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Types
The multiple subtypes of cardiac amyloidosis have varying epidemiological, diagnostic, and prognostic characteristics.

Light Chain (AL-CM)

This relatively rare form of cardiac amyloidosis occurs in an estimated 6-10 cases per 1,000,000 people. Pathogenesis of this form is due to the aggregation of immunoglobulin lambda light chains. These chains are created by an abnormal expansion of plasma cells. Over time, these light chains deposit into the interstitial space within the myocardium.

Familial (ATTR$M$R-CM)

Due to the multiple number of potential genetic causes the incidence of this form is variable. The vast majority of familial cardiac amyloidosis still present after the age of 60.

It is estimated that 3.5 - 4% of African Americans in The United States have the Val 122lle mutation.

Cardiac manifestations of the TTR mutation present more often in The United States.

For the diagnosis of familial cardiac amyloidosis to be made a biopsy with histological evaluation must be obtained. In this histological evaluation special stains are utilized to visualize the amyloid deposits. One such stain is Congo Red, which binds specifically to the amyloid deposits and can be characterized by various lighting methods. Under polarized light, the amyloid deposits while show pathognomonic apple green birefringence, and under plain light the deposits will appear a light salmon pink color.

Senile (ATTRwt-CM)

Similar to the other subtypes of cardiac amyloidosis, a biopsy is required for diagnosis. However, formal diagnosis of Senile cardiac amyloidosis is a diagnosis of exclusion. Biopsy with histological evaluation can rule out Light chain and Familial subtypes, leaving the diagnosis of Senile.

The severity of the disease tends to be less than the Light chain and Familial variants. This is due to the amount of time that it takes to accumulate the amyloid depositions being longer in the Senile variant.

Echocardiography

Echocardiography is a safe and noninvasive method that can be used to assess structural and functional disease of the heart.

An echo can be used to evaluate for prognosis of the disease, measuring the different strains within the hear. Cardiac amyloidosis produces specific alterations to the functionality of the heart. Echocardiography can be utilized to detect this specific pattern (relative preservation of the apical myocardium with decreased longitudinal strain in the mid and basal sections), which is 90-95% sensitive and 80-85% specific for cardiac amyloidosis.

 Cardiac Biomarkers

Elevations in these biomarkers are a sign of poor prognosis

There are 2 main cardiac biomarkers used in the assessment of cardiac amyloidosis, troponin and N-terminal proBNP. These markers have been incorporated into the various staging/scoring systems used by physicians to determine severity of the disease and prognosis.

Prognosis
Overall prognosis is dependent on the extent of cardiac dysfunction.

Light chain (AL-CM) Prognosis: Well treated light chain cardiac amyloidosis has a 4 year survival rate of around 90%. In patients that undergo stem cell transplant the average survival time increases to 10 years. Staging systems have been developed to stratify severity of the disease, including the Mayo Biomarker Stage.

 Familial (ATTRm-CM) Prognosis: Due to the extensive number of variables involved in this subtype, prognosis varies depending on the specific type of familial cardiac amyloidosis. Variables involve mutant vs wild type transthyretin mutation and age of onset of symptoms. In comparison to light chain amyloidosis, the familial subtype is slower to progress and has a more favorable prognosis. However, the Val 122lle mutation (most common cause of familial cardiac amyloidosis) has a 4 year survival rate of 16% with an average length of 26 months. A delay in recognition plays a major factor in this reduced survival rate.

Treatment
Cardiac amyloidosis: An underdiagnosed/underappreciated disease

Liver transplantation in transthyretin amyloidosis: Issues and challenges

Treatment info from the above paper.

The majority of treatment is aimed at preserving heart function and treating heart failure symptoms.

AL-CM Section:

Since the cause of this subtype of cardiac amyloidosis is the excessive production of free light chains, the major goal of treatment is the reduction in concentration of light chains. One of the major routes to decrease the production of these excess light chains is to kill the abnormal cells that are producing them. Chemotherapeutic agents such as melphalan or bortezomib can be used to kill off the abnormal cell line that is producing the free light chains. Following chemotherapy, a bone marrow transplant can be utilized to restore the normal cell lines. There are newer medications (ixazomib, carfilzomib, daratumumab, elotuzumab) under research for the treatment of multiple myeloma that can help to decrease the production of free light chains. New data suggests that orthotopic heart transplant followed by melphalan and stem cell transplant produces results similar to non cardiac amyloidosis indicated heart transplant.

ATTR section:

In recent years there have been developments in the treatment of Familial/Transthyretin cardiac amyloidosis including methods to suppress transthyretin production, stabilize amyloid fibrils, and medications that can destroy already existing fibrils.


 * Suppression of transthyretin production: liver transplantation and medications that decreases the activity of the transthyretin genes (patisiran and inotersen). In patients with familial transthyretin mutations, liver transplantation can provide the body with a source of normal transthyretin. By changing the source of transthyretin from a the original liver that contains the mutated transthyretin to a healthy liver, there will be no more production of the abnormal protein. However, liver transplant does not reverse the disease. The goal of liver transplant is to prevent additional amyloid deposition and prevent new symptoms/complications from happening. These medications bind to the mRNA of transthyretin and prevent the production of the transthyretin protein, thus decreasing the overall amount of transthyretin that can accumulate in the body.
 * Stabilization of abnormal transthyretin: There are medications that can stabilize the normally folded transthyretin, preventing misfolding and subsequent amyloid deposition. These medications include Tafamidis, the NSAID Diflunisal, and AG10. Tafamidis is a medication that binds to transthyretin and keeps it in its normal shape, stopping it from aggregating into amyloid fibrils. Diflunisal and AG10 work in a similar manner to Tafamidis in their ability to bind to and stabilize Transthyretin.
 * Destruction of existing amyloid fibrils: There are multiple medications that show amyloid destroying properties, Doxycycline, Tauro-ursodeoxy-cholic acid (TUDCA), and monoclonal antibodies.

The use of pacemakers (both right ventricular pacing and biventricular pacing) or implantable cardioverter defibrillators remains questionable in cardiac amyloidosis.

Diagnosis
Scintigraphy/Radionuclide Imaging

Technetium radionuclide scans can now reliably diagnosis cardiac amyloidosis, with certain scanning methods having greater than 99% sensitivity (but only 91% specific for amyloidosis). In this method of imaging, radiolabeled technetium is injected into the body where it binds to cardiac amyloid deposits. A subsequent scan is taken to determine where the tracer stays, therefore highlighting the amyloid deposition in the heart. This method allows for a noninvasive definitive diagnosis of cardiac amyloidosis (as in the past an endomyocardial biopsy was required)

American College of Cardiology Guidelines.
References: