What is transthyretin amyloid cardiomyopathy (ATTR-CM)?
Transthyretin amyloid cardiomyopathy (ATTR-CM) is a serious and underdiagnosed condition in which misfolded transthyretin proteins accumulate in the heart muscle, leading to stiffening of the ventricular walls and eventually heart failure. These misfolded proteins form amyloid deposits that impair the heart’s ability to fill and pump blood efficiently.

What are the types of ATTR-CM?
There are two primary types of ATTR-CM: hereditary ATTR-CM (hATTR-CM), caused by a mutation in the TTR gene and passed down in families, and wild-type ATTR-CM (wATTR-CM), which occurs without any genetic mutation, usually in elderly men.

What are the risk factors for ATTR-CM?
Risk factors for hereditary ATTR-CM include a family history of the disease, older age, male sex, and being of Black descent. For wild-type ATTR-CM, older age and male sex are the main risk factors.

What are the symptoms of ATTR-CM?
Symptoms include those typical of heart failure such as shortness of breath, lower extremity swelling, coughing, wheezing, abdominal bloating, and fatigue. Additional symptoms may include palpitations, numbness or tingling in the hands and feet, carpal tunnel syndrome, spinal stenosis, and cognitive difficulties.

How is ATTR-CM diagnosed?
Diagnosis involves a combination of imaging techniques and laboratory tests. These include ECG (which may show low voltage or pseudo-infarct patterns), echocardiography (showing thickened walls and “apical sparing” on strain imaging), cardiac MRI (highlighting amyloid deposits via late gadolinium enhancement), and nuclear imaging with technetium-labeled tracers like Tc-PYP. Genetic testing can confirm hereditary forms, and a biopsy may be required if monoclonal proteins are present.

How is ATTR-CM treated?
Although there is no cure, treatment focuses on slowing disease progression and managing heart failure symptoms. The drugs stabilize the TTR protein or reduce the production of abnormal proteins. In advanced cases, heart or liver transplantation may be considered.

What is the prognosis or outlook for patients with ATTR-CM?
ATTR-CM is a progressive disease, but new therapies like tafamidis have shown improved survival rates and quality of life. Regular monitoring and early intervention are essential to manage symptoms and slow progression.

Can ATTR-CM be prevented?
While wild-type ATTR-CM cannot be prevented, those with the hereditary form can consider genetic counseling and preimplantation genetic diagnosis (PGD) to reduce the risk of passing the disease to offspring.

What are the complications of ATTR-CM?
Complications include heart failure, atrial fibrillation, and conduction abnormalities. Amyloid deposits can also affect the nervous system, leading to peripheral neuropathy, carpal tunnel syndrome, and spinal stenosis. Tendon ruptures and aortic stenosis are other potential complications.