If you or a loved one are living with hereditary ATTR amyloidosis with cardiomyopathy (hATTR-CM), you are likely well-acquainted with the challenges of heart health. You know the fatigue, the shortness of breath, and the routine of cardiac checkups. However, a landmark study from the University of Toronto suggests that for more than half of patients, the heart is only part of the picture.
The research, recently published in the journal CJC Open, reveals that over 50 percent of adults with hATTR-CM also have significant nerve damage (polyneuropathy). This is what doctors call a “mixed phenotype”—a profile where the disease attacks both the heart and the nervous system simultaneously.
For many patients, this discovery is the missing link. Understanding this connection isn’t just about labeling symptoms; it is the key to qualifying for additional, life-changing therapies that were previously out of reach.
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Understanding the Two Faces of hATTR
Hereditary ATTR is a rare genetic condition where a protein called transthyretin (TTR) misfolds and forms toxic clumps known as amyloid deposits. Think of these deposits like a sticky, hard wax that builds up where it doesn’t belong.
Traditionally, doctors viewed this disease through two lenses:
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The Heart (hATTR-CM): Deposits build up in the heart, making the muscle stiff and weak.
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The Nerves (hATTR-PN): Deposits build up in the nerves, leading to pain, numbness, and weakness.
The University of Toronto study proves that these two categories aren’t as separate as we once thought. In fact, for most patients, they overlap. The study found that even when a patient feels their symptoms are primarily “heart-related,” a closer look at the nerves often tells a different story.
The “Hidden” Symptoms: What to Look For
One of the most striking findings of the study was that nerve damage can be “silent.” Out of the 60 patients studied, 10 percent had nerve damage that only showed up on clinical tests, even though the patients hadn’t noticed any symptoms yet.
For others, the symptoms were present but perhaps overshadowed by their heart condition. Common signs of polyneuropathy include:
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Tingling or “Pins and Needles”: Often starting in the toes or fingers.
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Muscle Weakness: Difficulty climbing stairs or opening jars.
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Carpal Tunnel Syndrome: Numbness and pain in the wrist and hand (found in over 36% of the patients with nerve damage in the study).
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Loss of Balance: Feeling unsteady on your feet.
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Temperature Sensitivity: Being unable to feel if water is too hot or cold.
Why This Matters for Your Treatment
The most important reason to identify nerve damage is access to medication.
Currently, certain disease-modifying therapies (DMTs)—drugs that actually stop the body from producing the toxic proteins—are specifically approved only for patients with polyneuropathy. This means that if you are only diagnosed with cardiomyopathy (the heart form), you might be ineligible for these treatments, even though they could help stop the progression of your disease.
By identifying a “mixed phenotype,” your medical team can build a stronger case for you to receive these advanced therapies. Without a formal neurological diagnosis, you may be missing out on the most powerful tools available to fight hATTR.
What the Research Says About Your Genes
The study looked closely at different genetic mutations. While the Val142Ile mutation is most commonly linked to heart issues, the researchers found it was still the most frequent mutation in patients who also had nerve damage.
Furthermore, patients with the Val50Met mutation were even more likely to have this mixed profile. The takeaway for patients is clear: Your mutation doesn’t limit your symptoms. Just because your mutation is “supposed” to affect the heart doesn’t mean your nerves aren’t also at risk.
Your Next Steps: Advocacy and Assessment
The researchers are now calling for a “systematic referral” process. This means that every single person with an hATTR-CM diagnosis should be seen by a neurologist who specializes in amyloidosis, regardless of whether they feel “nerve pain” yet.
“Patients with hATTR-CM may often have underlying [polyneuropathy] that goes unrecognized,” the study authors concluded.
How to Take Action:
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Request a Referral: Ask your cardiologist for a referral to a neurologist for a “baseline neurological assessment.”
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Ask for an NCS: Request a Nerve Conduction Study (NCS). This test measures how fast electrical signals move through your nerves and can catch damage before you feel it.
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Track Your Symptoms: Keep a log of any numbness, tingling, or weakness, no matter how minor it seems.
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Discuss DMTs: Ask your doctor, “If we find nerve involvement, does that change which treatments I am eligible for?”
You are the most important member of your care team. By staying informed about the “mixed phenotype,” you can advocate for the comprehensive testing you deserve. Detecting nerve damage early isn’t just about managing pain—it’s about opening the door to the best possible treatment for your heart, your nerves, and your future.
