Transthyretin amyloid cardiomyopathy (ATTR-CM) is a progressive heart condition. It develops when a protein called transthyretin (TTR) becomes misshapen and accumulates as abnormal deposits, amyloid fibrils, within the heart muscle. Over time, these deposits cause the heart walls to stiffen, making it difficult for the heart to relax and fill with blood, which can lead to heart failure. This condition is often underdiagnosed, but an early and accurate diagnosis is important for effective management and to improve outcomes.
Recognizing the Clues
Symptoms of ATTR-CM can be subtle and often overlap with those of other, more common heart conditions, making diagnosis challenging. Common cardiac symptoms include shortness of breath, fatigue, and swelling in the lower legs and feet. Individuals may also experience an irregular heartbeat, atrial fibrillation, or other heart rhythm abnormalities.
Beyond cardiac manifestations, ATTR-CM can present with various non-cardiac symptoms. These include carpal tunnel syndrome and spinal stenosis, causing lower back pain. Other signs might involve bicep tendon rupture, peripheral neuropathy causing numbness or tingling, and digestive issues. The presence of multiple, seemingly disparate symptoms should prompt consideration for ATTR-CM.
The Diagnostic Pathway
Diagnosing ATTR-CM involves a sequence of tests, beginning with cardiac evaluations. An electrocardiogram (ECG) may show signs such as low voltage, conduction abnormalities, or a pseudo-infarct pattern, even without a history of heart attack. Echocardiography, an ultrasound of the heart, can reveal characteristic findings like increased ventricular wall thickness and impaired heart function, often with a preserved ejection fraction.
Advanced imaging techniques aid in diagnosis. Cardiac magnetic resonance imaging (CMR) provides detailed images of the heart and can show patterns of amyloid infiltration, such as late gadolinium enhancement, showing amyloid deposits. These imaging results can strongly suggest ATTR-CM but are not definitive on their own.
Non-invasive confirmation involves a technetium pyrophosphate (Tc-99m PYP) scintigraphy, commonly referred to as a bone scan. This nuclear imaging test uses a radiotracer that binds to amyloid deposits in the heart, making them visible. A positive scan, combined with the absence of a monoclonal gammopathy, is highly specific for ATTR-CM, often eliminating the need for a heart biopsy. To rule out another form of amyloidosis, AL amyloidosis, blood and urine tests such as serum and urine protein electrophoresis and free light chain assays are performed. If non-invasive tests are inconclusive, or if AL amyloidosis cannot be definitively excluded, a cardiac biopsy may be performed to examine heart tissue for amyloid deposits.
Genetic Testing and Ruling Out Other Conditions
Once ATTR-CM is suspected or diagnosed, genetic testing plays an important role in identifying the type of the condition. There are two main forms: wild-type ATTR-CM, which is associated with aging and not inherited, and hereditary ATTR-CM, which results from a genetic mutation and can be passed down through families. Genetic testing helps differentiate between these types, which is important for understanding implications for family members and guiding treatment strategies.
Doctors must also differentiate ATTR-CM from other conditions that present with similar symptoms or imaging findings. Differential diagnosis is important because ATTR-CM can mimic more common conditions such as heart failure with preserved ejection fraction, hypertensive cardiomyopathy, or hypertrophic cardiomyopathy. The presence of overlapping symptoms requires thorough evaluation to ensure accurate diagnosis and prevent misattribution.
The Importance of Early Diagnosis
Early and accurate diagnosis of ATTR-CM is important because it enables timely intervention. The disease is progressive, and early identification enables disease-modifying therapies to slow progression. These therapies work best when started before significant heart damage has occurred.
Timely diagnosis also helps improve the patient’s quality of life and can extend survival. It enables appropriate management of symptoms and complications. For individuals with hereditary ATTR-CM, early diagnosis facilitates genetic counseling and screening for at-risk family members to consider early monitoring or preventive measures.