Saturday, March 31, 2018

Article Review (2012) - Amyloid diseases of the heart: Current and future therapies

It looks like I did not begin 2018 with one post per month, but maybe I can still finish the year with a total of 12 to get the average up to one per month. Since my last article review was published in August of 2016, I should probably start doing those again. I have not yet reviewed all the ones listed on the resources page and I have also found a few more that are not listed there. So this blog post will be my first article review in 18 months.

Before beginning the article review I thought I would mention that the XVIth (16th) International Symposium on Amyloidosis was recently held in Japan, and there were a couple of posters shown that were related to fibrinogen amyloidosis. One of the posters discussed the results of a small cohort of AFib patients (6) in Portugal who received kidney transplants. Although I have only seen a low-resolution picture of that poster, I suspect the results were mixed and showed rapid recurrence of amyloid in some of the transplanted kidneys, as we have seen in many of the articles I have previously reviewed.

The other poster I am aware of was titled "Fibrinogen A alpha-chain (AFib) renal amyloidosis: Is liver transplant alone sufficient? A case report." I have not yet seen a high-quality photo of that poster either, but from what I could tell of the picture posted in one of the Facebook groups, the case report was regarding the person with AFib who received a liver-only transplant at Mayo Clinic in March of 2017. The poster gave some data on this patient as recently as four months after the transplant, and it definitely showed improvement in kidney function. If I get a more readable version of that poster I will present some of that data in a future blog post.

The last bullet point in the Conclusions section of this poster was "Further studies are needed to assess long-term outcomes as well as the appropriate timing of the procedure during the course of the disease." Unfortunately there are only two patients available to study as far as we know, with one being the patient discussed in this case report and the other one being the patient who received a liver-only transplant in July of 2010. Hopefully earlier diagnosis and genetic testing of family members will lead to more AFib patients pursuing liver-only transplants in the near future.

Now to the article review . . .

Title: Amyloid diseases of the heart: Current and future therapies (1)

Authors: Dubrey, S. W. and Comenzo, R. L. (Hillingdon Hospital, Middlesex, UK; Tufts Medical Center, Boston, MA, USA)

Journal: QJM: An International Journal of Medicine (July 2012)

Abstract:

Amyloid diseases in man are caused by as many as 23 different pre-cursor proteins already described. Cardiologists predominantly encounter three main types of amyloidosis that affect the heart: light chain (AL) amyloidosis, senile systemic amyloidosis (SSA) and hereditary amyloidosis, most commonly caused by a mutant form of transthyretin. In the third world, secondary amyloid (AA) is more prevalent, due to chronic infections and inadequately treated inflammatory conditions. Much less common, are the non-transthyretin variants, including mutations of fibrinogen, the apolipoproteins apoA1 and apoA2 and gelsolin. These rarer types do not usually cause significant cardiac compromise. Occurring worldwide, later in life and of less clinical significance, isolated atrial amyloid (IAA) also involves the heart. Heart involvement by amyloid often has devastating consequences. Clinical outcome depends on amyloid type, the extent of systemic involvement and the treatment options available. An exact determination of amyloid type is critical to appropriate therapy. In this review we describe the different approaches required to treat this spectrum of amyloid cardiomyopathies.

Here is a link to the article: http://qjmed.oxfordjournals.org/content/105/7/617.long

After an introduction to the effects of amyloid on the heart and the methods of treatment, the article then has specific sections for each of the types of amyloidosis mentioned in the abstract. I will not cover any of those sections other than fibrinogen in this review.

The Fibrinogen Amyloidosis section of this article begins by stating nine fibrinogen mutations causing amyloidosis have been identified to date. (As of 2018, the number of mutations is 15 according to the data at amyloidosismutations.com.) It then presents some general information about fibrinogen amyloidosis we are very familiar with, such as the usual presentation being nephropathy leading to kidney failure if left untreated. It then mentions kidney transplantation as a treatment option, which usually leads to rapid recurrence of amyloid in the transplanted kidney.

In the section on combined liver and kidney transplantation for fibrinogen amyloidosis, the article mentions a study of nine patients in which six survived with good results. There is also a mention that a liver-only transplant may be an option to prevent progression of the disease to other organs. It does state that no patient has undergone a combined liver and heart transplant for AFib.

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There is not really any new information in this article that has not been covered in previous articles. We know fibrinogen amyloidosis initially affects kidney function, but in the later stages of the disease it can affect other organs such as the spleen, liver and heart. But I am aware of only one documented case of significant cardiac involvement in a patient with fibrinogen amyloidosis. That case was described in a 2008 article in the New England Journal of Medicine, which I reviewed in the blog on January 6, 2014. Oddly enough, that 2008 NEJM article was not listed among the references for this 2012 article for some reason.



=====Monthly Blog Status Update=====

As of January 31, 2018:

Total posts: 182 (1 in January)

Total pageviews: 82,800 (~1600 in January)

Email subscribers: 14 (unchanged)

Total number of countries that have viewed the blog: 145

No new countries viewed the blog in January.

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=====Monthly Blog Status Update=====

As of February 28, 2018:

Total posts: 182 (0 in February)

Total pageviews: 84,700 (~1900 in February)

Email subscribers: 14 (unchanged)

Total number of countries that have viewed the blog: 145

No new countries viewed the blog in February.


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Citation:

(1) Dubrey SW, Comenzo RL. Amyloid diseases of the heart: current and future therapies. QJM. 2012;105(7):617-631.

Tuesday, January 30, 2018

Happy New Year!!!!!!

Welcome to 2018 everyone. In keeping with my tradition, there are six exclamation points in the title since this is my sixth Happy New Year post in the history of this blog.



Here is what happened with the blog in 2017:

  • 8 new blog posts were written. (Down from 11 in 2016)
  • No new articles were reviewed.   :-(
  • 13 additional countries visited the blog, bringing the total to 145.
  • The blog received 13 spam comments in 2017, two of which complimented me on my excellent use of colors in the design of the blog.

The big news in the world of fibrinogen amyloidosis this year, which I mentioned in the December 31, 2017 post, is that another liver-only transplant for fibrinogen amyloidosis was performed in March of 2017.

In personal news, my problem with anemia that was being investigated in 2016 is definitely behind me, and I remain asymptomatic as of August of 2017. The really big non-medical news for me in 2017 was a move from Texas to North Carolina in June. That kept me rather busy and was a handy excuse to keep from spending much time on the blog, so now that we are settled in I can hopefully get back to publishing an article monthly or almost monthly.



=====Monthly Blog Status Update=====

As of December 31, 2017:

Total posts: 181 (1 in December)

Total pageviews: 80,900 (~5800 in December, thanks to another spike of ~4500 in one day from Israel)

Email subscribers: 15 (unchanged)

Total number of countries that have viewed the blog: 145

No new countries viewed the blog in December.
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Sunday, December 31, 2017

Charlotte Support Group Meeting: November 18, 2017

End-of-year greetings, loyal blog readers. In this post I have some exciting news in the world of fibrinogen amyloidosis, followed by a report of a local support group meeting, some interesting data I recently gathered, and finally the oh-so-exciting monthly blog stats.

First, the exciting news. In November, shortly after I returned from the hereditary amyloidosis support group meeting in Chicago, I learned that another liver-only transplant for fibrinogen amyloidosis occurred in March of 2017 at Mayo Clinic. As far as I know, this is only the second liver-only transplant ever for fibrinogen amyloidosis, with the first one occurring in 2010. The most recent transplant recipient is a female in her early 50s who initially presented with proteinuria in August of 2015. She is currently doing very well post-transplant. The outcome of this case will be very important to patients in a similar position in the future, since this transplant occurred relatively early in the progression of the disease. I may have some more to say about this particular case in the near future as part of a larger discussion about organ transplants for fibrinogen amyloidosis.

On Saturday, November 18 I attended the amyloidosis support group meeting in Charlotte, North Carolina. But David, don't you go to the Dallas support group meetings? Well, not any more since we moved to North Carolina this summer. The closest support group meeting to me now is in Charlotte, and currently those are held once per year. At this meeting there were two local doctors from Levine Cancer Institute, and Dr. Eli Muchtar from Mayo Clinic in Rochester. I think there were around 45 people in attendance at this meeting, and almost all patients had AL or ATTR. I think there were one or two patients with localized amyloidosis (including the facilitator), and I was the only one with a rare hereditary type.

Now, the interesting data I recently gathered has to do with the number of other people I have been in contact with who also have fibrinogen amyloidosis. I first became aware of fibrinogen amyloidosis when my mother was diagnosed in 2010, and I started this blog in 2012, so I've been in contact with many patients with AFib through the blog and various other web sites over the past seven years. But I did not realize how many until I started going through some old emails and consolidating that information. I will use the term "kindred" here instead of "family." (People in the same kindred are biologically related, whereas people in the same family can be related biologically or by other means such as marriage or adoption.) Not counting my own kindred, I have been in contact with people from 12 other kindreds in which at least one person has been diagnosed with fibrinogen amyloidosis. I believe seven of these kindreds are based primarily in the US and the other five are based primarily in the UK.

There is another large kindred in the UK (Scotland) I have not been in contact with but am somewhat familiar with because their story has been told in at least three separate articles on the internet (see below). You won't see the word "fibrinogen" in any of those articles, but some excellent detective work by somebody (not me) did uncover the fact that fibrinogen amyloidosis is the type this family has.

http://www.eveningtimes.co.uk/news/13271564.Help_beat_the_disease_that_killed_my_mum__aunt__uncle_and_grandfather/

http://www.dailymail.co.uk/news/article-3425394/Four-members-family-killed-genetic-condition-surviving-relatives-chance-suffering-too.html

https://www.sundaypost.com/news/scottish-news/one-by-one-our-family-is-dying-from-a-deadly-genetic-defect-as-survivors-agonise-over-test-choice/


On a separate note, I received an email this week announcing that the 2019 Hereditary Amyloidosis Support Group Meeting will be October 25, 26 and 27 in Chicago. So mark your calendars. (If you have a 2019 calendar.)

That's it for 2017. I'll see you all next year.

=====Monthly Blog Status Update=====

As of November 30, 2017:

Total posts: 180 (3 in November)

Total pageviews: 75,100 (~1300 in November)

Email subscribers: 15 (unchanged)

Total number of countries that have viewed the blog: 145

One new country viewed the blog in November:

Belize
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