What is cardiac amyloidosis?

From the Guidelines

Cardiac amyloidosis is a serious condition characterized by the accumulation of abnormal proteins called amyloids in the heart tissue, leading to stiffening of the heart and impaired function, with two main types: light chain (AL) amyloidosis and transthyretin (ATTR) amyloidosis, which can be either hereditary or age-related. This condition is more common than previously thought, with ATTR amyloidosis being more prevalent, especially in older adults and certain populations such as African Americans with the Val122Ile variant 1. The symptoms of cardiac amyloidosis include shortness of breath, fatigue, swelling in the legs, irregular heartbeat, and chest pain, and diagnosis typically involves blood tests, heart imaging (echocardiogram, cardiac MRI), and sometimes tissue biopsy 1.

Key Characteristics of Cardiac Amyloidosis

• The accumulation of amyloid fibrils in the interstitial space between cardiac myocytes, leading to cellular injury and impaired compliance 1
• Two main types: light chain (AL) amyloidosis, caused by abnormal antibody proteins from bone marrow cells, and transthyretin (ATTR) amyloidosis, which can be either hereditary or age-related 1
• Symptoms include shortness of breath, fatigue, swelling in the legs, irregular heartbeat, and chest pain
• Diagnosis typically involves blood tests, heart imaging (echocardiogram, cardiac MRI), and sometimes tissue biopsy 1

Importance of Early Diagnosis and Treatment

• Early diagnosis is crucial as the condition progressively damages the heart muscle, leading to heart failure if left untreated 1
• Treatment depends on the type but may include chemotherapy for AL amyloidosis, medications like tafamidis for ATTR amyloidosis, and supportive care with diuretics to manage fluid buildup 1
• Heart transplantation is occasionally considered for severe cases
• A team-based approach to care, involving physicians and advanced-practice providers across a wide array of specialties, is essential to optimize outcomes in patients with cardiac amyloidosis 1

From the FDA Drug Label

VYNDAQEL and VYNDAMAX are prescription medicines used to treat adults with cardiomyopathy of wild-type or hereditary transthyretin-mediated amyloidosis (ATTR-CM) to reduce death and hospitalization related to heart problems. The FDA drug label does not directly define cardiac amyloidosis. However, it mentions transthyretin-mediated amyloidosis (ATTR-CM), which is a type of cardiac amyloidosis.

• Key points about transthyretin-mediated amyloidosis (ATTR-CM) include:
  • It is a condition treated by VYNDAQEL and VYNDAMAX.
  • The treatment aims to reduce cardiovascular mortality and cardiovascular-related hospitalization 2, 2, 2. No direct conclusion can be drawn about the definition of cardiac amyloidosis from the provided drug labels.

From the Research

Definition and Pathophysiology

• Cardiac amyloidosis is a restrictive cardiomyopathy that results from the deposition of misfolded light chain or transthyretin proteins in cardiac tissue 3, 4.
• It is characterized by the accumulation of amyloid fibrils in the extracellular space, leading to restrictive cardiomyopathy and heart failure 5, 6.
• The disease has two main subtypes: transthyretin cardiac amyloidosis (ATTR-CA) and immunoglobulin light chain cardiac amyloidosis (AL-CA) 5.

Clinical Manifestations

• Cardiac amyloidosis can display an array of clinical manifestations, from impaired relaxation of the ventricular myocardium to severe restrictive disease or even progressive systolic heart failure 3.
• It is a systemic disease that can result in multiorgan dysfunction, making treatment challenging 3.
• Patients with cardiac amyloidosis often present with unexplained diastolic heart failure, and earlier diagnosis is crucial for implementing disease-altering therapy 6.

Diagnosis and Management

• Advances in diagnostic cardiac imaging, such as nuclear scintigraphy and cardiac magnetic resonance imaging, have improved early detection and disease management 5, 7.
• Artificial intelligence has emerged as a diagnostic tool for cardiac amyloidosis, improving accuracy and enabling earlier intervention 7.
• Management strategies include volume control, specific pharmacotherapies like tafamidis, and addressing arrhythmias and advanced heart failure 7.
• Treatment options have expanded to include novel therapeutics that disrupt specific stages of amyloidogenesis, and several therapeutics have been recently approved 4.