Heart disease remains the leading cause of death in the United States, responsible for more than 695,000 deaths each year. Yet within this broad category exists a lesser-known form of heart failure that is frequently misdiagnosed, especially in Black patients: transthyretin amyloid cardiomyopathy (ATTR-CM). This condition, though serious, often goes unnoticed for years because its symptoms mimic more common illnesses. Understanding ATTR-CM is critical, particularly for Black Americans who face a significantly higher risk.

ATTR-CM is caused by the misfolding of a protein called transthyretin (TTR). When this protein misfolds, it clumps together into amyloid deposits that gradually infiltrate the heart muscle. Over time, these deposits stiffen the heart, impairing its ability to pump blood. Unlike typical heart failure, the heart may look strong on the outside but function poorly because it cannot expand or contract as it should.

Because the early symptoms are subtle and nonspecific—fatigue, mild swelling in the legs, or shortness of breath—patients often dismiss them, or clinicians attribute them to aging, stress, or high blood pressure.

A Genetic Risk Hiding in Plain Sight

One of the most important findings in ATTR-CM research is that a specific genetic change dramatically increases risk among Black Americans. The V122I TTR variant (also called V142I in some numbering systems) is found in 3–4% of African Americans, or roughly 1 in 25 individuals. This makes hereditary ATTR-CM one of the most common genetic contributors to heart failure worldwide—yet it receives little attention in routine care.

This variant causes TTR proteins to become unstable and more likely to misfold, increasing the chances of amyloid buildup in the heart. Despite this well-established risk, most Black patients are never screened for the variant, even when they present with typical symptoms of ATTR-CM.

Studies show:

• Up to 10–15% of older adults with heart failure and preserved ejection fraction (HFpEF) may have ATTR-CM.
• ATTR-CM is twice as common in Black patients as previously thought once modern imaging is used.
• Many Black men over age 60 with unexplained heart failure likely have undiagnosed hereditary ATTR-CM.

In other words, ATTR-CM isn’t rare — it’s under-recognized.

Why ATTR-CM Is Difficult to Detect

ATTR-CM affects both the heart and other tissues, which means the symptoms can resemble a wide range of unrelated conditions. This contributes to long delays in diagnosis—often averaging 3–5 years from symptom onset.

Key symptoms include:

• Chronic fatigue
• Shortness of breath during routine activities
• Swelling in legs or ankles
• Irregular heartbeat (atrial fibrillation is common)
• Hand numbness or tingling
• Carpal tunnel syndrome (especially if it occurs in both hands)
• Weakness or tingling in the feet
• Difficulty climbing stairs
• Unexplained weight loss
• A “thickened” heart on imaging that doesn’t behave like typical hypertension-related thickening

Because these symptoms overlap with very common conditions—hypertension, diabetes, aging, arthritis—ATTR-CM is often overlooked.

For many Black patients, this overlap is especially problematic because hypertension and diabetes rates are already higher in the Black community. As a result, symptoms that should raise suspicion for amyloidosis instead get attributed to those better-known conditions.

The Diagnostic Gap in Black Communities

Several systemic issues contribute to ATTR-CM being missed more often in Black patients:

1. Limited awareness in primary care settings

Although specialists increasingly recognize ATTR-CM, many primary care providers and even some cardiologists are unfamiliar with the V122I variant’s prevalence.

2. Overlapping symptoms with common chronic diseases

Fatigue, swelling, neuropathy, and heart thickening are often written off as complications of diabetes or high blood pressure.

3. Delayed referrals to amyloidosis specialists

Patients in underserved communities may struggle to access cardiologists familiar with ATTR-CM or the specialized testing it requires.

4. Lack of access to advanced diagnostic tools

Definitive diagnosis typically requires:

• PYP (pyrophosphate) nuclear imaging scans
• Genetic testing
• Cardiac MRI in some cases
  These tools may not be readily available in community hospitals or rural areas.

5. Underrecognition of early warning signs

Conditions like bilateral carpal tunnel syndrome, unexplained neuropathy, or tendon ruptures are now recognized as possible early indicators of hereditary ATTR—but these signs are frequently missed in Black patients.

How ATTR-CM Is Diagnosed

Modern diagnosis of ATTR-CM relies on a combination of clinical history, imaging, and genetic testing. The goal is to identify amyloid deposits early—before significant heart damage occurs.

Typical tests include:

• Technetium-99m pyrophosphate (PYP) scan: The most accurate non-invasive test for ATTR-CM
• Genetic testing for TTR variants such as V122I
• Echocardiogram showing increased wall thickness
• Electrocardiogram (EKG) showing low voltage despite thickened heart walls
• Cardiac MRI to assess tissue characteristics

If ATTR-CM is diagnosed early, FDA-approved medication now exists that can slow the progression of the disease. Treatment does not remove amyloid already present, but it stabilizes the TTR protein, reducing further damage.

What Early Detection Could Mean

Catching ATTR-CM early can:

• Extend life expectancy
• Preserve heart function
• Reduce hospitalizations
• Prevent severe heart failure
• Maintain independence and mobility
• Improve quality of life for years

Because hereditary ATTR-CM tends to progress faster in individuals with the V122I variant, early identification is especially important in Black families.

How to Advocate for Yourself or a Loved One

If heart failure symptoms persist despite treatment — especially if there is a family history of early heart disease — it is appropriate to ask:

• “Could this be ATTR-CM?”
• “Should I be tested for the V122I genetic variant?”
• “Can I get a PYP scan?”
• “Can I be referred to a cardiologist who specializes in amyloidosis?”

Self-advocacy matters. Studies show that people who proactively ask about amyloidosis receive diagnosis months or even years earlier.

The Bottom Line

ATTR-CM is not rare among Black patients — it is underdiagnosed.
With 1 in 25 Black Americans carrying the V122I variant, awareness is crucial. Early recognition can mean the difference between manageable disease and irreversible heart failure.

Understanding the symptoms, knowing the genetic risks, and requesting appropriate tests are powerful steps toward protecting yourself and your family.

Knowledge saves lives. Awareness empowers communities. And asking the right questions can change the course of this silent, often overlooked disease.