activities, and howto care for the device. It also includes achecklist, resource page, and glossary.

To Mend a Broken Heart -Pediatric Heart SurgeryAvailable in English or Spanish

Written for parents, this resource helps parents take a more active role in their child’s healing and recovery following heart surgery. Illustrated witheasy-to-understand diagrams, it coversanatomy and physiology as well as thechild’s health care team, types of surgeryand testing, what to expect before,during and after surgery, terminology, andfollow-up care. It also includes interactivefill-in pages and a resource page.

The Beat Goes On!A book for young adults living with a pacemaker or ICD

Written for young adults, this bookletexplains what a pacemaker andimplantable cardioverter defibrillator(ICD) are, how they work, what precautions to take, and how the device is monitored. Diagrams, illustrations,and wording are user-friendly. Interactivewriting exercises educate young adults on symptoms, follow-up, daily activities,and device care.

Family Resource CenterA Review of Pritchett & Hull’sCARDIAC PUBLICATIONS

Based in Atlanta, GA, Pritchett & Hull Associates(P&H) develops patient education materials covering cardiology and pulmonology, amongnumerous other health topics. They offer a seriesof cardiomyopathy-related educationalbooklets that are 30-64 pages longand are written in a conversationaltone (4th-8th grade reading level) that makes the information easy tounderstand. P&H booklets use eye-catching art, anatomical drawings, andcartoons to communicate basic facts inan amusing way. Booklets range from$2.95 to $4.45, and they are availableonline at www.p-h.com, or by callingPritchett & Hull at 1-800-241-4925.

Spring•Summer 2008 Heart toHeart 9

Traditional IDsThere are several retailers offering traditional medical ID jewelry and finishes,including classic bracelets, pendants,watches, charms, and tags in silver, gold,and surgical stainless steel. These includeAmerican Medical ID (www.american-medical-ID.com) and Sticky Jewelry(www.stickyj.com). Non-corrosive 316L stainless steel is recommended for outdoor physical activities over sterling silver or gold, which may be more prone to scratching.

Fashion-Forward Medical IDsMedical ID jewelry can be fun, and a child can select one that reflects his/her personality from cool and funky to pretty and sophisticated. Popular choicesfor active boys are the rubber/jelly andstainless bracelets or colorful sportsbands. Girls like the do-it-yourself sets,which allow them to select the beads,colors, charms, clasps and ID tag of theirchoice. Engraving your child’s name onthe front can make it more personal, andchanging the straps to coordinate withdifferent outfits can make them seemmore fashionable. Companies offeringmore “designer” options include Beaded Daisy (www.beadeddaisy.com),

Lauren’s Hope (www.laurenshope.com),N-Style ID (www.n-styleID.com),and Petite Baubles Boutique(www.petitebaublesboutique.com).

High-Tech IDsMedicAlert offers medical ID jewelry inconjunction with a 24-hour emergencyresponse service. Upon phone contact,it relays critical medical information toemergency personnel and also contactsthe child’s family.

A new type of medical ID alert is the E-HealthKey or MedicTag, a smallUSB-enabled storage device that can beworn on a necklace, lanyard or keychain.Due to the memory capacity on the flash drive, these USB medical alert tagsare capable of carrying much more information than conventional medical ID bracelets. In addition to recordingbasic emergency information, it can store medical images and a child’s completemedical history as well. Emergency personnel can instantly access the information with any computer.It is available through MedicAlert (www.medicalert.org) and MedicTag(www.medictag.com).

With so many medial ID options available, children with cardiomyopthy can now be stylish and safe at the same time.

New MEDICAL ID OPTIONS for ChildrenAs spring and summer approach, many families return to a more active, outdoor lifestyle. The use of medical identificationjewelry can provide peace of mind during these warm weathermonths when your child may be more involved in activities such as swimming, baseball, or day camp.

In the past, medical ID jewelry was negatively viewed as boringand ugly but now there is a broad selection of formats and stylesto please everyone. Formats vary from bracelets, pendants,necklaces and sports bands to watches, charms and traditional“dog tags.” The main purpose of medical ID jewelry is to makeothers aware of your child's medical and health conditions as well as any medications he/she may be taking. This is particularlyimportant if your child needs emergency medical attention whenyou are not with him/her. All medical IDs feature the Caduceus orthe Staff of Asclepius, which are internationally recognized medicalemergency symbols. Typically, the child’s name, medical condition, allergies, medications,doctor’s name and contact number and/or parent’s name and contact number areengraved on the front or back of the plaque. The information engraved on the medical ID ensures appropriate and timely medical care from first responders andmedical personnel, preventing possible misdiagnosis and medical errors.

Although the safety benefits are apparent, convincing a child with a medical conditionto wear medical ID jewelry can sometimes be challenging. A child may feel self-conscious about wearing something that calls attention to their heart condition. But with the wide variety of style choices now available, kids canproudly wear a medical ID bracelet or necklace their friends will envy withoutcompromising on safety. Medical ID retailers offer different jewelry styles and metalfinishes to suit the lifestyle of young children, teens, and young adults. Aside fromthe traditional stainless steel necklace or bracelet, retailers now offer fashionablebeads such as pearls, gemstones, and Swarovski crystal as well as higher-end materials such as 14K gold, sterling silver, and titanium. Bracelets come in the traditional metal chains and also with interchangeable rubber, beaded, leather, or polyester “sports” bands.

10 Heart toHeart Spring•Summer 2008

New Guide for MediaOutreach Available Do you have a compelling story to tell about your child’s experience withcardiomyopathy? Are you willing to share your story to raise awareness ofthe disease? If so, you may be interestedin CCF’s newly-developed “MediaOutreach Handbook.” This newresource was created to help familiesreach out to their local media andincrease awareness of cardiomyopathyand CCF. The handbook provides step-by-step instructions on how to target and approach the media, as well as tipsand letter templates to pitch yourstory. To receive a pdf version of thehandbook, please contact Pauline at ppierrot@childrenscardiomyopathy.org or 866-808-2873, ext. 902.

Shopping for a Cause

The best thing about online shopping is that you can buy from the comfort of your home while avoiding the mallcrowds and limited parking. When you shop through Igive.com andGoodsearch.com, and select theChildren’s Cardiomyopathy Foundation,CCF will receive a donation averaging 3% on all your purchases. Both sites feature an online shopping mall with hundreds of well-known retailers,including Best Buy, Macy’s, Apple, Nike,eBay, Gap, and Target among others.You receive the same prices and services as if you went directly to the store’s website, and you have theadded satisfaction of contributing to CCF in a hassle-free way.

Curebands Are Here!A new batch of CCF curebands havearrived. The red rubber wristbands areembossed with “A Cause for Today... ACure for Tomorrow” and CCF’s websiteaddress, and packaged in a clear polybagwith a CCF sticker. Popular as fundraisingand awareness building pieces, they alsomake great party giveaways. Curebandsare $5 each, with the net proceeds goingtoward CCF’s patient support fund. Todownload an order form, please visit ourwebsite: www.childrenscardiomyopathy.org/site/merchandise.php

Tribute Gifts for EveryType of GatheringHaving a birthday party, wedding, shower,bar mitzvah, or other celebration comingup? In lieu of gifts, why not ask friends and family to make a tribute donation to CCF in honor of yourself, the partyhost, or someone special. Your guests willbe pleased to know that their gift has special meaning to you and others. CCFcan provide cards to include with yourinvites to inform guests of this gift option.

All tribute gifts are tax deductible and will be acknowledged by CCF. The recipient will also receive a notification letter or tribute card informing them that a donation has been made in theirname, along with the sender’s contact information. This is truly a unique way to make a difference while making your event extra special.

Scrapping with Heart FundraiserCCF parent Jenni Hughes hosted a scrapbooking event, Scrapping with Heart, on October 26, 2007 in Idaho Falls, ID in honor of her one year olddaughter, Emersyn, who has hypertrophiccardiomyopathy.

Scrapbooking is a popular and creativehobby that combines photos, memorabilia,and stories into a keepsake scrapbook.Twenty-five friends and family membersworked with various materials and tech-niques to create scrapbooking pages toraise funds for CCF. Attendees enjoyeddinner, and local merchants donated itemsthat were given away as door prizes.

Hope for Little HeartsEvent Raises Over $8,000On February 28, 2008, CCF family members Melissa and Jake Sabin hosted a fundraiser for CCF in honor of theirson, Brody. Last summer, Brody was diagnosed with left ventricular non-compaction cardiomyopathy. “As his parents, we felt so helpless like there

was nothing we could do...focusing my energy on a fundraiserwas better then researching thenegative outcomes of this diseaseon a daily basis,” explained Melissa.

The Sabins planned the inaugural Hope for Little Hearts Benefit held at the SwissSportsman Club Park in BonneyLake,WA. The event includeddinner, live entertainment, raffles,

UPDATES: COMMUNITY FUNDRAISING AND AWARENESS

Jenni Hughes (right) and friends

Brody Sabin

Spring•Summer 2008 Heart toHeart 11

Join us for this annual event on

MONDAY, JULY 21, 2008

at the historic MONTCLAIR GOLF CLUB25 Prospect Avenue, West Orange, New Jersey

To reserve your playing spot or inquire about sponsorship packages, please contact Pauline

at 866-808-CURE (2873), ext 902.

and various auctions. CCF curebandbracelets were also sold. The eventattracted 200 people and raised over$8,200 for CCF. “It was so great to feel like I was helping other familiesbesides mine,” said Melissa. The Sabinsplan to make the Hope for LittleHearts Benefit an annual event. “Wehope that we can raise more moneyeach year; we are delighted that thefunds will be used towards researchfor a cure,” added Melissa.

Locks of Love for CCFCCF family members Greg and CindyRyan organized a Cut-A-Thon withSalon Easy Street in honor of their son, Jack Ryan, who has dilated cardiomyopathy. The Ryans planned the event to increase public awarenessof cardiomyopathy and to raise moneyfor research. The community eventtook place on Sunday, April 6, 2008 inClark, NJ. Haircuts were $20, and thebeauticians volunteered their time. Theevent was well-attended and raisedover $4,000 for CCF.

“The money raised will go towards a great cause. Jack celebrated his second birthday on April 10th, and has been progressing well since hisdiagnosis,”said Cindy. Loyal supportersof CCF, the Ryans previously raisednearly$1,500 selling CCF curebandsand secured more than $9,000 worthof donated printing services for CCF.

We Want to Hear from You!Let us know what you would like covered in future newsletters. We encourage parents, relatives, physicians, and nurses to submit items for consideration. Articlescan be a maximum of two pages and sent as an attached MS Word document to newsletter@childrenscardiomyopathy.org. Photographs or artwork should besubmitted as image files (.tif, .gif, .jpeg). The deadline for our Fall 2008/Winter 2009 issue is September 1, 2008.

AWARENESS

Golden Heart CircleThank you to all our donors who contributed to our

“Hope Lives” year-end appeal! We especially appreciate the generosity of our Golden Heart Circle donors.

Donations of $1,000 or more from 12/18/08 to 4/4/08

Our Spring 2008 Appeal Campaign is now underway. Please help us tocontinue our work – supporting critical research and providing valuable programsand services for the children and families impacted by this disease.

Jeff AltmanKevin and Ursula Corgan

Emil CostaJames CroomTom DosterJared Epstein

Robert GallivanRobert Hamwee

Andrew HeeDavid JohnsonStephen Lehner

Patrick and Kelly LynchAlain Marcus

Posman BooksDonald and Mary Lou Rossi

Edgar SabounghiScott and Sarah Snell

Van Der Linden FamilyFoundation

Vanessa’s Big Heart FoundationAndrew Wise

Edward Yu

The Ryan’s Cut-A-Thon at Salon Easy Street

HearttoHeart

P.O. Box 547,Tenafly, NJ 07670

Address Service Requested

Non-Profit Org.U.S. Postage

P A I DPermit No. 74

Tenafly, NJ07670

Volume 5, Number 1 • Spring • Summer 2008

New Jersey TRIATHLETE to Compete

for CCFOn June 14, 2008, thousands ofspectators will cheer for CCF supporter Michael Hausler as he competes in the 26th AnnualWyckoff/Franklin Lakes, NJTriathlon organized by the YMCAand Rotary Club of NJ. Michael will swim 1/2 mile, bike 17 miles and run 5 miles to raise funds forCCF. Michael, himself, overcameminor heart conditions in his youth.When CCF was brought to hisattention, he decided to compete inthe triathlon in honor of all childrenwith cardiomyopathy.

Sponsorships are still needed to help Michael meet his fund-raising goal. Sponsors will receiverecognition at the race and withinthe tri-state community. If you,your employer, or business is interested in sponsoring Michael,please contact him atmikehaus@gmail.com and request a sponsorship form.

recently donated $1,000 to the Children’sCardiomyopathy Foundation on behalf of Kirk Pfrangle, a Medtronic 2007Global Hero. Medtronic Global Heroes is a unique program that brings runnerstogether to compete in the MedtronicTwin Cities Marathon, celebrating theaccomplishments of those who run with medical devices. Kirk successfullycompleted the TC 10 Mile in 1:32:15.

An avid runner from Alpharetta, GA, Kirkhas an implanted cardiac defibrillator, amedical device that many cardiomyopathypatients have. “Prior to a virus-caused

episode of ventricular tachycardia two andone-half years ago, I had been a seriouslycompetitive runner and coach for over 40years,” stated Kirk. “As I lay in the hospitalfor two weeks in 2004, I feared that myrunning days were over.”

“The little piece of extraordinarily sophis-ticated technology that is implanted in my chest, however, has allayed my fearsand concerns. I live my life with a highdegree of energy and enthusiasmbecause of the defibrillator, and for that I am extremely thankful.”

This year’s Medtronic Twin CitiesMarathon will be held October 5,2008 and is open to all runners with approved medical devices (any manufacturer). For more information,visit www.medtronic.com/globalheroes.

Medtronic GLOBAL HERORuns for CCF

The Medtronic Foundation

Global Heroes is a unique program that brings runners together to compete in the

Medtronic Twin Cities Marathon,celebrating the accomplishments

of those who run with medical devices.

Kirk Pfrangle, Medtronic Global Hero