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Breaking the Chain in Cardiac Amyloidosis

Rohan Goswami, MD, Director of Heart Transplant Innovation and Research, Mayo Clinic

Caitlyn Luce, Research Fellow, Division of Advanced Heart Failure and Transplant, Mayo Clinic

Cardiac amyloidosis is a significantly underdiagnosed disease that is a large contributor to poor prognosis of heart failure in the elderly population. As a result, the following information is crucial to consider when diagnosing a patient with advanced heart failure.

What is Cardiac Amyloidosis?

Cardiac amyloidosis is the buildup of misfolded proteins in cardiac muscle, known as amyloid fibrils. Amyloid fibrils are an umbrella term for any misshapen proteins. As a result, several types of cardiac amyloidosis result in the heart muscle's thickening and stiffening. This limitation of cardiac muscle function can result in advanced forms of heart failure when treated improperly.

Under Recognition of Cardiac Amyloidosis

Studies using the 2019 Medicare database have shown that an alarming number of autopsy reports of heart failure patients presented with undiagnosed amyloid built up in heart muscle, which may have contributed to worsening heart failure symptoms with improper treatment (Gilstrap et al, 2019). Further studies found that there was a median 22-month delay of diagnosis for cardiac amyloidosis following the initial hospitalization of heart failure patients (Bishop et al., 2018).

Prevalence Trends

The figure above represents the increasing prevalence rates of cardiac amyloidosis from 2004 to 2018, with a significant increase following 2006 (Gilstrap et al., 2019). As more individuals are diagnosed with cardiac amyloidosis, there are more individuals with restricted heart muscle movement. Hence, the increase of chains around the heart.

Diagnosing Cardiac Amyloidosis

The underlying cause of the underdiagnosis of cardiac amyloidosis is the overlapping of signs and symptoms of several other cardiovascular myopathies. Recent technologies, such as cardiovascular MRI (CMR) have allowed for the noninvasive detection of amyloid buildup in heart muscle. Other diagnosing modalities include low QRS voltages in electrocardiograms (ECG), cardiac biomarkers in blood tests, diastolic dysfunction in echocardiograms, and fibril detection in endomyocardial biopsy. Awareness of risk factors, such as male gender, African American ethnicity, elderly age, and genetic risks, along with these modalities hold the potential to enhance early detection, prevent plaque accumulation, and lower the severity of heart disease.


The buildup of plaque in cardiac muscle is an irreversible process. Early diagnosis and treatment are essential to slowing the progression of this fatal disease. Figures 2 and 3 represent the multisystem clinical signs and symptoms that in conjunction with cardiomyopathic and neurologic symptoms give rise to further amyloid evaluation (Nativi et al., 2021).

Following the recognition of multidisciplinary symptoms and signs from the various diagnostic modalities, the diagnostic pathway below represents an algorithm to confirm the diagnosis of cardiac amyloidosis and identify the correct type of amyloid depositions (Kittleson et al., 2023).

Novel therapies

Though there are few treatments for cardiac amyloidosis, recent therapy developments hold promises for preserving the functional capacity of patients with various forms of this fatal cardiomyopathy. Tafadamis remains one of the only U.S. Food and Drug Administration medications approved for the treatment of amyloid transthyretin cardiac amyloidosis (ATTR). This therapy slows the formation of transthyretin (TTR) fibril and cardiac plaque formation (Kittleson et al., 2023). Patisiran is a novel drug that is currently in the third phase of clinical trials and functions to inhibit the production of TTR via RNA interference (Maurer et al., 2023). The first human trial for in vivo gene editing took place in 2021 for single intravenous infusion of NTLA-2001. The gene editing therapy shows consistent reduction in serum TTR and indicates a potential therapeutic option for amyloid cardiomyopathy (Gilmore et al., 2021).

Healthcare costs

The high medication cost and limited access to amyloid specialists pose an economic burden to the healthcare system. Not only do patients experience a variety of financial implications, such as high out-of-pocket expenses and difficulty in prescription authorization. Our healthcare system misevaluates amyloidosis as a rare disease and thus mispriced several therapeutic drugs. If all ATTR cardiomyopathy patients were treated, annual healthcare spending is estimated to increase by over $30 billion (Kittleson et al., 2023). Given the effectiveness of such recently discovered therapies and increasing prevalence of amyloid cardiomyopathy, it is imperative to reconsider pricing and lower the burden on the economy and patient.


Cardiac amyloidosis is one of the most overlooked, undiagnosed, and treatable cardiovascular diseases (Rubin & Maurer, 2020). Despite its ability to be treated, it still serves as a common preexisting condition for heart failure patients that rarely gets discovered before it is too late. With the recent development of noninvasive diagnostics and physician awareness of the disease, the inclusion of cardiac amyloidosis in the initial workup of heart failure hospitalizations over the age of 65 could potentially revolutionize the heart failure mortality rate. The pathway for treatment is constantly evolving and shifting towards a more multidisciplinary approach, making the common goal of improving patient outcomes more attainable.


Banypersad, S. M., Moon, J. C., Whelan, C., Hawkins, P. N., & Wechalekar, A. D. (n.d.). Updates in Cardiac Amyloidosis: A Review. Journal of the American Heart Association, 1(2), e000364. Bishop, E., Brown, E. E., Fajardo, J., Barouch, L. A., Judge, D. P., & Halushka, M. K. (2018). Seven factors predict a delayed diagnosis of cardiac amyloidosis. Amyloid, 25(3), 174 179.

Gillmore, J. D., Gane, E., Taubel, J., Kao, J., Fontana, M., Maitland, M. L., Seitzer, J., O'Connell, D., Walsh, K. R., Wood, K., Phillips, J., Xu, Y., Amaral, A., Boyd, A. P., Cehelsky, J. E., McKee, M. D., Schiermeier, A., Harari, O., Murphy, A., Kyratsous, C. A., … Lebwohl, D. (2021). CRISPR-Cas9 In Vivo Gene Editing for Transthyretin Amyloidosis. The New England journal of medicine, 385(6), 493–502.

Gilstrap, L. G., Dominici, F., Wang, Y., El-Sady, M. S., Singh, A., Di Carli, M. F., Falk, R. H., & Dorbala, S. (2019). Epidemiology of Cardiac Amyloidosis–Associated Heart Failure Hospitalizations Among Fee-for-Service Medicare Beneficiaries in the United States. Circulation: Heart Failure, 12(6), e005407.

Kittleson, M, Ruberg, F. et al. 2023 ACC Expert Consensus Decision Pathway on Comprehensive Multidisciplinary Care for the Patient With Cardiac Amyloidosis: A Report of the American College of Cardiology Solution Set Oversight Committee. J Am Coll Cardiol. 2023 Mar, 81 (11) 1076–1126.

Oghina, S., Bougouin, W., B, ézard M., Kharoubi, M., Komajda, M., Cohen, -Solal Alain, Mebazaa, A., Damy, T., & Bodez, D. (2021). The Impact of Patients With Cardiac Amyloidosis in HFpEF Trials. JACC: Heart Failure, 9(3), 169–178.

Nativi-Nicolau, J. N., Karam, C., Khella, S., & Maurer, M. S. (2022). Screening for ATTR amyloidosis in the clinic: overlapping disorders, misdiagnosis, and multiorgan awareness. Heart failure reviews, 27(3), 785–793.

Rapezzi, C., Lorenzini, M., Longhi, S., Milandri, A., Gagliardi, C., Bartolomei, I., Salvi, F., & Maurer, M. S. (2015). Cardiac amyloidosis: The great pretender. Heart Failure Reviews, 20(2), 117–124. 9480-0

Rubin, J., & Maurer, M. S. (2020). Cardiac Amyloidosis: Overlooked, Underappreciated, and Treatable. Annual Review of Medicine, 71, 203–219.

Sepehrvand, N., Youngson, E., Fine, N., Venner, C. P., Paterson, I., Bakal, J., Westerhout, C., Mcalister, F. A., Kaul, P., & Ezekowitz, J. A. (2022). The Incidence and Prevalence of Cardiac Amyloidosis in a Large Community-Based Cohort in Alberta, Canada. Journal of Cardiac Failure, 28(2), 237–246.

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Author Bio

Rohan Goswami

Dr. Goswami is a Transplant Cardiologist practicing at Mayo Clinic in Florida. He is a graduate of the American University of the Caribbean School of Medicine and completed his internal medicine residency at Columbia University College of Physicians and Surgeons – Stamford Hospital, a cardiology fellowship at The University of Tennessee Memphis, and a Transplant Fellowship in 2017 at Mayo Clinic in Florida. He has a keen interest in clinically focused artificial intelligence research to improve outcomes in patients with advanced heart failure. He has published articles in the field of both heart transplantation and artificial intelligence, as well as presented at Ai4 in 2020 on the future impact of AI in healthcare and invited lectures at the International Society of Heart and Lung Transplantation in both 2021 and 2022. He looks forward to one day utilizing AI integration to prevent organ failure.

Caitlyn Luce

Caitlyn Luce recently graduated from the University of Florida with a degree in Biology and a minor in Health Science. She is currently applying to medical school while working as a Research Fellow in the Division of Advanced Heart Failure and Transplant at the Mayo Clinic in Jacksonville, Florida. My goals in research include embracing lifelong learning, providing holistic healthcare, minimizing health disparities, and contributing to humanity in medicine. I am eager to meet these goals as I continue to grow my research throughout medical school and future training.

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