Transthyretin amyloid cardiomyopathy (ATTR-CM) is a serious heart condition caused by the buildup of abnormal proteins, called amyloid fibrils, in the heart. These deposits stiffen the heart muscle, hindering its ability to pump blood effectively. This progressive stiffening can lead to heart failure, where the heart cannot adequately meet the body’s demands. Understanding ATTR-CM is important for recognizing its signs, timely diagnosis, and exploring treatment options.
Understanding ATTR Cardiomyopathy
In ATTR cardiomyopathy, the specific protein involved is transthyretin (TTR), which normally circulates in the bloodstream and helps transport thyroid hormone and vitamin A. When TTR proteins become unstable, they misfold and aggregate into amyloid fibrils. These fibrils deposit in the heart muscle, leading to thickening and stiffening of the ventricles. This impaired function makes it difficult for the heart to pump blood efficiently, eventually leading to heart failure.
There are two main types of ATTR cardiomyopathy: hereditary ATTR (hATTR or ATTRv) and wild-type ATTR (wATTR or senile amyloidosis). Hereditary ATTR is caused by a genetic mutation in the TTR gene. Symptoms can manifest as early as 30 years of age, though they often appear later. This form is more prevalent in certain populations, including those of African, Portuguese, Brazilian, Swedish, and Japanese descent. Wild-type ATTR does not involve a genetic mutation and affects older adults, most commonly men over 60, without a family history.
Recognizing the Signs
Symptoms of ATTR cardiomyopathy can be subtle and often mimic other heart conditions, leading to delayed diagnosis. Progressive shortness of breath may occur even at rest or with minimal exertion. Patients may also experience fatigue, swelling in the legs, ankles, and feet, and abdominal bloating due to fluid retention. Irregular heartbeats or palpitations are common as amyloid deposits disrupt the heart’s electrical conduction system.
ATTR cardiomyopathy can also present with non-cardiac signs due to amyloid deposition in other tissues. Carpal tunnel syndrome, causing pain, numbness, and tingling in the hands and fingers, is a common non-cardiac indicator, often affecting both wrists. Spinal stenosis, a narrowing of the spinal canal that can compress nerves, may precede cardiac involvement, especially in wild-type ATTR. Peripheral neuropathy, characterized by numbness, tingling, or pain in the hands and feet, is another symptom, particularly in hereditary ATTR. Gastrointestinal issues can also occur due to amyloid affecting the digestive tract.
The Diagnostic Journey
Diagnosing ATTR cardiomyopathy can be challenging due to its non-specific symptoms. The process begins with a thorough medical history and physical examination, where ATTR-CM may be suspected in older patients with recurrent heart failure.
An echocardiogram, an ultrasound of the heart, can reveal thickened heart muscle and restrictive filling patterns characteristic of amyloid deposits. Cardiac magnetic resonance imaging (MRI) provides more detailed images of the heart’s structure and identifies amyloid infiltration patterns. Nuclear scintigraphy, using technetium-99m pyrophosphate (PYP) scans, is a key diagnostic tool. This scan involves injecting a radiotracer that binds to amyloid deposits, allowing visualization with a gamma camera. A positive PYP scan (visual grade 2 or 3), combined with tests ruling out light chain amyloidosis, can provide a definitive diagnosis without a heart biopsy.
Genetic testing is crucial once ATTR-CM is confirmed, regardless of age. This testing differentiates between hereditary and wild-type forms by identifying TTR gene mutations. Knowing the specific type guides treatment selection and allows for screening of at-risk family members. Early and accurate diagnosis leads to better treatment outcomes and can help prevent disease progression.
Treatment Approaches and Management
Treatment for ATTR cardiomyopathy focuses on two main strategies: targeting the underlying disease process by stabilizing or reducing TTR protein production, and providing supportive care to manage symptoms.
TTR stabilizers, such as tafamidis, bind to the TTR protein, preventing it from misfolding and forming amyloid fibrils. Tafamidis is an approved medication shown to slow disease progression, reduce mortality, and improve quality of life for patients with both wild-type and hereditary forms. TTR gene silencers, like patisiran and inotersen, reduce TTR protein production by interfering with its genetic instructions in the liver. While initially approved for hereditary ATTR polyneuropathy, patisiran has also shown beneficial effects on cardiac function, including reducing left ventricular wall thickness and improving cardiac biomarkers.
Supportive care measures manage ATTR-CM symptoms. Diuretics help reduce fluid retention and alleviate shortness of breath and swelling. Medications to control heart rhythm problems, such as atrial fibrillation, are prescribed. Lifestyle adjustments, including dietary changes and exercise, support overall heart health. In advanced cases where other treatments are insufficient, a heart transplant may be considered, though this is rare. Management of ATTR-CM involves a multidisciplinary team of specialists, including cardiologists, neurologists, and genetic counselors, to ensure coordinated and individualized care.