Fibromuscular Dysplasia: The Registry and Results
Registry data regarding patients with fibromuscular dysplasia (FMD) was recently published in Circulation.1Cath Lab Digest talks with Pam Mace, RN, FMD patient, Executive Director, Fibromuscular Dysplasia Society of America, Rocky River, Ohio, about the registry and her long experience with FMD.
Can you describe fibromuscular dysplasia?
Fibromuscular dysplasia (FMD) is a non-inflammatory vascular disease that causes the artery to form abnormally, leading to areas of stenosis in the artery. FMD can also cause aneurysms, dissections, and total occlusion of the artery. There are different classifications of FMD. The most common is called “medial fibroplasia”. On angiography, you see what looks like a string of beads; this is the typical form of FMD in adults. The most common form of FMD in children is called “intimal fibroplasia”.
Is the artery itself structurally different, or is it biologically or chemically different?
FMD causes abnormal cell growth in the arterial wall, but we don’t know enough about it. Since the majority of the patients are women, the thought is that hormones may play a role. There is no known cause or cure for FMD.
FMD typically occurs in women?
Yes, about 90% of the patients are women.
That being said, men and children are diagnosed with the disease. The youngest child diagnosed that I am aware of was a 9-day-old male. With children, there seem to be just as many young boys with the disease as young girls, but we are not sure why that is.
Is FMD present at birth?
That is a good question; we do not know. FMD can occur at any age, but the majority of the patients are diagnosed between the age of 20 and 60. I was diagnosed at the age of 37 with sudden onset hypertension, bilateral carotid and a left vertebral dissection. We don’t know the trigger that causes some people to be diagnosed as children and the majority as adults, or why some patients never have any symptoms at all.
Once FMD is discovered, how is it treated?
Treatment for FMD depends on which artery is affected and the severity of the disease. Some cases can be totally asymptomatic. If FMD is in the carotids, for example, and if the patient is not experiencing any or mild symptoms, then the doctor may choose to simply put the patient on an antiplatelet. Angioplasty may be necessary for patients who experience transient ischemic attacks (TIAs) or stroke, and in cases of a dissection or aneurysm, stenting may be required.
For someone with hypertension and FMD, medication alone may work. Others may require balloon angioplasty (stenting is typically not required) and in severe cases or with an aneurysm where endovascular therapy is not an option, surgical revascularization may be required.
If disease is found in one artery, does that mean it is localized there or could it be potentially elsewhere in the body as well?
In many patients, FMD affects more than one vascular bed. The thought used to be that 70% of FMD cases were renal, but now we are finding the statistics show something very different. The data recently published from the FMD Patient Registry shows that we have just as many cerebrovascular cases as we do renal. FMD can appear in any artery in the body, but the two most common arteries affected in adults are the renal and the carotids.
With children, it is different — it seems to be more renal and mesenteric.
What is the rate of occurrence of FMD?
The first case of FMD was diagnosed in 1938, and up until now, there has really been no interest in the disease or research being done, as the disease was thought to be very rare. The only way that we have been able to look at the incidence of the disease is through several studies done in the past. One study, by Harris and McCormick in 1971, did 1,862 renal angiograms on potential renal donors. Nearly four percent (3.8%) were incidentally found to have FMD. There was also another study on renal donors and the findings were very similar.
In 2009, The Wall Street Journal wrote an article on FMD, “The Rare Disease That Isn’t.”2 The WSJ journalists took those statistics and put them against the population, and estimated that 5 million Americans could have FMD.
Today, we are fortunate to have better technology, like computed tomography, magnetic resonance imaging, and even angiography. It wasn’t until the Fibromuscular Dysplasia Society of America (FMDSA) came along that FMD was even considered worth studying. Initially, the society’s goal was to raise awareness of the disease. We had no idea that so many people would end up getting diagnosed.
As an organization, we are contacted almost daily by newly diagnosed patients from all over the world. FMDSA is a small organization. We have tried to set up support groups in different states, and have identified support people in different countries, to help us respond to the increasing number of patients contacting us. Outside of the United States, the majority of patients that contact us are from Canada and Australia.
Can you tell us more about the registry and how it was designed?
Dr. Jeff Olin, Professor of Medicine at Mount Sinai School of Medicine and Director of the Mount Sinai Vascular Medicine and Vascular Diagnostic Laboratory, is the chair of our medical advisory board. Several years ago, we discussed what would be necessary to do in order to find answers about FMD. One of the first things we discussed was setting up a patient registry. We began working with a University of Michigan entity called MCORRP, the Michigan Clinical Outcomes Research and Reporting Program. MCORRP has experience with other registries, such as for aortic dissection. The FMD registry is coordinated through MCORRP and data entry began in 2009. The registry allows for the collection of FMD cases from different centers around the U.S., and will give us a better understanding of the disease, its epidemiology, how patients present, clinical characteristics, and how to manage and treat FMD. Participating centers have a data form with questions about medical history, presenting symptoms, imaging and treatment. All of that data is then entered into a database and analyzed. Currently, 12 centers are participating (Figure 1), and to date, 586 FMD patients have participated in the registry.
How long do you plan to run the registry?
As long as we can fund it, and until we can find answers. We are hoping to make it an international registry and to continue adding more centers. One of the 12 centers recently added was Children’s Hospital of Philadelphia. We hope to start learning more about children, because the majority of the centers are dealing with adults and medial FMD. By adding Children’s Hospital of Philadelphia, we are going to be able to study children with intimal disease.
The registry’s first report was recently published in Circulation.1 What did it show?
One thing we learned (and something FMDSA as an organization had become aware of years ago) is that cerebrovascular disease is at least as common as renal disease in FMD patients. The most common presenting symptoms for patients were hypertension, headaches, pulsatile tinnitus (swishing noise in the ear), dizziness, cervical bruit, and neck pain. About 17% of the patients had an aneurysm and 20% a dissection somewhere in the body. Almost six percent of the patients were asymptomatic at the time of their diagnosis.
Only 7.3% of the patients reported a confirmed family member also affected with FMD. Family history showed that 53% had a family history of stroke, 23% a family history of aneurysms, and 19% had a family history of sudden death.
Years ago, my FMD story aired on a TV show called “Mystery Diagnosis.” It mentioned pulsatile tinnitus as a symptom, and I can’t tell you how many patients saw that episode, said they had that noise in their ear, wondered if they could have FMD, and then went on to be diagnosed with FMD, just based on that swishing noise in the ear.
How are research efforts being funded?
To date, the majority of our funding has come from our patients. FMDSA has never received a government grant or a grant from the National Institutes of Health to help us fund any of our efforts. It is only in the last couple years that doctors have started to really pay attention to this disease, mostly because of various conferences FMDSA attends, raising awareness of the disease, and published articles (one of which was published by Cath Lab Digest in 20083).
I was asked to speak at a Vascular Interventional Advances (VIVA) conference in 2009, and when I was done, VIVA presented me with a check to our organization for $50,000. It was a very emotional moment for me. While I was thrilled for the money, more importantly to me, it signified that the medical community was finally standing behind us. Because before that, it felt like all of our efforts were an uphill battle. I think we are there and the medical community is on board at this point, and things are going to start moving a lot faster.
FMD is being diagnosed more and is getting more attention. Several FMD programs and FMD clinics have opened up in the U.S., and we are being contacted with increasing frequency by people who are hoping to open one as well. Groups in Europe and Canada are focusing on opening centers. The centers here in the U.S. can be found at http://www.fmdsa.org/patient_support/fmd_clinics/. I would like to give Dr. Heather Gornik credit for starting the first formal FMD program at The Cleveland Clinic in 2008. She has been instrumental and if not for her efforts, I am not sure the other clinics would have developed.
Figure 5. VIVA presented Pam Mace, Executive Director of FMDSA, with a check for $50,000 in 2009.
What are your long-term goals for the registry?
We hope to continue adding centers and make it an international registry. Hopefully, we will be able to better understand the epidemiology of the disease, clinical characteristics, and management. FMD is a lifelong disease, and most patients go in yearly for checkups, but again, there are no set protocols for treating the disease, so it depends on the physician. Hopefully, one day we will be able to establish protocols.
To view some of the other research projects happening in the U.S., including several bio repositories and research at the NIH, please visit the FMDSA website (http://www.fmdsa.org/fmd_info/research_studies).
It sounds like the society, FMDSA, has been an epicenter for supporting research efforts in the United States.
Yes, FMDSA is the only organization in the world with a focus on FMD and we have been working hard since 2003. We are really encouraging collaboration around the world. Dr. Jackie Saw in Vancouver, Canada is researching sudden coronary artery dissection and FMD. Last year, Dr. Jeff Olin and I flew to Paris and met with researchers from France whose efforts are being led by Pierre-François Plouin, MD, PhD. This past April, I was invited to London to speak at the European Society for Hypertension with several European physicians during a two-hour symposium on FMD. It is not just in the U.S., but around the world that awareness is being raised about the disease, and researchers are starting to work together.
What is your own history in the cath lab, with FMD, and with FMDSA?
I was diagnosed with FMD in 2000 after dissecting my bilateral carotid and left vertebral arteries. From my dissections, I had formed pseudoaneurysms. I also have bilateral renal FMD.
About the time of my diagnosis, I had moved to Chicago and I worked in a cath lab there. I learned a great deal about stenting and angiography as I was actually going through the process myself of needing stents. I ended up having my first stent, a Multi-Link Tetra, placed in my left carotid artery in 2001. In 2002, I had a Jo-Med stent placed in my right carotid artery.
When I was diagnosed in 2000, there was not much information out there. A small support group had been started with FMD patients, and eventually, the Fibromuscular Dysplasia Society of America (FMDSA) was formed in 2003. I came along several months after it was founded, was asked to join the board, stepped up as the president, and then became executive director. My 19-year nursing career has helped to open up a lot of doors. I was able to get the disease listed on the National Organization for Rare Diseases and then get it recognized by the National and American Stroke Associations as a cause of stroke.
My background is actually emergency room and critical care, so I was able to talk with many physician groups/organizations and encourage them to get involved and start helping us. In 2006, I flew to Belgium to meet with several genetic doctors to discuss what we should be planning to do, and that meeting led to current research that is being done in Rotterdam.
Any final thoughts?
We have come a long way! But there is still a lot that remains both unknown and misunderstood about FMD. Recently, there have been several articles published on sudden coronary artery dissection and FMD, and we have family members contacting us about losing a loved one to sudden death where FMD is being diagnosed in the atrioventricular (AV) or sinoatrial (SA) node. It is clear that we still have a lot to learn.
It is interesting that FMD was first diagnosed in 1938 and no substantive research into the disease was conducted until FMDSA came along in 2003. There was an article that came out of Yale in 1979 about the genetics of fibromuscular dysplasia, authored by Dr. Alan Rushton.4 I contacted his group (including Dr. Kenneth Kidd) in 2006, and was told, “We know no more about that disease now than we did 30 years ago.” It was such an amazing moment for me. Had research been done into this disease decades ago, my outcome in 2000 probably would have been very different. The FMD Patient Registry and the work that is being done now will benefit patients for generations to come.
Pam Mace can be contacted at email@example.com.
Save the date! The FMDSA Annual Meeting in Cleveland, Ohio, takes place on May 18, 2013. Learn more at fmdsa.org.
- Olin JW, Froehlich J, Gu X, Bacharach JM, Eagle K, Gray BH, Jaff MR, Kim ES, Mace P, Matsumoto AH, McBane RD, Kline-Rogers E, White CJ, Gornik HL. The United States registry for fibromuscular dysplasia: results in the first 447 patients. Circulation 2012 Jun 26;125(25):3182-3190.
- Burton TM. The 'rare' disease that isn't. Wall Street Journal. June 27, 2009. Available online at http://online.wsj.com/article/SB124605981966763611.html. Accessed July 13, 2012.
- Meyers KEC, Sharma N. Fibromuscular dysplasia in children and adolescents. Cath Lab Digest 2008;16(6). Available online at http://www.cathlabdigest.com/articles/Fibromuscular-Dysplasia-Children-a.... Accessed July 13, 2012.
- Rushton AR. The genetics of fibromuscular dysplasia. Arch Intern Med 1980 Feb;140(2):233-236.