Amyloidosis is a rare disease in which amyloid fibrils misfold and aggregate into toxic oligomers that build up extracellularly in the tissue [1]. It can affect different organs, most commonly the heart, kidneys, liver, spleen, peripheral nerves, and gastrointestinal tract [1,2]. There are different types of amyloidosis according to the nature of the misfolded protein. Immunoglobulin light chain amyloidosis (AL) and transthyretin amyloidosis (ATTR) are the main two types of amyloidosis that affect the heart [2,3]. The first results from abnormal plasma cell production of monoclonal light chain fragments that misfold, causing myocardial toxicity [2,4]. The latter results from the dissociation and misfolding of the transthyretin (TTR), the protein that transports thyroxine (T4) and retinol-binding protein (RBP) in the serum and cerebrospinal fluid [2,5]. Both forms together account for nearly 95% of all cardiac amyloidosis cases [2,3,6]. TTR is mainly produced by the liver (90%) and circulates as a homotetramer. The choroid plexus and retinal epithelium produce the remaining 10% [7,8]. Destabilization of the tetramer results in the dissociation and aggregation of amyloid fibrils, which then accumulate in the interstitial space of various organs, causing progressive loss of function [9,10]. Transthyretin amyloid cardiomyopathy (ATTR-CM) is a rare, progressively debilitating disease that occurs when TTR builds up in the myocardium along with the peripheral and autonomic nervous systems [10]. ATTR-CM often presents with progressive heart failure with right- and left-sided symptoms, complicated by arrhythmias, most commonly atrial fibrillation, owing to conduction abnormalities [10,11]. However, cardiac symptoms are often proceeded by musculoskeletal manifestation (e.g., carpal tunnel syndrome) [12]. There are two forms of ATTR-CM, hereditary and wild type. Hereditary ATTR-CM (ATTRv) is characterized by a single amino acid substitution caused by a point mutation in the TTR gene, located on the long arm of chromosome 18 [13,14]. The most common mutation in ATTRv-CM is V122I, present in African Americans at a prevalence of 3.4% [15]. The prevalence of the V122I mutation in non-African American descents is low or possibly under-estimated. Wild-type ATTR-CM (ATTRwt), previously termed senile cardiac amyloidosis (SSA), is a non-familial form of the disease that predominantly presents in elderly male patients [16,17]. Both ATTR-CM forms are associated with impaired survival rates. The median survival of untreated ATTR-CM is 2.5 years for ATTRv V122I and 3.6 years for ATTRwt [18]. ATTR-CM is usually misdiagnosed, particularly early in its course owing to non-specific symptoms and multi-system involvement [19,20]. Lately, ATTR-CM is increasingly being recognized in clinical practice as a result of increased disease awareness and enhanced diagnostic techniques. Echocardiography-measured strain indices, advanced magnetic resonance imaging modalities, including T1 mapping and extracellular volume evaluation, as well as bone scintigraphy provide the necessary tools for the non-invasive diagnosis of ATTR-CM [20]. Moreover, genetic testing is instrumental to confirm the diagnosis of ATTRv. A definitive diagnosis could be reached with the aforementioned non-invasive tools, yet endomyocardial biopsy (EMB) evaluation is recommended in cases where AL amyloidosis cannot be ruled out via serum analysis [21]. However, histologic differentiation between ATTR and AL amyloidosis cannot be based solely on the Congo red staining. There is a compelling medical need to develop therapies for ATTR-CM, being an incapacitative illness that is eventually fatal if left untreated [22]. For many decades, the treatment of ATTRv-CM consisted of liver transplantation to remove the source of misfolded TTR or combined liver/heart transplantation, besides symptomatic treatments or solely heart transplantation in advanced ATTRwt-CM [23]. After the positive results of the ATTR-ACT study [24], the United States Food and Drug Administration (FDA) and the European Medicines Agency (EMA) have granted tafamidis 61 mg capsules marketing authorization for ATTRv and ATTRwt-CM. 

2. Symptomatic Treatments

3. Supportive Therapy with Epigallocatechin-3-Gallate (Green Tea)