This post was developed as part of the Heart Failure Awareness Week 2021 Heart Failure Top Innovations Countdown. 

Submitted by Michelle M. Kittleson MD PhD, Director of Education in Heart Failure and Transplantation, Director of Heart Failure Research, Professor of Medicine, Department of Cardiology, Smidt Heart Institute, Cedars-Sinai @MKittlesonMD  

Drug classes for cardiac amyloidosis diagnosis and treatment

Cardiac amyloidosis is a condition where a protein the body produces naturally deposits in tissues throughout the body, including the heart, causing symptoms of shortness of breath and fatigue.  The protein can either be transthyretin or an immunoglobulin light chain.  While the condition of cardiac amyloidosis has been known about for hundreds of years, it has gained more attention recently because of important innovations in diagnosis and treatment. 

The symptoms can be nonspecific.  Not all patients have heart failure.  Some just have fatigue, and the key to the diagnosis is the other organs that can be involved, including the musculoskeletal system, gastrointestinal tract, and the nervous system.  So fatigue alone is not a red flag, but fatigue in conjunction with cardiac conditions such as atrial fibrillation or aortic valve disease; musculoskeletal conditions such as carpal tunnel syndrome or spinal stenosis; gastrointestinal conditions such as nausea, diarrhea, and weight loss; and nervous system issues such as orthostatic hypotension (lightheadedness with standing) or neuropathy (numbness, tingling, pain in the hands and feet), suggest that amyloidosis may be the underlying cause of all the symptoms. 

The diagnosis cannot be made with routine blood and imaging tests.  Your treating clinician needs to have a high index of suspicion based on your symptoms to order the appropriate tests to make the diagnosis.  The diagnosis of the transthyretin form (transthyretin cardiac amyloidosis or TTR amyloidosis) can be made noninvasively with a series of blood and imaging tests.  The diagnosis of the immunoglobulin light chain form (light chain cardiac amyloidosis, or AL amyloidosis) requires blood tests and a biopsy of an affected organ. 

Making the diagnosis is important because there are multiple advances in therapy to help patients feel better and live longer, and the therapies are very different for TTR amyloidosis vs AL amyloidosis.  Most important, the earlier a diagnosis is made, the more successful the treatments may be. 

The exciting therapeutic advances for TTR amyloidosis include medications that prevent the TTR protein from depositing in the body and medications that prevent the liver from synthesizing the abnormal TTR protein.  The medication that prevents the TTR protein from depositing in the body is called tafamidis.  It stabilizes the transthyretin protein to prevent it from forming amyloid fibrils that deposit in the heart muscle.  In a landmark clinical trial, patients who received tafamidis for 30 months were less likely to die or be hospitalized for heart failure.  The medications that prevent the TTR protein from being synthesized are patisiran and inotersen.  Both are forms of RNA that interfere with the liver’s ability to produce the transthyretin protein from the RNA code.   In clinical trials, these two medications prevent progression of neuropathy though it’s not yet clear if they impact the cardiac involvement from transthyretin amyloidosis. 

The exciting therapeutic advances for AL amyloidosis include medications that prevent production of abnormal immunoglobulin light chains, including bortezomib and daratumumab.  Bortezomib is in a class of medications calls proteosome inhibitors and daratumuab is a monoclonal antibody that targets immune cells. Both medications target the plasma cells so that production of the harmful immunoglobulin light chains is blocked. 

To be an active partner in your health, it’s important to ask your health care professional to consider this diagnosis if you have the combination of symptoms outlined above, as making the diagnosis can lead to therapies that can improve your quality of life and survival.