**Abstract**

Cardiac amyloidosis is a protein-folding disorder mostly caused by abnormal deposition of either transthyretin proteins or light chain (AL) proteins, into one or more organs, including the heart. The main cardiac manifestations are right ventricular heart failure and arrhythmias. Extracardiac symptoms usually precede cardiac symptoms and are evident several years before the development of symptomatic cardiac problems. The prognosis is poor without appropriate management. Non-invasive evaluation with multi-imaging modalities has allowed earlier diagnosis, particularly when used in combination with monoclonal gammopathy evaluation. Management will vary depending on the subtype of amyloidosis. It consists of supportive treatment of cardiac-related symptoms, pharmacological treatment that targets amyloid fibrils formation and deposition, thus attacking the underlying disease, and addressing the management of extracardiac symptoms to improve the patients' quality of life.

**Keywords:** cardiac amyloidosis (CA), transthyretin cardiomyopathy (ATTR-CM), wild type-ATTR (wtATTR), hereditary (variant, mutant) transthyretin cardiomyopathy (hATTR, vATTR), systemic (AL) cardiac amyloidosis (AL-CM), atrial fibrillation (AF), heart failure (HF)

### **1. Introduction**

Amyloidosis is an infiltrative disorder primarily caused by extracellular tissue deposition of amyloid fibrils. It occurs when the misfolded protein assembles with similar proteins to form oligomers, which circulate in the blood and deposit as highly ordered fibrils, in the interstitial space of target organs [1]. These deposits are comprised of insoluble low molecular weight protein subunits ranging from 5 to 25 kD leading to the outlined systemic disease [2]. Up to date there are at least 25 different human and 8 different animal amyloidogenic proteins identified [1]. Tissue infiltration occurs in many organs such as kidney, liver, autonomic nervous system, and heart. However, >95% of cardiac amyloidosis is secondary to immunoglobulin light chain amyloidosis (AL) and transthyretin amyloidosis (ATTR) [3].

It was previously understood that cardiac amyloidosis was a rare and fatal disease. Nevertheless, with the emergence of advanced cardiac imaging studies as well as the availability of new pharmacological treatment for transthyretin amyloidosis and increased awareness of the disease among physicians, and better guidance for accurate diagnosis there has been a marked increase in diagnosis of this previously underrecognized medical condition. Nevertheless, despite increased awareness of the disease, sociodemographic disparities in diagnosis and management of cardiac

amyloidosis exist, thus leading to a delay in treatment and increased disease severity at time of diagnosis within certain sociodemographic groups [4, 5].

In this chapter, we will discuss in detail the clinical presentation, identification process, and implications for early detection of cardiac amyloidosis to improve patient outcomes. Additionally, we will discuss new emerging therapeutic approaches and the importance of socioeconomic disparities within the disease.
