hATTR Amyloidosis in Black Adults: The V122I Stiff-Heart Variant

Hereditary transthyretin amyloidosis, written hATTR, is an inherited disease in which a blood protein called transthyretin misfolds and builds up in tissue. When it collects in the walls of the heart, the muscle stiffens and cannot relax and fill properly. The result is heart failure that often gets labeled something else for years. One specific variant, V122I (also written p.V142I), is carried by roughly 3 to 4 percent of Black Americans, which makes it a major and under-recognized driver of heart failure in this population.

Transthyretin is a normal protein your liver makes to carry thyroid hormone and vitamin A. In a healthy body it stays folded as a stable four-part structure. A variant like V122I makes that structure come apart more easily. The loose pieces stick together into deposits called amyloid fibrils, which settle into organs. In transthyretin cardiac amyloidosis, those deposits pack the heart muscle, thicken the walls, and turn a flexible pump into a stiff one. Blood backs up, pressure rises in the lungs and the legs, and the body reads it as heart failure.

Because the heart still squeezes, the ejection fraction often looks normal on an echocardiogram. That is why this disease hides inside the diagnosis of heart failure with preserved ejection fraction. The pump number reads fine, the patient feels worse every month, and the real cause sits in the muscle wall.

The V122I variant is concentrated in people of West African ancestry. In 1997, a New England Journal of Medicine study reported that about 3.9 percent of Black Americans carry it, and that isolated cardiac amyloidosis after age 60 was roughly four times more common in Black than in white people. A 2015 study of nearly 4,000 Black adults in the Atherosclerosis Risk in Communities cohort confirmed that carriers had a higher risk of heart failure and a shorter time free of it than non-carriers.

Carrying the variant is not the same as having the disease. Many carriers never develop symptoms. But the variant is common enough, and the disease serious enough, that any Black adult over 60 with unexplained heart failure, thick heart walls, or the warning signs below deserves to have it ruled out. Carriers also face higher rates of irregular heart rhythm: a 2021 analysis found V122I was linked to more atrial fibrillation and ischemic stroke among Black Americans.

Amyloid does not start in the heart. It often shows up first in the wrists and the nerves, sometimes a decade before any breathlessness. The pattern below should raise the question, especially together:

• Bilateral carpal tunnel syndrome. Numb, tingling hands in both wrists, often years before heart symptoms. In one study of older adults having carpal tunnel surgery, about 10 percent had amyloid in the wrist tissue.
• Heart failure with preserved ejection fraction. Shortness of breath, swelling, and fatigue while the echo ejection fraction reads normal.
• Thick walls on echo with low voltage on the ECG. The heart walls look thickened, but the electrical signal on the ECG is unexpectedly small. That mismatch is a classic clue, because amyloid is dead weight, not working muscle.
• Trouble tolerating standard heart-failure medicines. Drugs like beta-blockers, ACE inhibitors, and ARBs can drop blood pressure too far in a stiff amyloid heart, so patients feel worse instead of better.
• Numbness, tingling, or burning in the feet and legs. Peripheral neuropathy from amyloid in the nerves, sometimes mistaken for diabetic nerve damage.
• A lumbar spinal stenosis or biceps tendon rupture history that came earlier or worse than expected.

The diagnosis used to require a heart biopsy. It does not anymore. A nuclear imaging test called a technetium pyrophosphate scan, often shortened to PYP or Tc-99m PYP, lights up transthyretin amyloid in the heart. A 2016 multicenter study showed this scan can diagnose transthyretin cardiac amyloidosis without a biopsy in most cases, as long as one other type of amyloid is excluded first.

That exclusion step matters. There are two main forms of cardiac amyloidosis: transthyretin (ATTR) and light-chain (AL), which comes from a blood-cell disorder and is treated completely differently and more urgently. Before reading a PYP scan as positive, doctors check blood and urine for abnormal light chains. Genetic testing then tells whether the transthyretin amyloid is hereditary, like V122I, or the age-related wild-type form. The genetic result also flags whether relatives should be tested, since V122I is autosomal dominant: each child of a carrier has a 50 percent chance of inheriting it.

For years there was nothing to slow this disease. That changed. Tafamidis, a pill that stabilizes the transthyretin protein so it stops falling apart, was tested in the ATTR-ACT trial published in 2018. Across 441 patients, tafamidis lowered death and cardiovascular hospitalizations compared with placebo over 30 months. It is now FDA-approved for transthyretin cardiac amyloidosis.

A newer stabilizer, acoramidis, was tested in the ATTRibute-CM trial published in 2024 and also improved a combined measure of survival, hospitalization, and heart function against placebo. Other approaches that lower transthyretin production are approved or in trials for the nerve form of the disease. The shared lesson is the same: the earlier the diagnosis, the more heart muscle there is left to protect.

Start with the cardiologist or primary doctor who manages your heart and say the word amyloidosis out loud. Bring the warning-sign list. If you carry V122I or have a confirmed diagnosis, ask for referral to an amyloidosis or advanced heart-failure center, where PYP scans, genetic counseling, and the newer drugs are routine. Many Black patients report being heard faster by clinicians who understand the V122I risk in this community. You can find a Black cardiologist or Black-serving heart specialist in our directory. If a relative has been diagnosed, share that result with your own doctor, since first-degree relatives can be tested.