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)


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:

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 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.


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.


=====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.



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