Advanced Heart Failure

Amyloid Heart Disease Yaser Nemshah, MBBS, 1,2 Alex Clavijo, MD, 1 and Gyanendra Sharma, MD, FACC, FASE 1 1. Medical College of Georgia at Augusta University, Augusta, GA; 2. King Fahad Medical City, Riyadh, Saudi Arabia

Abstract Cardiac amyloidosis is a group of disorders that develop secondary to the deposition of misfolded proteins in the heart. It can occur in isolation or as part of a systemic disease and can be inherited or acquired. Amyloid light chain (AL) and amyloid transthyretin (ATTR) are the two main forms of amyloid proteins that can infiltrate the heart. With the increased use of advanced imaging techniques and protocols, the recognition and diagnosis of cardiac amyloidosis, especially ATTR, has become easier. New therapies intended to improve survival and quality of life in patients with cardiac amyloidosis are emerging. This article provides an up-to-date review of cardiac amyloidosis.

Keywords Cardiac amyloidosis, immunoglobulin light chain amyloidosis, transthyretin amyloidosis, cardiovascular MRI, echocardiography, scintigraphy Disclosure: The authors have no conflicts of interest to declare. Submitted: July 2, 2018 Accepted: July 24, 2018 Citation: US Cardiology Review 2018;12(2):113–8. DOI: https://doi.org/10.15420/usc.2018.5.1 Correspondence: Yaser Nemshah, 1120 15th Street-BBR 6518, Augusta, Georgia 30912, USA. E: ynemshah@gmail.com. Gyanendra Sharma; E: gsharma@augusta.edu

Amyloidosis is a heterogenous group of disorders that develops secondary to the deposition of abnormally folded proteins, amyloid fibrils, in the extracellular space. Amyloidosis is classified according to the type of the precursor protein that results in the formation of amyloid fibrils. It can be inherited or acquired, and can involve multiple organs, including the heart. Amyloidosis that involves the heart is referred to as cardiac amyloidosis (CA) in this review.

Epidemiology Immunoglobulin light chain amyloidosis (AL amyloidosis) and transthyretin amyloidosis (ATTR amyloidosis) are the two most common forms of systemic amyloidosis. AL amyloidosis is a rare disease, with an incidence of approximately 9–15.2 cases per million person-years.1,2 However, autopsy studies have shown that acquired ATTR amyloidosis (formerly called senile cardiac amyloidosis) is not uncommon, affecting 10–25 % of people aged over 80 years, and 50  % of those over 90 years.3–5 The prevalence of ATTR amyloidosis is higher in the US than in Asia.5 CA has a higher prevalence in patients with severe aortic stenosis. Recent published data showed that 13.9–16 % of patients who undergo transcatheter aortic valve replacement have CA.6,7 The median survival of people with AL and ATTR amyloidosis is 211–330 days and 961–2,250 days, respectively.8,9

immunoglobulin while ATTR is derived from misfolded unstable liverbased transthyretin protein. ATTR can be hereditary caused by a mutation in the ATTR gene; known as mutant ATTR (ATTRm). It can also be acquired; the acquired type is known as ATTR wild-type (ATTRwt) and used to be called senile cardiac amyloidosis. Amyloid fibrils can be deposited in any structure in the heart. They can be found in the atria and ventricles, and involve the pericardium, myocardium and endocardium. The valves, the conduction system and the coronary vessels can be affected as well. Depositions vary from small nodules to complete replacement of the cardiac tissue.11 High-grade deposition(>50 % of the myocardium) and frequent (90  %) vascular involvement have been noted in hearts with AL amyloidosis compared with low-grade deposits and infrequent (4  %) vascular involvement in the ATTR type.12 Myocardial deposition can lead to stiff ventricles early in the course of the disease, resulting in diastolic dysfunction and usually followed by left ventricular systolic dysfunction.13,14

Clinical Manifestations The impact of cardiac amyloid deposition can range from being asymptomatic to a rapidly fatal disease. CA tends to be evident clinically when the deposition exceeds 10 % of the myocardium.12 Early recognition can be important to reduce the disease burden and improve survival.

Pathophysiology An amyloid fibril protein is defined as a protein that is deposited as insoluble fibrils, mainly in the extracellular spaces of organs and tissues as a result of sequential changes in protein folding resulting in a condition known as amyloidosis.10 In humans, there are 31 extracellular precursor proteins that can lead to amyloid fibril formation.10 Among those, the AL and ATTR amyloid proteins are those that traditionally involve the heart. AL is an amyloid protein derived from light chain

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AL amyloidosis can affect any organ except the central nervous system leading to variety of symptoms. Outside the heart, it can result in the development of carpal tunnel syndrome, nephrotic syndrome, autonomic neuropathy, malabsorption syndromes, hepatomegaly, macroglossia (27.2 %), and periorbital purpura (12.5 %). Fatigue and weakness are the most common presenting symptoms. AL cardiac amyloidosis is unusual in isolation (3.9 % of patients).15

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