Key Information
Cardiac amyloidosis is a type of amyloidosis that deserves special attention as organ involvement significantly worsens the prognosis. Cardiac amyloidosis can be grouped under three main headings: immunoglobulin light chain (AL) amyloidosis that is dependent on amyloidogenic monoclonal light chain production; hereditary Transthyretin (TTR) amyloidosis that results from accumulation of mutated TTR; and wild-type (non-hereditary) TTR amyloidosis formerly known as senile amyloidosis. Although all three types cause morbidity and mortality due to severe heart failure when untreated, they contain differences in their pathogenesis, clinical findings, and treatment. In this article, the clinical features, pathogenesis, diagnosis, and treatment methods of cardiac amyloidosis will be explained with an overview, and an awareness will be raised in the diagnosis of this disease.
DEFINITION and HISTORY
Amyloidoses are a group of diseases that exhibit heterogeneity. Their common feature is that they have accumulations of abnormal proteins that result in tissue and organ damage. Historically, the term “amyloid” (a normal amylous component in plants) was first suggested in 1838 by German botanist Matthias Schleiden (1external link, opens in a new tab). He named it “corpora amylacea”, describing the small round structures in the nervous system that give a characteristic color reaction (brown to blue) with sulfuric acid andiodine, which is typical for starch (2external link, opens in a new tab). In 1861, Dr. T. Grainger Stewart described the deposits in the kidney (in Bright’s disease) as a “waxy or amyloid form” (3external link, opens in a new tab). Pathologist John W. Budd was the first scientist to report one of the cardiac amyloidosis (CA) cases in the literature, saying, “Although primary amyloid disease of the heart is very rare, the cases reported in the literature show that hyaline material can accumulate in the epicardium, myocardium, endocardium, valves or walls of adjacent blood vessels” (4external link, opens in a new tab).
INCIDENCE
The reported incidence for CA is 18-55 per 100,000 person-years. In fact, its prevalence is difficult to determine precisely, because the disease is often overlooked as it often presents with non-specific symptoms (5external link, opens in a new tab). A population-based autopsy study suggests that 25% of people aged 80-85 years have cardiac amyloid deposition (6external link, opens in a new tab). The UK National Amyloidosis Center database report, which includes data on 11006 patients between 1997 and 2019, reports that the number of patients suffering from amyloidosis increased by 670% from 1987-1999 to 2010-2019 (7external link, opens in a new tab). Again, the same report emphasizes that the incidence of CA, which was less than 3% of all cases in the 1987-2009 period, increased to 14% in the 2010-2015 period and to 25% in the last 4 years. It is conceivable that this increased incidence may be the result of increased awareness of amyloidosis and diagnostic cardiac imaging.
CLINICAL FEATURES
The disease usually first presents with shortness of breath secondary to exertion, which is partly rapidly progressing and results in peripheral edema and/or ascites. Left ventricular diastolic dysfunction results in dyspnea. However, significant hardening of the auricles likely contributes to exertional dyspnea. The first signs of the disease include cardiac arrhythmias (atrial/ventricular) and heart block of varying degrees (8external link, opens in a new tab,9external link, opens in a new tab). Deposits in the atrium cause dysfunction, and thrombi can form even if the heart is operating in sinus rhythm. This causes thromboembolism to be seen as an early sign of the disease. If the clinician is not aware of the phenomenon of left atrial systolic dysfunction that is the source of neurological or systemic embolism, the disease can easily be overlooked (10external link, opens in a new tab). Electrical conduction disturbances in the heart due to amyloid deposition, embolic events, and syncope are some of the reasons for hospital admission for affected individuals. However, patients often come to the health institution with cardiogenic shock. In recent years, it can be said that awareness of cardiac dysfunction caused by amyloidosis has increased (11external link, opens in a new tab). In addition, it is reported that toxic infiltrative cardiomyopathy from cardiac amyloidosis is much more common than previously believed and is an underrecognized cause of diastolic heart failure in particular (12external link, opens in a new tab).