Mom has also begun to notice some signs of edema around her ankles and under her eyes. She had not thought of the puffiness around her eyes as being due to edema until she read the previous blog post, in which the patient initially presented with edema around the ankles and eyes. Hopefully she can talk to her new nephrologist about that and get them to remove more fluid during the dialysis sessions.
My update is regarding my annual physical exam I had this week. I am happy to report that I am still asymptomatic for fibrinogen amyloidosis. There was no proteinuria, my creatinine was 1.0, and my GFR was over 59. I really don't know what the right word is for how I feel right before getting the results of my lab work each year. I'm certainly not scared, probably because I already have a plan of action and I know what the next steps are likely to be. I will admit to being a little anxious to get the results each time, and I suppose there is some relief when everything looks good. But I don't get myself so worked up that I breathe a huge sigh of relief when the numbers are good. (Those of you who know me are well aware that I don't get myself worked up over much of anything.) Perhaps this is just the normal anxiety people feel when they know they have a genetic mutation for a disease but they cannot predict if or when things will start happening. Anyway, that was some free introspection for my loyal readers out there, and for my future self. ("Hey David, remember that blog post from 2014 when you said you weren't scared because you have a plan of action?")
Today's article under review focuses on amyloidosis of the heart. Since cardiac involvement is much more prevalent with other types of amyloidosis than it is with fibrinogen amyloidosis, this article only briefly mentions fibrinogen amyloidosis. But I think it is good to know this article is out there just in case you do have cardiac involvement, or to offer it to people with other types of amyloidosis who have or suspect they may have cardiac involvement. (I did that within this past week, actually.)
Title: Amyloid Heart Disease (1)
Authors: Rodney H. Falk, Simon W. Dubrey (Harvard Medical School, Boston, MA; Hillingdon Hospital Uxbridge, United Kingdom)
Journal: Progress in Cardiovascular Diseases (2010)
The systemic amyloidoses are an uncommon group of disorders characterized by the extracellular deposition of amyloid in one or more organs. Cardiac deposition, leading to an infiltrative/restrictive cardiomyopathy, is a common feature of amyloidosis. It may be the presenting feature of the disease or may be discovered while investigating a patient presenting with non-cardiac amyloidosis. In this article we review the features of cardiac amyloidosis and its varied manifestations. The need for a high index of suspicion and the critical importance of precise biochemical typing of the amyloid deposits is stressed in light of recent advances in therapy which can, when appropriately used, significantly improve prognosis.
Here is a link to the PDF if you would like to follow along: http://brighamandwomens.org/Departments_and_Services/medicine/services/cvcenter/Amyloidosis/Images/AmyloidReview.pdf
As I mentioned at the top of this post, this will be a rather short review, especially considering the length of the article (12 pages plus three pages of references). This article is very detailed in its descriptions of how cardiac amyloidosis affects the heart and how it is treated. I could not do it justice even if I did take the time to read it thoroughly and make sure I understand at least the basics. So I think what I will do is simply give the outline of the article based on the section headings, but only discuss a few things along the way. The first paragraph of the article is a very broad overview of amyloidosis. It mentions Congo red staining, types of amyloidosis, and organ involvement. Then it starts discussing heart involvement in particular. In the text below, section headings from the article are in bold or bold italics.
Amyloid heart disease: general overview
If a person is diagnosed with amyloidosis before cardiac symptoms develop, cardiac involvement is usually detected fairly quickly. (I would consider that good news for someone known to have fibrinogen amyloidosis, since amyloidosis should be suspected with any signs of heart abnormalities.) But if amyloidosis is isolated to the heart, a diagnosis of amyloidosis usually occurs much later in the progression of the disease, if at all. This section includes a picture of a cutaway section of a heart severely affected by AL amyloidosis, clearly showing the thickened walls.
Cardiac amyloidosis is very similar to typical cases of congestive heart failure from a clinical standpoint, which is one reason the diagnosis is often missed. Doctors familiar with cardiac amyloidosis will always mention that the ejection fraction, a measure of what percentage of the blood coming into the heart is pumped out with each heartbeat, will often be normal in a heart affected by amyloid. The problem is the walls of the heart become thicker and stiffer, such that not as much blood is pulled into the heart when it expands. But the heart muscle itself is still strong enough to pump out the blood, so the ejection fraction is unaffected. The volume of blood pumped with each heartbeat is reduced, and that is the problem.
This section discusses the use of echocardiography, electrocardiography, and MRI in the diagnosis of cardiac amyloidosis. An interesting figure in this section is a series of electrocardiograms over a 10-year period from a patient with one of the ATTR mutations. The decline in voltage, indicated by the size of the spikes on the graphs, is clearly evident as the years progress.
Types of amyloidosis and heart involvement
Treatment of AL cardiac amyloidosis
Prevention of sudden cardiac death
Management of hereditary forms of amyloid heart disease
The section on hereditary amyloidosis focuses primarily on ATTR, although fibrinogen is mentioned a few times. The article does state that although fibrinogen amyloidosis almost exclusively affects the kidneys, rare cases with cardiac involvement have been reported. (It refers to one of the articles reviewed in the January 6, 2014 blog post.) Then in two different places the article states that the precursor protein for fibrinogen amyloidosis is produced in the liver, and liver-kidney transplantation has been successful.
The article states that the only specific treatment for amyloidosis due to transthyretin, fibrinogen or apolipoprotein mutations is organ transplantation. That was true at the time this article was written, but there are now some drugs available specifically for ATTR that have shown promising results in clinical trials. They were in early clinical trials at the time the article was published, but they are mentioned in the section on potential new therapies.
Senile systemic amyloid
This type of amyloidosis, which has nothing to do with becoming senile, is not due to a mutation at all. The word "senile" is used in this case to mean the second definition currently found at dictionary.com, which is: "of or belonging to old age or aged persons; gerontological; geriatric." It is a buildup of normal (wild-type) transthyretin to form amyloid deposits. About 25% of people over the age of 80 will have some amyloid deposits due to this, but it only becomes clinically significant when it affects the heart.
Potential new therapies
Secondary (AA) amyloidosis
AA amyloidosis is a buildup of amyloid in response to chronic inflammation. The amyloid is "secondary" to the inflammation. Only about 2% of AA amyloidosis cases have cardiac involvement.
Isolated atrial amyloid
This is a disease of the elderly caused by a buildup of a substance (atrial natriuretic peptide, or ANP) that is produced by the heart. The article states that up to 95% of people in their 80s will have this to some extent. So if you need something to worry about as you get older, I suppose this would be one of the more rational things to worry about, given its prevalence. You're welcome.
The summary is rather short, given the length of the article. I did notice one sentence in the summary regarding genetic testing that I thought was worth repeating here: "The identification of a patient with familial amyloidosis should lead to genetic counseling and, possibly, genetic screening of offspring, as new therapies, currently in clinical trials, may offer a way to prevent or delay the onset of the disease, and early detection in offspring may permit better disease management." So if someone tells you they are not interested in genetic testing because there is no treatment available other than an organ transplant, be sure to inform them that is no longer true.
Although this article does not really add anything to what we already know about fibrinogen amyloidosis from earlier articles, as I said earlier I think it is good to know this article is out there should the need arise, either for yourself or for someone else. It is also interesting to see some discussion of early clinical trials in an article published four years ago, even though they were not applicable to fibrinogen amyloidosis.
Speaking of clinical trials, the next article up for review is about a clinical trial that is applicable to fibrinogen amyloidosis.
(1) Falk RH, Dubrey SW. Amyloid heart disease. Prog Cardiovasc Dis. 2010;52(4):347-361.