Section 1: Excerpts from the Original Query
Section 2: About Those Who Responded
Section 3: Responses to the Query

This document addresses a set of questions asked by ARVD diagnosed people about the subject of exercise.  Following are the questions, an introduction to those who responded, and the responses.

August 15, 2002

Dear doctor, scientist, researcher

... we remain in close contact with hundreds of ARVD patients across the globe.  It is for this reason that I come to you.

Recently the issue of strenuous/competitive exercise has AGAIN arisen as a topic of conversation in our ARVD support group.  This issue has CONSISTENTLY arisen for 3 years, and particularly because:

a.) we have been warned that strenuous/competitive exercise "could" progress ARVD AND that recent ARVD genetic discoveries give an explanation for "how" it could do so.

b.) we have a GREAT MANY ARVD support group friends who were once competitive athletes OR those who took GREAT interest in a vigorous exercise routine.

Without ceasing, the patient community has grappled with the question "So what exercise, if any, can I do?"  ARVD patients seriously seek to heed the advice of researchers, while remembering that they were once taught to exercise for the health of their hearts.

To my knowledge, patients who have once strenuosly/competitively exercised did so within a certain sport (tennis, racquetball, fencing, marathons, running, jogging, swimming, weight lifting, mountain climbing, etc.), in a gym (stair master, weight lifting, treadmill etc.) and/or with the thought of keeping their heart rate up to a certain height for a certain length of time.

The ARVD patient community is NEARLY BEGGING for answers from those who can offer them wisdom for their situation.  What can they really do for exercise and for their health, without further compromising the health of their hearts.  Here are two questions that were recently received from patients:

Patient 1:
"I know that we have all been warned about the dangers of strenuous exercise, but 'strenuous' is a relative term.  Does anyone know the experts' definition of strenuous?"

Patient 2:
"I'm also very curious about this sort of statement. I was wondering if anyone knows of any sort of guidelines that we should follow, such as getting your heart rate above a certain number or not doing certain activities. I know it has been discussed quite a bit in the group, but where do we cross the line between exercising enough to maintain a "healthy" heart and doing too much? What exactly is the cause of the disease progressing (if it is known) when exercising?"

You are receiving this e-mail because you are known to those of us who have been diagnosed with ARVD as one who is respected in its treatment/study/research.  We realize that all patients are different, but many patient's doctors have told them to go about life as they once did...yet they are held back by research information they are reading.  The ARVD patient group LONGS for a smattering of opinions from which they can make considerations for their lives and their hearts.

Experts on the subject of ARVD responded to the above query.  Much could be written about the accomplishments of each, as well as the great deal of caring and friendship they have offered to the ARVD diagnosed community.  An Internet search on any of their names will lead to further information about their work in general, as well as their work with ARVD.  As a very brief introduction to those who responded, and in the order of their responses, the following is submitted.

• Dr. Gian Antonio Danieli; Professor of Human Genetics, Medical School, University of Padua

Dr. Danieli has been working as one of the most integral parts of ARVD genetic research for more than 8 years. He is a member of the respected ARVD research team in Padua, Italy. In late 2001, Dr. Danieli gained additional time to serve his passion for research after stepping from the very busy position as head of his department at the University of Padua. Within the last two years, Dr. Danieli and his group at the lab in Padua, have been responsible for two of the present three ARVD gene identifications. In sincere care of those his efforts serve, Dr. Danieli is active in research and writing about ARVD. He also works closely with those of the NIH Multidisciplinary Study of Right Ventricular Dysplasia, as well as other ARVD study groups.

http://telethon.bio.unipd.it/ARVDnet/arvd_in_padua.html

• Guy Fontaine MD PhD; Director of Research, Bicetre, Paris, France

Dr. Fontaine's pioneer work in the field of electrophysiology led to the discovery and naming of ARVD in approximately 1977.  As a result, the first clinical descriptions of this condition were published.  Since that time, over 25 years, Dr. Fontaine has researched and studied this disease.  His continuing scientific observations have increased the body of knowledge on ARVD.   His deep regard for and treatment of those diagnosed with it, has expanded the clinicians' ability to understand and assist the ARVD patient.  Dr. Fontaine's years of lectures have educated professionals and patients around the globe.  Adviser to patient and doctor alike, he remains in full time research, collecting and analyzing data, as well as seeing patients.

http://www.arvd-arvc-info.com/WebX?233@@.6858d68b!enclosure=.6858d68c
 

• Dr. Frank Marcus; Professor of Medicine, University of Arizona, Tucson, Arizona

Dr. Marcus, a respected cardiologist of many years, became intrigued with cardiac arrhythmias in 1979.  Taking a year sabbatical, Dr. Marcus joined Dr. Fontaine in Paris.  They worked together on the study of ARVD which had previously been barely discussed in English literature.  Throughout 20 years of determined ARVD research, Dr. Marcus has meticulously reviewed and considered the cases of those diagnosed with ARVD.  He has confirmed or denied the diagnoses of many, compassionately treated patients, and counseled many others who have shared their records with the International ARVD registry.  Currently, Dr. Marcus is the Principal Investigator (PI) and Director of the NIH Multidisciplinary Study of Right Ventricular Dysplasia. 

http://www.arvd.org

• Dr. Hugh Calkins; Professor of Medicine and Director of the Johns Hopkins ARVD project

Dr. Calkins has been the concerned and energetic director of the Johns Hopkins ARVD project since 1999.   His personal contact with patients in sharing a 2nd opinion, his invitation of exceptional guests to the yearly patient conferences he has hosted, and the subject matter he has chosen for the ever increasing number of new initiatives begun by this project reflect Dr. Calkins' well rounded consideration of the ARVD diagnosed life.  Not only does Dr. Calkins show a dedication to discovery of this disease, his efforts also reveal a compassion for that which affects the patient from the moment of diagnosis through day to day living.  Dr. Calkins also holds the position of Co-PI and Director of the NIH Multidisciplinary Study of Right Ventricular Dysplasia.

http://www.arvd.com

NOTE: The contributors in this document are listed on the following webpage:
http://www.arvd.com/doctors/

From: Dr. Gian Antonio Danieli
Professor of Human Genetics, Medical School, University of Padua

"A preliminary remark...
ARVD is a genetic disease characterized by degeneration of myocardial tissue, almost exclusively in the right ventricle. The appearance of  the damaged heart tissue in ARVD is very similar to that observed in skeletal muscles in individuals affected with inherited muscular dystrophies.  We learned from muscular dystrophies that degeneration is a progressive phenomenon; it may be accelerated by several factors, among  which [are] viral infections and exercise.

The open question is: Why the right ventricle? 

My hypothesis is the following. Right ventricular wall is thinner and more extensible that the left one.  When the body starts to be engaged in a heavy exercise (e.g. running), among first physiological modifications there is the increase of the volume of circulating blood. While this novel situation doesn't affect left ventricle (which thickness "resist" to volume overload), right ventricle free wall is stretched.

If myocardial tissue have an intrinsically (i.e. genetically) defective response to stretch, a damage would be generated almost exclusively in the right ventricle. It is interesting to notice that in ARVD the ventricular free wall is severely damaged, while interventricular septum is usually spared.

So far three genes involved in ARVDs have been identified. In two cases (Naxos disease and the novel ARVD8) the defect is in desmosomes (subcellular structures involved in cell-to-cell adhesion); in ARVD2 the defect is in regulation of intracellular calcium concentration. It is known that the tissue stretch acts on inter-cellular connections and produces influx of calcium into the cells. Increase of intracellular calcium concentration triggers apoptosis (cellular deaths), which was indeed observed in ARVD hearts.

Therefore, as far as we know, "defective stretch" hypothesis is plausible. I guess that the the more frequent would be the stretch of the ventricular wall, induced by volume overload, the more rapid could be the progression of the disease. 

QUESTION: "So what exercise, if any, can I do?"

RESPONSE: "There is not a general rule. Only the Cardiologist who follows up the patient might give him/her the proper reply" 

QUESTION: "I know that we have all been warned about the dangers of strenuous exercise, but 'strenuous' is a relative term.  Does anyone know the 'experts' definition of strenuous?"

RESPONSE: "In my view, any physical exercise which implies a sudden volume overload to the right ventricle might have adverse effects on ARVD myocardium. Sports like tennis, racquetball, fencing, marathon, running, jogging, swimming, weight lifting, mountain climbing, are risky.

The meaning of 'strenuous' is 'requiring effort.' In general, each person is able to judge if a given activity requires effort. However, effort may be precisely measured by a cycloergometer, during cardiological assessment.

In some cases (e.g. in ARVD2 patients) polymorphic tachyarrhythmias start at given level of effort, variable from person to person." 

QUESTION: "I'm also very curious about this sort of statement. I was wondering if anyone knows of any sort of guidelines that we should follow, such as getting your heart rate above a certain number or not doing certain activities. I know it has been discussed quite a bit in the group, but where do we cross the line between exercising enough to maintain a 'healthy' heart and doing too much?"

RESPONSE: "There is a general consensus about what to do to maintain an 'healthy' heart:  a healthy individual should avoid smoking, reduce stress, control his blood pressure and cholesterol level and do regular and moderate exercise (walking).  I doubt that exercise other than walking could help in maintaining a 'healthy' heart in ARVD patients."

QUESTION: "What exactly is the cause of the disease progressing (if it is known) when exercising?"

RESPONSE: "See the hypothesis in my introductory remarks."

From:  Guy Fontaine MD PhD
Director of Research, Bicetre, Paris, France
AND
From:  Dr. Frank Marcus
Professor of Medicine, University of Arizona, Tucson, Arizona

Strenuous, competitive exercise increases the amount of blood returning to the right pumping chamber of the heart (the right ventricle) resulting in stretching of the thin walled right ventricle.  In ARVD the right ventricular free wall is partially replaced by fat and the right ventricular contraction is weaker than normal.  With an increased load on the right ventricle during exercise, the right ventricle will dilate more easily than a normal heart.  If the dilatation is frequent and repetitive as with strenuous exercise the right ventricle remains dilated and enlarged.  A dilated right ventricle predisposes to abnormal rapid heart rhythms from this chamber.  These rhythms are known as ventricular tachycardia or ventricular fibrillation.  Under these circumstances the heart can beat so fast that the individual with ARVD may faint; rarely it can result in sudden death.  Therefore, strenuous and particularly competitive sport activities can be dangerous.  However, engaging in sports that do not require major effort and that are not sustained or involve competitive activities is acceptable.  These include walking, intermittent jogging, bicycling, swimming and other recreational sports.

Once again, competitive or sustained strenuous exercise is not good for the heart in a patient who has ARVD.  It should be emphasized that athletic sports activity do not improve heart function, even though it improves skeletal muscle function.  Serious rapid heart rhythm abnormalities are more common with competitive sports activities in patients with ARVD.  The above advice is based on personal observation and is well documented in the literature.  The above cautions should not prevent you from enjoying a regular active life.

Update note from Dr. Frank Marcus: April 14, 2006

"Since our replies in 2002, there have been several new genes found in patients with ARVD. Of particular interest is that one gene, plakophillin 2, has been implicated in up to 30% of patients with a familial history of this disease. The gene defects all relate to abnormal proteins that bind the heart cells together. I use the term "defective glue" binding the heart cells. This information reinforces the recommendation that competitive exercise should be avoided not only in those affected with the disease, but also in family members who have the gene defect but have no clinical evidence of structural or functional abnormality of the heart.

Experimental evidence to reinforce the concept that strenuous, repetitive exercise can worsen this condition was obtained by exercising mice who had the gene defect of ARVD. The right hearts of these mice were considerably larger that those with the gene defect who were not exercised. This data has not yet been published. The definition of the amount of exertion that an individual with this disease can do safely is not known.

The recommendation to avoid participating in competitive sports or those that require prolonged duration of strenuous exercise is still the best advice.

Frank Marcus"

From:  Dr. Hugh Calkins
Professor of Medicine and Director of the Johns Hopkins ARVD project

ARVD is a mysterious disease which presents many unanswered questions.  One of these concerns the apparent relationship between exercise and the development of symptoms that lead to the diagnosis of ARVD. It is striking how many patients with ARVD are extremely athletic.  This link between exercise and ARVD may result from the increased pressures experienced by the heart during exercise. This may cause a right ventricle which is genetically susceptible to the development of ARVD to begin to dilate. Once the ventricle dilates the walls thin, leading to more dilation. Basic research has shown that increased "load" on the heart can alter ionic currents even under normal situations. It therefore would make sense that a genetically susceptible right ventricle may experience even greater changes in the ionic currents that control myocardial contraction. The link between exercise, increased load on the right ventricle, and the development of ARVD is also consistent with the discovery that at least some of the genes responsible for ARVD are involved in cell to cell adherence.

With that background I will try to address the question at hand but, I must caution everyone that there is extremely little hard data.   As was pointed out in one of the questions, there is a big range of activity levels between the activities of daily living and being a marathoner.  I generally recommend that patients avoid competitive athletics.  If exercise is not a big part of their life, then things like walking, golf, etc. seem reasonable.  If they love running, I will usually suggest limited runs 3 - 4 times each week (i.e. 3-5 mile runs not 10 mile runs and not at peak or near peak heart rate.) It is important to remember, that we do not have all of the answers.  I look forward to working with the ARVD community to answer these, and other questions.

Update note from Dr. Hugh Calkins: July 18, 2007

"Since I last commented on exercise and ARVD new data has emerged to support a link between exercise and the development of ARVD. This data results from the identification of multiple disease causing mutations of the desmosome - which is the part of the heart that links the heart cells together. There is also new data from animal (mouse) models suggesting that exercise plays a role in the development of arrhythmias.

We now recommend that patients with ARVD limit their activities to low level activities such as walking and golf. We discourage weight lifting, running, and swimming - particularly at high levels and for long periods of time.

Some patients choose to continue to participate in athletics until they receive their first ICD shock. This generally results in an immediate decrease in activity level. We are interesting in following patients who do and do not choose to exercise to determine if there are differences in the rate of development of arrhythmias or other evidence of progression of ARVD.

We also are working hard to unfold the many mysteries of ARVD.

Hugh Calkins"