Cardiac amyloidosis is a subcategory of amyloidosis where there is depositing of the protein amyloid in the heart muscle and sometimes other organs or structures. Amyloid, a misfolded and insoluble protein, can become a deposit in the heart's atria, valves, or ventricles. These deposits can cause thickening of different sections of the heart, leading to decreased cardiac function and heart failure. The overall decrease in cardiac function leads to a plethora of symptoms. This multisystem disease was often misdiagnosed, with a definitive diagnosis only during autopsy. Advancements of technologies have led to earlier and more accurate diagnosis. However diagnosis may still be delayed as the disease may remain asymptomatic for years as amyloid deposits in the heart and other organs or tissues. Diagnosis may be delayed further as the disease may be misdiagnosed or confused for other more common conditions that cause heart enlargement (such as hypertension or other forms of heart failure).

Cardiac amyloidosis has multiple sub-types including light chain, hereditary transthyretin amyloidosis (due to genetic variants leading to misfolded transthyretin protein depositing in the heart and other tissues), and wild type transthyretin amyloidosis (where misfolded transthyretin builds up in heart muscle and other tissues, but with an absence of any mutations). The genetic variants responsible for hereditary transthyretin amyloidosis are inherited in an autosomal dominant manner, with the penetrance and prevalence in a population being dependent on the specific genetic variant and other factors. Being more common in older adults, the mean age of diagnosis for both the genetic variant and wild-type variant of transthyretin cardiac amyloidosis is between age 74–90.

One of the most studied types is light chain cardiac amyloidosis. Prognosis depends on the extent of the deposits in the body and the type of amyloidosis. New treatment methods are actively being researched in regards to the treatment of heart failure and specific cardiac amyloidosis problems.

The multiple subtypes of cardiac amyloidosis have varying epidemiological, diagnostic, and prognostic characteristics. Seventy five percent of transthyretin (TTR) cardiac amyloidosis is the wild-type and 25% if the inherited type.

This relatively rare form of cardiac amyloidosis occurs in an estimated six to ten cases per 1,000,000 people. This sub- type usually affects males over the age of 60 and is rapidly progressive. 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 tissue within the myocardium. Diagnostic tests includes serum and urine electrophoresis, laboratory testing for the determination of elevated levels of troponin and BNP, and ECGs showing low QRS voltages.

This type is caused by mutations of genes encoding amino acids of the transthyretin protein (TTR) causing transthyretin misfolding. Due to the multiple number of potential genetic causes (approximately 130 gene variants are known) the incidence of this form is variable in different populations, depending on the genetic variant. The vast majority of familial cardiac amyloidosis still present after the age of 60. A common mutation is the TTR gene mutation Val122Ile. It is estimated that 3.5–4% of African Americans in the United States have the Val 122lle mutation. This type of amyloidosis can be identified by genetic testing for protein mutation. Histological evaluation involves special stains being 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 characteristic apple green birefringence, and under plain light the deposits will appear a light salmon pink color. Familial amyloidosis usually causes a combination of heart failure and peripheral neuropathy or autonomic neuropathy. Whereas wild-type transthyretin amyloidosis usually causes heart failure, with neuropathy being more rare.

This type has no mutations in the TTR gene but TTR deposits still form in the heart and other tissues. Males are more commonly affected, at ages over 70 years. Carpal tunnel syndrome may form as well as amyloid deposits in the carpal tunnel causing compression of the median nerve. Amyloid deposits in the carpal tunnel or other ligaments (causing tendon rupture) or the spinal canal causing spinal stenosis may precede the development of heart failure by 10-15 years.

Wild type ATTR cardiac amyloidosis (and the genetic variant) can be diagnosed with cardiac nuclear scintigraphy to visualize amyloid deposits in the heart walls. Serum free light chains, serum and urine electrophoresis with immunofixation can rule out AL amyloidosis. If the diagnosis is unclear, a biopsy may be obtained. Biopsy with histological evaluation can rule out light chain and genetic testing can rule out familial subtypes. This type is often misdiagnosed. However, greater use of cardiac magnetic resonance has increased the rate of diagnosis. 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 wild-type variant.