Amyloidosis in Cardiology Practice: A Race Against Time

Panelists

Program Overview

• CA is an underappreciated and underdiagnosed cause of heart failure (HF)
• It is attributable to extracellular deposition of fibrillary proteins

Epidemiology and Clinical Presentation of Amyloidosis With a Focus on Cardiac Manifestations

CA: Epidemiology ^[1]

• There are 2 pathophysiologic substrates for CA ^[2]
  • Immunoglobulin light-chain (AL) amyloidosis (also known as primary amyloidosis): the amyloid fibrils are composed of immunoglobulin light chains, produced by a clonal population of plasma cells in the bone marrow
  • Transthyretin-related amyloidosis (ATTR): misfolded monomers or dimers of the normally tetrameric transthyretin (TTR) protein, a transport protein synthesized in the liver
  • 2 types of ATTR:
    • Hereditary ATTR (hATTR; also known as familial ATTR or mutant ATTR [ATTRmt])
    • Wild-type ATTR (ATTRwt, also known as senile systemic amyloidosis)
• ATTRmt is caused by more than 100 mutations in the TTR protein that are inherited in an autosomal dominant fashion and can affect individuals of all ages
• ATTRwt is predominantly described in older men

Identifying Populations at Risk: Older Adults -- THAOS Registry ^[3]

• THOAS is a global registry of ATTR (ATTRmt and ATTRwt)
• ATTRwt most common form in US adults

Prevalence of ATTRwt: Almost Doubles Every 5 Years From Age 75 ^[4]

• Myocardial uptake of bone tracers (bone scintigraphy) has emerged as useful tool for the early detection of ATTR
• Myocardial uptake in bone scan is very prevalent with aging

Identifying Populations at Risk: Patients With HFpEF ^[5]

• ATTRwt is an underdiagnosed cause of HFpEF
• ATTRwt can be diagnosed noninvasively with scintigraphy

Identifying Populations at Risk: Patients With Severe AS Undergoing TAVR ^[6]

• Cardiac ATTR is prevalent in 16% of patients with severe calcific aortic stenosis (AS) undergoing transcatheter aortic valve replacement (TAVR)
• It is associated with a severe AS phenotype of low-flow low-gradient with mildly reduced ejection fraction (EF)

Identifying Populations at Risk: Afro-Caribbean Patients With HF ^[7]

• In Afro-Caribbean patients, ATTR V122I is an underappreciated cause of HF
• Cardiomyopathy is often misattributed to hypertension

Most Common Symptoms of CA ^[8]

• Patients with CA present with multiple nonspecific symptoms
• A high suspicion index is required to facilitate early diagnosis
• Carpel tunnel (CT) syndrome (especially bilateral), spinal stenosis, and atrial fibrillation (especially ablation refractory) are 3 red flags for amyloidosis in cardiac patients

Diagnostic Tools: ECG ^[9]

• Low voltage is classically reported as an electrocardiographic (ECG) finding in CA
• Low voltage is a relatively late finding in CA and may not be useful for early identification

Diagnostic Tools: Cardiac MRI ^[10]

• Global transmural or subendocardial late gadolinium enhancement (LGE) is most common, but focal patchy LGE is also observed in CA
• Focal patchy LGE may not be labeled as CA

Diagnostic Tools: Echocardiography ^[11]

• Echocardiography is the cornerstone for the diagnosis and management of patients with CA
• Increased left ventricular (LV) wall thickness, often with a restrictive filling pattern, is a classic feature of advanced CA
• Misdiagnosis as true LV hypertrophy (LVH) is frequent

CA: Survival ^[12,13]

• HF in ATTR progresses slowly, whereas HF in AL amyloidosis progresses rapidly
• AL amyloidosis is a medical emergency
• Echocardiographic results cannot distinguish between AL amyloidosis and ATTR

Patient Journey: Survey of Patients With AL Amyloidosis ^[1]

• CA is often misdiagnosed
• Delayed diagnosis has significant consequences for patients