Cardiac amyloidosis is a subcategory of amyloidosis where there is depositing of the protein amyloid in the cardiac muscle and surrounding tissues. 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. The overall decrease in cardiac function leads to a plethora of symptoms. This multisystem disease was often misdiagnosed, with a corrected analysis only during autopsy. Advancements of technologies have increased earlier accuracy of diagnosis. Cardiac amyloidosis has multiple sub-types including light chain, familial, and senile. 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.
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 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.
Familial (ATTRm-CM) This type is caused by mutations of proteins involved in amyloid formation, including transthyretin (TTR), fibrinogen, apolipoprotein A1, or apolipoprotein A2. 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. 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. 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 deposit 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. Familial amyloidosis symptoms are centered around neuropathological and cardiac problems. Cardiac manifestations of the TTR mutation present more often in The United States.
Wild-type (ATTRwt-CM) This type is considered the wild-type mutation which leads to the development of TTR deposits. It usually affects males over 70 years with the manifestation of carpal tunnel syndrome. 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. 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 Senile variant.
Symptoms and signs
Symptoms of cardiac amyloidosis are a combination of heart failure and amyloid deposition in various other organs. Amyloid deposition in the heart causes restrictive diastolic heart failure that progresses to systolic heart failure.
Cardiac manifestations include: Dyspnea on exertion Peripheral edema and ascites Pericardial effusion Arrhythmias (secondary to disruption of the normal electrical system of the heart) Atrial arrhythmias (such as atrial fibrillation) First/second degree heart blocks Syncope Elevated neck veins and jugular venous pressure Myocardial ischemia/Angina (secondary to amyloid deposition in the small arteries of the heart) Myocardial oxygen demand is increased in patients with cardiac amyloidosis, regardless of changes to coronary perfusion.