While I was enjoying my weekly phone call with my grandma, our conversation inspired me to get my blog on. She had just picked up her medication for her rare heart disease, and as she casually mentioned it, I realized many people may be unaware of this condition and thought it would make for a good post. It’s called cardiac amyloidosis. Now y’all bear with me for a second because it gets a little wild.
Cardiac amyloidosis belongs to a broader group of disorders called systemic amyloidosis, which happens when certain proteins in the body misfold and clump together as amyloid fibrils. These fibrils settle in the extracellular space and disrupt normal organ function. Within the body there are over 30 different proteins that have the potential to misfold like this. Depending on which protein goes rogue, the disease presents itself in different ways.
Among these amyloid-forming proteins, two types commonly infiltrate the heart:
- Immunoglobulin light chain (AL) amyloidosis
- Transthyretin (ATTR) amyloidosis
When these proteins accumulate in the heart, they create an infiltrative cardiomyopathy. The heart muscle becomes stiff due to build up of amyloid deposits between the cardiac cells. What’s tricky is that the heart walls appear thick, but it isn’t true muscle hypertrophy, it's infiltration! As the heart stiffens, its ability to relax and fill properly drops, leading to a domino effect of physiological problems:
- Low stroke volume and reduced cardiac output
- High filling pressures → enlarged atria
- Arrhythmias like atrial fibrillation or conduction blocks
- Symptoms such as fatigue, swelling, shortness of breath, dizziness, and orthostatic hypotension
Because these changes develop slowly and mimic other cardiac conditions, cardiac amyloidosis is easy to miss early on.
AL amyloidosis is caused by abnormal plasma cells that produce misfolded immunoglobulin light chains, which can deposit in multiple organs, including the heart, kidneys, liver, and nerves. This version tends to progress quickly, making it the more aggressive form. In contrast, ATTR amyloidosis results from deposits of transthyretin (TTR), a protein made by the liver. ATTR comes in two forms:
- Age-related ATTR-wild type, seen mostly in older adults
- Hereditary ATTR, caused by mutations in the TTR gene
ATTR usually progresses more slowly than AL amyloidosis and often comes with a better overall prognosis.
With that said, thankfully my grandmother was diagnosed with the age-related ATTR-wild type form about 4 years ago. For a long time, her condition was quite the mystery. She had heart problems for years which necessitated her pacemaker over a decade ago, but nothing ever fully explained her symptoms. It wasn’t until she underwent a cardiac MRI (CMR) that the picture finally became clear. CMR is able to detect amyloids in the heart because it shows how the amyloid infiltrates the tissue and expands the extracellular space. This imaging technique has actually transformed how early and accurately physicians can diagnose cardiac amyloidosis.
Today, she’s able to manage her condition with newer medications designed to stabilize the transthyretin protein and slow disease progression. And honestly, for a woman about to celebrate her 91st birthday in January, she’s doing impressively well. She is an absolute rock star, and I hope to be at least half as cool as she is when I’m 90!
Here is an adorable photo of my grandma last year featuring my pup George when he was so so little 😊
If you're extra curious, a recent clinical trial has brought encouraging news for people living with ATTR cardiomyopathy. The study showed that vutrisiran, an RNA interference (RNAi) therapy that reduces transthyretin production, significantly lowered the risk of death and cardiovascular events compared with a placebo in ATTR-CM patients. Based on this success, vutrisiran received FDA approval in March 2025 as the first RNAi treatment for ATTR-CM! This is a huge breakthrough in slowing disease progression and improving outcomes for this condition.
References:
Fontana, M., Berk, J. L., Gillmore, J. D., Witteles, R. M., Grogan, M., Drachman, B., Damy, T., Garcia-Pavia, P., Taubel, J., Solomon, S. D., Sheikh, F. H., Tahara, N., González-Costello, J., Tsujita, K., Morbach, C., Pozsonyi, Z., Petrie, M. C., Delgado, D., Van der Meer, P., Jabbour, A., … HELIOS-B Trial Investigators (2025). Vutrisiran in Patients with Transthyretin Amyloidosis with Cardiomyopathy. The New England journal of medicine, 392(1), 33–44. https://doi.org/10.1056/NEJMoa2409134
Martinez-Naharro, A., Hawkins, P. N., & Fontana, M. (2018). Cardiac amyloidosis. Clinical medicine (London, England), 18(Suppl 2), s30–s35. https://doi.org/10.7861/clinmedicine.18-2-s30
How interesting! Glad to hear your grandma is doing well!! Out of curiosity, I wanted to ask if this has any correlation to the protein mis-folding that occurs in dementia and Alzheimer's patients. While there is not a clear connection, there is strong thought that there is a connection between the two of them in terms of how they form and act. I wonder if some of the medication treatments that you discussed could be translated to Alzheimer's treatment?
ReplyDeleteLachmann, H. J., & Hawkins, P. N. (2006). Systemic amyloidosis. Current Opinion in Pharmacology, 6(2), 214–220. https://doi.org/10.1016/J.COPH.2005.10.005
Tennent, G. A., Lovat, L. B., & Pepys, M. B. (1995). Serum amyloid P component prevents proteolysis of the amyloid fibrils of Alzheimer disease and systemic amyloidosis. Proceedings of the National Academy of Sciences, 92(10), 4299–4303. https://doi.org/10.1073/PNAS.92.10.4299