Consider attending this 11th annual, very informative and valuable patient and family seminar with others who will arrive from across the US and world.

By MICHELINE LONG
Published: July 30, 2009

EDUCATIONAL OPPORTUNITY

CARDIOLOGY/ELECTROPHYSIOLOGY STUDENTS/DOCTORS -- NEW BOOK

If you have ever attended an ISHNE online symposium, you almost certainly had the pleasure of experiencing Professor Dr. Andrés Ricardo Pérez Riera. My first introduction to this ever giving, learning, and teaching educator came during the first online ARVD symposium. The internet discussion which accompanied the symposium was woven with contributions from Dr. Pérez Riera. He shared lists of facts, supported those facts with references, and displayed such an obvious dedication to medical professionals and patients that he became unforgettable to me.

This author eventually had the pleasure to meet Dr. Pérez Riera on a more personal level through email contact aimed at helping ARVD/C patients. Now I have the pleasure to announce his valuable teachings through yet another media.

If you are a student or doctor of cardiology or electrophysiology looking to expand your knowledge, consider the following announcement from Dr. Pérez Riera. He has recently released a new book:

"I think you will probably find it surprising that in the 21st century, a new book is being released -- 'Atlas-book on Vectorcardiography' -- a methodology currently relegated to a few research centers around the world. After more than 3 decades of practice with the method, I'm certain I cannot be the 'last of the Mohicans' with a method that clearly allows us to improve diagnostic accuracy, specificity, and sensitivity in several aspects. The electrocardiographist that analyzes the tracing in light of a comparative VCG, undoubtedly, has a wider and clearer view of the electrical phenomena of the heart. This type of point of view led us, in all cases, to perform an ECG/VCG correlation in the frontal and horizontal planes.

The book 'Atlas' attempts to show in a didactic way the electrical phenomena in the different entities, approaching the heart as a three-dimensional organ. If after reading this work a desire arises in some of the readers, to learn about vectorcardiography and actually practice it, the author will feel largely rewarded."

By MICHELINE LONG
Published: July 27, 2009

NEWS BULLETIN

EXTRA EXTRA! RESULTS FROM THE NIH ARVD STUDY

Great news! The results of the "Multidisciplinary Study of Right Ventricular Dysplasia" have been published in HeartRhythm, the official journal of the Heart Rhythm Society and the Cardiac Electrophysiology Society.

Don't miss out on updating your knowledge of ARVD and the newest research article. Go listen to a podcast regarding the article -- an interview between Dr. Frank I. Marcus, Principal Investigator of the NIH study, and Dr. Douglas P. Zipes, the editor of HeartRhythm.

For those who would like to download and read the full text pdf of the article entitled Arrhythmogenic right ventricular cardiomyopathy/dysplasia clinical presentation and diagnostic evaluation: Results from the North American Multidisciplinary Study click here.

Our thanks to all of the patients and researchers who participated in the study and to all of the authors of the new article:

Frank I. Marcus, MD, Wojciech Zareba, MD, Hugh Calkins, MD, Jeffrey A. Towbin, MD, Cristina Basso, MD, David A. Bluemke, MD, PhD, N.A. Mark Estes, III, MD, Michael H. Picard, MD, Danita Sanborn, MD, Gaetano Thiene, MD, Thomas Wichter, MD, David Cannom, MD, David J. Wilber, MD, Melvin Scheinman, MD, Henry Duff, MD, James Daubert, MD, Mario Talajic, MD, Andrew Krahn, MD, Michael Sweeney, MD, Hasan Garan, MD, Scott Sakaguchi, MD, Bruce B. Lerman, MD, Charles Kerr, MD, Jack Kron, MD, Jonathan S. Steinberg, MD, Duane Sherrill, PhD, Kathleen Gear, RN, Mary Brown, MS, Patricia Severski, BS, Slava Polonsky, MS, Scott McNitt, MS

Zipes: So is there a gold standard Frank that you can tell our listeners? We have a patient who presents with a VT that looks left bundle, we think its coming from the right ventricle, we're worried about arrhythmogenic right ventricular cardiomyopathy/dysplasia, what do I do next?

Marcus: Well, I think what you do is to look at the whole picture and I think that it is very important to see if the patient meets the guidelines that were proposed and published in 1994 by McKenna and his task force on criteria for the diagnosis of RV dysplasia, the important part is that there is no gold standard and that any one test does not make the diagnosis ...

Zipes: So one has to put the whole constellation of data together to be able to make a diagnosis?

Click hear to listen to the podcast.

Following are a few quotes from a July 6th news release on the HeartRhythm website.

* New research strongly indicates the need for a revision of criteria to effectively evaluate the presence of right ventricular structural, functional and electrical abnormalities.

* From 2001 to 2008, the North American Multidisciplinary Study led by Frank Marcus, MD, of the section of Cardiology at the University of Arizona, enrolled a total of 108 newly diagnosed patients with suspected ARVC/D in 18 centers within the United States and Canada.

* "When not properly diagnosed, ARVC/D can result in sudden cardiac death or unnecessary implantation of an ICD," stated Dr. Marcus. "It has been many years since the first clinical profile of ARVC/D was published. It was our objective to study the clinical characteristics and diagnostic evaluation of a large group of newly diagnosed ARVC/D patients."

* This study substantiates the need for multiple diagnostic tests as well as updated, more well-defined criteria for diagnosing the disease.

If you would like to read our past news articles about the diagnostic criteria modification conferences, read:

By MICHELINE LONG
Published: July 10, 2009

GENETIC TESTING

QUESTIONS AND ANSWERS

Not long ago, we learned that a new test for ARVD had been found (see the April 6, 2009 news article "Researchers Discover New Test for Diagnosing ARVD/C"). This new test is in the early research stages, but has proven to be promising. This good news caused me to wonder about genetic testing, is there still a place for this in ARVD/C?

The questions that I had plagued me, particularly after hearing from a friend who had been tested for 5 of the known ARVD gene mutations and afterwards felt cleared of ARVD (they were not found with one of the latter gene mutations). I wondered, "Are they cleared? Were they well informed of what their gene testing did and did not mean?"

I pursued answers from a source that will go unnamed, but one that I trust very much for their expertise. Below, I share the questions and answers.

Question 1:
How many ARVD gene mutations have now been identified?

Answer 1:
"A lot, and many new ones are being identified as more and more individuals are being screened. Here is a database of the various mutations: http://www.arvcdatabase.info/

Question 2:
Why is the present clinical testing only for 5 of the known ARVD gene mutations?

Answer 2:
"I can only assume they have chosen this group of 5 because they are the genes that have been identified as having the most changes thought to be pathogenic in the US. I'm sure there is a financial reason as well. They are working on new technology to be able to screen many genes in less time for less money. Www.genetests.com is a website that can tell you the names of the labs that are currently testing for each of the genes associated with ARVD."

Question 3:
If a person is negative for the 5 ARVD gene mutations for which they are testing (ARVD/C Panel: DSP, DSG2, DSC2, PKP2, TMEM43), does this mean they do not have ARVD?

Answer 3:
"Absolutely not. There is more to a diagnosis than genetics. Cardiac testing still plays a very important role in making a correct diagnosis. We believe there are many more genes that may be involved in the development of ARVD and that is why research is important."

Question 4:
Granting the answer to #3 above is "No, it does not mean they do not have ARVD, it only means that they do not have one of the 5 ARVD gene mutations for which they were tested," what is the solution for finding out which gene mutation they might have? Or, what might you advise as a solution?

Answer 4:
"There is no easy answer to this. It is important for people to be involved in research. Unfortunately, many research labs are not allowed to release results, but that is where the important work is done. Again, unfortunately, genetic research can take many years. We have several patients in whom a genetic mutation responsible for their ARVD has been identified. It is frustrating, but in most of these cases we feel that ARVD is the correct diagnosis based on their cardiac testing. It's important to keep in touch and be involved in research as our knowledge will continue to improve over the years. Unfortunately, not knowing the genetic change responsible for ARVD means that complete cardiac screening will continue to be recommended for family members."

Question 5:
Considering the new ARVD test which looks at the desmosome in biopsied heart material, what will be the consideration for genetic mutation testing in the future? Will it continue - does it continue to be important?

Answer 5:
"The new testing with biopsy heart material is still only in the research phase and it is too early to tell what impact this will have on genetic mutation testing. You have to remember that a cardiac biopsy is much more invasive than a simple blood draw and so I think genetic testing will always be around. I think the new testing might be more useful in autopsy cases."

Question 6:
Are scientists still looking for more ARVD gene mutations? What might be their expectations? Do they expect to find more/other gene mutations, do they expect that finding these might be more or less difficult to find than the gene mutations already found?

Answer 6:
"Research continues to work to identify new genes and other possible causes of ARVD. I would assume that the easy ones have been identified and additional genes involved will be more difficult to identify."

My continuing comments/questions:
Recently a patient mentioned that they were negative for the 5 ARVD gene panel. Their response seemed to be that they now felt that they had been cleared of ARVD (despite their having the diagnostic criteria for ARVD). Is this an appropriate response? IF a patient is negative for the 5 gene panel, if they have the diagnostic criteria, what is the likelihood or percentage of likelihood that they really do not have ARVD? My concern is that this particular person does not want to be ARVD, because they really want to continue exercising. I am concerned that being negative for the 5 genes is like a false sense of assurance.

Comments/answers:
"If a patient meets the diagnostic criteria for ARVD based on the results of their cardiac testing and is found not to have a genetic mutation in one of the 5 genes that are currently being screened, this does not mean they don't have ARVD. It just means they don't know the cause of their ARVD. Obviously, I would encourage this individual to seek a second opinion and would have recommended that they meet with a genetic counselor prior to testing so that they were aware of the possible outcomes and what that might mean. The genetics of ARVD are complex and not well understood. And there are some families with more than one mutation. The overall detection rate of a genetic change or mutation by screening patients with clinical symptoms or features of ARVD with the 5-gene panel is about 50%."

Finally... I share the above with our readers in hopes that the information can answer some of their questions about the possible importance of genetic testing, as well as clinical evaluation for ARVD. There are expert sources for expert answers pertaining to ARVD/C.

Our site refers to ARVD.com and ARVD.org and those who work very hard at the ARVD Project at Johns Hopkins Hospital and the University of Arizona on the behalf of all with ARVD.

By GARY DEXHEIMER and MICHELINE LONG
Published: May 8, 2009

ARVD/C FAMILY COMMUNITY NEWSNOTES

THE JOHNS HOPKINS ARVD PROJECT DOES IT AGAIN

Living with ARVD/C columnist Gary Dexheimer recently did what many ARVD community friends have done. He and his wife packed a bag and headed to the annual Johns Hopkins ARVD Family Seminar in Baltimore. This year's seminar was the 10th held and, not at all surprisingly, the 10th enjoyed by first-time and repeat attendees. It was seminar success for a 10th year!

Within the midst of their online support group, Gary and another group member shared their reflections with close friends. I asked their permission to share these with our site readers.

Gary wrote ...

"The following are a few of my thoughts and observations on the recent ARVD Family Seminar. My wife took extensive notes and at a later date I will recap the statistics, data and research shared with all the attendees at the conference.

Overall, both of us thought that the conference was great and would absolutely recommend it to anyone who has thought about attending but to date has not. Between flights, hotel and meals this was not an inexpensive weekend for us. However, we both concurred that it was a valuable investment in our future. While traveling to Baltimore, we had decided that we would not plan on attending every year. By Saturday evening, we had decided we couldn’t afford not to attend annually. We met so many wonderful people and will look forward to seeing those individuals again next year.

We also enjoyed a wonderful meal at a nice family owned restaurant, with good company, much laughter and great conversation filled with compassion and concern. We made a personal call to our hopeful benefactor, assuming that the pleas of this anonymous support group member's parents would convince the aforementioned member to offer us his credit card number, but we couldn't get him to buy in. Our next call was to our support group's 'mother hen,' but by now, we had given up hope of finding someone to subsidize us -- instead, we just shared with our colleague the enjoyment we were experiencing.

It would be an understatement to claim such positive impressions of physicians and support staff so renowned in their field, and yet these people volunteered a Saturday, at their expense, to reach out to a diverse group of individuals in an obviously heartfelt and caring manner. These gifted doctors presented a wealth of meaningful data at a level that could be understood by the least experienced of the audience. Further, they made a point to be easily accessible to those individuals that hoped their questions might be answered.

With consideration to their role as counselors, the genetic counseling staff not only organized and directed every small detail of the conference, but without question put their hearts into making sure that every item and individual was attended.

I was struck by the fact that the conference presented a microcosm of society; there were families, children, young adults, seniors, professionals, working class, various ethnicities, shapes and sizes. There were 183 participants in attendance. Of those who attended, 69 were diagnosed with ARVD, 13 were pending diagnosis, and 55 had ICDs. The mean age was 38.

As I reflected on the stories that were shared, I thought about the differences between tragedy and hope. After all there must be hope, particularly if in a new marriage you lose your spouse and face raising your children in memory of the person to whom you dedicated your life.

Humankind is a composite of personalities. Some lean toward a pessimistic attitude and others always look at the glass as half full. I believe that -- regardless of our spiritual differences -- we all have faith in the goodness of life and accept that to live is to experience many diversions in our journey's path.

On the plane trip home my wife observed that for all of the difficulties I may have experienced as a carrier of ARVD and for all those issues yet to come, ARVD has changed me. I have found renewed passion and strength in our marriage. Within my aggressive and driven personality, I have found patience and that was a quality long desired by my wife. At that moment, while on the airplane, I saw a quote that summed it all up, 'Sometimes you feel lucky because you've been given this chance to change your life.'

In the bottom line, the conference offers hope in the knowledge, technical advances and further research that are constantly ongoing by a very determined and dedicated staff. This offers us all trust that in just living we can find a sense of peace in each others existence and our shared knowledge of ARVD.

I had committed to be one of two from the attending family community that had been asked to speak at the seminar. The thought of this became all consuming when I realized that I would be at a lecture hall podium in front of almost 200 individuals. Overcoming my nerves and the beads of sweat on my forehead, I not only got through this, but appreciated the opportunity to reach out and share my personal feelings on the changes associated with a new normal and my hope for the future.

On a final note, along with all the benefits experienced, we were also well fed. It would not have been unusual to charge to attend this conference. For me, that provides motivation to consider how I might help with the needed fund raising. After all, I am a direct recipient of the continuing research efforts."

"I thought that the seminar was just wonderful … it's unbelievable that we weren't charged a large fee for everything that was offered to us! I thought all of the hand-outs were exceptionally well done and helpful ... especially for someone new to all of this."

Hearing of ARVD/C in a 1st degree family member can affect different people in different ways. Some people turn in denial -– they either cannot or will not face that they might also be affected by this genetic disease. They refuse to be evaluated for ARVD/C, causing great distress to their affected relatives who know the cost of undiagnosed, untreated ARVD/C. Other people react by searching for knowledge and the best medical care they can get.

The JH seminar gave this family that for which they were looking.

"I met so many wonderful people there ... Thank you to those I was able to talk to later, to hear some of your personal stories ... I learned so much from just listening ..."

"Gary, I thought you did an excellent job as speaker! Thank you for your eye contact and the way you connected with people. It was awesome and your UPBEAT presentation was wonderful."

The Johns Hopkins ARVD Family seminar makes it very easy to approach touchable, caring and skilled staff. Not only that, this staff probably has the greatest corporate ARVD/C education and experiences with affected patients in existence.

Having availed themselves of an excellent opportunity, the above young person finished their comments with:

"I was able to meet with Amy and Dr. Calkins and will get my 'marching orders' soon ... a whole EP work-up I guess. I'm putting on my seatbelt and ready to find out where I am in all of this. … I thank God for a great team of professionals, as well as for new friends with similar situations to learn from. Thank you."

Thank you for another enriching seminar and all that you do for the ARVD/C family community! Thank you for introducing this community to the phenomenal Dr. Frank Marcus, dedicated long time ARVD/C researcher.

Editorial note: Gary, I think there is going to be a large group of us looking forward to your recapping of the statistics, data and research shared! Can't wait to hear!

By MICHELINE LONG
Published: April 6, 2009

MEDICAL BREAKTHROUGH

RESEARCHERS DISCOVER NEW TEST FOR DIAGNOSING ARVD/C

Did you know that a new test for diagnosing ARVD/C has arrived? According to Dr. Hari Tandri of the Johns Hopkins Hospital ARVD project, "This diagnostic test is the first novel test since the task force criteria published in 1994."

The task force criteria (TFC) were created to help physicians diagnose ARVD/C. Unfortunately, while using the TFC to establish a diagnosis is the appropriate way to do so at this point in time, it is an imperfect way. First, a number of varied tests must be performed upon a person (EKG, SAEKG, Holter, Echo, MRI etc.) Next, test results must be analyzed. Finally, if a person's tests reveal a minimum number of major and/or minor criteria for diagnosis, they may receive a diagnosis of ARVD/C.

There are several distinct weaknesses in using the TFC to diagnose this cardiac disease:

Misdiagnosis or lack of diagnosis may result in missing out on the most appropriate treatment, advice or both. Worse, a lack of diagnosis and treatment may result in sudden cardiac death (SCD). Undetected, untreated, concealed phase ARVD can result in SCD.

The exciting and hopeful news is that very soon a far better way to test for ARVD/C may be widely available. One singular test may become useful in determining the absence or presence of ARVD/C.

If you have been hoping for a single, definitive, readily available, easy, painless and affordable test to determine if ARVD/C is absent OR present in yourself or one of your loved ones, your hope "may" soon be realized. That hope is still not quite here with this new test, which is not "off the charts" in terms of "reasonably safe to perform in the appropriate situations," BUT it is not necessarily easy, painless or risk free to perform at this time (heart biopsy entailed). The test soon may be the former, your hope, IF researchers can finely tune it, IF they can find a means to replicate the test results through an easy, painless and risk free means (read on), and IF they can do so in a large group of people who do not necessarily show distinct signs and symptoms i.e. if they can do so in asymptomatic family members -- and they will be working on it.

On March 12, 2009 the New England Journal of Medicine (NEJM) published the article entitled,"A new diagnostic test for arrhythmogenic right ventricular cardiomyopathy" (N Engl J Med 2009; 360: 1075-1084.) The article details the path which led researchers to the following conclusions:

"Routine immunohistochemical analysis of a conventional endomyocardial-biopsy sample appears to be a highly sensitive and specific diagnostic test for ARVC."

"In conclusion, we have developed a new diagnostic test for ARVC that could prove useful if adopted in clinical practice."

"Such a test could be performed in most pathology departments in which immunoperoxidase has become a standard method of tissue diagnostics."

The Novel Test
According to the article, the researchers have already used "immunohistochemical analysis" on the "heart-biopsy samples" of a group of patients. After doing so, they were able to predict those who did and did not have ARVD/C with a high percentage of accuracy.

I can already hear many of you asking, "Hasn't heart biopsy already proven to be of limited value in predicting ARVD/C?" and "Yes, but ... how can it be reasonable to do such an invasive test on someone who is not having any symptoms or showing any heart problems, someone who may not be carrying a gene mutation capable of causing ARVD/C?"

"Yes, correct." Formerly, heart biopsies "were" of limited value in determining ARVD/C. They were a hit and miss affair. Samples of tissue were looked at for the presence of fat and fibrosis but, if it was not found in the samples from one area of the heart, it did not mean that it would not be found in samples from other areas. Further, sampling tissue from the area of the heart which was the most likely to produce real answers (the right ventricle) was risky business, thus often avoided. Of course, many of us have been informed that myocardial biopsy is an invasive procedure that carries a small but definite risk.

The novel test looks at biopsied material in a completely different way. In addition, the material needed for analysis can come from differing areas within the heart and still produce accurate results (e.g. right or left ventricle, interventricular septum.) Even though the present new test requires a heart biopsy, tissue taken with less risk still has the potential to deliver valuable answers.

Now, about the question concerning the performance of an invasive procedure on someone who has no known symptoms or problems, and who may not have the actual potential to be affected by ARVD/C ... The researchers will be working on this concern. They wrote:

"It is also possible that equivalent diagnostic information could be derived from more accessible tissues containing desmosomes, such as skin, hair follicles, and buccal mucosa."

We asked world reknown ARVD/C research Dr. Marcus, Professor Emeritus, to help us understand the new test:

No ARVD/C ( - )                     ARVD/C ( + )        In the above simulation, heart cells are represented in blue. Left: the white represents fluorescing "normal" adhesive proteins. Right: the adhesive proteins are altered, defective and do not fluoresce.

"The basic concept of the test is simple.

It is known that the defect in ARVC is an alteration in the proteins that bind the myocardial cells together. These proteins react to a special stain by fluorescing. In ARVC this stain will not cause illumination of the defective protein. Therefore, the test consists of inserting a catheter into a neck vein, guiding it to the muscle between the right and left ventricles (the septum) and removing tiny bits of tissue by closing a small clamp at the end of the catheter.

The tissue is stained and examined for the presence or absence of the protein. Jeff Saffitz and coworkers found that the test appears quite specific i.e. if the heart is affected by ARVC there is no staining of these adhesive proteins; if not, the stain attaches to the normal connecting proteins and fluoresces."
 

Still need a little help in understanding how the new test indicates ARVD/C?
Have you ever seen a "glow stick?" A glow stick is a plastic tube containing liquid which "fluoresces" or glows in the dark. If you totally darken a room full of people, you cannot see their locations as they generally do not glow in the dark. If, on the other hand, each person removes a glowing fluorescent stick from their pocket and holds it up, they reveal their location and presence.

Now then, a doctor may attempt to explain how it is that ARVD/C causes fat and fibrosis to develop. In simplistic terms, they may explain it this way, "Those who have this cardiac disease have something similar to a defective glue holding the cells of their heart muscle together. If the defective glue holding a small group of cells together lets loose, the cells come apart and die. When they do, the body's defense system rushes in to patch up the damage. The eventual result is a patch of scar tissue composed of fibrosis and fat."

Using Dr. Marcus' explanation, the understanding of how a glow stick helps us to locate a presence, and the thought of defective glue, the following offers a simple explanation of how the new test is used to diagnose ARVD/C:

Simple Explanation of the Novel Test:
Doctors use a test to remove small bits of heart tissue which contains heart cells. Lab technicians wash over the tissue with a liquid. The liquid will stick to "normal" heart cell glue making it glow. Areas of heart cell glue is examined.
• If the glue glows: negative test, no ARVD/C.
• If the glue does not glow: positive test, ARVD/C.

The Known and the Unknown
The researchers know that the new test is notably accurate in diagnosing ARVD/C when the test is performed on people who have advanced phases of this disease. What they do not yet know is if it will be equally accurate in diagnosing ARVD/C in people who have early phase disease. Dr. Marcus summed it up this way:

"As you know the diagnosis of ARVC has been difficult and relies on a combination of abnormal findings such as changes in the ECG, echo, MRI etc. These abnormalities may be subtle and difficult to differentiate from normal; particularly since the right ventricle is an irregularly shaped structure that doesn't contract symmetrically. Thus, if these findings can be substantiated in a larger series and in patients with early disease, it would be a significant diagnostic achievement."

"Angeliki Asimaki, Ph.D., Harikrishna Tandri, M.D., Hayden Huang, Ph.D., Marc K. Halushka, M.D., Ph.D., Shiva Gautam, Ph.D., Cristina Basso, M.D., Ph.D., Gaetano Thiene, M.D., Adalena Tsatsopoulou, M.D., Nikos Protonotarios, M.D., William J. McKenna, M.D., D.Sc., Hugh Calkins, M.D., and Jeffrey E. Saffitz, M.D., Ph.D."

We also look forward to further investigation which will hopefully produce a single, definitive, readily available, easy, painless and affordable test to determine if ARVD/C is absent or present.

By MICHELINE LONG
Published: March 24, 2009

REMINDER

ROOMS FOR JH FAMILY SEMINAR GOING FAST

Saturday May 2nd, 2009 is the date set for the 10th annual ARVD Family Seminar at the Johns Hopkins Hospital in Baltimore, Maryland. This yearly event has been a favorite of many in the International ARVD Family Support Network for nearly 10 years now. Be sure to read Gary Dexheimer's news article of January 25, 2009 for more details.

In the meanwhile, we have learned of some recent news from Crystal Tichnell, program coordinator for the ARVD project at JH. She mentioned that the block of rooms at the Holiday Inn will only be held until 3pm April 10th, and that the rooms are going fast -- they may not even last that long. If you miss the April 10th deadline, be sure to contact Crystal (ctichnell@jhmi.edu) to learn of other possible accommodations in the area.

RED HOT TIP: This is the year to go to the JH Family Seminar! There are two extremely exciting news items that will almost assuredly be discussed:

Both of the above news items are "firsts" since about 1994! To read more about the Task Force Criteria (TFC) and that which has gone into getting the TFC modified, you can check out several articles in our news archives. Look for the articles published on June 15, 2007 ("Breaking News") and November 18, 2007 ("Progress Reports"). To read more about the new test for ARVD/C, stay tuned ... we should have a news article on this shortly.

By MICHELINE LONG and GARY DEXHEIMER
Published: March 9, 2009

NEWS BULLETIN: SCIENTIFIC COMMUNICATION

SPORADIC ARVC/D DUE TO A DE NOVO MUTATION

People who have been diagnosed with ARVC/D, who have no family history of heart problems, and who have not been found with one of the known and inheritable ARVD causing gene mutations often ask, "Well then how did I get this disease?" While in of itself a new article does not hold all of the answers to the question, it is significant that -- due to the case cited within the article -- it holds at least one possible answer. The subject of the article, a man of 41 years old, was found with a first generation gene mutation.

Recently ARVD-ARVC-Info.com learned of an important communication published online first, January 16, 2009. Printed in the March edition of the Journal of the European Society of Cardiology (Europace 2009 11(3):379-381), the article is entitled, Sporadic Arrhythmogenic Right Ventricular Cardiomyopathy/Dysplasia Due to a De Novo Mutation.

In order to better understand the importance of the article, we searched for answers to "What is meant by 'sporadic' ARVC/D?" and "What is a 'de novo' mutation?" "Sporadic," we mused, "ARVC/D is considered somewhat rare, aren't all cases considered sporadic?" ("No," was the eventual answer.) "De novo? This sure sounds like Latin to me!" Quite right, we learned that "de novo" actually was/is a Latin expression meaning "afresh" or "anew." Good enough. One of us eventually formed this description, "A de novo mutation is an alteration in a gene, one which presents for the very first time in a particular family member, and one which resulted from a change in one of the parent's germ cells (an egg or sperm) or the fertilized egg itself." That description seemed like it might be accurate and, maybe, the "easy listening" version of that which one scientist explained about the article:

"Therefore a genetic mistake has been observed 'out-of-the-blue' and due to a minor replication disorder in the reproduction process."

"So, what is 'sporadic' ARVC/D and what is 'a de novo mutation'?"

"I'm happy to provide some definitions for you.

The terms 'sporadic' and 'de novo' go hand in hand. A de novo mutation is a new mutation that is not inherited from either parent. A gene change or mutation has to begin with someone. Essentially, the person in which this new mutation occurs is referred to as a sporadic case. We usually aren't able to track every mutation back to the person it started with. It's important to understand that even though this mutation was not inherited from either of this individual's parents, it can still be passed on to his children."

Title: Sporadic Arrhythmogenic Right Ventricular Cardiomyopathy/Dysplasia Due to a De Novo Mutation.

Authors: Estelle Gandjbakhch, Véronique Fressart, Géraldine Bertaux, Laurence Faivre, Françoise Simon, Robert Frank, Guy Fontaine, Eric Villard, Catherine Coirault, Bernard Hainque, and Philippe Charron.

Reference: Europace 2009 11(3):379-381

Article Review
The doctor/scientists who wrote this communication reported the case of a 41 year old man of European origin. He had been referred to a cardiologist due to complaints of "atypical" (unusual) chest pains. He had no medical history or other symptoms, and he did not mention any recent bouts of viral or other inflammatory diseases. Evidently, had he done so, it might have suggested to his cardiologist that he was being affected by a myocarditis. The authors of the communication also noted that this young man exercised daily, cycling an average of 40km weekly.

The report mentions the medical evaluation that was undertaken; the specific tests and test results were noted in the text. Eventually, those who were evaluating this man learned that he was not affected by ischemia (a restricted blood flow). The latter might have explained his chest pains; it didn't. Also eventually, it was learned that the fellow was affected by a number of the same cardiac issues normally found in those diagnosed with right ventricular cardiomyopathy/dysplasia (inverted T-waves from V1 to V5, polymorphic ventricular ectopies with left bundle branch block morphology, RV wall motion abnormalities, local thinning of the RV wall, global mild RV dilatation etc.) Based upon this young man's test results, he received a positive diagnosis of ARVC, one made according to the International Task Force diagnostic criteria.

Oddly -- and perhaps you can relate to this -- the subject of this report had a family history that was "unremarkable." In other words, there didn't appear to be any family medical conditions or sudden deaths that could help the cardiologist understand the man's present heart condition. Further, cardiac examinations of his relatives were normal.

Due to the "unremarkable" and normal cardiac tests in relatives, genetic testing was done on this individual. The mutation screening was of the four desmosomal genes which have been shown to be the major ones involved in ARVC to this point in time: PKP2 (plakophilin-2), DSP (desmoplakin), DSG2 (desmoglein-2), and DSC2 (desmocollin-2). Screening documented that this 41 year old man had a mutation in DSG2. Subsequently, his parents were screened for the same gene mutation. Neither parent was found with it.

In the case of the young man cited in this article, it was determined that he had a de novo gene mutation, since the mutation was absent in both parents. According to the best knowledge of those who wrote this article, they – within this particular article -- were the first to describe a "de novo causal mutation identified in ARVC." The authors mentioned that this mechanism had already been observed in other cardiac diseases such as hypertropic cardiomyopathy and long-QT syndrome.

The report's authors concluded their writing by detailing the important implications of their observation. Perhaps the most significant implication was that the information learned by these scientists could now be applied in doctors' offices to assist patients. You see, according to the authors, a de novo ARVC gene mutation is one that can be inherited by offspring.

The conclusion of this article's communication contains:

"This observation has important implications..."

1. "...the appearance of a de novo mutation in the desmoglein-2 gene provides compelling genetic evidence for the involvement of this gene in ARVC..."

2. "...it provides evidence that sporadic ARVC is not a separate non-genetic entity but a particular case of a monogenic disease. ..."

3. "...our findings have direct clinical applications since individuals with sporadic ARVC caused by a de novo mutation can transmit the disease gene to 50% of their offspring."

ARVD-ARVC-Info.com would like to thank the authors for their research work and writing this important communication. We would also like to thank Crystal Tichnell for her ever present assistance in "checking and helping" us, as well as answering the questions of the International ARVD Family Support Network. If you would like to contact Crystal Tichnell (ctichne1@jhmi.edu) about participating in the ARVD Project at Johns Hopkins Hospital, she is ready to hear from you.

By GARY DEXHEIMER
Published: January 25, 2009

ANNOUNCEMENT

10TH ANNUAL JOHNS HOPKINS ARVD FAMILY SEMINAR

For all individuals with ARVD, communications through the private online ARVD support group, as well as articles on the public ARVD-ARVC-Info website are an amazing wealth of information. However, to get all of the latest research data available you need to plan a May trip to Johns Hopkins. Visit Baltimore, MD on the first weekend in May and participate in the 2009 ARVD Family Seminar. Spend an extra day and take in the attractions at the Inner Harbor.

This year’s seminar will take place On Saturday May 2nd at the Mountcastle Auditorium in the preclinical teaching building located at 725 North Wolfe Street. The schedule includes an informal Friday evening social at the Holiday Inn-Inner Harbor from 7 – 9 PM. Room accommodations have been reserved at the Holiday Inn at the rate of $139.00/night. You can make your reservations by calling 1 (800) 287-0037 or 1 (888) Holiday. Make sure that you ask for the Johns Hopkins ARVD Family Seminar rate. The morning session will conclude with a lunch reception at 1:15 PM and the afternoon session will conclude at 4:30 PM.

This year’s speakers include Dr. Hugh Calkins, Director Johns Hopkins ARVD Program, Dr. Frank Markus, Dr. Hari Tandri, Dr. Daniel Judge, Dr. Stuart Russell, and Johns Hopkins Genetic Counselors. The agenda includes discussions on the NIH Multidisciplinary Study of ARVD/C, revised diagnostic criteria, ARVD genetics, heart failure and heart transplant, and catheter ablation for ARVD. Conference attendees will provide some shared personal experiences with ARVD. There will also be two different discussion group and research sessions.

This seminar presents a pro-active opportunity for patients and family to understand more about their personal journey with ARVD and to assist their primary physicians in insuring their patient’s best care.

To register for the Johns Hopkins Family Seminar and to locate additional details visit this link which takes you to ARVD.com. Attendees may either register on line or by downloading the registration form. You may also contact Crystal Tichnell by fax: (443) 609-4061 or email: ctichnell@jhmi.edu.

I am personally looking forward to meeting those that I have had the pleasure to correspond with, finally putting a face to those individuals. It will be a wonderful time for learning, sharing experiences, good conversation and a dose of laughter.

Gary Dexheimer joined the writing staff of ARVD-ARVC-Info.com in January 2009. We are delighted to have him on board. Be sure to read and keep up with his new column "Living with ARVD/C." Drop him a line or, better yet, head for the Johns Hopkins family seminar in May to meet him.

By GARY DEXHEIMER
Published: January 24, 2009

FUND RAISING EVENT

HEALING HEARTS PRESENTS THE 4TH ANNUAL BULL & OYSTER ROAST

The upcoming Friday, February 20, 2009 event is in its 4th year and is an annual fund raiser for ARVD research. The Bull & Oyster Roast is organized by the founders of Healing Hearts.

This event kicks off at 7 PM and will be held at the Ten Oaks Ballroom, 5000 Signal Bell Court, Clarksville, Maryland. Tickets at $40.00 per person and raffle tickets for $10.00 each may be purchased in advance by contacting either: Shannon Murr at at healingheartsmd@yahoo.com or Crystal Tichnell at ctichnell@jhmi.edu. You do not have to be an attendee to purchase raffle tickets.

Scheduled activities include a silent auction of autographed sports memorabilia, a weekend condo in Ocean City Maryland, Longaberger Baskets, and other items. Raffle items include a $1,000.00 grand prize and gift cards to restaurants and grocery stores. There will be a DJ and dancing, as well as money wheels. Joining in on this event, or participating long distance by buying raffle tickets is a wonderful way to further the ARVD research that Johns Hopkins undertakes.

Healing Hearts was established in 2005 following the untimely death of Bonnie Milner who was only 26 years old. Her cause of death was ARVD. The mission of this charitable volunteer organization is to promote an awareness of ARVD and to raise funds to help support the Johns Hopkins Heart Institute's ARVD research program. Through this mission approach, Healing Hearts hopes to honor the legacy of a devoted daughter and beloved best friend.

To date, over $50,000.00 in research funds has been raised due to this group's efforts to coordinate events and activities. Those who have ARVD, and those who support others with ARVD, benefit from the fund raising efforts. Other past scheduled events have included a guest bartending event, an August (3rd annual) golf tournament, and a scavenger hunt.

ARVD-ARVC-Info.com may be the first point of contact for many who have recently been diagnosed with ARVD. We, as a resource for learning to live with ARVD, significantly appreciate the Johns Hopkins ARVD project, their website, and the legacy of one young woman which provides monetary support for continued research.

Our thanks to Melissa Bush, one of the nine founding members of Healing Heart, for updating us on the above information. To learn more about Healing Hearts visit HealingHeartsMD.org.

By MICHELINE LONG
Published: December 27, 2008

NEWS UPDATE

A BRIEF FROM DR. FRANK MARCUS, AND COMMENTARY

Dr. Frank Marcus, Professor Emeritus at the University of Arizona, has been researching ARVD since the 1970s. He has goals to carry on his valuable investigations which have long provided professionals and the ARVD community with the answers they have sought. In the meanwhile, Dr. Marcus has written us to report some of the most important ARVD news in 14 years.

As a note to our readers who are not already aware, Dr. Marcus was not only the Principal Investigator of the NIH funded Multidisciplinary Study of Right Ventricular Dysplasia, but he was also the director of the Task Force Criteria modification committee.

Dr. Marcus has reported the submission of a manuscript describing the suggested modifications of the Task Force Criteria for diagnosing ARVD. The document was coauthored by Dr. Bill McKenna of London and 25 experts (see News Archive #3, November 18, 2007 Progress Report).

The original Task Force Criteria (TFC) for the diagnosing of ARVD was published in 1994. Due to the huge influx of information about ARVD over the last 14 years, modifications of the TFC became a necessity. Soon these modifications will be published in easily accessible medical journals.

After 2 conferences and 2 years of painstaking and meticulous work, the modification manuscript is nearly on the table for all to read. Submitted to an important US medical journal, a request was made that the manuscript be published simultaneously in an important European journal.

About the document, Dr. Marcus has emphatically stated:

"I think it is an important contribution and will aid physicians in making the correct diagnosis of this disease."

Patients looking for help need their disease recognized if they are to be appropriately diagnosed and treated. For those with ARVD, having their disease go unrecognized, undiagnosed, untreated and/or ill advised could mean sudden cardiac death or a progression into congestive heart failure. For those who have been misdiagnosed with ARVD when they actually have Sarcoidosis, it could mean missing out on a treatment which could assist in sparing their heart from a rapid decline leading to heart transplant.

An ARVD patient, long time medical professional, and the leader of an over 350 member online ARVD support group for 10 years, Pat O'Neil was asked what she thought about the importance of the TFC modifications that will arrive:

"Before commenting on the actual importance of the particular modifications, I would like to see what they are. Will these modifications result in a more stringent or less stringent criteria for the diagnosis of ARVD. Are there actual measurements and values to some of the testing? Are there changes in the testing?"

"Well, there were no criteria prior to 1994. You have to start somewhere, no matter how imperfect the beginning may be. After that, you revise as more information is gained. The '94 criteria were absolutely instrumental in getting this disease diagnosed and recognized."

In further news Dr. Marcus mentioned:

"The multicenter NIH grant that provided support for our work from 2001 to 2008 has now expired. The increase in our knowledge of ARVD has been exponential in part due to the research we have done. There are now 7 genes identified. There is some experimental and clinical evidence that vigorous exercise may make the disease worse. It is possible that early treatment with drugs that decrease the force of contraction of the heart such as beta blockers, if given in early childhood may prevent the clinical expression of the disease or if given later may retard the disease. Also, new diagnostic techniques such as immunoflorescense in a myocardial biopsy may be definitive in making the diagnosis.

Our multicenter group is applying to the NIH for a grant to study this and other aspects of ARVD. We are planning to submit a grant by July 1, 2009 and hopefully to receive funding by April 30, 2010."

According to Dr. Marcus, the assistance of his long time associate, ARVD research nurse Kathy Gear, is critical to the continuance of the above mentioned research. Ms. Gear's experience and expertise is necessary for analyzing the data. Funding of at least $70,000 will be needed between July 1, 2009 and April 30, 2010 if this particular research is to be supported.

ARVD research relies largely upon private donations. Funding from individuals and foundations is essential. Researchers are available and willing to press forward in learning that which those affected by ARVD want to know. Please be a part of research. Consider making a large donation toward this analytic research or contact a foundation that you know would be generous in doing so. Click here to learn more about Dr. Marcus and get the contact information for sending your donations.

ARVD-ARVC-Info.com wishes to thank the private individuals, foundations and NIH, all of whom helped to make the TFC conferences and the resulting modifications a possibility. Additionally, our deep gratitude goes to the physician and scientist investigators who have long served the ARVD community with their knowledge, dedication, and time. Physicians and patients around the globe will benefit for many years to come.