How Is ATTR-CM Diagnosed?

ATTR-CM (transthyretin amyloid cardiomyopathy) is a rare heart condition that can lead to heart failure. However, with an early and accurate diagnosis, ATTR-CM is often treatable.

One challenge in obtaining a reliable diagnosis is that because the condition is uncommon and its symptoms often duplicate the early stages of heart failure, many doctors are not looking for ATTR-CM. A 2020 study suggests that the condition’s “elusive diagnosis” too often leads to misdiagnosis or a late diagnosis, but that new trends in viewing the heart via imaging are providing accurate assessments of ATTR-CM without relying on invasive tissue biopsy procedures.

What is ATTR-CM?

Transthyretin is a protein manufactured in the liver that circulates throughout the body, carrying substances such as thyroid hormone and vitamin A. In ATTR-CM, this protein doesn’t form normally. The malformed version of transthyretin develops into amyloid fibrils, which then form clumps in the wall of the heart. Thickened by the amyloid buildup, the heart muscle becomes stiff and unable to pump with the rigor necessary to supply blood to meet the body’s needs.

But ATTR-CM is not just a disease of the heart. The amyloid fibrils can build up in the nervous system, causing various forms of neuropathy, as well as other organs. That means getting a definitive diagnosis requires a thorough examination, testing, and review of symptoms. “When one makes a diagnosis here, one must be meticulous and careful in looking at the other organs, including the eye, to make sure that that this condition is not going on behind someone’s back,” says New York cardiologist Dr. Philip Weintraub.

Diagnosing ATTR-CM

Typically, an individual experiencing signs of heart failure might be evaluated for ATTR-CM. Common symptoms include:

• Awareness of a laboring or racing heart
• Coughing when lying down
• Fatigue
• Fluid retention or swelling, particularly in the lower limbs
• Lightheadedness
• Shortness of breath

And because ATTR-CM can present as neuropathy (tingling in the hands and feet), and particularly carpal tunnel syndrome, an individual with these complaints may be an especially good candidate for an ATTR-CM evaluation. One common form of ATTR-CM is known as “wild-type” ATTR-CM, because it has no genetic or other obvious origin or trigger. Another type of ATTR-CM can be hereditary—the result of a mutation of the transthyretin gene. If you have a relative with hereditary ATTR-CM, your diagnostic screening may also include a genetic test to see if you share the mutation.

“ATTR cardiomyopathy is, unfortunately, an underdiagnosed condition,” says Dr. Aeshita Dwivedi, a cardiologist at Lenox Hill Hopsital in New York.  “And as physicians, we always have to maintain a high suspicion for this disease. The common ways to diagnose it is starting with an ECG (electrocardiogram) and a physical exam.”

Electrocardiogram

An ECG is a non-invasive test that measures the electrical activity of the heart. A heart with increased thickness of the left ventricle (left ventricular hypertrophy) that produces a low-voltage ECG pattern should be further evaluated for ATTR-CM. A 2021 report notes that the low-voltage result occurs in about 25 to 40 percent of ATTR-CM cases, but is helpful in ruling out some other causes of left ventricular hypertrophy.

Echocardiogram

An echocardiogram, or “echo,” uses sound waves to create images of a beating heart. Recent advances in echocardiographic technology involving strain imaging can provide more detailed information about how the heart muscle is functioning at rest and when contracting. Certain abnormal strain images can suggest that ATTR-CM may be the cause.

MRI

Magnetic resonance imaging employs a combination of high-powered magnets and special x-rays to produce detailed images of soft tissue, such as heart muscle. Dr. Dwivedi suggests that an MRI of the heart using certain radioactive tracers or contrast dyes can help solidify an ATTR-CM diagnosis.

A 2019 study also notes that cardiac MRI may be especially helpful in making a diagnosis, however, an MRI is less helpful in distinguishing ATTR-CM from basic amyloidosis, which is the buildup of amyloid in the heart or other organs unrelated to changes in transthyretin.

Multigated Acquisition Scan (MUGA)

MUGA uses a radioactive tracer and special camera to measure the pumping ability of the ventricles. It’s helpful in determining whether reduced pumping function may be related to a type of cardiomyopathy or other cause.
“Recently we’ve learned that amyloid is more prevalent than we once thought,” Dr. Weintraub says. “And so therefore we need to diagnose it. Its presence can be isolated using what’s called a MUGA scan, that can demonstrate certain properties that are lost in terms of the heart’s ability to relax.”

Biopsy

While non-invasive screenings can be helpful in suggesting the presence of ATTR-CM, an endomyocardial biopsy—the removal of a small piece of heart muscle tissue—is still the “gold standard for ATTR-CM diagnosis,” according to a 2020 review of the condition’s diagnostic and treatment guidelines in the Journal of the American College of Cardiology (JACC).

“To do a cardiac biopsy, it’s usually done under conscious sedation, meaning you’re in a ‘twilight’ and not general anesthesia,” Dr. Dwivedi says. “We can thread the catheter through a vein and into the heart and take a small piece of the heart to look under the microscope.”  The JACC review also explains that for a definitive diagnosis, samples should be taken from four different locations to increase the chances of identifying the malformed transthyretin proteins.

What to Ask Your Doctor

• Could my symptoms be caused by ATTR-CM?
• What diagnostic options do I have to determine if I have ATTR-CM?
• How is ATTR-CM treated?
• Can ATTR-CM develop into other heart issues?
• Should I seek a second opinion?

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